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  • 1.
    Alassaad, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Improving the Quality and Safety of Drug Use in Hospitalized Elderly: Assessing the Effects of Clinical Pharmacist Interventions and Identifying Patients at Risk of Drug-related Morbidity and Mortality2014Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Older people admitted to hospital are at high risk of rehospitalization and medication errors. We have demonstrated, in a randomized controlled trial, that a clinical pharmacist intervention reduces the incidence of revisits to hospital for patients aged 80 years or older admitted to an acute internal medicine ward. The aims of this thesis were to further study the effects of the intervention and to investigate possibilities of targeting the intervention by identifying predictors of treatment response or adverse health outcomes.

    The effect of the pharmacist intervention on the appropriateness of prescribing was assessed, by using three validated tools. This study showed that the quality of prescribing was improved for the patients in the intervention group but not for those in the control group. However, no association between the appropriateness of prescribing at discharge and revisits to hospital was observed.

    Subgroup analyses explored whether the clinical pharmacist intervention was equally effective in preventing emergency department visits in patients with few or many prescribed drugs and in those with different levels of inappropriate prescribing on admission. The intervention appeared to be most effective in patients taking fewer drugs, but the treatment effect was not altered by appropriateness of prescribing.

    The most relevant risk factors for rehospitalization and mortality were identified for the same study population, and a score for risk-estimation was constructed and internally validated (the 80+ score). Seven variables were selected. Impaired renal function, pulmonary disease, malignant disease, living in a nursing home, being prescribed an opioid and being prescribed a drug for peptic ulcer or gastroesophageal reflux disease were associated with an increased risk, while being prescribed an antidepressant drug (tricyclic antidepressants not included) was linked with a lower risk. These variables made up the components of the 80+ score. Pending external validation, this score has potential to aid identification of high-risk patients.

    The last study investigated the occurrence of prescription errors when patients with multi-dose dispensed (MDD) drugs were discharged from hospital. Twenty-five percent of the MDD orders contained at least one medication prescription error. Almost half of the errors were of moderate or major severity, with potential to cause increased health-care utilization. 

    Delarbeid
    1. Effects of Pharmacists' Interventions on Appropriateness of Prescribing and Evaluation of the Instruments' (MAI, STOPP and STARTs') Ability to Predict Hospitalization-Analyses from a Randomized Controlled Trial
    Åpne denne publikasjonen i ny fane eller vindu >>Effects of Pharmacists' Interventions on Appropriateness of Prescribing and Evaluation of the Instruments' (MAI, STOPP and STARTs') Ability to Predict Hospitalization-Analyses from a Randomized Controlled Trial
    Vise andre…
    2013 (engelsk)Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 5, s. e62401-Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Background: Appropriateness of prescribing can be assessed by various measures and screening instruments. The aims of this study were to investigate the effects of pharmacists' interventions on appropriateness of prescribing in elderly patients, and to explore the relationship between these results and hospital care utilization during a 12-month follow-up period. Methods: The study population from a previous randomized controlled study, in which the effects of a comprehensive pharmacist intervention on re-hospitalization was investigated, was used. The criteria from the instruments MAI, STOPP and START were applied retrospectively to the 368 study patients (intervention group (I) n = 182, control group (C) n = 186). The assessments were done on admission and at discharge to detect differences over time and between the groups. Hospital care consumption was recorded and the association between scores for appropriateness, and hospitalization was analysed. Results: The number of Potentially Inappropriate Medicines (PIMs) per patient as identified by STOPP was reduced for I but not for C (1.42 to 0.93 vs. 1.46 to 1.66 respectively, p<0.01). The number of Potential Prescription Omissions (PPOs) per patient as identified by START was reduced for I but not for C (0.36 to 0.09 vs. 0.42 to 0.45 respectively, p<0.001). The summated score for MAI was reduced for I but not for C (8.5 to 5.0 and 8.7 to 10.0 respectively, p<0.001). There was a positive association between scores for MAI and STOPP and drug-related readmissions (RR 8-9% and 30-34% respectively). No association was detected between the scores of the tools and total re-visits to hospital. Conclusion: The interventions significantly improved the appropriateness of prescribing for patients in the intervention group as evaluated by the instruments MAI, STOPP and START. High scores in MAI and STOPP were associated with a higher number of drug-related readmissions.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-203295 (URN)10.1371/journal.pone.0062401 (DOI)000319107900008 ()
    Tilgjengelig fra: 2013-07-08 Laget: 2013-07-08 Sist oppdatert: 2017-12-06bibliografisk kontrollert
    2. The effects of pharmacist intervention on emergency department visits in patients 80 years and older: subgroup analyses by number of prescribed drugs and appropriate prescribing
    Åpne denne publikasjonen i ny fane eller vindu >>The effects of pharmacist intervention on emergency department visits in patients 80 years and older: subgroup analyses by number of prescribed drugs and appropriate prescribing
    Vise andre…
    2014 (engelsk)Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, nr 11, s. e111797-Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Background: Clinical pharmacist interventions have been shown to have positive effect on occurrence of drug-related issues as well as on clinical outcomes. However, evidence about which patients benefiting most from the interventions is limited. We aimed to explore whether pharmacist intervention is equally effective in preventing emergency department (ED) visits in patients with few or many prescribed drugs and in those with different levels of inappropriate prescribing. Methods: Patient and outcome data from a randomized controlled trial exploring the clinical effects of a ward-based pharmacist intervention in patients, 80 years and older, were used. The patients were divided into subgroups according to the number of prescribed drugs (< 5 or >= 5 drugs) and the level of inappropriate prescribing [using the Screening Tool Of Older People's potentially inappropriate Prescriptions (STOPP) and the Screening Tool to Alert doctors to Right Treatment (START) with a score of >= 2 (STOPP) and >= 1 (START) as cutoff points]. The effect of the intervention on the number of times the different subgroups visited the ED was analyzed. Results: The pharmacist intervention was more effective with respect to the number of subsequent ED visits in patients taking < 5 drugs on admission than in those taking >= 5 drugs. The rate ratio (RR) for a subsequent ED visit was 0.22 [95% confidence interval (CI) 0.09-0.52] for,5 drugs and 0.70 (95% CI 0.47-1.04) for >= 5 drugs (p = 0.02 for the interaction). The effect of intervention did not differ between patients with high or low STOPP or START scores. Conclusion: In this exploratory study, the pharmacist intervention appeared to be more effective in preventing visits to the ED for patients who were taking fewer drugs before the intervention. Our analysis of STOPP and START scores indicated that the level of inappropriate prescribing on admission had no effect on the outcomes of intervention with respect to ED visits.

    Emneord
    clinical pharmacy, medication review, inappropriate prescribing, polypharmacy, geriatrics
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-234485 (URN)10.1371/journal.pone.0111797 (DOI)000345558100122 ()25364817 (PubMedID)
    Tilgjengelig fra: 2014-10-20 Laget: 2014-10-20 Sist oppdatert: 2017-12-05bibliografisk kontrollert
    3. A tool for prediction of risk of rehospitalization and mortality in hospitalized elderly
    Åpne denne publikasjonen i ny fane eller vindu >>A tool for prediction of risk of rehospitalization and mortality in hospitalized elderly
    Vise andre…
    (engelsk)Artikkel i tidsskrift (Fagfellevurdert) Submitted
    Abstract [en]

    Importance: Older patients with multiple co-morbidities and multi-drug use are at high risk of revisits to hospital and mortality, which poses an increasing health economic burden.

    Objective: To construct and internally validate a risk score, the “80+ score”, for revisits to hospital and mortality for older patients, incorporating aspects of pharmacotherapy. Our secondary aim was to compare the discriminatory ability of the score with that of three validated tools for measuring inappropriate prescribing: Screening Tool of Older Person’s Prescriptions (STOPP), Screening Tool to Alert doctors to Right Treatment (START) and Medication Appropriateness Index (MAI).

    Design: Secondary use of data from a randomized controlled trial investigating effects of a comprehensive pharmacist intervention, conducted in 2005-2006.

    Setting: Two acute internal medicine wards at Uppsala University hospital.

    Participants: Data from 368 patients, 80 years and older, admitted to one of the study wards.

    Main outcomes and measures: Time to rehospitalization or death during the year after discharge from hospital. Candidate variables were selected among a large number of clinical and drug-specific variables. After a selection process, a score for risk-estimation was constructed.  The score was internally validated, and the discriminatory ability of the new score and of STOPP, START and MAI was assessed using C-statistics.

    Results: Seven variables were selected for the 80+ score. Impaired renal function, pulmonary disease (chronic obstructive pulmonary disease [COPD or asthma]), malignant disease (past or present), living in nursing home, being prescribed an opioid or being prescribed a drug for peptic ulcer or gastroesophageal reflux disease was associated with an increased risk, while being prescribed an antidepressant drug (tricyclic antidepressants not included) was linked to a lower risk of the outcome. These variables made up the components of the 80+ score. The C-statistics were 0.71 (80+ score), 0.57 (STOPP), 0.54 (START) and 0.63 (MAI).

    Conclusion and Relevance: We developed and internally validated a score for prediction of risk of rehospitalization and mortality in hospitalized older people. The score discriminated risk considerably better than available tools for inappropriate prescribing. Pending external validation, this score can aid in clinical identification of high-risk patients and targeting of interventions. 

    Emneord
    Geriatrics, drugs, risk-estimation, polypharmacy, pharmacotherapy
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-234487 (URN)
    Tilgjengelig fra: 2014-10-20 Laget: 2014-10-20 Sist oppdatert: 2015-02-03bibliografisk kontrollert
    4. Prescription and transcription errors in multidose-dispensed medications on discharge from hospital: an observationaland interventional study
    Åpne denne publikasjonen i ny fane eller vindu >>Prescription and transcription errors in multidose-dispensed medications on discharge from hospital: an observationaland interventional study
    Vise andre…
    2013 (engelsk)Inngår i: Journal of Evaluation In Clinical Practice, ISSN 1356-1294, E-ISSN 1365-2753, Vol. 19, nr 1, s. 185-191Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Background 

    Medication errors frequently occur when patients are transferred between health care settings. The main objective of this study was to investigate the frequency, type and severity of prescribing and transcribing errors for drugs dispensed in multidose plastic packs when patients are discharged from the hospital. The secondary objective was to correct identified errors and suggest measures to promote safe prescribing.

    Methods 

    The drugs on the patients' multidose drug dispensing (MDD) order sheets and the medication administration records were reconciled prior to the MDD orders being sent to the pharmacy for dispensing. Discrepancies were recorded and the prescribing physician was notified and given the opportunity to change the order. Discrepancies categorized as unintentional and related to the discharge process were subject to further analysis.

    Results 

    Seventy-two (25%) of the 290 reviewed MDD orders had at least one discharge error. In total, 120 discharge errors were identified, of which 49 (41%) were assessed as being of moderate and three (3%) of major severity. Orders with a higher number of medications and orders from the orthopaedic wards had a significantly higher error rate.

    Conclusion 

    The main purpose of the MDD system is to increase patient safety by reducing medication errors. However, this study shows that prescribing and transcribing errors frequently occur when patients are hospitalized. Because the population enrolled in the MDD system is an elderly, physically vulnerable group with a high number of prescribed drugs, preventive measures to ensure safe prescribing of MDD drugs are warranted.

    Emneord
    medication error, medication reconciliation, multi-dose dispensed medications, patient safety, prescription error, transition of care
    HSV kategori
    Forskningsprogram
    Farmaceutisk vetenskap; Farmakokinetik och läkemedelsterapi
    Identifikatorer
    urn:nbn:se:uu:diva-167137 (URN)10.1111/j.1365-2753.2011.01798.x (DOI)000314114400026 ()
    Tilgjengelig fra: 2012-01-22 Laget: 2012-01-22 Sist oppdatert: 2018-01-12
  • 2.
    Almandoz-Gil, Leire
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Lindström, Veronica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Sigvardson, Jessica
    BioArctic, Stockholm, Sweden.
    Kahle, Philipp J.
    Univ Tubingen, Hertie Inst Clin Brain Res, Dept Neurodegenerat, Lab Funct Neurogenet, Tubingen, Germany.;German Ctr Neurodegenerat Dis, Tubingen, Germany..
    Lannfelt, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Ingelsson, Martin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Bergström, Joakim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Mapping of Surface-Exposed Epitopes of In Vitro and In Vivo Aggregated Species of Alpha-Synuclein2017Inngår i: Cellular and molecular neurobiology, ISSN 0272-4340, E-ISSN 1573-6830, Vol. 37, nr 7, s. 1217-1226Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aggregated alpha-synuclein is the main component of Lewy bodies, intraneuronal deposits observed in Parkinson's disease and dementia with Lewy bodies. The objective of the study was to identify surface-exposed epitopes of alpha-synuclein in vitro and in vivo formed aggregates. Polyclonal immunoglobulin Y antibodies were raised against short linear peptides of the alpha-synuclein molecule. An epitope in the N-terminal region (1-10) and all C-terminal epitopes (90-140) were found to be exposed in an indirect enzyme-linked immunosorbent assay (ELISA) using recombinant monomeric, oligomeric, and fibrillar alpha-synuclein. In a phospholipid ELISA, the N-terminus and mid-region of alpha-synuclein (i.e., 1-90) were associated with phosphatidylserine and thus occluded from antibody binding. The antibodies that reacted most strongly with epitopes in the in vitro aggregates (i.e., 1-10 and epitopes between positions 90-140) also labeled alpha-synuclein inclusions in brains from transgenic (Thy-1)-h[A30P] alpha-synuclein mice and Lewy bodies and Lewy neurites in brains of patients with alpha-synucleinopathies. However, differences in reactivity were observed with the C-terminal antibodies when brain tissue from human and transgenic mice was compared. Taken together, the study shows that although similar epitopes are exposed in both in vitro and in vivo formed alpha-synuclein inclusions, structural heterogeneity can be observed between different molecular species.

  • 3.
    Almkvist, Ove
    et al.
    Karolinska Inst, Ctr Alzheimer Res, Dept Neurobiol Care Sci & Soc, Div Translat Alzheimer Neurobiol, Stockholm, Sweden.;Karolinska Univ Hosp Huddinge, Dept Geriatr Med, Stockholm, Sweden.;Stockholm Univ, Dept Psychol, Stockholm, Sweden..
    Rodriguez-Vieitez, Elena
    Karolinska Inst, Ctr Alzheimer Res, Dept Neurobiol Care Sci & Soc, Div Translat Alzheimer Neurobiol, Stockholm, Sweden..
    Thordardottir, Steinunn
    Karolinska Univ Hosp Huddinge, Dept Geriatr Med, Stockholm, Sweden.;Karolinska Inst, Div Neurogeriatr, Dept Neurobiol Care Sci & Soc, Ctr Alzheimer Res, Stockholm, Sweden..
    Amberla, Kaarina
    Karolinska Univ Hosp Huddinge, Dept Geriatr Med, Stockholm, Sweden..
    Axelman, Karin
    Karolinska Univ Hosp Huddinge, Dept Geriatr Med, Stockholm, Sweden..
    Basun, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Kinhult-Stahlbom, Anne
    Karolinska Univ Hosp Huddinge, Dept Geriatr Med, Stockholm, Sweden.;Karolinska Inst, Div Neurogeriatr, Dept Neurobiol Care Sci & Soc, Ctr Alzheimer Res, Stockholm, Sweden..
    Lilius, Lena
    Karolinska Univ Hosp Huddinge, Dept Geriatr Med, Stockholm, Sweden..
    Remes, Anne
    Univ Eastern Finland, Inst Clin Med Neurol, Dept Neurol, Kuopio, Finland..
    Wahlund, Lars-Olof
    Karolinska Univ Hosp Huddinge, Dept Geriatr Med, Stockholm, Sweden.;Karolinska Inst, Div Clin Geriatr, Dept Neurobiol Care Sci & Soc, Ctr Alzheimer Res, Stockholm, Sweden..
    Viitanen, Matti
    Karolinska Univ Hosp Huddinge, Dept Geriatr Med, Stockholm, Sweden.;Karolinska Inst, Div Clin Geriatr, Dept Neurobiol Care Sci & Soc, Ctr Alzheimer Res, Stockholm, Sweden.;Turku City Hosp, Dept Geriatr, Turku, Finland.;Univ Turku, Turku, Finland..
    Lannfelt, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Graff, Caroline
    Karolinska Univ Hosp Huddinge, Dept Geriatr Med, Stockholm, Sweden.;Karolinska Inst, Div Neurogeriatr, Dept Neurobiol Care Sci & Soc, Ctr Alzheimer Res, Stockholm, Sweden..
    Predicting Cognitive Decline across Four Decades in Mutation Carriers and Non-carriers in Autosomal-Dominant Alzheimer's Disease2017Inngår i: Journal of the International Neuropsychological Society, ISSN 1355-6177, E-ISSN 1469-7661, Vol. 23, nr 3, s. 195-203Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives: The aim of this study was to investigate cognitive performance including preclinical and clinical disease course in carriers and non-carriers of autosomal-dominant Alzheimer's disease (adAD) in relation to multiple predictors, that is, linear and non-linear estimates of years to expected clinical onset of disease, years of education and age. Methods: Participants from five families with early-onset autosomal-dominant mutations (Swedish and Arctic APP, PSEN1 M146V, H163Y, and I143T) included 35 carriers (28 without dementia and 7 with) and 44 non-carriers. All participants underwent a comprehensive clinical evaluation, including neuropsychological assessment at the Memory Clinic, Karolinska University Hospital at Huddinge, Stockholm, Sweden. The time span of disease course covered four decades of the preclinical and clinical stages of dementia. Neuropsychological tests were used to assess premorbid and current global cognition, verbal and visuospatial functions, short-term and episodic memory, attention, and executive function. Results: In carriers, the time-related curvilinear trajectory of cognitive function across disease stages was best fitted to a formulae with three predictors: years to expected clinical onset (linear and curvilinear components), and years of education. In non-carriers, the change was minimal and best predicted by two predictors: education and age. The trajectories for carriers and non-carriers began to diverge approximately 10 years before the expected clinical onset in episodic memory, executive function, and visuospatial function. Conclusions: The curvilinear trajectory of cognitive functions across disease stages was mimicked by three predictors in carriers. In episodic memory, executive and visuospatial functions, the point of diverging trajectories occurred approximately 10 years ahead of the clinical onset compared to non-carriers.

  • 4. Antonios, Gregory
    et al.
    Saiepour, Nasrin
    Bouter, Yvonne
    Richard, Bernhard C
    Paetau, Anders
    Verkkoniemi-Ahola, Auli
    Lannfelt, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Ingelsson, Martin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Kovacs, Gabor G
    Pillot, Thierry
    Wirths, Oliver
    Bayer, Thomas A
    N-truncated Abeta starting with position four: early intraneuronal accumulation and rescue of toxicity using NT4X-167, a novel monoclonal antibody2013Inngår i: Acta neuropathologica communications, ISSN 2051-5960, Vol. 1, nr 1, s. 56-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: The amyloid hypothesis in Alzheimer disease (AD) considers amyloid β peptide (Aβ) deposition causative in triggering down-stream events like neurofibrillary tangles, cell loss, vascular damage and memory decline. In the past years N-truncated Aβ peptides especially N-truncated pyroglutamate AβpE3-42 have been extensively studied. Together with full-length Aβ1-42 and Aβ1-40, N-truncated AβpE3-42 and Aβ4-42 are major variants in AD brain. Although Aβ4-42 has been known for a much longer time, there is a lack of studies addressing the question whether AβpE3-42 or Aβ4-42 may precede the other in Alzheimer's disease pathology.

    RESULTS: Using different Aβ antibodies specific for the different N-termini of N-truncated Aβ, we discovered that Aβ4-x preceded AβpE3-x intraneuronal accumulation in a transgenic mouse model for AD prior to plaque formation. The novel Aβ4-x immunoreactive antibody NT4X-167 detected high molecular weight aggregates derived from N-truncated Aβ species. While NT4X-167 significantly rescued Aβ4-42 toxicity in vitro no beneficial effect was observed against Aβ1-42 or AβpE3-42 toxicity. Phenylalanine at position four of Aβ was imperative for antibody binding, because its replacement with alanine or proline completely prevented binding. Although amyloid plaques were observed using NT4X-167 in 5XFAD transgenic mice, it barely reacted with plaques in the brain of sporadic AD patients and familial cases with the Arctic, Swedish and the presenilin-1 PS1Δ9 mutation. A consistent staining was observed in blood vessels in all AD cases with cerebral amyloid angiopathy. There was no cross-reactivity with other aggregates typical for other common neurodegenerative diseases showing that NT4X-167 staining is specific for AD.

    CONCLUSIONS: Aβ4-x precedes AβpE3-x in the well accepted 5XFAD AD mouse model underlining the significance of N-truncated species in AD pathology. NT4X-167 therefore is the first antibody reacting with Aβ4-x and represents a novel tool in Alzheimer research.

  • 5. Arkkukangas, Marina
    et al.
    Söderlund, Anne
    Eriksson, Staffan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Fysioterapi.
    Johansson, Ann-Christin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås.
    Fall Preventive Exercise With or Without Behavior Change Support for Community-Dwelling Older Adults: A Randomized Controlled Trial With Short-Term Follow-up2019Inngår i: Journal of Geriatric Physical Therapy, ISSN 1539-8412, E-ISSN 2152-0895, Vol. 42, nr 1, s. 9-17Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND AND PURPOSE: In Western countries, falls and fall-related injuries are a well-known threat to health in the aging population. Studies indicate that regular exercise improves strength and balance and can therefore decrease the incidence of falls and fall-related injuries. The challenge, however, is to provide exercise programs that are safe, effective, and attractive to the older population. The aim of this study was to investigate the short-term effect of a home-based exercise program with or without motivational interviewing (MI) compared with standard care on physical performance, fall self-efficacy, balance, activity level, handgrip strength, adherence to the exercise, and fall frequency.

    METHOD: A total of 175 older adults participated in this randomized controlled study. They were randomly allocated for the Otago Exercise Program (OEP) (n = 61), OEP combined with MI (n = 58), or a control group (n = 56). The participants' mean age was 83 years. The recruitment period was from October 2012 to May 2015. Measurements of physical performance, fall self-efficacy, balance, activity level, handgrip strength, adherence to the exercise, and fall frequency were done before and 12 weeks after randomization.

    RESULTS AND DISCUSSION: A total of 161 participants were followed up, and there were no significant differences between groups after a period of 12 weeks of regular exercise. Within the OEP + MI group, physical performance, fall self-efficacy, physical activity level, and handgrip strength improved significantly; likewise, improved physical performance and fall self-efficacy were found in the control group. A corresponding difference did not occur in the OEP group. Adherence to the exercise was generally high in both exercise groups.

    CONCLUSION: In the short-term perspective, there were no benefits of an exercise program with or without MI regarding physical performance, fall self-efficacy, activity level, handgrip strength, adherence to the exercise, and fall frequency in comparison to a control group. However, some small effects occurred within the OEP + MI group, indicating that there may be some possible value in behavioral change support combined with exercise in older adults that requires further evaluation in both short- and long-term studies.

  • 6.
    Bask, Miia
    Department of Sociology, University of Bergen, Bergen, Norway.
    Patterns of Psycho-Social Distress Among Ageing Swedes2015Inngår i: Journal of Population Ageing, ISSN 1874-7884, E-ISSN 1874-7876, Vol. 8, nr 4, s. 261-278Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    This paper examines psycho-social distress among middle-aged and elderly Swedes. We analysed data on 3221 individuals who were 55 to 99 years old. Based on a latent class analysis, we identified four latent classes. Two classes were associated with higher levels of psycho-social problem accumulation. The class with the lowest level of problem accumulation contained the greatest number of individuals, whereas the classes with the highest level of psycho-social distress contained the least number of individuals. The analysis showed that being a man, being married, being a native Swede, or having several hobbies was associated with a low likelihood of belonging to a latent class that was characterised by psycho-social distress. Moreover, being a woman, being between 55 and 65 years of age, or being a widow was associated with a high likelihood of belonging to a latent class that was characterised by the highest levels of problem accumulation.

  • 7.
    Bask, Miia
    Department of Sociology, University of Bergen, Bergen, Norway.
    Patterns of Psycho-Social Distress among Middle-Aged and Elderly Swedes2015Konferansepaper (Fagfellevurdert)
  • 8.
    Bauer, Juergen M.
    et al.
    Carl von Ossietzky Univ Oldenburg, Dept Geriatr Med, D-26133 Oldenburg, Germany..
    Verlaan, Sjors
    Nutricia Adv Med Nutr, Nutricia Res, Utrecht, Netherlands.;Vrije Univ Amsterdam, Med Ctr, Dept Internal Med, Sect Gerontol & Geriatr, Amsterdam, Netherlands..
    Bautmans, Ivan
    Vrije Univ Brussel, Frailty Ageing Res Grp FRIA, Brussels, Belgium..
    Brandt, Kirsten
    Newcastle Univ, Inst Ageing, Sch Agr Food & Rural Dev, Human Nutr Res Ctr, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England..
    Donini, Lorenzo M.
    Univ Roma La Sapienza, Sect Med Pathophysiol Endocrinol & Human Nutr, Dept Expt Med, I-00185 Rome, Italy..
    Maggio, Marcello
    Univ Parma, Univ Hosp, Dept Clin & Expt Med, Sect Geriatr,Movement Disorders & Prevent Disabil, I-43100 Parma, Italy.;Univ Parma, Univ Hosp, Dept Clin & Expt Med, Sect Geriatr,Food Sci Unit, I-43100 Parma, Italy.;Univ Parma, Univ Hosp, Dept Clin & Expt Med, Sect Geriatr,Endocrinol Aging Unit, I-43100 Parma, Italy..
    McMurdo, Marion E. T.
    Univ Dundee, Ninewells Hosp & Med Sch, Ninewells Hosp, Ageing & Hlth, Dundee DD1 9SY, Scotland..
    Mets, Tony
    Vrije Univ Brussel, Frailty Ageing Res Grp FRIA, Brussels, Belgium..
    Seal, Chris
    Newcastle Univ, Inst Ageing, Sch Agr Food & Rural Dev, Human Nutr Res Ctr, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England..
    Wijers, Sander L.
    Nutricia Adv Med Nutr, Nutricia Res, Utrecht, Netherlands..
    Ceda, Gian Paolo
    Univ Parma, Univ Hosp, Dept Clin & Expt Med, Sect Geriatr,Movement Disorders & Prevent Disabil, I-43100 Parma, Italy.;Univ Parma, Univ Hosp, Dept Clin & Expt Med, Sect Geriatr,Food Sci Unit, I-43100 Parma, Italy.;Univ Parma, Univ Hosp, Dept Clin & Expt Med, Sect Geriatr,Endocrinol Aging Unit, I-43100 Parma, Italy..
    De Vito, Giuseppe
    Univ Coll Dublin, Inst Sport & Hlth, Dublin 2, Ireland..
    Donders, Gilbert
    Femicare, Clin Res Women, Tienen, Belgium..
    Drey, Michael
    Klinikum Univ Munchen LMU, Schwerpunkt Akutgeriatrie, Med Klin & Poliklin 4, Munich, Germany..
    Greig, Carolyn
    Univ Birmingham, Sch Sport Exercise & Rehabil Sci, Birmingham, W Midlands, England.;Univ Birmingham, Ctr Musculoskeletal Ageing Res, Birmingham, W Midlands, England..
    Holmbäck, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Narici, Marco
    Univ Nottingham, Royal Derby Hosp, MRC ARUK Ctr Musculoskeletal Ageing Res, Fac Med, Derby, England..
    McPhee, Jamie
    Manchester Metropolitan Univ, Sch Healthcare Sci, All Saints, Manchester M15 6BH, Lancs, England..
    Poggiogalle, Eleonora
    Univ Roma La Sapienza, Sect Med Pathophysiol Endocrinol & Human Nutr, Dept Expt Med, I-00185 Rome, Italy..
    Power, Dermot
    Mater Misericordiae Univ Hosp, Dept Med Older Persons, Dublin, Ireland.;Univ Coll Dublin, Dublin 2, Ireland..
    Scafoglieri, Aldo
    Vrije Univ Brussel, Frailty Ageing Res Grp FRIA, Brussels, Belgium..
    Schultz, Ralf
    St Marien Hosp, Clin Geriatr, Cologne, Germany..
    Sieber, Cornel C.
    Univ Erlangen Nurnberg, Inst Biomed Ageing, Nurnberg, Germany..
    Cederholm, Tommy
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Effects of a Vitamin D and Leucine-Enriched Whey Protein Nutritional Supplement on Measures of Sarcopenia in Older Adults, the PROVIDE Study: A Randomized, Double-Blind, Placebo-Controlled Trial2015Inngår i: Journal of the American Medical Directors Association, ISSN 1525-8610, E-ISSN 1538-9375, Vol. 16, nr 9, s. 740-747Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Age-related losses of muscle mass, strength, and function (sarcopenia) pose significant threats to physical performance, independence, and quality of life. Nutritional supplementation could positively influence aspects of sarcopenia and thereby prevent mobility disability. Objective: To test the hypothesis that a specific oral nutritional supplement can result in improvements in measures of sarcopenia. Design: A multicenter, randomized, controlled, double-blind, 2 parallel-group trial among 380 sarcopenic primarily independent-living older adults with Short Physical Performance Battery (SPPB; 0-12) scores between 4 and 9, and a low skeletal muscle mass index. The active group (n = 184) received a vitamin D and leucine-enriched whey protein nutritional supplement to consume twice daily for 13 weeks. The control group (n = 196) received an iso-caloric control product to consume twice daily for 13 weeks. Primary outcomes of handgrip strength and SPPB score, and secondary outcomes of chair-stand test, gait speed, balance score, and appendicular muscle mass (by DXA) were measured at baseline, week 7, and week 13 of the intervention. Results: Handgrip strength and SPPB improved in both groups without significant between-group differences. The active group improved more in the chair-stand test compared with the control group, between-group effect (95% confidence interval): -1.01 seconds (-1.77 to -0.19), P = .018. The active group gained more appendicular muscle mass than the control group, between-group effect: 0.17 kg (0.004-0.338), P = .045. Conclusions: This 13-week intervention of a vitamin D and leucine-enriched whey protein oral nutritional supplement resulted in improvements in muscle mass and lower-extremity function among sarcopenic older adults. This study shows proof-of-principle that specific nutritional supplementation alone might benefit geriatric patients, especially relevant for those who are unable to exercise. These results warrant further investigations into the role of a specific nutritional supplement as part of a multimodal approach to prevent adverse outcomes among older adults at risk for disability.

  • 9.
    Benedict, Christian
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Jacobsson, Josefin A
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Rönnemaa, Elina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Sällman Almén, Markus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Brooks, Samantha
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Schultes, Bernd
    Interdisciplinary Obesity Center, Kantonsspital St. Gallen.
    Fredriksson, Robert
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Lannfelt, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Kilander, Lena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Schiöth, Helgi B
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    The fat mass and obesity gene is linked to reduced verbal fluency in overweight and obese elderly men2011Inngår i: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 32, nr 6, s. 1159.e1-1159.e5Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Humans carrying the prevalent rs9939609 A allele of the fat mass and obesity-associated (FTO) gene are more susceptible to developing obesity than noncarries. Recently, polymorphisms in the FTO gene of elderly subjects have also been linked to a reduced volume in the frontal lobe as well as increased risk for incident Alzheimer disease. However, so far there is no evidence directly linking the FTO gene to functional cognitive processes. Here we examined whether the FTO rs9939609 A allele is associated with verbal fluency performance in 355 elderly men at the age of 82 years who have no clinically apparent cognitive impairment. Retrieval of verbal memory is a good surrogate measure reflecting frontal lobe functioning. Here we found that obese and overweight but not normal weight FTO A allele carriers showed a lower performance on verbal fluency than non-carriers (homozygous for rs9939609 T allele). This effect was not observed for a measure of general cognitive performance (i.e., Mini-Mental State Examination score), thereby indicating that the FTO gene primarily affects frontal lobe-dependent cognitive processes in elderly men.

  • 10.
    Benetou, V.
    et al.
    Univ Athens, WHO Collaborating Ctr Nutr & Hlth, Unit Nutr Epidemiol & Nutr Publ Hlth, Dept Hyg Epidemiol & Med Stat,Sch Med, 75 Mikras Asias St, Athens 11527, Greece.
    Orfanos, P.
    Hellen Hlth Fdn, Athens, Greece;Univ Athens, WHO Collaborating Ctr Nutr & Hlth, Unit Nutr Epidemiol & Nutr Publ Hlth, Dept Hyg Epidemiol & Med Stat,Sch Med, 75 Mikras Asias St, Athens 11527, Greece.
    Feskanich, D.
    Harvard Med Sch, Boston, MA USA;Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Pettersson-Kymmer, U.
    Umea Univ, Dept Pharmacol & Clin Neurosci, Umea, Sweden;Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden.
    Byberg, Liisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Eriksson, S.
    Umea Univ, Dept Community Med, Umea, Sweden.
    Grodstein, F.
    Harvard Med Sch, Boston, MA USA;Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.
    Wolk, Alicja
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi. Karolinska Inst, Inst Environm Med, Div Nutr Epidemiol, Stockholm, Sweden.
    Jankovic, N.
    Wageningen Univ, Div Human Nutr, Wageningen, Netherlands;Univ Duisburg Essen, Inst Med Informat Biometry & Epidemiol, Ctr Clin Epidemiol, Fac Med, Essen, Germany.
    de Groot, L. C. P. G. M.
    Wageningen Univ, Div Human Nutr, Wageningen, Netherlands.
    Boffetta, P.
    Icahn Sch Med Mt Sinai, Inst Translat Epidemiol, New York, NY 10029 USA;Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA.
    Trichopoulou, A.
    Hellen Hlth Fdn, Athens, Greece.
    Mediterranean diet and hip fracture incidence among older adults: the CHANCES project2018Inngår i: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 29, nr 7, s. 1591-1599Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The association between adherence to Mediterranean diet (MD) and hip fracture incidence is not yet established. In a diverse population of elderly, increased adherence to MD was associated with lower hip fracture incidence. Except preventing major chronic diseases, adhering to MD might have additional benefits in lowering hip fracture risk. Hip fractures constitute a major public health problem among older adults. Latest evidence links adherence to Mediterranean diet (MD) with reduced hip fracture risk, but still more research is needed to elucidate this relationship. The potential association of adherence to MD with hip fracture incidence was explored among older adults. A total of 140,775 adults (116,176 women, 24,599 men) 60 years and older, from five cohorts from Europe and the USA, were followed-up for 1,896,219 person-years experiencing 5454 hip fractures. Diet was assessed at baseline by validated, cohort-specific, food-frequency questionnaires, and hip fractures were ascertained through patient registers or telephone interviews/questionnaires. Adherence to MD was evaluated by a scoring system on a 10-point scale modified to be applied also to non-Mediterranean populations. In order to evaluate the association between MD and hip fracture incidence, cohort-specific hazard ratios (HR), adjusted for potential confounders, were estimated using Cox proportional-hazards regression and pooled estimates were subsequently derived implementing random-effects meta-analysis. A two-point increase in the score was associated with a significant 4% decrease in hip fracture risk (pooled adjusted HR 0.96; 95% confidence interval (95% CI) 0.92-0.99, p(heterogeneity) = 0.446). In categorical analyses, hip fracture risk was lower among men and women with moderate (HR 0.93; 95% CI 0.87-0.99) and high (HR 0.94; 95% CI 0.87-1.01) adherence to the score compared with those with low adherence. In this large sample of older adults from Europe and the USA, increased adherence to MD was associated with lower hip fracture incidence.

  • 11.
    Berglund, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Measurement Variability Related to Insulin Secretion and Sensitivity: Assessment and Implications in Epidemiological Studies2009Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    There is a growing interest in random measurement variability of biological variables. In regression models, such variability of the predictors yields biased estimators of coefficients (regression dilution bias). The objectives of this thesis were to develop an efficient method to correct for such bias, to reveal the relative importance of insulin sensitivity and insulin secretion, corrected for regression dilution bias, on glucose tolerance, and to explore the seasonal nature of the variability of insulin sensitivity.

    A reliability study is often designed to randomly select subjects from the main study. Our idea was to collect replicates for subjects with extreme values on their first measurement. The extreme selection design, in combination with maximum likelihood estimation, resulted in an efficient estimator of a corrected regression coefficient in a simple linear regression model. Results were presented theoretically and with an application: The relation between insulin sensitivity and fasting insulin in Uppsala Longitudinal Study of Adult Men (ULSAM) where the extreme selection design decreased the standard error of the estimated regression coefficient with 28 per cent compared with the random sampling design.

    We estimated the partial longitudinal effects of the predictors insulin sensitivity and insulin secretion, corrected for regression dilution bias, on glucose tolerance in ULSAM. The effects of the predictors, when corrected, were similar.

    Insulin sensitivity in ULSAM increased during summer and decreased during winter and insulin secretion exposed opposite variation keeping glucose homeostasis nearly constant. Insulin sensitivity was related to outdoor temperature.

    In summary, we developed a cost-efficient reliability design for correction for regression dilution bias. Insulin sensitivity and insulin secretion had similar longitudinal effects on glucose tolerance, which implies that interventions aimed at these targets are equally important. Further, we revealed the seasonal nature of variations of insulin sensitivity and insulin secretion. This result has implications on glycaemic control in diabetic patients.

    Delarbeid
    1. Correction for regression dilution bias using replicates from subjects with extreme first measurements
    Åpne denne publikasjonen i ny fane eller vindu >>Correction for regression dilution bias using replicates from subjects with extreme first measurements
    2007 (engelsk)Inngår i: Statistics in Medicine, ISSN 0277-6715, E-ISSN 1097-0258, Vol. 26, nr 10, s. 2246-2257Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    The least squares estimator of the slope in a simple linear regression model will be biased towards zero when the predictor is measured with random error, i.e. intra-individual variation or technical measurement error. A correction factor can be estimated from a reliability study where one replicate is available on a subset of subjects from the main study. Previous work in this field has assumed that the reliability study constitutes a random subsample from the main study.We propose that a more efficient design is to collect replicates for subjects with extreme values on their first measurement. A variance formula for this estimator of the correction factor is presented. The variance for the corrected estimated regression coefficient for the extreme selection technique is also derived and compared with random subsampling. Results show that variances for corrected regression coefficients can be markedly reduced with extreme selection. The variance gain can be estimated from the main study data. The results are illustrated using Monte Carlo simulations and an application on the relation between insulin sensitivity and fasting insulin using data from the population-based ULSAM study.In conclusion, an investigator faced with the planning of a reliability study may wish to consider an extreme selection design in order to improve precision at a given number of subjects or alternatively decrease the number of subjects at a given precision.

    Emneord
    regression dilution bias, reliability study, extreme selection, corrected regression coefficient, insulin sensitivity
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-10991 (URN)10.1002/sim.2698 (DOI)000245965200008 ()16969892 (PubMedID)
    Tilgjengelig fra: 2007-05-08 Laget: 2007-05-08 Sist oppdatert: 2017-12-11bibliografisk kontrollert
    2. Maximum likelihood estimation of correction for dilution bias in simple linear regression using replicates from subjects with extreme first measurements
    Åpne denne publikasjonen i ny fane eller vindu >>Maximum likelihood estimation of correction for dilution bias in simple linear regression using replicates from subjects with extreme first measurements
    Vise andre…
    2008 (engelsk)Inngår i: Statistics in Medicine, ISSN 0277-6715, E-ISSN 1097-0258, Vol. 27, nr 22, s. 4397-4407Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    The least-squares estimator of the slope in a simple linear regression model is biased towards zero when the predictor is measured with random error. A corrected slope may be estimated by adding data from a reliability study, which comprises a subset of subjects from the main study. The precision of this corrected slope depends on the design of the reliability study and estimator choice.Previous work has assumed that the reliability study constitutes a random sample from the main study. A more efficient design is to use subjects with extreme values on their first measurement. Previously, we published a variance formula for the corrected slope, when the correction factor is the slope in the regression of the second measurement on the first. In this paper we show that both designs improve by maximum likelihood estimation (MLE). The precision gain is explained by the inclusion of data from all subjects for estimation of the predictor's variance and by the use of the second measurement for estimation of the covariance between response and predictor. The gain of MLE enhances with stronger true relationship between response and predictor and with lower precision in the predictor measurements. We present a real data example on the relationship between fasting insulin, a surrogate market, and true insulin sensitivity measured by a gold-standard euglycaemic insulin clamp, and simulations, where the behavior of profile-likelihood-based confidence intervals is examined. MLE was shown to be a robust estimator for non-normal distributions and efficient for small sample situations.

    Emneord
    regression dilution bias, maximum likelihood estimation, reliability study, extreme selection, corrected regression coefficient
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-17699 (URN)10.1002/sim.3312 (DOI)000259550200002 ()18618419 (PubMedID)
    Tilgjengelig fra: 2008-08-15 Laget: 2008-08-15 Sist oppdatert: 2017-12-08bibliografisk kontrollert
    3. Early Insulin Response and Insulin Sensitivity are Equally Important as Predictors of Glucose Tolerance after Correction for Measurement Errors
    Åpne denne publikasjonen i ny fane eller vindu >>Early Insulin Response and Insulin Sensitivity are Equally Important as Predictors of Glucose Tolerance after Correction for Measurement Errors
    Vise andre…
    2009 (engelsk)Inngår i: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 86, nr 3, s. 219-224Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Aims: We estimated measurement error (ME) corrected effects of   insulin sensitivity (M/I), from euglycaemic insulin clamp, and insulin   secretion, measured as early insulin response (EIR) from oral glucose   tolerance test (OGTT), on fasting plasma glucose, HbA1c and type 2   diabetes longitudinally and cross-sectional.   Methods: : In a population-based study (n = 1128 men) 17 men made   replicate measurements to estimate ME at age 71 years. Effect of 1 SD   decrease of predictors M/I and EIR on longitudinal response variables   fasting plasma glucose (FPG) and HbA1c at follow-ups up to 11 years,   were estimated using uncorrected and ME-corrected (with the regression   calibration method) regression models.   Results: : Uncorrected effect on FPG at age 77 years was larger for M/I   than for EIR (effect difference 0.10 mmol/l, 95% CI 0.00;0.21), while   ME-corrected effects were similar (0.02 mmol/l, 95% CI -0.13;0.15   mmol/l). EIR had greater ME-corrected impact than M/I on HbA1c at age   82 years (-0.11%, -0.28; -0.01%).   Conclusions: : Due to higher ME effect of EIR on glycaemia is   underestimated as compared with M/I. By correcting for ME valid   estimates of relative contributions of insulin secretion and insulin   sensitivity on glycaemia are obtained.

    HSV kategori
    Forskningsprogram
    Geriatrik
    Identifikatorer
    urn:nbn:se:uu:diva-99497 (URN)10.1016/j.diabres.2009.09.016 (DOI)000272521800010 ()19811847 (PubMedID)
    Tilgjengelig fra: 2009-03-18 Laget: 2009-03-15 Sist oppdatert: 2017-12-13bibliografisk kontrollert
    4. Seasonal variations of insulin sensitivity from a euglycemic insulin clamp in elderly men
    Åpne denne publikasjonen i ny fane eller vindu >>Seasonal variations of insulin sensitivity from a euglycemic insulin clamp in elderly men
    Vise andre…
    2012 (engelsk)Inngår i: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 117, nr 1, s. 35-40Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Introduction

    Seasonal variations in hemoglobin-A1c have been reported in diabetic patients, but the underlying mechanisms have not been elucidated.

    Aims

    To study if insulin sensitivity, insulin secretion, and fasting plasma glucose showed seasonal variations in a Swedish population-based cohort of elderly men.

    Methods

    Altogether 1117 men were investigated with a euglycemic insulin clamp and measurements of fasting plasma glucose and insulin secretion after an oral glucose tolerance test. Values were analyzed in linear regression models with an indicator variable for winter/summer season and outdoor temperature as predictors.

    Results

     During winter, insulin sensitivity (M/I, unit = 100 × mg × min-1 × kg-1/(mU × L-1)) was 11.0% lower (4.84 versus 5.44, P = 0.0003), incremental area under the insulin curve was 16.4% higher (1167 versus 1003 mU/L, P = 0.007). Fasting plasma glucose was, however, not statistically significantly different (5.80 versus 5.71 mmol/L, P = 0.28) compared to the summer season. There was an association between outdoor temperature and M/I (0.57 units increase (95% CI 0.29–0.82, P < 0.0001) per 10°C increase of outdoor temperature) independent of winter/summer season. Adjustment for life-style factors, type 2 diabetes, and medication did not alter these results.Read More:http://informahealthcare.com/doi/abs/10.3109/03009734.2011.628422

    Conclusions

    Insulin sensitivity showed seasonal variations with lower values during the winter and higher during the summer season. Inverse compensatory variations of insulin secretion resulted in only minor variations of fasting plasma glucose. Insulin sensitivity was associated with outdoor temperature. These phenomena should be further investigated in diabetic patients.

    Emneord
    Seasonal variations, insulin sensitivity, clamp, insulin secretion, temperature
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-165044 (URN)10.3109/03009734.2011.628422 (DOI)000300304000006 ()22066936 (PubMedID)
    Tilgjengelig fra: 2012-01-02 Laget: 2012-01-02 Sist oppdatert: 2017-12-08bibliografisk kontrollert
  • 12.
    Berglund, Lars
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Berne, Christian
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Svärdsudd, Kurt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Allmänmedicin och klinisk epidemiologi.
    Garmo, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Zethelius, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Seasonal variations of insulin sensitivity from a euglycemic insulin clamp in elderly men2012Inngår i: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 117, nr 1, s. 35-40Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Introduction

    Seasonal variations in hemoglobin-A1c have been reported in diabetic patients, but the underlying mechanisms have not been elucidated.

    Aims

    To study if insulin sensitivity, insulin secretion, and fasting plasma glucose showed seasonal variations in a Swedish population-based cohort of elderly men.

    Methods

    Altogether 1117 men were investigated with a euglycemic insulin clamp and measurements of fasting plasma glucose and insulin secretion after an oral glucose tolerance test. Values were analyzed in linear regression models with an indicator variable for winter/summer season and outdoor temperature as predictors.

    Results

     During winter, insulin sensitivity (M/I, unit = 100 × mg × min-1 × kg-1/(mU × L-1)) was 11.0% lower (4.84 versus 5.44, P = 0.0003), incremental area under the insulin curve was 16.4% higher (1167 versus 1003 mU/L, P = 0.007). Fasting plasma glucose was, however, not statistically significantly different (5.80 versus 5.71 mmol/L, P = 0.28) compared to the summer season. There was an association between outdoor temperature and M/I (0.57 units increase (95% CI 0.29–0.82, P < 0.0001) per 10°C increase of outdoor temperature) independent of winter/summer season. Adjustment for life-style factors, type 2 diabetes, and medication did not alter these results.Read More:http://informahealthcare.com/doi/abs/10.3109/03009734.2011.628422

    Conclusions

    Insulin sensitivity showed seasonal variations with lower values during the winter and higher during the summer season. Inverse compensatory variations of insulin secretion resulted in only minor variations of fasting plasma glucose. Insulin sensitivity was associated with outdoor temperature. These phenomena should be further investigated in diabetic patients.

  • 13.
    Björk, Anne
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrinologi och mineralmetabolism.
    Ribom, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Johansson, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Allmänmedicin och preventivmedicin.
    Scragg, R.
    Univ Auckland, Sch Populat Hlth, Sect Epidemiol & Biostat, Auckland, New Zealand.
    Mellstrom, D.
    Univ Gothenburg, Inst Med, Dept Internal Med & Clin, Geriatr Med,Nutr, Gothenburg, Sweden.
    Grundberg, E.
    McGill Univ, Dept Human Genet, Montreal, PQ, Canada;McGill Univ, Genome Quebec Innovat Ctr, Montreal, PQ, Canada.
    Ohlsson, C.
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Ctr Bone & Arthrit Res, Gothenburg, Sweden.
    Karlsson, M.
    Lund Univ, Skane Univ Hosp, Dept Clin Sci & Orthoped Surg, Malmo, Sweden.
    Ljunggren, Östen
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrinologi och mineralmetabolism.
    Kindmark, Andreas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrinologi och mineralmetabolism.
    Variations in the vitamin D receptor gene are not associated with measures of muscle strength, physical performance, or falls in elderly men: Data from MrOS Sweden2019Inngår i: Journal of Steroid Biochemistry and Molecular Biology, ISSN 0960-0760, E-ISSN 1879-1220, Vol. 187, s. 160-165Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The vitamin D receptor (VDR) has been proposed as a candidate gene for several musculoskeletal phenotypes. However, previous results on the associations between genetic variants of the VDR with muscle strength and falls have been contradictory. The MrOS Sweden survey, a prospective population-based cohort study of 3014 elderly men (mean age 75 years, range 69-81) offered the opportunity to further investigate these associations. At baseline, data were collected on muscle strength and also the prevalence of falls during the previous 12 months. Genetic association analysis was performed for 7 Single Nucleotide Polymorphisms (SNPs), covering the genetic region surrounding the VDR gene in 2924 men with available samples of DNA. Genetic variations in the VDR were not associated with five different measurements of muscle strength or physical performance (hand grip strength right and left, 6 m walking test (easy and narrow) and timed-stands test). However, one of the 7 SNPs of the gene for the VDR receptor, rs7136534, was associated with prevalence of falls (33.6% of the AA, 14.6% of the AG and 16.5% of the GG allele). In conclusion, VDR genetic variants are not related to muscle strength or physical performance in elderly Swedish men. The role of the rs7136534 SNP for the occurrence of falls is not clear.

  • 14.
    Blom, Elin
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Genetic Studies of Alzheimer's Disease2008Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Patients with Alzheimer's disease (AD) often have a family history of the disease, implicating genetics as a major risk factor. Three genes are currently known to cause familial early-onset AD (<65 years): the amyloid precursor protein (APP) and the presenilins (PSEN1 and PSEN2). For the much more common late-onset disease (>65 years), only the APOE gene has repeatedly been associated to AD, where the ε4 allele increases disease risk and decreases age at onset. As APOE ε4 only explains part of the total estimated disease risk, more genes are expected to contribute to AD.

    This thesis has focused on the study of genetic risk factors involved in AD. In the first study, we conducted a linkage analysis of six chromosomes previously implicated in AD in a collection of affected relative pairs from Sweden, the UK and the USA. An earlier described linkage peak on chromosome 10q21 could not be replicated in the current sample, while significant linkage was demonstrated to chromosome 19q13 where the APOE gene is located. The linkage to 19q13 was further analyzed in the second study, demonstrating no significant evidence of genes other than APOE contributing to this peak.

    In the third study, the prevalence of APP duplications, a recently reported cause of early-onset AD, was investigated. No APP duplications were identified in 141 Swedish and Finnish early-onset AD patients, implying that this is not a common disease mechanism in the Scandinavian population.

    In the fourth study, genes with altered mRNA levels in the brain of a transgenic AD mouse model (tgAPP-ArcSwe) were identified using microarray analysis. Differentially expressed genes were further analyzed in AD brain. Two genes from the Wnt signaling pathway, TCF7L2 and MYC, had significantly increased mRNA levels in both transgenic mice and in AD brains, implicating cell differentiation and possibly neurogenesis in AD.

    Delarbeid
    1. Further analysis of previously implicated linkage regions for Alzheimer’s disease in affected relative pairs
    Åpne denne publikasjonen i ny fane eller vindu >>Further analysis of previously implicated linkage regions for Alzheimer’s disease in affected relative pairs
    Vise andre…
    2009 (engelsk)Inngår i: BMC Medical Genetics, ISSN 1471-2350, E-ISSN 1471-2350, Vol. 10, s. 122-Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Background: Genome-wide linkage studies for Alzheimer's disease have implicated several chromosomal regions as potential loci for susceptibility genes. Methods: In the present study, we have combined a selection of affected relative pairs (ARPs) from the UK and the USA included in a previous linkage study by Myers et al. (Am J Med Genet, 2002), with ARPs from Sweden and Washington University. In this total sample collection of 397 ARPs, we have analyzed linkage to chromosomes 1, 9, 10, 12, 19 and 21, implicated in the previous scan. Results: The analysis revealed that linkage to chromosome 19q13 close to the APOE locus increased considerably as compared to the earlier scan. However, linkage to chromosome 10q21, which provided the strongest linkage in the previous scan could not be detected. Conclusion: The present investigation provides yet further evidence that 19q13 is the only chromosomal region consistently linked to Alzheimer's disease.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-97803 (URN)10.1186/1471-2350-10-122 (DOI)000272822700001 ()19951422 (PubMedID)
    Tilgjengelig fra: 2008-11-21 Laget: 2008-11-21 Sist oppdatert: 2017-12-14bibliografisk kontrollert
    2. Does APOE explain the linkage of Alzheimer’s disease to chromosome 19q13?
    Åpne denne publikasjonen i ny fane eller vindu >>Does APOE explain the linkage of Alzheimer’s disease to chromosome 19q13?
    Vise andre…
    2008 (engelsk)Inngår i: American Journal of Medical Genetics Part B: Neuropsychiatric Genetics American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, ISSN 1552-485X, Vol. 147B, nr 6, s. 778-83Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    We have studied the impact of the apolipoprotein E gene (APOE) on the chromosome 19 linkage peak from an analysis of sib-pairs affected by Alzheimer's disease. We genotyped 417 affected sib-pairs (ASPs) collected in Sweden and Norway (SWE), the UK and the USA for 10 microsatellite markers on chromosome 19. The highest Zlr (3.28, chromosome-wide P-value 0.036) from the multi-point linkage analysis was located approximately 1 Mb from APOE, at marker D19S178. The linkage to chromosome 19 was well explained by APOE in the whole sample as well as in the UK and USA subsamples, as identity by descent (IBD) increased with the number of epsilon 4 alleles in ASPs. There was a suggestion from the SWE subsample that linkage was higher than would be expected from APOE alone, although the test for this did not reach formal statistical significance. There was also a significant age at onset (aao) effect on linkage to chromosome 19q13 in the whole sample, which manifested itself as increased IBD sharing in relative pairs with lower mean aao. This effect was partially, although not completely, explained by APOE. The aao effect varied considerably between the different subsamples, with most of the effect coming from the UK sample. The other samples showed smaller effects in the same direction, but these were not significant.

    Emneord
    Alzheimer's disease, APOE, linkage, age at onset, apolipoprotein E
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-97804 (URN)10.1002/ajmg.b.30681 (DOI)000259050100016 ()18161859 (PubMedID)
    Tilgjengelig fra: 2008-11-21 Laget: 2008-11-21 Sist oppdatert: 2009-09-02bibliografisk kontrollert
    3. Low prevalence of APP duplications in Swedish and Finnish patients with early onset Alzheimer's disease
    Åpne denne publikasjonen i ny fane eller vindu >>Low prevalence of APP duplications in Swedish and Finnish patients with early onset Alzheimer's disease
    Vise andre…
    2008 (engelsk)Inngår i: European Journal of Human Genetics, ISSN 1018-4813, E-ISSN 1476-5438, Vol. 16, nr 2, s. 171-5Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Familial early-onset Alzheimer's disease with cerebral amyloid angiopathy (EOAD/CAA) was recently associated with duplications of the gene for the amyloid-beta precursor protein (APP). In this study, we have screened for duplications of APP in patients with EOAD from Sweden and Finland. Seventy-five individuals from families with EOAD and 66 individuals with EOAD without known familial inheritance were screened by quantitative PCR. On the basis of the initial results, a portion of the samples was also investigated with quantitative multiplex PCR. No duplications of APP were identified, whereby we conclude that this is not a common cause of EOAD in the Swedish and Finnish populations, at least not in our collection of families and cases.

    Emneord
    early-onset Alzheimer's disease, amyloid beta precursor protein, gene dose, APP, duplication
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-97805 (URN)10.1038/sj.ejhg.5201966 (DOI)000252426500007 ()18043715 (PubMedID)
    Tilgjengelig fra: 2008-11-21 Laget: 2008-11-21 Sist oppdatert: 2017-12-14bibliografisk kontrollert
    4. Increased mRNA levels of TCF7L2 and MYC of the Wnt pathway in tgAPP-ArcSwe mice and Alzheimer's disease brain
    Åpne denne publikasjonen i ny fane eller vindu >>Increased mRNA levels of TCF7L2 and MYC of the Wnt pathway in tgAPP-ArcSwe mice and Alzheimer's disease brain
    Vise andre…
    Manuskript (Annet vitenskapelig)
    Identifikatorer
    urn:nbn:se:uu:diva-97806 (URN)
    Tilgjengelig fra: 2008-11-21 Laget: 2008-11-21 Sist oppdatert: 2010-01-13bibliografisk kontrollert
  • 15. Bogo, Renata
    et al.
    Farah, Ahmed
    Johnson, Ann-Christin
    Karlsson, Kjell K.
    Pedersen, Nancy L.
    Svartengren, Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Skjonsberg, Asa
    The Role of Genetic Factors for Hearing Deterioration Across 20 Years: A Twin Study2015Inngår i: The journals of gerontology. Series A, Biological sciences and medical sciences, ISSN 1079-5006, E-ISSN 1758-535X, Vol. 70, nr 5, s. 647-653Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background. Hearing deterioration at advanced ages is associated with environmental exposures (eg, to noise and solvents) and genetic influences may also be important. Little is known about the role of genetic influences on hearing when evaluated longitudinally. We sought to investigate longitudinal hearing loss in a cohort of adult male twins to evaluate the importance of genetic and environmental factors for hearing deterioration over time. Methods. Hearing using conventional clinical audiometry was assessed in 583 male twins (128 monozygotic twin pairs and 111 dizygotic twin pairs) aged 34-79 at baseline and again two decades later. The hearing thresholds at two time points were compared at each frequency and in two different frequency regions. Genetic analyses were based on structural equation models. Bivariate Cholesky decomposition was used for longitudinal analysis. Results. The prevalence of hearing loss increased over time in better and worse ear. The hearing threshold shift was more pronounced in the high-frequency region, especially at 8000 Hz. Genetic influences were moderate (heritability: 53%-65%) for pure-tone averages at both lower and higher frequencies, and were of equal magnitude at baseline and follow-up. In contrast, environmental influences were of substantial importance (55%-88%) for rate of change of the hearing threshold over the 18-year period. Conclusions. Genetic factors are of considerable importance for level of hearing acuity, but environmental factors are more important for rate of change over an 18-year period.

  • 16.
    Bromseth, Janne H.
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Historisk-filosofiska fakulteten, Centrum för genusvetenskap.
    Re-Working Norms In Geriatric Care: Exploring An LGBTQ-Sensitive And Intersectional Approach2015Inngår i: The Gerontologist, ISSN 0016-9013, E-ISSN 1758-5341, Vol. 55, s. 437-437Artikkel i tidsskrift (Annet vitenskapelig)
  • 17.
    Byberg, Liisa
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Gedeborg, Rolf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Cars, Thomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Medicin.
    Berglund, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Kilander, Lena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Prediction of fracture risk in men: A cohort study2012Inngår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 27, nr 4, s. 797-807Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    FRAX is a tool that identifies individuals with high fracture risk who will benefit from pharmacological treatment of osteoporosis. However, a majority of fractures among elderly occur in people without osteoporosis and most occur after a fall. Our aim was to accurately identify men with a high future risk of fracture, independent of cause. In the population-based Uppsala Longitudinal Study of Adult Men (ULSAM) and using survival analysis we studied different models' prognostic values (R(2) ) for any fracture and hip fracture within 10 years from age 50 (n = 2322), 60 (n = 1852), 71 (n = 1221), and 82 (n = 526). During the total follow-up period from age 50, 897 fractures occurred in 585 individuals. Of these, 281 were hip fractures occurring in 189 individuals. The rates of any fracture were 5.7/1000 person-years at risk from age 50 and 25.9/1000 person-years at risk from age 82. Corresponding hip fractures rates were 2.9 and 11.7/1000 person-years at risk. The FRAX model included all variables in FRAX except bone mineral density. The full model combining FRAX variables, comorbidity, medications, and behavioral factors explained 25-45% of all fractures and 80-92% of hip fractures, depending on age. The corresponding prognostic values of the FRAX model were 7-17% for all fractures and 41-60% for hip fractures. Net reclassification improvement (NRI) comparing the full model with the FRAX model ranged between 40 and 53% for any fracture and between 40 and 87% for hip fracture. Within the highest quintile of predicted fracture risk with the full model, 1/3 of the men will have a fracture within 10 years after age 71 years and 2/3 after age 82 years. We conclude that the addition of comorbidity, medication and behavioral factors to the clinical components of FRAX can substantially improve the ability to identify men at high risk of fracture, especially hip fracture. 

  • 18.
    Carstensen, Gunilla
    et al.
    DalarnaUniv, Sch Technol & Business Studies, Falun, Sweden.
    Rosberg, Birgitta
    Uppsala Univ Hosp, Akad Sjukhuset, Dept Rehabil Med, Uppsala, Sweden.
    Mc Kee, Kevin J.
    Dalarna Univ, Sch Educ Hlth & Social Studies, S-79188 Falun, Sweden.
    Åberg, Anna Cristina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik. Dalarna Univ, Sch Educ Hlth & Social Studies, S-79188 Falun, Sweden.
    Before evening falls: Perspectives of a good old age and healthy ageing among oldest-old Swedish men2019Inngår i: Archives of gerontology and geriatrics (Print), ISSN 0167-4943, E-ISSN 1872-6976, Vol. 82, s. 35-44Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The late life experiences of men in the oldest-old age group have been under-researched, and their perspectives on ageing successfully neglected. This study explored the perspectives of oldest-old Swedish men on what a 'good old age' and ageing successfully meant to them. A purposive sample of 17 men, aged 85-90 years, was drawn from the Uppsala Longitudinal Study of Adult Men. An interview guide explored participants' perspectives on their ageing experiences and how they viewed ageing successfully. Participants were interviewed twice, with 1-2 weeks between interviews, and both interviews were recorded and transcribed. Content analysis identified four themes: i) Adaptation, concerning the ability to adapt to growing old with increasing limitations; ii) Sustaining Independence, related to financial resources and good health as the foundation for independence; iii) Belongingness, representing close relationships, established friendships, and the significance of the spouse; and iv) Perspectives of Time, also a common thread in all themes, in which past life experiences create an existential link between the past, the present and the future, establishing continuity of the self and enhancing life satisfaction. The participants presented themselves as active agents involved in maintaining meaning and achieving life satisfaction; a process related to the ability to manage changes in life. Our findings have resonance with models of healthy or successful ageing, but also diverge in important ways, since such models do not consider the significance of an individual's life history for their present well-being, and primarily conceptualise health as an outcome, rather than as a resource.

  • 19.
    Cederbom, Sara
    et al.
    OsloMet Oslo Metropolitan Univ, Fac Hlth Sci, Dept Physiotherapy, Postboks 4,St Olays Plass, N-0130 Oslo, Norway.
    Arkkukangas, Marina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Fysioterapi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Impact of the fall prevention Otago Exercise Programme on pain among community-dwelling older adults: a short- and long-term follow-up study2019Inngår i: Clinical Interventions in Aging, ISSN 1176-9092, E-ISSN 1178-1998, Vol. 14, s. 721-726Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Pain is a major public health issue among community-dwelling older adults, with a prevalence of 45-80%. In addition to being strongly associated with reduced physical function, loss of independence, psychological distress, lower quality of life, and risk of earlier death. Recent research has also found that pain in older adults is associated with a higher risk of falls, which itself is another major health concern. Long-term and high-intensity pain are predictors of chronic pain and pain-related disability. Therefore, establishing an evidence-based intervention that can reduce both pain and falls in older adults is of high importance.

    Purpose: This study aimed to investigate whether a home-based fall-preventive exercise-program can reduce pain in the target population over both the short and long term.

    Patients and methods: This was a quasi-experimental study with a 1-group pretest-posttest design. We included 119 participants who had participated in a recent 2-year fall prevention intervention in a randomized controlled trial. The intervention included exercises based on the Otago Exercise Programme (OEP), an individually tailored and prescribed program that involves home-based exercises supervised by a physiotherapist. Pain was measured using an item from the EuroQol-5D questionnaire.

    Results: Pain was significantly reduced from baseline (n=119) at 3 (n=105, p=0.003), 12 (n=96, p=0.041), and 24 (n=80, p=0.028) months following the commencement of OEP-based exercises.

    Conclusions: These results indicate that the OEP could be a suitable evidence-based program for both pain management and fall prevention among community-dwelling older people who live with pain and are at a higher risk of falling. Our study highlights an effective technique for better pain management and fall prevention in older adults.

  • 20.
    Cederholm, Tommy
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Sarkopeni: ett "nytt" begrepp med klinisk betydelse för den äldre2008Inngår i: Nordisk Geriatrik, Vol. 11, nr 1, s. 30-32Artikkel i tidsskrift (Fagfellevurdert)
  • 21. Cho, Karl
    et al.
    Cederholm, Tommy
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Lökk, Johan
    Calcium intake in elderly patients with hip fractures2008Inngår i: Food & nutrition research, ISSN 1654-6628, Vol. 52, s. 1654-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Dietary calcium intake is assumed important in the prevention and treatment of osteoporosis. However, people in countries with a high calcium intake from commodities such as milk and milk products have a high incidence of hip fracture. The effect and influence of calcium intake in the prevention of osteoporotic fracture vary from different studies. OBJECTIVE: To investigate premorbid daily calcium intake in patients with low energy hip fractures during four consecutive years. DESIGN: In total 120 patients (mean age 78+/-8.5 (SD) years) were included between 2002 and 2005. The patients answered a structured food frequency questionnaire (FFQ) and interviews on patients' daily calcium intake from food and supplements took place during a 6-month period before the fracture. Dual energy X-ray absorptiometry (DEXA) was performed in a subgroup of 15 patients. RESULTS: The mean daily calcium intake from food and supplementation was 970+/-500 mg. However, 38% of patients had an intake below the recommended 800 mg/day. There was no significant relationship between calcium intake and age, gender, bone mineral density, serum calcium or albumin, type of fracture or body mass index. The mean free plasma calcium concentration was 2.3+/-0.1, i.e. within the reference limit. In 2005, 80% of the patients who underwent DEXA had manifest osteoporosis. There was a trend towards decreased calcium intake over the observation period, with a mean calcium intake below 800 mg/day in 2005. CONCLUSIONS: Hip fracture patients had a mean calcium intake above the recommended daily intake, as assessed by a FFQ. However, more than one-third of patients had an intake below the recommended 800 mg/day. The intake appeared to decrease over the investigated years. The relationship between calcium intake and fracture susceptibility is complex.

  • 22. Crinelli, Raffaella
    et al.
    Östberg, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Logopedi.
    Folstein's Mini-Mental State Examination: fat chance or slim hope?2008Inngår i: Journal of The American Geriatrics Society, ISSN 0002-8614, E-ISSN 1532-5415, Vol. 56, nr 1, s. 171-172Artikkel i tidsskrift (Annet vitenskapelig)
  • 23.
    Cruz-Jentoft, Alfonso J.
    et al.
    Hosp Univ Ramon y Cajal IRYCIS, Serv Geriatr, Madrid, Spain.
    Bahat, Gülistan
    Istanbul Univ, Istanbul Med Sch, Div Geriatr, Dept Internal Med, Istanbul, Turkey.
    Bauer, Jürgen
    Heidelberg Univ, Ctr Geriatr Med, Agaples Bethanien Krankenhaus, Heidelberg, Germany.
    Boirie, Yves
    CHU Clermont Ferrand, Res Dept, Clermont Ferrand, France.
    Bruyere, Olivier
    Univ Liege, Dept Publ Hlth Epidemiol & Hlth Econ, Liege, Belgium.
    Cederholm, Tommy
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism. Karolinska Univ Hosp, Theme Ageing, Stockholm, Sweden.
    Cooper, Cyrus
    Univ Southampton, MRC Lifecourse Epidemiol Unit, Southampton, Hants, England;Univ Oxford, Dept Epidemiol, Ox, England.
    Landi, Francesco
    Univ Cattolica Sacro Cuore, Inst Med Interna & Geriatria, Rome, Italy.
    Rolland, Yves
    Hosp & Univ Toulouse, Dept Geriatr, Toulouse, France.
    Sayer, Avan Aihie
    Newcastle Upon Tyne Hosp NHS Fdn Trust, NIHR Newcastle Biomed Res Ctr, Newcastle, England;Newcastle Univ, Fac Med Sci, Newcastle, England.
    Schneider, Stephane M.
    Univ Cote Azur, CHU Nice, Dept Gastroenterol & Clin Nutr, Nice, France.
    Sieber, Cornel C.
    Friedrich Alexander Univ, Inst Biomed & Ageing, Dept Internal Med Geriatr, Erlangen, Germany.
    Topinkova, Eva
    Charles Univ Prague, Fac Med 1, Dept Geriatr, Prague, Czech Republic;Gen Fac Hosp, Prague, Czech Republic.
    Vandewoude, Maurits
    Univ Antwerp, Dept Geriatr, Ziekenhuisnetwerk Antwerpen ZNA, Antwerp, Belgium.
    Visser, Marjolein
    Vrije Univ Amsterdam, Fac Sci, Dept Hlth Sci, Amsterdam, Netherlands;Amsterdam Publ Hlth Res Inst, Amsterdam, Netherlands.
    Zamboni, Mauro
    Univ Verona, Geriatr Sect, Dept Med, Verona, Italy.
    Sarcopenia: revised European consensus on definition and diagnosis2019Inngår i: Age and Ageing, ISSN 0002-0729, E-ISSN 1468-2834, Vol. 48, nr 1, s. 16-31Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: In 2010, the European Working Group on Sarcopenia in Older People (EWGSOP) published a sarcopenia definition that aimed to foster advances in identifying and caring for people with sarcopenia. In early 2018, the Working Group met again (EWGSOP2) to update the original definition in order to reflect scientific and clinical evidence that has built over the last decade. This paper presents our updated findings.

    Objectives: To increase consistency of research design, clinical diagnoses and ultimately, care for people with sarcopenia.

    Recommendations: Sarcopenia is a muscle disease (muscle failure) rooted in adverse muscle changes that accrue across a lifetime; sarcopenia is common among adults of older age but can also occur earlier in life. In this updated consensus paper on sarcopenia, EWGSOP2: (1) focuses on low muscle strength as a key characteristic of sarcopenia, uses detection of low muscle quantity and quality to confirm the sarcopenia diagnosis, and identifies poor physical performance as indicative of severe sarcopenia; (2) updates the clinical algorithm that can be used for sarcopenia case-finding, diagnosis and confirmation, and severity determination and (3) provides clear cut-off points for measurements of variables that identify and characterise sarcopenia.

    Conclusions; EWGSOP2's updated recommendations aim to increase awareness of sarcopenia and its risk. With these new recommendations, EWGSOP2 calls for healthcare professionals who treat patients at risk for sarcopenia to take actions that will promote early detection and treatment. We also encourage more research in the field of sarcopenia in order to prevent or delay adverse health outcomes that incur a heavy burden for patients and healthcare systems.

  • 24. Cruz-Jentoft, Alfonso J
    et al.
    Landi, Francesco
    Schneider, Stéphane M
    Zúñiga, Clemente
    Arai, Hidenori
    Boirie, Yves
    Chen, Liang-Kung
    Fielding, Roger A
    Martin, Finbarr C
    Michel, Jean-Pierre
    Sieber, Cornel
    Stout, Jeffrey R
    Studenski, Stephanie A
    Vellas, Bruno
    Woo, Jean
    Zamboni, Mauro
    Cederholm, Tommy
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Prevalence of and interventions for sarcopenia in ageing adults : a systematic review: Report of the International Sarcopenia Initiative (EWGSOP and IWGS)2014Inngår i: Age and Ageing, ISSN 0002-0729, E-ISSN 1468-2834, Vol. 43, nr 6, s. 748-759Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: to examine the clinical evidence reporting the prevalence of sarcopenia and the effect of nutrition and exercise interventions from studies using the consensus definition of sarcopenia proposed by the European Working Group on Sarcopenia in Older People (EWGSOP).

    METHODS: PubMed and Dialog databases were searched (January 2000-October 2013) using pre-defined search terms. Prevalence studies and intervention studies investigating muscle mass plus strength or function outcome measures using the EWGSOP definition of sarcopenia, in well-defined populations of adults aged ≥50 years were selected.

    RESULTS: prevalence of sarcopenia was, with regional and age-related variations, 1-29% in community-dwelling populations, 14-33% in long-term care populations and 10% in the only acute hospital-care population examined. Moderate quality evidence suggests that exercise interventions improve muscle strength and physical performance. The results of nutrition interventions are equivocal due to the low number of studies and heterogeneous study design. Essential amino acid (EAA) supplements, including ∼2.5 g of leucine, and β-hydroxy β-methylbutyric acid (HMB) supplements, show some effects in improving muscle mass and function parameters. Protein supplements have not shown consistent benefits on muscle mass and function.

    CONCLUSION: prevalence of sarcopenia is substantial in most geriatric settings. Well-designed, standardised studies evaluating exercise or nutrition interventions are needed before treatment guidelines can be developed. Physicians should screen for sarcopenia in both community and geriatric settings, with diagnosis based on muscle mass and function. Supervised resistance exercise is recommended for individuals with sarcopenia. EAA (with leucine) and HMB may improve muscle outcomes.

  • 25.
    Degerman Gunnarsson, Malin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Biomarkers as Monitors of Drug Effect, Diagnostic Tools and Predictors of Deterioration Rate in Alzheimer’s Disease2013Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Decreased amyloid-ß42 (Aß42), increased total tau (t-tau) and phosphorylated tau (p-tau) in cerebrospinal fluid (CSF) reflect histopathological core changes in the most common dementia disorder, Alzheimer’s disease (AD). They discriminate AD from healthy controls and predict conversion to AD with a relatively high accuracy. Memantine, an uncompetitive NMDA-receptor antagonist, is indicated for symptomatic treatment of AD. The first aim of this thesis was to investigate effects of memantine on CSF concentrations of Aβ42, tau and p-tau. Secondly, the aim was to explore the relation between these CSF biomarkers and retention of the amyloid biomarker Pittsburgh compound B using positron emission tomography (PIB PET), regional glucose metabolism measured with 18Fluoro-2-deoxy-d-glucose (FDG) PET and neuropsychological test performance. The third aim was to investigate their possible utility as predictors of future rate of AD dementia deterioration. All patients in the studies were recruited from the Memory Clinic, Uppsala University Hospital. In study I CSF p-tau concentrations in 11 AD patients were reduced after twelve months treatment with memantine, indicating that this compound may affect a key pathological process in AD. Results from study II showed that the concentrations of CSF Aß42 are lower in PIB+ patients than in PIB- patients, and that the PIB retention was stable during 12 months. In study III 10 patients with the diagnoses AD (6 PIB+/4 PIB-) and 8 subjects (1 PIB+/7 PIB-) with frontotemporal dementia were included. PIB+ patients had lower psychomotor speed measured by performance on the Trail Making Test A and impaired visual episodic memory compared to the PIB- patients. The initial clinical diagnoses were changed in 33% of the patients (6/18) during follow-up. Study IV is the first-ever report of an association between high CSF tau and dying in severe dementia. These 196 AD patients were followed up to nine years after baseline lumbar puncture. Moreover, CSF t-tau concentrations above median was associated with an increased risk of rapid cognitive decline (OR 3.31 (95% CI 1.53-7.16), independently of baseline functional stage. Thus, a clear association between high levels of CSF t-tau and p-tau and a more aggressive course of the disease was shown.

    Delarbeid
    1. Reduction of Phosphorylated Tau during Memantine Treatment of Alzheimer's Disease
    Åpne denne publikasjonen i ny fane eller vindu >>Reduction of Phosphorylated Tau during Memantine Treatment of Alzheimer's Disease
    2007 (engelsk)Inngår i: Dementia and Geriatric Cognitive Disorders, ISSN 1420-8008, E-ISSN 1421-9824, Vol. 24, nr 4, s. 247-252Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Background: Memantine is a moderate affinity N-methyl-D-aspartate receptor antagonist approved for treatment of Alzheimer's disease (AD). In AD, tau is abnormally hyperphosphorylated. However, no significant changes of phosphorylated tau levels in CSF are found at follow-up in studies with AD patients. It has been shown in vitro that memantine reverse induced abnormal hyperphosphorylation of tau in hippocampal neurons of rats. Methods: Eleven AD patients were examined with cognitive tests and interviews of relatives. CSF analyses were performed before starting treatment with memantine as well as after 1 year. Results: A statistically significant reduction of CSF phosphorylated tau at the 1-year follow-up was seen, from median 126 (interquartile range 107-153) to 108 (88-133) ng/l (p = 0.018). No statistically significant differences of total tau or A42 were found. Conclusion: The results may reflect effects of memantine on a key pathological feature in AD in line with previous in vitro findings.

    Emneord
    Alzheimer's disease, Memantine, Phosphorylated tau, Cerebrospinal fluid
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-11724 (URN)10.1159/000107099 (DOI)000249536700002 ()17700020 (PubMedID)
    Tilgjengelig fra: 2007-10-15 Laget: 2007-10-15 Sist oppdatert: 2017-12-11bibliografisk kontrollert
    2. Pittsburgh compound-B and Alzheimer's disease biomarkers in CSF, plasma and urine: An exploratory study
    Åpne denne publikasjonen i ny fane eller vindu >>Pittsburgh compound-B and Alzheimer's disease biomarkers in CSF, plasma and urine: An exploratory study
    Vise andre…
    2010 (engelsk)Inngår i: Dementia and Geriatric Cognitive Disorders, ISSN 1420-8008, E-ISSN 1421-9824, Vol. 29, nr 3, s. 204-212Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Background:

    The positron emission tomography (PET) radiotracer Pittsburgh Compound-B (PIB) is an in vivo ligand for measuring β-amyloid (Aβ) load. Associations between PET PIB and cerebrospinal fluid (CSF) Aβ1–42 and apolipoprotein E ε4 (APOE ε4) have been observed in several studies, but the relations between PIB uptake and other biomarkers of Alzheimer’s disease (AD) are less investigated.

    Method:

    PET PIB, PET 18Fluoro-2-deoxy-D-glucose and different AD biomarkers were measured twice in CSF, plasma and urine 12 months apart in 10 patients with a clinical diagnosis of mild to moderate AD.

    Results:

    PIB retention was constant over 1 year, inversely related to low CSF Aβ1–42 (p = 0.01) and correlated positively to the numbers of the APOE ε4 allele (0, 1 or 2) (p = 0.02). There was a relation between mean PIB retention and CSF ApoE protein (r = –0.59, p = 0.07), and plasma cystatin C (r = –0.56, p = 0.09).

    Conclusion:

    PIB retention is strongly related to CSF Aβ1–42, and to the numbers of the APOE ε4 allele.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-132548 (URN)10.1159/000281832 (DOI)000276783100003 ()20332638 (PubMedID)
    Tilgjengelig fra: 2010-10-21 Laget: 2010-10-21 Sist oppdatert: 2017-12-12bibliografisk kontrollert
    3. Re-evaluation of clinical dementia diagnoses with PET-PIB
    Åpne denne publikasjonen i ny fane eller vindu >>Re-evaluation of clinical dementia diagnoses with PET-PIB
    Vise andre…
    (engelsk)Manuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Objectives: There is an overlap regarding Pittsburgh Compound-B (PIB) retention in patients clinically diagnosed as Alzheimer’s disease (AD) and non-AD dementia.  The aim of the present study was to investigate whether there are any differences between PIB+ and PIB PIB- patients in a mixed cohort of patients with neurodegenerative dementia of mild severity regarding neuropsychological test performance and regional cerebral glucose metabolism measured with 18 Fluoro-2-deoxy-d-glucose (FDG) PET.

    Methods: Eighteen patients clinically diagnosed as probable AD or frontotemporal dementia were examined with  PIB PET, FDG PET and neuropsychological tests and followed for 5-9 years in a clinical setting.

    Results:  The PIB+ patients (7/18) had slower psychomotor speed and more impaired visual episodic memory than the PIB- patients, otherwise performance did not differ between groups. The initial clinical diagnoses were changed in one third of the patients (6/18) during follow-up.  

    Conclusions: The subtle differences in neuropsychological performance, the overlap of hypometabolic patterns and clinical features between AD and non-AD dementia highlight the need of amyloid biomarkers and readiness to re-evaluate the initial diagnosis.

    Emneord
    Alzheimer’s disease, PIB PET, Dementia with Lewy Bodies, Frontotemporal dementia, ß-amyloid, amyloid biomarker, FDG PET, neuropsychological tests, TMT A, episodic memory
    HSV kategori
    Forskningsprogram
    Medicinsk vetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-196962 (URN)
    Tilgjengelig fra: 2013-03-15 Laget: 2013-03-15 Sist oppdatert: 2013-08-30
    4. High Tau Levels in Cerebrospinal Fluid Predict Rapid Decline and Increased Dementia Mortality in Alzheimer's Disease
    Åpne denne publikasjonen i ny fane eller vindu >>High Tau Levels in Cerebrospinal Fluid Predict Rapid Decline and Increased Dementia Mortality in Alzheimer's Disease
    Vise andre…
    2014 (engelsk)Inngår i: Dementia and Geriatric Cognitive Disorders, ISSN 1420-8008, E-ISSN 1421-9824, Vol. 37, nr 3-4, s. 196-206Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Objective: Cerebrospinal fluid (CSF) amyloid beta(42) (A beta(42)), total tau (t-tau) and phosphorylated tau (p-tau) are useful as predictors of conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD) dementia. However, results are contradictory as to whether these biomarkers reflect the future rate of clinical decline. Methods: This is a retrospective study on 196 patients with AD [mild/moderate AD (n = 72) or AD-MCI (n = 124) at baseline] with a follow-up period of 2-9 years' duration (median 6 years). Lumbar punctures were performed at baseline as a part of the diagnostic procedure. Results: We found an increased risk of rapid cognitive decline defined as a drop in the Mini-Mental State Examination score of = 4 points/year in patients with CSF t-tau concentrations above the median (OR 3.31, 95% CI 1.53-7.16) and CSF p-tau above the median (OR 2.53, 95% CI 1.21-5.26). Patients with CSF t-tau in the highest quartile had a higher risk of dying in severe dementia (HR 4.67, 95% CI 1.16-18.82). Conclusions: In this large AD cohort, we found an association between high levels of CSF t-tau and p-tau and a more aggressive course of the disease, measured as a rapid cognitive decline and a higher risk of dying in severe dementia.

    Emneord
    Alzheimer’s disease, tau, p-tau, beta-amyloid, CSF, rapid cognitive decline, dying in severe dementia, mortality
    HSV kategori
    Forskningsprogram
    Medicinsk vetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-196964 (URN)10.1159/000355556 (DOI)000335227300006 ()
    Tilgjengelig fra: 2013-03-15 Laget: 2013-03-15 Sist oppdatert: 2018-01-11bibliografisk kontrollert
  • 26.
    Degerman Gunnarsson, Malin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Lannfelt, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Ingelsson, Martin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Basun, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Kilander, Lena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    High Tau Levels in Cerebrospinal Fluid Predict Rapid Decline and Increased Dementia Mortality in Alzheimer's Disease2014Inngår i: Dementia and Geriatric Cognitive Disorders, ISSN 1420-8008, E-ISSN 1421-9824, Vol. 37, nr 3-4, s. 196-206Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: Cerebrospinal fluid (CSF) amyloid beta(42) (A beta(42)), total tau (t-tau) and phosphorylated tau (p-tau) are useful as predictors of conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD) dementia. However, results are contradictory as to whether these biomarkers reflect the future rate of clinical decline. Methods: This is a retrospective study on 196 patients with AD [mild/moderate AD (n = 72) or AD-MCI (n = 124) at baseline] with a follow-up period of 2-9 years' duration (median 6 years). Lumbar punctures were performed at baseline as a part of the diagnostic procedure. Results: We found an increased risk of rapid cognitive decline defined as a drop in the Mini-Mental State Examination score of = 4 points/year in patients with CSF t-tau concentrations above the median (OR 3.31, 95% CI 1.53-7.16) and CSF p-tau above the median (OR 2.53, 95% CI 1.21-5.26). Patients with CSF t-tau in the highest quartile had a higher risk of dying in severe dementia (HR 4.67, 95% CI 1.16-18.82). Conclusions: In this large AD cohort, we found an association between high levels of CSF t-tau and p-tau and a more aggressive course of the disease, measured as a rapid cognitive decline and a higher risk of dying in severe dementia.

  • 27.
    Degerman Gunnarsson, Malin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Lindau, M
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Santillo, A F
    Wall, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för nuklearmedicin och PET.
    Engler, H
    Lannfelt, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Basun, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Kilander, Lena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Re-evaluation of clinical dementia diagnoses with pittsburgh compound B positron emission tomography2013Inngår i: Dementia and geriatric cognitive disorders extra, ISSN 1664-5464, Vol. 3, nr 1, s. 472-481Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVES:

    There is an overlap regarding Pittsburgh compound B (PIB) retention in patients clinically diagnosed as Alzheimer's disease (AD) and non-AD dementia. The aim of the present study was to investigate whether there are any differences between PIB-positive and PIB-negative patients in a mixed cohort of patients with neurodegenerative dementia of mild severity regarding neuropsychological test performance and regional cerebral glucose metabolism measured with [(18)F]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET).

    METHODS:

    Eighteen patients clinically diagnosed as probable AD or frontotemporal dementia were examined with PIB PET, FDG PET and neuropsychological tests and followed for 5-9 years in a clinical setting.

    RESULTS:

    The PIB-positive patients (7 out of 18) had slower psychomotor speed and more impaired visual episodic memory than the PIB-negative patients; otherwise performance did not differ between the groups. The initial clinical diagnoses were changed in one third of the patients (6 out of 18) during follow-up.

    CONCLUSIONS:

    The subtle differences in neuropsychological performance, the overlap of hypometabolic patterns and clinical features between AD and non-AD dementia highlight the need for amyloid biomarkers and a readiness to re-evaluate the initial diagnosis.

  • 28.
    Degerman Gunnarsson, Malin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Lindau, Maria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Wall, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för nuklearmedicin och PET.
    Blennow, K
    Darreh-Shori, T
    Basu, Samar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Oxidativ stress och inflammation.
    Nordberg, A
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Lannfelt, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Basun, H
    Kilander, Lena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Pittsburgh compound-B and Alzheimer's disease biomarkers in CSF, plasma and urine: An exploratory study2010Inngår i: Dementia and Geriatric Cognitive Disorders, ISSN 1420-8008, E-ISSN 1421-9824, Vol. 29, nr 3, s. 204-212Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background:

    The positron emission tomography (PET) radiotracer Pittsburgh Compound-B (PIB) is an in vivo ligand for measuring β-amyloid (Aβ) load. Associations between PET PIB and cerebrospinal fluid (CSF) Aβ1–42 and apolipoprotein E ε4 (APOE ε4) have been observed in several studies, but the relations between PIB uptake and other biomarkers of Alzheimer’s disease (AD) are less investigated.

    Method:

    PET PIB, PET 18Fluoro-2-deoxy-D-glucose and different AD biomarkers were measured twice in CSF, plasma and urine 12 months apart in 10 patients with a clinical diagnosis of mild to moderate AD.

    Results:

    PIB retention was constant over 1 year, inversely related to low CSF Aβ1–42 (p = 0.01) and correlated positively to the numbers of the APOE ε4 allele (0, 1 or 2) (p = 0.02). There was a relation between mean PIB retention and CSF ApoE protein (r = –0.59, p = 0.07), and plasma cystatin C (r = –0.56, p = 0.09).

    Conclusion:

    PIB retention is strongly related to CSF Aβ1–42, and to the numbers of the APOE ε4 allele.

  • 29.
    Dent, E.
    et al.
    Torrens Univ Australia, Wakefield St, Adelaide, SA, Australia;Baker Heart & Diabet Inst, Melbourne, Vic, Australia.
    Morley, J. E.
    St Louis Univ, Sch Med, Div Geriatr Med, St Louis, MO 63104 USA.
    Cruz-Jentoft, A. J.
    Hosp Univ Ramon y Cajal IRYCIS, Serv Geriatr, Madrid, Spain.
    Arai, H.
    Natl Ctr Geriatr & Gerontol, Obu, Japan.
    Kritchevsky, S. B.
    Wake Forest Sch Med, Sticht Ctr Hlth Aging & Alzheimers Prevent, Winston Salem, NC USA.
    Guralnik, J.
    Bauer, J. M.
    Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA;Heidelberg Univ Agaples Bethanien Krankenhaus, Ctr Geriatr Med, Heidelberg, Germany.
    Pahor, M.
    Univ Florida, Dept Aging & Geriatr Res, Gainesville, FL USA.
    Clark, B. C.
    OMNI, Athens, OH USA.
    Cesari, M.
    Fdn IRCCS Ca Granda Osped Maggiore Policlin, Geriatr Unit, Milan, Italy;Univ Milan, Dept Clin Sci & Community Hlth, Milan, Italy.
    Ruiz, J.
    Univ Miami, Miller Sch Med, Div Geriatr & Palliat Med, Miami, FL 33136 USA.
    Sieber, C. C.
    Aubertin-Leheudre, M.
    Friedrich Alexander Univ Erlangen Nurnberg, Inst Biomed Ageing, Nurnberg, Germany;Univ Quebec Montreal, Fac Sci, Dept Sci Act Phys, Montreal, PQ, Canada.
    Waters, D. L.
    Univ Otago, Dept Med, Sch Physiotherapy, Dunedin, New Zealand.
    Visvanathan, R.
    Univ Adelaide, Fac Hlth & Med Sci, Adelaide Med Sch, Adelaide Geriatr Training & Res Aged Care GTRAC C, Adelaide, SA, Australia.
    Landi, F.
    Fdn Policlin A Gemelli, Rome, Italy.
    Villareal, D. T.
    Michael E DeBakey VA Med Ctr, Ctr Translat Res Inflammatory Dis, Houston, TX USA;Baylor Coll Med, Houston, TX 77030 USA.
    Fielding, R.
    Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Nutr Exercise Physiol & Sarcopenia Lab, Boston, MA 02111 USA.
    Won, C. W.
    Kyung Hee Univ, Coll Med, Dept Family Med, Elderly Frailty Res Ctr, Seoul, South Korea.
    Theou, O.
    Univ Adelaide, Fac Hlth & Med Sci, Adelaide Med Sch, Adelaide Geriatr Training & Res Aged Care GTRAC C, Adelaide, SA, Australia;Dalhousie Univ, Dept Med, Halifax, NS, Canada.
    Martin, F. C.
    Chinese Univ Hong Kong, Populat Hlth Sci, London, England.
    Dong, B.
    Sichuan Univ, West China Hosp, Natl Clin Res Ctr Geriatr, Chengdu, Sichuan, Peoples R China.
    Woo, J.
    Chinese Univ Hong Kong, Dept Med, Hong Kong, Peoples R China.
    Flicker, L.
    Univ Western Australia, Med Sch, Western Australian Ctr Hlth & Ageing, Perth, WA, Australia.
    Ferrucci, L.
    NIA, Intramural Res Program, Bethesda, MD 20892 USA.
    Merchant, R. A.
    Natl Univ Hlth Syst, Natl Univ Hosp, Div Geriatr Med, Dept Med, Singapore, Singapore.
    Cao, L.
    Sichuan Univ, West China Hosp, Ctr Gerontol & Geriatr, Chengdu, Sichuan, Peoples R China.
    Cederholm, Tommy
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism. Theme Aging, Karolinska Univ Hosp, Stockholm, Sweden.
    Ribeiro, S. M. L.
    Univ Sao Paulo, Sch Publ Hlth, Sao Paulo, SP, Brazil.
    Rodriguez-Manas, L.
    Hosp Univ Getafe, Serv Geriatr, Madrid, Spain.
    Anker, S. D.
    Charite, Dept Cardiol CVK, Berlin, Germany;Charite, Berlin Brandenburg Ctr Regenerat Therapies BCRT, Berlin, Germany;Charite, German Ctr Cardiovasc Res DZHK Partner Site Berli, Berlin, Germany;Univ Gottingen, Med Sch, Dept Cardiol & Pneumol, Gottingen, Germany.
    Lundy, J.
    Perry Cty Mem Hosp, Perryville, MO USA.
    Gutierrez Robledo, L. M.
    Natl Inst Geriatr, Mexico City, DF, Mexico.
    Bautmans, I.
    VUB, Gerontol Dept, Laarbeeklaan 103, B-1090 Brussels, Belgium;VUB, Frailty Ageing FRIA Res Dept, Laarbeeklaan 103, B-1090 Brussels, Belgium;Univ Ziekenhuis Brussel UZ Brussel, Geriatr Dept, Laarbeeklaan 101, B-1090 Brussels, Belgium.
    Aprahamian, I.
    Fac Med Jundiai, Div Geriatr, Dept Internal Med, Jundiai, Brazil.
    Schols, J. M. G. A.
    Maastricht Univ, FHML, Caphri, Dept Hlth Serv Res, Maastricht, Netherlands;Maastricht Univ, Sect Old Age Med, Maastricht, Netherlands.
    Izquierdo, M.
    Univ Publ Navarra, Dept Hlth Sci, CIBER Fragilidad & Envejecimiento Saludable, Navarrabiomed,IdiSNA,Navarra Inst Hlth Res, Navarra, Spain.
    Vellas, B.
    CHU Toulouse, Gerontopole Clin, Toulouse, France.
    International Clinical Practice Guidelines for Sarcopenia (ICFSR): Screening, Diagnosis and Management2018Inngår i: The Journal of Nutrition, Health & Aging, ISSN 1279-7707, E-ISSN 1760-4788, Vol. 22, nr 10, s. 1148-1161Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives: Sarcopenia, defined as an age-associated loss of skeletal muscle function and muscle mass, occurs in approximately 6 - 22 % of older adults. This paper presents evidence-based clinical practice guidelines for screening, diagnosis and management of sarcopenia from the task force of the International Conference on Sarcopenia and Frailty Research (ICSFR).

    Methods: To develop the guidelines, we drew upon the best available evidence from two systematic reviews paired with consensus statements by international working groups on sarcopenia. Eight topics were selected for the recommendations: (i) defining sarcopenia; (ii) screening and diagnosis; (iii) physical activity prescription; (iv) protein supplementation; (v) vitamin D supplementation; (vi) anabolic hormone prescription; (vii) medications under development; and (viii) research. The ICSFR task force evaluated the evidence behind each topic including the quality of evidence, the benefit harm balance of treatment, patient preferences/values, and cost-effectiveness. Recommendations were graded as either strong or conditional (weak) as per the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Consensus was achieved via one face-to-face workshop and a modified Delphi process.

    Recommendations: We make a conditional recommendation for the use of an internationally accepted measurement tool for the diagnosis of sarcopenia including the EWGSOP and FNIH definitions, and advocate for rapid screening using gait speed or the SARC-F. To treat sarcopenia, we strongly recommend the prescription of resistance-based physical activity, and conditionally recommend protein supplementation/a protein-rich diet. No recommendation is given for Vitamin D supplementation or for anabolic hormone prescription. There is a lack of robust evidence to assess the strength of other treatment options.

  • 30. Deutz, M.E
    et al.
    Bauer, J.M
    Barazzoni, R
    Biolo, G
    Boirie, Y
    Bosy-Westphal, A
    Cederholm, Tommy
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Cruz-Jentoft, A
    Krznariç, Z
    Nair, K.S
    Singer, P
    Teta, Daniel
    Tipton, K
    Calder, P.C
    Protein intake and exercise for optimal muscle function with aging: Recommendations from the ESPEN Expert Group2014Inngår i: Clinical Nutrition, ISSN 0261-5614, E-ISSN 1532-1983, Vol. 33, nr 6, s. 929-936Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The aging process is associated with gradual and progressive loss of muscle mass along with lowered strength and physical endurance. This condition, sarcopenia, has been widely observed with aging in sedentary adults. Regular aerobic and resistance exercise programs have been shown to counteract most aspects of sarcopenia. In addition, good nutrition, especially adequate protein and energy intake, can help limit and treat age-related declines in muscle mass, strength, and functional abilities. Protein nutrition in combination with exercise is considered optimal for maintaining muscle function.

    With the goal of providing recommendations for health care professionals to help older adults sustain muscle strength and function into older age, the European Society for Clinical Nutrition and Metabolism (ESPEN) hosted a Workshop on Protein Requirements in the Elderly, held in Dubrovnik on November 24 and 25, 2013. Based on the evidence presented and discussed, the following recommendations are made (a) for healthy older people, the diet should provide at least 1.0–1.2 g protein/kg body weight/day, (b) for older people who are malnourished or at risk of malnutrition because they have acute or chronic illness, the diet should provide 1.2–1.5 g protein/kg body weight/day, with even higher intake for individuals with severe illness or injury, and (c) daily physical activity or exercise (resistance training, aerobic exercise) should be undertaken by all older people, for as long as possible.

  • 31.
    Emami Khoonsari, Payam
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Proteomics Studies of Subjects with Alzheimer’s Disease and Chronic Pain2017Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Alzheimer’s disease (AD) is a neurodegenerative disease and the major cause of dementia, affecting more than 50 million people worldwide. Chronic pain is long-lasting, persistent pain that affects more than 1.5 billion of the world population. Overlapping and heterogenous symptoms of AD and chronic pain conditions complicate their diagnosis, emphasizing the need for more specific biomarkers to improve the diagnosis and understand the disease mechanisms.

    To characterize disease pathology of AD, we measured the protein changes in the temporal neocortex region of the brain of AD subjects using mass spectrometry (MS). We found proteins involved in exo-endocytic and extracellular vesicle functions displaying altered levels in the AD brain, potentially resulting in neuronal dysfunction and cell death in AD.

    To detect novel biomarkers for AD, we used MS to analyze cerebrospinal fluid (CSF) of AD patients and found decreased levels of eight proteins compared to controls, potentially indicating abnormal activity of complement system in AD.

    By integrating new proteomics markers with absolute levels of Aβ42, total tau (t-tau) and p-tau in CSF, we improved the prediction accuracy from 83% to 92% of early diagnosis of AD. We found increased levels of chitinase-3-like protein 1 (CH3L1) and decreased levels of neurosecretory protein VGF (VGF) in AD compared to controls.

    By exploring the CSF proteome of neuropathic pain patients before and after successful spinal cord stimulation (SCS) treatment, we found altered levels of twelve proteins, involved in neuroprotection, synaptic plasticity, nociceptive signaling and immune regulation.

    To detect biomarkers for diagnosing a chronic pain state known as fibromyalgia (FM), we analyzed the CSF of FM patients using MS. We found altered levels of four proteins, representing novel biomarkers for diagnosing FM. These proteins are involved in inflammatory mechanisms, energy metabolism and neuropeptide signaling.

    Finally, to facilitate fast and robust large-scale omics data handling, we developed an e-infrastructure. We demonstrated that the e-infrastructure provides high scalability, flexibility and it can be applied in virtually any fields including proteomics. This thesis demonstrates that proteomics is a promising approach for gaining deeper insight into mechanisms of nervous system disorders and find biomarkers for diagnosis of such diseases.

    Delarbeid
    1. Increased levels of extracellular microvesicle markers and decreased levels of endocytic/exocytic proteins in the Alzheimer’s disease brain
    Åpne denne publikasjonen i ny fane eller vindu >>Increased levels of extracellular microvesicle markers and decreased levels of endocytic/exocytic proteins in the Alzheimer’s disease brain
    Vise andre…
    2016 (engelsk)Inngår i: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 54, nr 4, s. 71s. 1671-1686Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Background: Alzheimer's disease (AD) is a chronic neurodegenerative disorder accounting for more than 50% of all dementia cases. AD neuropathology is characterized by the formation of extracellular plaques and intracellular neurofibrillary tangles consisting of aggregated amyloid-beta and tau, respectively. The disease mechanism has only been partially elucidated and is believed to also involve many other proteins.

    Objective: This study intended to perform a proteomic profiling of post mortem AD brains and compare it with control brains as well as brains from other neurological diseases to gain insight into the disease pathology.

    Methods: Here we used label-free shotgun mass spectrometry to analyze temporal neocortex samples from AD, other neurological disorders, and non-demented controls, in order to identify additional proteins that are altered in AD. The mass spectrometry results were verified by antibody suspension bead arrays.

    Results: We found 50 proteins with altered levels between AD and control brains. The majority of these proteins were found at lower levels in AD. Pathway analyses revealed that several of the decreased proteins play a role in exocytic and endocytic pathways, whereas several of the increased proteins are related to extracellular vesicles. Using antibody-based analysis, we verified the mass spectrometry results for five representative proteins from this group of proteins (CD9, HSP72, PI42A, TALDO, and VAMP2) and GFAP, a marker for neuroinflammation.

    Conclusions: Several proteins involved in exo-endocytic pathways and extracellular vesicle functions display altered levels in the AD brain. We hypothesize that such changes may result in disturbed cellular clearance and a perturbed cell-to-cell communication that may contribute to neuronal dysfunction and cell death in AD.

    Publisher
    s. 71
    Emneord
    Brain, Proteomics, Mass spectrometry, Alzheimer's disease
    HSV kategori
    Forskningsprogram
    Kemi med inriktning mot analytisk kemi
    Identifikatorer
    urn:nbn:se:uu:diva-277617 (URN)10.3233/JAD-160271 (DOI)000386749900034 ()27636840 (PubMedID)
    Forskningsfinansiär
    VINNOVALars Hierta Memorial FoundationSwedish Research Council, P29797-1; 621-2011-4423Knut and Alice Wallenberg FoundationStiftelsen Gamla Tjänarinnor
    Tilgjengelig fra: 2016-02-22 Laget: 2016-02-22 Sist oppdatert: 2019-04-29bibliografisk kontrollert
    2. Analysis of the Cerebrospinal Fluid Proteome in Alzheimer's Disease
    Åpne denne publikasjonen i ny fane eller vindu >>Analysis of the Cerebrospinal Fluid Proteome in Alzheimer's Disease
    Vise andre…
    2016 (engelsk)Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, nr 3, artikkel-id e0150672Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Alzheimer's disease is a neurodegenerative disorder accounting for more than 50% of cases of dementia. Diagnosis of Alzheimer's disease relies on cognitive tests and analysis of amyloid beta, protein tau, and hyperphosphorylated tau in cerebrospinal fluid. Although these markers provide relatively high sensitivity and specificity for early disease detection, they are not suitable for monitor of disease progression. In the present study, we used label-free shotgun mass spectrometry to analyse the cerebrospinal fluid proteome of Alzheimer's disease patients and non-demented controls to identify potential biomarkers for Alzheimer's disease. We processed the data using five programs (DecyderMS, Maxquant, OpenMS, PEAKS, and Sieve) and compared their results by means of reproducibility and peptide identification, including three different normalization methods. After depletion of high abundant proteins we found that Alzheimer's disease patients had lower fraction of low-abundance proteins in cerebrospinal fluid compared to healthy controls (p<0.05). Consequently, global normalization was found to be less accurate compared to using spiked-in chicken ovalbumin for normalization. In addition, we determined that Sieve and OpenMS resulted in the highest reproducibility and PEAKS was the programs with the highest identification performance. Finally, we successfully verified significantly lower levels (p<0.05) of eight proteins (A2GL, APOM, C1QB, C1QC, C1S, FBLN3, PTPRZ, and SEZ6) in Alzheimer's disease compared to controls using an antibody-based detection method. These proteins are involved in different biological roles spanning from cell adhesion and migration, to regulation of the synapse and the immune system.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-283774 (URN)10.1371/journal.pone.0150672 (DOI)000371990100049 ()26950848 (PubMedID)
    Forskningsfinansiär
    Knut and Alice Wallenberg FoundationMarianne and Marcus Wallenberg FoundationThe Swedish Brain FoundationSwedish Research Council FormasSwedish Research Council, P29797-1Swedish Research Council, 621-2011-4423
    Tilgjengelig fra: 2016-04-14 Laget: 2016-04-14 Sist oppdatert: 2019-04-29bibliografisk kontrollert
    3. Chitinase-3-like protein 1 (CH3L1) and Neurosecretory protein VGF (VGF) as two novel CSF biomarker candidates for improved diagnostics in Alzheimer’s disease
    Åpne denne publikasjonen i ny fane eller vindu >>Chitinase-3-like protein 1 (CH3L1) and Neurosecretory protein VGF (VGF) as two novel CSF biomarker candidates for improved diagnostics in Alzheimer’s disease
    Vise andre…
    (engelsk)Manuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Alzheimer’s disease (AD) is a chronic neurodegenerative disorder characterized by amyloid-β (Aβ) plaque deposition and accumulation of intracellular neurofibrillary tangles. This pathology is mirrored in the cerebrospinal fluid (CSF), where decreased Aβ42 together with increased total (t-tau) and phospho-tau (p-tau) today is used as a diagnostic marker. Although these biomarkers have a fairly good sensitivity and specificity, additional biomarkers are needed to further improve the accuracy for early disease detection and to monitor disease development. In this study, we used mass spectrometry-based shotgun proteomics to investigate the CSF proteome of patients with AD and mild cognitive impairment (MCI) as well as of non-demented controls. By combining the diagnostic markers (Aβ42, total t-tau, and p-tau) with a selection of proteomics biomarkers, the accuracy of predicting MCI to AD conversion increased from 83% to 92% with a specificity of 1.0 and sensitivity of 0.86. Among these markers, the levels of protein chitinase-3-like protein 1 (CH3L1) were significantly higher in AD and MCI converters compared to controls. In addition to Aβ42, t-tau, and p-tau the protein CH3L1 contributed mostly to the prediction accuracy. We also found statistically significant lower CSF levels of the neurosecretory protein VGF (VGF) in AD compared to controls. Taken together, our findings suggest that incorporating new CSF biomarkers can further enhance early diagnosis of AD.

    Emneord
    Alzheimer's disease, cerebrospinal fluid, biomarker, diagnostics, neurodegenerative disorder, dementia
    HSV kategori
    Forskningsprogram
    Geriatrik; Medicinsk vetenskap; Neurologi
    Identifikatorer
    urn:nbn:se:uu:diva-331711 (URN)
    Tilgjengelig fra: 2017-10-17 Laget: 2017-10-17 Sist oppdatert: 2018-01-13
    4. Spinal Cord Stimulation Alters Protein Levels in the Cerebrospinal Fluid of Neuropathic Pain Patients: A Proteomic Mass Spectrometric Analysis
    Åpne denne publikasjonen i ny fane eller vindu >>Spinal Cord Stimulation Alters Protein Levels in the Cerebrospinal Fluid of Neuropathic Pain Patients: A Proteomic Mass Spectrometric Analysis
    Vise andre…
    2016 (engelsk)Inngår i: Neuromodulation (Malden, Mass.), ISSN 1094-7159, E-ISSN 1525-1403, Vol. 19, nr 6, s. 549-562Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    ObjectivesElectrical neuromodulation by spinal cord stimulation (SCS) is a well-established method for treatment of neuropathic pain. However, the mechanism behind the pain relieving effect in patients remains largely unknown. In this study, we target the human cerebrospinal fluid (CSF) proteome, a little investigated aspect of SCS mechanism of action. MethodsTwo different proteomic mass spectrometry protocols were used to analyze the CSF of 14 SCS responsive neuropathic pain patients. Each patient acted as his or her own control and protein content was compared when the stimulator was turned off for 48 hours, and after the stimulator had been used as normal for three weeks. ResultsEighty-six proteins were statistically significantly altered in the CSF of neuropathic pain patients using SCS, when comparing the stimulator off condition to the stimulator on condition. The top 12 of the altered proteins are involved in neuroprotection (clusterin, gelsolin, mimecan, angiotensinogen, secretogranin-1, amyloid beta A4 protein), synaptic plasticity/learning/memory (gelsolin, apolipoprotein C1, apolipoprotein E, contactin-1, neural cell adhesion molecule L1-like protein), nociceptive signaling (neurosecretory protein VGF), and immune regulation (dickkopf-related protein 3). ConclusionPreviously unknown effects of SCS on levels of proteins involved in neuroprotection, nociceptive signaling, immune regulation, and synaptic plasticity are demonstrated. These findings, in the CSF of neuropathic pain patients, expand the picture of SCS effects on the neurochemical environment of the human spinal cord. An improved understanding of SCS mechanism may lead to new tracks of investigation and improved treatment strategies for neuropathic pain.

    Emneord
    Cerebrospinal fluid, mechanism of action, neuropathic pain, spinal cord stimulation
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-304434 (URN)10.1111/ner.12473 (DOI)000382755300001 ()27513633 (PubMedID)
    Forskningsfinansiär
    VINNOVASwedish Research Council
    Tilgjengelig fra: 2016-10-05 Laget: 2016-10-05 Sist oppdatert: 2019-04-29bibliografisk kontrollert
    5. Systematic Analysis of the Cerebrospinal Fluid Proteome of Fibromyalgia patients
    Åpne denne publikasjonen i ny fane eller vindu >>Systematic Analysis of the Cerebrospinal Fluid Proteome of Fibromyalgia patients
    Vise andre…
    2019 (engelsk)Inngår i: Journal of Proteomics, ISSN 1874-3919, E-ISSN 1876-7737, s. 35-43Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Fibromyalgia (FM) is a syndrome characterized by widespread muscular pain, fatigue and functional symptoms, which is known to be difficult to diagnose as the various symptoms overlap with many other conditions. Currently, there are no biomarkers for FM, and the diagnosis is made subjectively by the clinicians. We have performed shotgun proteomics on cerebrospinal fluid (CSF) from FM patients and non-pain controls to find potential biomarker candidates for this syndrome. Based on our multivariate and univariate analyses, we found that the relative differences in the CSF proteome between FM patients and controls were moderate. Four proteins, important to discriminate FM patients from non-pain controls, were found: Apolipoprotein C-III, Galectin-3-binding protein, Malate dehydrogenase cytoplasmic and the neuropeptide precursor protein ProSAAS. These proteins are involved in lipoprotein lipase (LPL) activity, inflammatory signaling, energy metabolism and neuropeptide signaling.

    Emneord
    cerebrospinal fluid, biomarker, chronic pain, fibromyalgia, inflammation, neuroinflammation, mass spectrometry
    HSV kategori
    Forskningsprogram
    Bioinformatik; Biologi med inriktning mot molekylärbiologi; Kemi med inriktning mot analytisk kemi; Medicinsk vetenskap; Klinisk kemi
    Identifikatorer
    urn:nbn:se:uu:diva-331615 (URN)10.1016/j.jprot.2018.04.014 (DOI)000450381500006 ()29656018 (PubMedID)
    Forskningsfinansiär
    Magnus Bergvall FoundationLars Hierta Memorial FoundationÅke Wiberg FoundationThe Karolinska Institutet's Research Foundation
    Tilgjengelig fra: 2017-10-16 Laget: 2017-10-16 Sist oppdatert: 2019-04-29bibliografisk kontrollert
    6. Interoperable and scalable metabolomics data analysis with microservices
    Åpne denne publikasjonen i ny fane eller vindu >>Interoperable and scalable metabolomics data analysis with microservices
    Vise andre…
    (engelsk)Manuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Developing a robust and performant data analysis workflow that integrates all necessary components whilst still being able to scale over multiple compute nodes is a challenging task. We here present a generic method based on microservice architecture, where software tools are encapsulated as Docker containers that can be connected into scientific workflows and executed in parallel using the Kubernetes container orchestrator. The method was developed within the PhenoMeNal consortium to support flexible metabolomics data analysis and was designed as a virtual research environment which can be launched on-demand on cloud resources and desktop computers. IT-expertise requirements on the user side are kept to a minimum, and established workflows can be re-used effortlessly by any novice user. We validate our method on two mass spectrometry studies, one nuclear magnetic resonance spectroscopy study and one fluxomics study, showing that the method scales dynamically with increasing availability of computational resources. We achieved a complete integration of the major software suites resulting in the first turn-key workflow encompassing all steps for mass-spectrometry-based metabolomics including preprocessing, multivariate statistics, and metabolite identification. Microservices is a generic methodology that can serve any scientific discipline and opens up for new types of large-scale integrative data analysis.

    Emneord
    Bioinformatics, e-infrastructure, microservices, metabolomics, kubernetes, Docker, container
    HSV kategori
    Forskningsprogram
    Bioinformatik
    Identifikatorer
    urn:nbn:se:uu:diva-331658 (URN)
    Tilgjengelig fra: 2017-10-16 Laget: 2017-10-16 Sist oppdatert: 2019-10-11
  • 32.
    Emami Khoonsari, Payam
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin.
    Haggmark, Anna
    KTH Royal Inst Technol, Sch Biotechnol, Affin Prote, Sci Life Lab, Stockholm, Sweden..
    Lönnberg, Maria
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Mikus, Maria
    KTH Royal Inst Technol, Sch Biotechnol, Affin Prote, Sci Life Lab, Stockholm, Sweden..
    Kilander, Lena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Lannfelt, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Ingelsson, Martin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Nilsson, Peter
    KTH Royal Inst Technol, Sch Biotechnol, Affin Prote, Sci Life Lab, Stockholm, Sweden..
    Kultima, Kim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin.
    Shevchenko, Ganna
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi. Uppsala Univ, Dept Chem BMC, Analyt Chem, Uppsala, Sweden..
    Analysis of the Cerebrospinal Fluid Proteome in Alzheimer's Disease2016Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, nr 3, artikkel-id e0150672Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Alzheimer's disease is a neurodegenerative disorder accounting for more than 50% of cases of dementia. Diagnosis of Alzheimer's disease relies on cognitive tests and analysis of amyloid beta, protein tau, and hyperphosphorylated tau in cerebrospinal fluid. Although these markers provide relatively high sensitivity and specificity for early disease detection, they are not suitable for monitor of disease progression. In the present study, we used label-free shotgun mass spectrometry to analyse the cerebrospinal fluid proteome of Alzheimer's disease patients and non-demented controls to identify potential biomarkers for Alzheimer's disease. We processed the data using five programs (DecyderMS, Maxquant, OpenMS, PEAKS, and Sieve) and compared their results by means of reproducibility and peptide identification, including three different normalization methods. After depletion of high abundant proteins we found that Alzheimer's disease patients had lower fraction of low-abundance proteins in cerebrospinal fluid compared to healthy controls (p<0.05). Consequently, global normalization was found to be less accurate compared to using spiked-in chicken ovalbumin for normalization. In addition, we determined that Sieve and OpenMS resulted in the highest reproducibility and PEAKS was the programs with the highest identification performance. Finally, we successfully verified significantly lower levels (p<0.05) of eight proteins (A2GL, APOM, C1QB, C1QC, C1S, FBLN3, PTPRZ, and SEZ6) in Alzheimer's disease compared to controls using an antibody-based detection method. These proteins are involved in different biological roles spanning from cell adhesion and migration, to regulation of the synapse and the immune system.

  • 33. Emami Khoonsari, Payam
    et al.
    Shevchenko, Ganna
    Herman, Stephanie
    Musunuri, Sravani
    Remnestål, Julia
    Brundin, RoseMarie
    Degerman Gunnarsson, Malin
    Kilander, Lena
    Zetterberg, Henrik
    Nilsson, Peter
    Lannfelt, Lars
    Ingelsson, Martin
    Kultima, Kim
    Chitinase-3-like protein 1 (CH3L1) and Neurosecretory protein VGF (VGF) as two novel CSF biomarker candidates for improved diagnostics in Alzheimer’s diseaseManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Alzheimer’s disease (AD) is a chronic neurodegenerative disorder characterized by amyloid-β (Aβ) plaque deposition and accumulation of intracellular neurofibrillary tangles. This pathology is mirrored in the cerebrospinal fluid (CSF), where decreased Aβ42 together with increased total (t-tau) and phospho-tau (p-tau) today is used as a diagnostic marker. Although these biomarkers have a fairly good sensitivity and specificity, additional biomarkers are needed to further improve the accuracy for early disease detection and to monitor disease development. In this study, we used mass spectrometry-based shotgun proteomics to investigate the CSF proteome of patients with AD and mild cognitive impairment (MCI) as well as of non-demented controls. By combining the diagnostic markers (Aβ42, total t-tau, and p-tau) with a selection of proteomics biomarkers, the accuracy of predicting MCI to AD conversion increased from 83% to 92% with a specificity of 1.0 and sensitivity of 0.86. Among these markers, the levels of protein chitinase-3-like protein 1 (CH3L1) were significantly higher in AD and MCI converters compared to controls. In addition to Aβ42, t-tau, and p-tau the protein CH3L1 contributed mostly to the prediction accuracy. We also found statistically significant lower CSF levels of the neurosecretory protein VGF (VGF) in AD compared to controls. Taken together, our findings suggest that incorporating new CSF biomarkers can further enhance early diagnosis of AD.

  • 34.
    Emami Khoonsari, Payam
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Shevchenko, Ganna
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Herman, Stephanie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Remnestal, Julia
    KTH Royal Inst Technol, Dept Prot Sci, Div Affin Prote, SciLifeLab, Stockholm, Sweden.
    Giedraitis, Vilmantas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Brundin, RoseMarie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Degerman Gunnarsson, Malin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Kilander, Lena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Zetterberge, Henrik
    Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Mölndal, Sweden; Sahlgrens Univ Hosp, Clin Neurochem Lab, Molndal, Sweden; UK Dementia Res Inst UCL, London, England; UCL Inst Neurol, Dept Mol Neurosci, Queen Sq, London, England.
    Nilsson, Peter
    KTH Royal Inst Technol, Dept Prot Sci, Div Affin Prote, SciLifeLab, Stockholm, Sweden.
    Lannfelt, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Ingelsson, Martin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Kultima, Kim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Improved Differential Diagnosis of Alzheimer's Disease by Integrating ELISA and Mass Spectrometry-Based Cerebrospinal Fluid Biomarkers2019Inngår i: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 67, nr 2, s. 639-651Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Alzheimer’s disease (AD) is diagnosed based on a clinical evaluation as well as analyses of classical biomarkers: Aβ42, total tau (t-tau), and phosphorylated tau (p-tau) in cerebrospinal fluid (CSF). Although the sensitivities and specificities of the classical biomarkers are fairly good for detection of AD, there is still a need to develop novel biochemical markers for early detection of AD.

    Objective: We explored if integration of novel proteins with classical biomarkers in CSF can better discriminate AD from non-AD subjects.

    Methods: We applied ELISA, mass spectrometry, and multivariate modeling to investigate classical biomarkers and the CSF proteome in subjects (n = 206) with 76 AD patients, 74 mild cognitive impairment (MCI) patients, 11 frontotemporal dementia (FTD) patients, and 45 non-dementia controls. The MCI patients were followed for 4–9 years and 21 of these converted to AD, whereas 53 remained stable.

    Results: By combining classical CSF biomarkers with twelve novel markers, the area of the ROC curves (AUROCS) of distinguishing AD and MCI/AD converters from non-AD were 93% and 96%, respectively. The FTDs and non-dementia controls were identified versus all other groups with AUROCS of 96% and 87%, respectively.

    Conclusions: Integration of new and classical CSF biomarkers in a model-based approach can improve the identification of AD, FTD, and non-dementia control subjects.

  • 35.
    Englund, Davis A.
    et al.
    Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Nutr Exercise Physiol & Sarcopenia Lab, Boston, USA.
    Kirn, Dylan R.
    Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Nutr Exercise Physiol & Sarcopenia Lab, Boston, USA.
    Koochek, Afsaneh
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Zhu, Hao
    Hebrew SeniorLife, Inst Aging Res, Boston, USA.
    Travison, Thomas G.
    Hebrew SeniorLife, Inst Aging Res, Boston, USA; Harvard Med Sch, Boston, USA.
    Reid, Kieran F.
    Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Nutr Exercise Physiol & Sarcopenia Lab, Boston, USA.
    von Berens, Åsa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Melin, Michael
    Karolinska Inst, Dept Lab Med, Stockholm, Sweden.
    Cederholm, Tommy
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Gustafsson, Thomas
    Karolinska Inst, Dept Lab Med, Stockholm, Sweden.
    Fielding, Roger A.
    Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Nutr Exercise Physiol & Sarcopenia Lab, Boston, USA.
    Nutritional Supplementation With Physical Activity Improves Muscle Composition in Mobility-Limited Older Adults, The VIVE2 Study: A Randomized, Double-Blind, Placebo-Controlled Trial2018Inngår i: The journals of gerontology. Series A, Biological sciences and medical sciences, ISSN 1079-5006, E-ISSN 1758-535X, Vol. 73, nr 1, s. 95-101Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Nutritional supplementation and physical activity have been shown to positively influence muscle mass and strength in older adults. The efficacy of long-term nutritional supplementation in combination with physical activity in older adults remains unclear.

    Methods: Mobility-limited (short physical performance battery [SPPB] ≤9) and vitamin D insufficient (serum 25(OH) D 9–24 ng/mL) older adults were recruited for this study. All subjects participated in a physical activity program. Subjects were randomized to consume a daily nutritional supplement (150 kcal, 20 g whey protein, 800 IU vitamin D, 119 mL beverage) or placebo (30 kcal, nonnutritive, 119 mL). In a prespecified secondary analysis, we examined total-body composition (dual energy X-ray absorptiometry), thigh composition (computed tomography), and muscle strength, power, and quality before and after the 6-month intervention.

    Results: One hundred and forty-nine subjects were randomized into the study [mean (standard deviation, SD) age 78.5 (5.4) years; 46.3% female; mean (SD) short physical performance battery 7.9 (1.2); mean (SD) vitamin D 18.7 (6.4) ng/mL]. After the intervention period both groups demonstrated improvements in muscle strength, body composition, and thigh composition. Nutritional supplementation lead to further losses of intermuscular fat (p = .049) and increased normal muscle density (p = .018).

    Conclusions: Six months of physical activity resulted in improvements in body composition, subcutaneous fat, intermuscular fat, and strength measures. The addition of nutritional supplementation resulted in further declines in intermuscular fat and improved muscle density compared to placebo. These results suggest nutritional supplementation provides additional benefits to mobility-limited older adults undergoing exercise training.

  • 36.
    Englund, Hillevi
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Soluble amyloid-β aggregates in Alzheimer’s disease2009Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Soluble oligomeric aggregates of the amyloid-β (Aβ) peptide are suggested to initiate Alzheimer's disease (AD), leading to impaired synapse signalling, widespread neuronal death and loss of cognitive functions. These aggregates seem tightly linked to disease progression, and have therefore gained much attention as potential novel disease markers. In this thesis soluble oligomeric Aβ aggregates in general, and the Aβ protofibril species in particular, have been investigated with the aim to quantify and determine their role in AD pathogenesis.

    Sandwich-ELISAs specifically measuring Aβ42 peptides are widely used both in AD research and as complements for clinical diagnosis. Here it was demonstrated that presence of soluble Aβ aggregates disturbs such analyses, making it difficult to interpret the results. This discovery was made through analyses of samples from cell- and mouse models carrying the AD causing 'Arctic' APP mutation. When analyzed by ELISA, Aβ42 levels were reduced in Arctic samples, in contrast to levels measured by denaturing SDS-PAGE Western blot. The same divergence in Aβ42-levels between analyses was observed in CSF samples from Down syndrome infants. The discrepancy between methods was hypothesized to be due to presence of soluble Aβ aggregates leading to impaired ELISA detection caused by epitope masking. This was confirmed by developing a protofibril specific ELISA, by which samples from Arctic cell- and mouse models were demonstrated to have enhanced Aβ protofibril levels.

    AD patients have reduced ELISA-measured Aβ42-levels in CSF compared to healthy controls. To test if this reduction was due to oligomeric Aβ species present in AD CSF, Aβ42-levels were analyzed under both denaturing and non-denaturing conditions. These two measures were combined and an Aβ42 oligomer ratio established. Higher ratios were found in AD patients than healthy controls, implying that Aβ oligomers are present in CSF during Alzheimer pathogenesis. The observations from AD patients and young Down syndrome individuals suggest that Aβ42 oligomer formation is an early mechanism of AD pathogenesis, which potentially could be used as a biomarker to monitor disease development.

    Delarbeid
    1. Amyloid-β oligomers are inefficiently measured by enzyme-linked immunosorbent assay
    Åpne denne publikasjonen i ny fane eller vindu >>Amyloid-β oligomers are inefficiently measured by enzyme-linked immunosorbent assay
    Vise andre…
    2005 Inngår i: Annals of Neurology, ISSN 0364-5134, Vol. 58, nr 1, s. 147-150Artikkel i tidsskrift (Fagfellevurdert) Published
    Identifikatorer
    urn:nbn:se:uu:diva-95486 (URN)
    Tilgjengelig fra: 2007-03-02 Laget: 2007-03-02bibliografisk kontrollert
    2. Increase in beta-Amyloid Levels in Cerebrospinal Fluid of Children with Down Syndrome
    Åpne denne publikasjonen i ny fane eller vindu >>Increase in beta-Amyloid Levels in Cerebrospinal Fluid of Children with Down Syndrome
    Vise andre…
    2007 (engelsk)Inngår i: Dementia and Geriatric Cognitive Disorders, ISSN 1420-8008, E-ISSN 1421-9824, Vol. 24, nr 5, s. 369-374Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Background: Individuals with Down syndrome (DS) invariably develop Alzheimer's disease (AD) during their life span. It is therefore of importance to study young DS patients when trying to elucidate early events in AD pathogenesis. Aim: To investigate how levels of different amyloid- (A) peptides, as well as tau and phosphorylated tau, in cerebrospinal fluid (CSF) from children with DS change over time. The first CSF sample was taken at 8 months and the following two samples at 20-40 and 54 months of age. Results: Individual levels of the A peptides, as well as total A levels in CSF increased over time when measured with Western blot. Tau in CSF decreased whereas there was no change in levels of phosphorylated tau over time. Conclusion: The increasing levels of A in CSF during early childhood of DS patients observed in this study are probably due to the trisomy of the A precursor APP, which leads to an overproduction of A. Despite the increased CSF concentrations of A, there were no signs of an AD-indicating tau pattern in CSF, since the levels of total tau decreased and phosphorylated tau remained unchanged. This observation further strengthens the theory of A pathology preceding tau pathology in AD.

    Emneord
    Alzheimer's disease, Down syndrome, Amyloid-beta, Tau, Cerebrospinal fluid
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-11726 (URN)10.1159/000109215 (DOI)000250314400007 ()17914261 (PubMedID)
    Tilgjengelig fra: 2008-04-14 Laget: 2008-04-14 Sist oppdatert: 2017-12-11bibliografisk kontrollert
    3. Sensitive ELISA detection of amyloid-β protofibrils in biological samples
    Åpne denne publikasjonen i ny fane eller vindu >>Sensitive ELISA detection of amyloid-β protofibrils in biological samples
    Vise andre…
    2007 (engelsk)Inngår i: Journal of Neurochemistry, ISSN 0022-3042, E-ISSN 1471-4159, Vol. 103, nr 1, s. 334-345Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Amyloid-β (Aβ) protofibrils are known intermediates of the in vitro Aβ aggregation process and the protofibrillogenic Arctic mutation (APPE693G) provides clinical support for a pathogenic role of Aβ protofibrils in Alzheimer's disease (AD). To verify their in vivo relevance and to establish a quantitative Aβ protofibril immunoassay, Aβ conformation dependent monoclonal antibodies were generated. One of these antibodies, mAb158 (IgG2a), was used in a sandwich ELISA to specifically detect picomolar concentrations of Aβ protofibrils without interference from Aβ monomers or the amyloid precursor protein (APP). The specificity and biological significance of this ELISA was demonstrated using cell cultures and transgenic mouse models expressing human APP containing the Swedish mutation (APPKN670/671ML), or the Swedish and Arctic mutation in combination. The mAb158 sandwich ELISA analysis revealed presence of Aβ protofibrils in both cell and animal models, proving that Aβ protofibrils are formed not only in vitro, but also in vivo. Furthermore, elevated Aβ protofibril levels in the Arctic-Swedish samples emphasize the usefulness of the Arctic mutation as a model of enhanced protofibril formation. This assay provides a novel tool for investigating the role of Aβ protofibrils in AD and has the potential of becoming an important diagnostic assay.

    Emneord
    Alzheimer's disease, Amyloid-β protofibril, Conformation-dependent antibody, Protofibril-specific ELISA
    HSV kategori
    Forskningsprogram
    Geriatrik
    Identifikatorer
    urn:nbn:se:uu:diva-98511 (URN)10.1111/j.1471-4159.2007.04759.x (DOI)000249949700030 ()17623042 (PubMedID)
    Tilgjengelig fra: 2009-02-24 Laget: 2009-02-24 Sist oppdatert: 2017-12-13bibliografisk kontrollert
    4. Oligomerization partially explains the lowering of Aβ42 in Alzheimer's disease cerebrospinal fluid
    Åpne denne publikasjonen i ny fane eller vindu >>Oligomerization partially explains the lowering of Aβ42 in Alzheimer's disease cerebrospinal fluid
    Vise andre…
    2009 (engelsk)Inngår i: Neuro-degenerative diseases, ISSN 1660-2862, Vol. 6, nr 4, s. 139-147Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Background/aim: The lowering of natively analyzed Aβ42 in cerebrospinal fluid (CSF) is used as a diagnostic tool in Alzheimer’s disease (AD). Presence of Aβ oligomers can interfere with such analyses causing underestimation of Aβ levels due to epitope masking. The aim was to investigate if the lowering of CSF Aβ42 seen is caused by oligomerization. Methods: Aβ42 was analyzed under both denaturing and non-denaturing conditions. An Aβ42 oligomer ratio was calculated from these quantifications. Presence of oligomers leads to Aβ42 epitope masking during non-denaturing assays, resulting in a higher ratio. Results: The Aβ42 oligomer ratio was used for assessment of oligomerized Aβ in human CSF, after being evaluated in transgenic mouse brain homogenates. AD and mild cognitive impairment (MCI) samples displayed the expected decrease in natively measured Aβ42 compared to healthy controls and frontotemporal dementia, but not when analyzing under denaturing conditions. Accordingly, AD and MCI CSF had a higher Aβ42 oligomer ratio in CSF. Conclusion: Combining denaturing and non-denaturing quantifications of Aβ42 into an oligomer ratio enables assessment of Aβ oligomers in biological samples. The increased Aβ42 oligomer ratio for AD and MCI indicates presence of oligomers in CSF and that the lowering of natively measured Aβ42 is caused by oligomerization.

    Emneord
    Alzheimer’s disease, CSF, Amyloid-β, oligomers
    HSV kategori
    Forskningsprogram
    Geriatrik
    Identifikatorer
    urn:nbn:se:uu:diva-98510 (URN)10.1159/000225376 (DOI)000269623400001 ()19521063 (PubMedID)
    Tilgjengelig fra: 2009-02-24 Laget: 2009-02-24 Sist oppdatert: 2010-07-08bibliografisk kontrollert
  • 37. Escott-Price, Valentina
    et al.
    Bellenguez, Celine
    Wang, Li-San
    Choi, Seung-Hoan
    Harold, Denise
    Jones, Lesley
    Holmans, Peter
    Gerrish, Amy
    Vedernikov, Alexey
    Richards, Alexander
    DeStefano, Anita L.
    Lambert, Jean-Charles
    Ibrahim-Verbaas, Carla A.
    Naj, Adam C.
    Sims, Rebecca
    Jun, Gyungah
    Bis, Joshua C.
    Beecham, Gary W.
    Grenier-Boley, Benjamin
    Russo, Giancarlo
    Thornton-Wells, Tricia A.
    Denning, Nicola
    Smith, Albert V.
    Chouraki, Vincent
    Thomas, Charlene
    Ikram, M. Arfan
    Zelenika, Diana
    Vardarajan, Badri N.
    Kamatani, Yoichiro
    Lin, Chiao-Feng
    Schmidt, Helena
    Kunkle, Brian
    Dunstan, Melanie L.
    Vronskaya, Maria
    Johnson, Andrew D.
    Ruiz, Agustin
    Bihoreau, Marie-Therese
    Reitz, Christiane
    Pasquier, Florence
    Hollingworth, Paul
    Hanon, Olivier
    Fitzpatrick, Annette L.
    Buxbaum, Joseph D.
    Campion, Dominique
    Crane, Paul K.
    Baldwin, Clinton
    Becker, Tim
    Gudnason, Vilmundur
    Cruchaga, Carlos
    Craig, David
    Amin, Najaf
    Berr, Claudine
    Lopez, Oscar L.
    De Jager, Philip L.
    Deramecourt, Vincent
    Johnston, Janet A.
    Evans, Denis
    Lovestone, Simon
    Letenneur, Luc
    Hernandez, Isabel
    Rubinsztein, David C.
    Eiriksdottir, Gudny
    Sleegers, Kristel
    Goate, Alison M.
    Fievet, Nathalie
    Huentelman, Matthew J.
    Gill, Michael
    Brown, Kristelle
    Kamboh, M. Ilyas
    Keller, Lina
    Barberger-Gateau, Pascale
    McGuinness, Bernadette
    Larson, Eric B.
    Myers, Amanda J.
    Dufouil, Carole
    Todd, Stephen
    Wallon, David
    Love, Seth
    Rogaeva, Ekaterina
    Gallacher, John
    St George-Hyslop, Peter
    Clarimon, Jordi
    Lleo, Alberto
    Bayer, Anthony
    Tsuang, Debby W.
    Yu, Lei
    Tsolaki, Magda
    Bossu, Paola
    Spalletta, Gianfranco
    Proitsi, Petra
    Collinge, John
    Sorbi, Sandro
    Garcia, Florentino Sanchez
    Fox, Nick C.
    Hardy, John
    Deniz Naranjo, Maria Candida
    Bosco, Paolo
    Clarke, Robert
    Brayne, Carol
    Galimberti, Daniela
    Scarpini, Elio
    Bonuccelli, Ubaldo
    Mancuso, Michelangelo
    Siciliano, Gabriele
    Moebus, Susanne
    Mecocci, Patrizia
    Del Zompo, Maria
    Maier, Wolfgang
    Hampel, Harald
    Pilotto, Alberto
    Frank-Garcia, Ana
    Panza, Francesco
    Solfrizzi, Vincenzo
    Caffarra, Paolo
    Nacmias, Benedetta
    Perry, William
    Mayhaus, Manuel
    Lannfelt, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Hakonarson, Hakon
    Pichler, Sabrina
    Carrasquillo, Minerva M.
    Ingelsson, Martin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Beekly, Duane
    Alvarez, Victoria
    Zou, Fanggeng
    Valladares, Otto
    Younkin, Steven G.
    Coto, Eliecer
    Hamilton-Nelson, Kara L.
    Gu, Wei
    Razquin, Cristina
    Pastor, Pau
    Mateo, Ignacio
    Owen, Michael J.
    Faber, Kelley M.
    Jonsson, Palmi V.
    Combarros, Onofre
    O'Donovan, Michael C.
    Cantwell, Laura B.
    Soininen, Hilkka
    Blacker, Deborah
    Mead, Simon
    Mosley, Thomas H., Jr.
    Bennett, David A.
    Harris, Tamara B.
    Fratiglioni, Laura
    Holmes, Clive
    de Bruijn, Renee F. A. G.
    Passmore, Peter
    Montine, Thomas J.
    Bettens, Karolien
    Rotter, Jerome I.
    Brice, Alexis
    Morgan, Kevin
    Foroud, Tatiana M.
    Kukull, Walter A.
    Hannequin, Didier
    Powell, John F.
    Nalls, Michael A.
    Ritchie, Karen
    Lunetta, Kathryn L.
    Kauwe, John S. K.
    Boerwinkle, Eric
    Riemenschneider, Matthias
    Boada, Merce
    Hiltunen, Mikko
    Martin, Eden R.
    Schmidt, Reinhold
    Rujescu, Dan
    Dartigues, Jean-Francois
    Mayeux, Richard
    Tzourio, Christophe
    Hofman, Albert
    Noethen, Markus M.
    Graff, Caroline
    Psaty, Bruce M.
    Haines, Jonathan L.
    Lathrop, Mark
    Pericak-Vance, Margaret A.
    Launer, Lenore J.
    Van Broeckhoven, Christine
    Farrer, Lindsay A.
    van Duijn, Cornelia M.
    Ramirez, Alfredo
    Seshadri, Sudha
    Schellenberg, Gerard D.
    Amouyel, Philippe
    Williams, Julie
    Gene-Wide Analysis Detects Two New Susceptibility Genes for Alzheimer's Disease2014Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, nr 6, s. e94661-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls. Principal Findings: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4x10(-6)) and 14 (IGHV1-67 p = 7.9x10(-8)) which indexed novel susceptibility loci. Significance: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.

  • 38.
    Fang, Xiaotian T.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Eriksson, Jonas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för Preklinisk PET-MRI. PET Centre, Uppsala University Hospital, 751 85 Uppsala, Sweden.
    Antoni, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för Preklinisk PET-MRI. Uppsala University Hospital, 751 85 Uppsala, SwedenUppsala University Hospital, 751 85 Uppsala, Sweden.
    Yngve, Ulrika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för Preklinisk PET-MRI. Uppsala University Hospital, 751 85 Uppsala, SwedenUppsala University Hospital, 751 85 Uppsala, Sweden.
    Cato, Linda
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Lannfelt, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Sehlin, Dag
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Syvänen, Stina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Brain mGluR5 in mice with amyloid beta pathology studied with in vivo [(11)C]ABP688 PET imaging and ex vivo immunoblotting2017Inngår i: Neuropharmacology, ISSN 0028-3908, E-ISSN 1873-7064, Vol. 113, nr Pt A, s. 293-300, artikkel-id S0028-3908(16)30459-2Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Alzheimer's disease (AD) is characterized by aggregation of amyloid beta (Aβ) into insoluble plaques. Intermediates, Aβ oligomers (Aβo), appear to be the mechanistic cause of disease. The de facto PET AD ligand, [(11)C]PIB, binds and visualizes Aβ plaque load, which does not correlate well with disease severity. Therefore, finding a dynamic target that changes with pathology progression in AD is of great interest. Aβo alter synaptic plasticity, inhibit long-term potentiation, and facilitate long-term depression; key mechanisms involved in memory and learning. In order to convey these neurotoxic effects, Aβo requires interaction with the metabotropic glutamate 5 receptor (mGluR5). The aim was to investigate in vivo mGluR5 changes in an Aβ pathology model using PET. Wild type C57/BL6 (wt) and AβPP transgenic mice (tg-ArcSwe), 4, 8, and 16 months old, were PET scanned with [(11)C]ABP688, which is highly specific to mGluR5, to investigate changes in mGluR5. Mouse brains were extracted postscan and mGluR5 and Aβ protofibril levels were assessed with immunoblotting and ELISA respectively. Receptor-dense brain regions (hippocampus, thalamus, and striatum) displayed higher [(11)C]ABP688 concentrations corresponding to mGluR5 expression pattern. Mice had similar uptake levels of [(11)C]ABP688 regardless of genotype or age. Immunoblotting revealed general decline in mGluR5 expression and elevated levels of mGluR5 in 16 months old tg-ArcSwe compared with wt mice. [(11)C]ABP688 could visualize mGluR5 in the mouse brain. In conclusion, mGluR5 levels were found to decrease with age and tended to be higher in tg-ArcSwe compared with wt mice, however these changes could not be quantified with PET.

  • 39.
    Farina, Nicolas
    et al.
    Brighton & Sussex Med Sch, Ctr Dementia Studies, Brighton BN1 9RY, E Sussex, England..
    Jernerén, Fredrik
    Univ Oxford, Dept Pharmacol, Oxford OX1 3QT, England.;Uppsala Univ, Dept Pharmaceut Biosci, S-75237 Uppsala, Sweden..
    Turner, Cheryl
    Univ Oxford, Dept Pharmacol, Oxford OX1 3QT, England..
    Hart, Kathryn
    Univ Surrey, Dept Nutrit Sci, Guildford GU2 7XH, Surrey, England..
    Tabet, Naji
    Brighton & Sussex Med Sch, Ctr Dementia Studies, Brighton BN1 9RY, E Sussex, England.;Sussex Partnership NHS Fdn Trust, Dementia Res Unit, Crowborough TN6 1HB, England..
    Homocysteine concentrations in the cognitive progression of Alzheimer's disease2017Inngår i: Experimental Gerontology, ISSN 0531-5565, E-ISSN 1873-6815, Vol. 99, s. 146-150Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives: Hyperhomocysteinemia in Alzheimer's disease (AD) is widely reported and appears to worsen as the disease progresses. While active dietary intervention with vitamins B12 and folate decreases homocysteine blood levels, with promising clinical outcomes in Mild Cognitive Impairment (MCI), this so far has not been replicated in established AD populations. The aim of the study is to explore the relationship between hyperhomocystenemia and relevant vitamins as the disease progresses. Methods: In this longitudinal cohort study, 38 participants with mild to moderate AD were followed for an average period of 13 months. Plasma folate, vitamin B12 and homocysteine concentrations were measured at baseline and at follow-up. Dietary intake of B vitamins was also measured. Spearman's correlations were conducted by homocysteine and B vitamin status. Results: As expected, cognitive status significantly declined over the follow-up period and this was paralleled by a significant increase in homocysteine concentrations (p = 0.006). However, during this follow-up period there was no significant decline in neither dietary intake, nor the corresponding blood concentrations of vitamin B12/folate, with both remaining within normal values. Changes in blood concentrations of B vitamins were not associated with changes in homocysteine levels (p > 0.05). Conclusion: In this study, the increase in homocysteine observed in AD patients as the disease progresses cannot be solely explained by dietary and blood levels of folate and vitamin B12. Other dietary and non-dietary factors may contribute to hyperhomocysteinemia and its toxic effect in AD, which needs to be explored to optimise timely intervention strategies.

  • 40.
    Fielding, R. A.
    et al.
    Tufts Univ, Nutr Exercise Physiol & Sarcopenia Lab, Jean Mayer USDA Human Nutr Res Ctr Aging, 711 Washington St, Boston, MA 02111 USA..
    Travison, T. G.
    Hebrew SeniorLife, Inst Aging Res, Boston, MA USA.;Harvard Med Sch, Boston, MA USA..
    Kirn, D. R.
    Tufts Univ, Nutr Exercise Physiol & Sarcopenia Lab, Jean Mayer USDA Human Nutr Res Ctr Aging, 711 Washington St, Boston, MA 02111 USA..
    Koochek, A.
    Uppsala Univ, Dept Publ Hlth & Caring Sci, Clin Nutr & Metab, Uppsala, Sweden..
    Reid, K. F.
    Tufts Univ, Nutr Exercise Physiol & Sarcopenia Lab, Jean Mayer USDA Human Nutr Res Ctr Aging, 711 Washington St, Boston, MA 02111 USA..
    von Berens, Åsa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Zhu, H.
    Hebrew SeniorLife, Inst Aging Res, Boston, MA USA..
    Folta, S. C.
    Tufts Univ, Friedman Sch Nutr Sci & Policy, 711 Washington St, Boston, MA 02111 USA..
    Sacheck, J. M.
    Tufts Univ, Friedman Sch Nutr Sci & Policy, 711 Washington St, Boston, MA 02111 USA..
    Nelson, M. E.
    Tufts Univ, Friedman Sch Nutr Sci & Policy, 711 Washington St, Boston, MA 02111 USA.;Univ New Hampshire, Sustainabil Inst, Durham, NH 03824 USA..
    Liu, C. K.
    Tufts Univ, Nutr Exercise Physiol & Sarcopenia Lab, Jean Mayer USDA Human Nutr Res Ctr Aging, 711 Washington St, Boston, MA 02111 USA.;Boston Univ, Sch Med, Sect Geriatr, Boston, MA 02118 USA..
    Åberg, Anna Cristina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik. School of Education, Health and Society, Dalarna University, Sweden.
    Nydahl, Margaretha
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik. School of Education, Health and Society, Dalarna University, Sweden.
    Lilja, M.
    Karolinska Inst, Dept Lab Med, Stockholm, Sweden..
    Gustafsson, T.
    Karolinska Inst, Dept Lab Med, Stockholm, Sweden..
    Cederholm, Tommy E.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Effect of structured physical activity and nutritional supplementation on physical function in mobility-limited older adults: Results from the VIVE2 randomized trial2017Inngår i: The Journal of Nutrition, Health & Aging, ISSN 1279-7707, E-ISSN 1760-4788, Vol. 21, nr 9, s. 936-942Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The interactions between nutritional supplementation and physical activity on changes in physical function among older adults remain unclear. The primary objective of this study was to examine the impact of nutritional supplementation plus structured physical activity on 400M walk capacity in mobility-limited older adults across two sites (Boston, USA and Stockholm, Sweden). All subjects participated in a physical activity program (3x/week for 24 weeks), involving walking, strength, balance, and flexibility exercises. Subjects were randomized to a daily nutritional supplement (150kcal, 20g whey protein, 800 IU vitamin D) or placebo (30kcal, non-nutritive). Participants were recruited from urban communities at 2 field centers in Boston MA USA and Stockholm SWE. Mobility-limited (Short Physical Performance Battery (SPPB) ae<currency>9) and vitamin D insufficient (serum 25(OH) D 9 - 24 ng/ml) older adults were recruited for this study. Primary outcome was gait speed assessed by the 400M walk. Results: 149 subjects were randomized into the study (mean age=77.5 +/- 5.4; female=46.3%; mean SPPB= 7.9 +/- 1.2; mean 25(OH)D=18.7 +/- 6.4 ng/ml). Adherence across supplement and placebo groups was similar (86% and 88%, respectively), and was also similar across groups for the physical activity intervention (75% and 72%, respectively). Both groups demonstrated an improvement in gait speed with no significant difference between those who received the nutritional supplement compared to the placebo (0.071 and 0.108 m/s, respectively (p=0.06)). Similar effects in physical function were observed using the SPPB. Serum 25(OH)D increased in supplemented group compared to placebo 7.4 ng/ml versus 1.3 ng/ml respectively. Results suggest improved gait speed following physical activity program with no further improvement with added nutritional supplementation.

  • 41.
    Flodin, Lena
    et al.
    Karolinska Univ Hosp, Dept Geriatr Med, Stockholm, Sweden.;Karolinska Inst, Dept Clin Sci Intervent & Technol CLINTEC, Stockholm, Sweden..
    Cederholm, Tommy
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Saaf, Maria
    Karolinska Univ Hosp, Dept Diabet Endocrinol & Metab, Stockholm, Sweden..
    Samnegard, Eva
    Danderyd Hosp, Karolinska Inst, Dept Clin Sci, Div Orthoped, Stockholm, Sweden..
    Ekstrom, Wilhelmina
    Karolinska Univ Hosp, Karolinska Inst, Dept Mol Med & Surg, Sect Orthoped & Sports Med, Stockholm, Sweden..
    Al-Ani, Amer N.
    Karolinska Univ Hosp, Dept Orthopaed, Stockholm, Sweden.;Karolinska Inst, Dept Clin Sci Intervent & Technol CLINTEC, Stockholm, Sweden..
    Hedstrom, Margareta
    Karolinska Univ Hosp, Dept Orthopaed, Stockholm, Sweden.;Karolinska Inst, Dept Clin Sci Intervent & Technol CLINTEC, Stockholm, Sweden..
    Effects of protein-rich nutritional supplementation and bisphosphonates on body composition, handgrip strength and health-related quality of life after hip fracture: a 12-month randomized controlled study2015Inngår i: BMC Geriatrics, ISSN 1471-2318, E-ISSN 1471-2318, Vol. 15, artikkel-id 149Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: The catabolic state that follows hip fracture contributes to loss of muscle mass and strength, that is sarcopenia, which impacts functional ability and health-related quality of life. Measures to prevent such long-term postoperative consequences are of important concern. The aim of this study was to evaluate the combined effects of protein-rich nutritional supplementation and bisphosphonate on body composition, handgrip strength and health-related quality of life following hip fracture. Methods: The study included 79 men and women with hip fracture, mean age 79 years (SD 9), without severe cognitive impairment, who were ambulatory and living independently before fracture. Patients were randomized postoperatively to receive liquid supplementation that provided 40 g of protein and 600 kcal daily for six months after the fracture, in addition to bisphosphonates once weekly for 12 months (group N, n = 26), or bisphosphonates alone once weekly for 12 months (group B, n = 28). All patients, including the controls (group C, n = 25) received calcium 1 g and vitamin D3 800 IU daily. Body composition as measured by dual-energy X-ray absorptiometry (DXA), handgrip strength (HGS) and health-related quality of life (HRQoL) were registered at baseline, six and 12 months postoperatively. Results: There were no differences among the groups regarding change in fat-free mass index (FFMI), HGS, or HRQoL during the study year. Intra-group analyses showed improvement of HGS between baseline and six months in the N group (P = 0.04). HRQoL decreased during the first year in the C and B groups (P = 0.03 and P = 0.01, respectively) but not in the nutritional supplementation N group (P = 0.22). Conclusions: Protein-rich nutritional supplementation was unable to preserve FFMI more effectively than vitamin D and calcium alone, or combined with bisphosphonate, in this relatively healthy group of hip fracture patients. However, trends toward positive effects on both HGS and HRQoL were observed following nutritional supplementation.

  • 42. Flodin, Lena
    et al.
    Saaf, Maria
    Cederholm, Tommy
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Al-Ani, Amer N.
    Ackermann, Paul W.
    Samnegard, Eva
    Dalen, Nils
    Hedstrom, Margareta
    Additive effects of nutritional supplementation, together with bisphosphonates, on bone mineral density after hip fracture: a 12-month randomized controlled study2014Inngår i: Clinical Interventions in Aging, ISSN 1176-9092, E-ISSN 1178-1998, Vol. 9, s. 1043-1050Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: After a hip fracture, a catabolic state develops, with increased bone loss during the first year. The aim of this study was to evaluate the effects of postoperative treatment with calcium, vitamin D, and bisphosphonates (alone or together) with nutritional supplementation on total hip and total body bone mineral density (BMD). Methods: Seventy-nine patients (56 women), with a mean age of 79 years (range, 61-96 years) and with a recent hip fracture, who were ambulatory before fracture and without severe cognitive impairment, were included. Patients were randomized to treatment with bisphosphonates (risedronate 35 mg weekly) for 12 months (B; n=28), treatment with bisphosphonates along with nutritional supplementation (40 g protein, 600 kcal daily) for the first 6 months (BN; n=26), or to controls (C; n=25). All participants received calcium (1,000 mg) and vitamin D3 (800 IU) daily. Total hip and total body BMD were assessed with dual-energy X-ray absorptiometry at baseline, 6, and 12 months. Marker of bone resorption C-terminal telopeptide of collagen I and 25-hydroxy vitamin D were analyzed in serum. Results: Analysis of complete cases (70/79 at 6 months and 67/79 at 12 months) showed an increase in total hip BMD of 0.7% in the BN group, whereas the B and C groups lost 1.1% and 2.4% of BMD, respectively, between baseline and 6 months (P=0.071, between groups). There was no change in total body BMD between baseline and 12 months in the BN group, whereas the B group and C group both lost BMD, with C losing more than B (P=0.009). Intention-to-treat analysis was in concordance with the complete cases analyses. Conclusion: Protein-and energy-rich supplementation in addition to calcium, vitamin D, and bisphosphonate therapy had additive effects on total body BMD and total hip BMD among elderly hip fracture patients.

  • 43.
    Franzon, Kristin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Independent Ageing in Very Old Swedish Men2019Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Predictors for survival have been investigated thoroughly, but less is known about how to reach high age with preserved physical and cognitive function. These functions are crucial to stay independent in daily life, which is highly valued by the oldest old.

    This thesis was based on data from the Uppsala Longitudinal Study in Adult Men. In 1970, all men born in 1920-24 and living in Uppsala were invited to the study, and 82% (n=2,322) participated in the first investigation. In this thesis, data are used from the investigations cycles at the ages of 50, 71, 87 and 92 years. Independent ageing was defined as follows: having independency in personal care and the ability to walk outdoors alone, being community-dwelling, having a Mini-Mental State Examination score of 25 points or greater, and having no diagnosed dementia.

    Thirty-seven percent of the original cohort survived to the age of 85. At a mean age of 87, 74% of the participants were independently aged, while at a mean age of 92 the prevalence of independent ageing was 64%. In Paper I, non-smoking and normal weight at a mean age of 50 were associated with independent ageing at a mean age of 87 years. In Paper II, never smoking, not being obese, and a high adherence to a Mediterranean-like diet at a mean age of 71 were associated with independent ageing at a mean age of 87. In both Papers I and II, high leisure time physical activity was associated with survival, but not with independent ageing. In Paper III, higher gait speed and hand grip strength and a faster chair stand test were cross-sectionally associated with independent ageing at a mean age of 87. Higher gait speed was also longitudinally associated with independent ageing five years. However, muscle mass and sarcopenia were not associated with the outcome. In Paper IV, a history of stroke, osteoarthritis, hip fracture and chronic obstructive pulmonary disease were associated with loss of independent ageing at a mean age of 92.

    Smoking, weight and diet are all modifiable risk factors associated with independent ageing. If decreased smoking and a normalised weight in the population could diminish stroke, hip fracture, chronic obstructive pulmonary disease and osteoarthritis, the prevalence of independent ageing could rise, even in nonagenarians. Additionally, a Mediterranean-like diet may contribute to both survival and independent ageing.

    Delarbeid
    1. Modifiable Midlife Risk Factors, Independent Aging, and Survival in Older Men: Report on Long-Term Follow-Up of the Uppsala Longitudinal Study of Adult Men Cohort
    Åpne denne publikasjonen i ny fane eller vindu >>Modifiable Midlife Risk Factors, Independent Aging, and Survival in Older Men: Report on Long-Term Follow-Up of the Uppsala Longitudinal Study of Adult Men Cohort
    2015 (engelsk)Inngår i: Journal of The American Geriatrics Society, ISSN 0002-8614, E-ISSN 1532-5415, Vol. 63, nr 5, s. 877-885Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    ObjectivesTo examine relationships between modifiable midlife factors, aging, and physical and cognitive function (independent aging) and survival in very old age. DesignProspective cohort. SettingUppsala Longitudinal Study of Adult Men, Uppsala, Sweden. ParticipantsSwedish men investigated in 1970-74 (aged 48.6-51.1) and followed up for four decades (N=2,293). MeasurementsConventional cardiovascular risk factors, body mass index (BMI), and dietary biomarkers were measured, and a questionnaire was used to gather information on lifestyle variables at age 50. Four hundred seventy-two men were reinvestigated in 2008-09 (aged 84.8-88.9). Independent aging was defined as survival to age 85, Mini-Mental State Examination score of 25 or greater, not living in an institution, independent in personal care and hygiene, able to walk outdoors without personal help, and no diagnosis of dementia. The National Swedish Death Registry provided survival data. ResultsThirty-eight percent of the cohort survived to age 85. Seventy-four percent of the participants in 2008-09 were aging independently. In univariable analyses, high leisure-time physical activity predicted survival but not independent aging. Low work-time physical activity was associated more strongly with independent aging (odds ratio (OR)=1.84, 95% confidence interval (CI)=1.18-2.88) than with survival (OR=1.27, 95% CI=1.05-1.52). In multivariable analyses, midlife BMI was negatively associated (OR=0.80/SD, 95% CI=0.65-0.99/SD), and never or former smoking was positively associated (OR=1.66, 95% CI=1.07-2.59), with independent aging. As expected, conventional cardiovascular and lifestyle risk factors were associated with mortality. ConclusionA normal midlife BMI and not smoking were associated with independent aging close to four decades later, indicating that normal weight at midlife has the potential not only to increase survival, but also to preserve independence with aging.

    Emneord
    independent aging, successful aging, obesity, smoking, longitudinal
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-256538 (URN)10.1111/jgs.13352 (DOI)000354726400005 ()25919442 (PubMedID)
    Tilgjengelig fra: 2015-06-25 Laget: 2015-06-24 Sist oppdatert: 2019-03-26bibliografisk kontrollert
    2. Predictors of Independent Aging and Survival: A 16-Year Follow-Up Report in Octogenarian Men
    Åpne denne publikasjonen i ny fane eller vindu >>Predictors of Independent Aging and Survival: A 16-Year Follow-Up Report in Octogenarian Men
    Vise andre…
    2017 (engelsk)Inngår i: Journal of The American Geriatrics Society, ISSN 0002-8614, E-ISSN 1532-5415, Vol. 65, nr 9, s. 1953-1960Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    OBJECTIVES: To examine the longitudinal associations between aging with preserved functionality, i.e. independent aging and survival, and lifestyle variables, dietary pattern and cardiovascular risk factors.

    DESIGN: Cohort study.

    SETTING: Uppsala Longitudinal Study of Adult Men, Sweden.

    PARTICIPANTS: Swedish men (n = 1,104) at a mean age of 71 (range 69.4-74.1) were investigated, 369 of whom were evaluated for independent aging 16 years later, at a mean age of 87 (range 84.8-88.9).

    MEASUREMENTS: A questionnaire was used to obtain information on lifestyle, including education, living conditions, and physical activity. Adherence to a Mediterranean-like diet was assessed according to a modified Mediterranean Diet Score derived from 7-day food records. Cardiovascular risk factors were measured. Independent aging at a mean age of 87 was defined as lack of diagnosed dementia, a Mini-Mental State Examination score of 25 or greater, not institutionalized, independence in personal activities of daily living, and ability to walk outdoors alone. Complete survival data at age 85 were obtained from the Swedish Cause of Death Register.

    RESULTS: Fifty-seven percent of the men survived to age 85, and 75% of the participants at a mean age of 87 displayed independent aging. Independent aging was associated with never smoking (vs current) (odds ratio (OR) = 2.20, 95% confidence interval (CI) = 1.05-4.60) and high (vs low) adherence to a Mediterranean-like diet (OR = 2.69, 95% CI = 1.14-6.80). Normal weight or overweight and waist circumference of 102 cm or less were also associated with independent aging. Similar associations were observed with survival.

    CONCLUSION: Lifestyle factors such as never smoking, maintaining a healthy diet, and not being obese at age 71 were associated with survival and independent aging at age 85 and older in men.

    Emneord
    Mediterranean diet, healthy aging, longitudinal, obesity, smoking
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-334423 (URN)10.1111/jgs.14971 (DOI)000411060500016 ()28685810 (PubMedID)
    Tilgjengelig fra: 2017-11-23 Laget: 2017-11-23 Sist oppdatert: 2019-03-26bibliografisk kontrollert
    3. The impact of muscle function, muscle mass and sarcopenia on independent ageing in very old Swedish men
    Åpne denne publikasjonen i ny fane eller vindu >>The impact of muscle function, muscle mass and sarcopenia on independent ageing in very old Swedish men
    2019 (engelsk)Inngår i: BMC Geriatrics, ISSN 1471-2318, E-ISSN 1471-2318, Vol. 19, artikkel-id 153Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Background Preserved functions of daily life and cognition are cornerstones of independent aging, which is crucial for maintaining a high quality of life. The aim of this study was to examine the impact of sarcopenia, and its underlying components, on independent ageing in a cohort study of very old men.

    Methods The presence of sarcopenia and independent ageing at a mean age of 87 was investigated in 287 men from the Uppsala Longitudinal Study of Adult Men. Five years later 127 men were re-evaluated for independent ageing. Sarcopenia was defined by two different definitions from the European Working Group on Sarcopenia in Older People. In the first definition sarcopenia was defined as skeletal muscle index < 7.26 kg/m2 and either gait speed ≤0.8 m/s or hand grip strength < 30 kg. In the later up-dated definition, HGS < 27 kg and/or chair stand test > 15 s defines probable sarcopenia, which is confirmed by SMI < 7.0 kg/m2. Independent ageing was defined as a Mini-Mental State Examination score of ≥25 points, absence of diagnosed dementia, community-dwelling, independency in personal care and ability to walk outdoors alone.

    Results Sarcopenia at baseline was observed in 21% (60/287) and 20% (58/287), respectively, due to definition. The prevalence of independent ageing was 83% (239/288) at baseline and 69% (87/127) five years later. None of the sarcopenia diagnoses were associated with independent ageing. In contrast, gait speed was both in cross-sectional (odds ratio (OR) per one standard deviation increase 2.15, 95% confidence interval (CI) 1.47–3.15), and in longitudinal multivariate analyses (OR 1.84, 95% CI 1.19–2.82). In the cross-sectional analysis also higher hand grip strength was associated with independent ageing (OR 1.58, 95% CI 1.12–2.22), while a slower chair stand test was inversely associated (OR 0.61, 95% CI 0.43–0.86). Muscle mass; i.e. skeletal muscle index, was not associated with independent ageing.

    Conclusions For very old men, especially a higher gait speed, but also a higher hand grip strength and a faster chair stand test, were associated with independent ageing, while skeletal muscle index alone, and the composite sarcopenia phenotype measured with two different definitions, were not.

    Emneord
    Sarcopenia, EWGSOP1, EWGSOP2, Muscle mass, Muscle function, Gait speed, Hand grip strength, Chair stand test, Independent ageing
    HSV kategori
    Forskningsprogram
    Geriatrik
    Identifikatorer
    urn:nbn:se:uu:diva-380155 (URN)10.1186/s12877-019-1142-y (DOI)000469459000001 ()31142271 (PubMedID)
    Tilgjengelig fra: 2019-03-25 Laget: 2019-03-25 Sist oppdatert: 2019-06-20bibliografisk kontrollert
    4. Influence of somatic morbidity on independent ageing in nonagenarian men. A report from the Uppsala Longitudinal Study of Adult men
    Åpne denne publikasjonen i ny fane eller vindu >>Influence of somatic morbidity on independent ageing in nonagenarian men. A report from the Uppsala Longitudinal Study of Adult men
    (engelsk)Manuskript (preprint) (Annet vitenskapelig)
    HSV kategori
    Forskningsprogram
    Geriatrik
    Identifikatorer
    urn:nbn:se:uu:diva-380159 (URN)
    Tilgjengelig fra: 2019-03-25 Laget: 2019-03-25 Sist oppdatert: 2019-03-26
  • 44.
    Franzon, Kristin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Byberg, Liisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Sjögren, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Zethelius, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik. Med Prod Agcy, Uppsala, Sweden.
    Cederholm, Tommy
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Kilander, Lena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Predictors of Independent Aging and Survival: A 16-Year Follow-Up Report in Octogenarian Men2017Inngår i: Journal of The American Geriatrics Society, ISSN 0002-8614, E-ISSN 1532-5415, Vol. 65, nr 9, s. 1953-1960Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVES: To examine the longitudinal associations between aging with preserved functionality, i.e. independent aging and survival, and lifestyle variables, dietary pattern and cardiovascular risk factors.

    DESIGN: Cohort study.

    SETTING: Uppsala Longitudinal Study of Adult Men, Sweden.

    PARTICIPANTS: Swedish men (n = 1,104) at a mean age of 71 (range 69.4-74.1) were investigated, 369 of whom were evaluated for independent aging 16 years later, at a mean age of 87 (range 84.8-88.9).

    MEASUREMENTS: A questionnaire was used to obtain information on lifestyle, including education, living conditions, and physical activity. Adherence to a Mediterranean-like diet was assessed according to a modified Mediterranean Diet Score derived from 7-day food records. Cardiovascular risk factors were measured. Independent aging at a mean age of 87 was defined as lack of diagnosed dementia, a Mini-Mental State Examination score of 25 or greater, not institutionalized, independence in personal activities of daily living, and ability to walk outdoors alone. Complete survival data at age 85 were obtained from the Swedish Cause of Death Register.

    RESULTS: Fifty-seven percent of the men survived to age 85, and 75% of the participants at a mean age of 87 displayed independent aging. Independent aging was associated with never smoking (vs current) (odds ratio (OR) = 2.20, 95% confidence interval (CI) = 1.05-4.60) and high (vs low) adherence to a Mediterranean-like diet (OR = 2.69, 95% CI = 1.14-6.80). Normal weight or overweight and waist circumference of 102 cm or less were also associated with independent aging. Similar associations were observed with survival.

    CONCLUSION: Lifestyle factors such as never smoking, maintaining a healthy diet, and not being obese at age 71 were associated with survival and independent aging at age 85 and older in men.

  • 45.
    Franzon, Kristin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Zethelius, Bjorn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Cederholm, Tommy
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Kilander, Lena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Modifiable Midlife Risk Factors, Independent Aging, and Survival in Older Men: Report on Long-Term Follow-Up of the Uppsala Longitudinal Study of Adult Men Cohort2015Inngår i: Journal of The American Geriatrics Society, ISSN 0002-8614, E-ISSN 1532-5415, Vol. 63, nr 5, s. 877-885Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    ObjectivesTo examine relationships between modifiable midlife factors, aging, and physical and cognitive function (independent aging) and survival in very old age. DesignProspective cohort. SettingUppsala Longitudinal Study of Adult Men, Uppsala, Sweden. ParticipantsSwedish men investigated in 1970-74 (aged 48.6-51.1) and followed up for four decades (N=2,293). MeasurementsConventional cardiovascular risk factors, body mass index (BMI), and dietary biomarkers were measured, and a questionnaire was used to gather information on lifestyle variables at age 50. Four hundred seventy-two men were reinvestigated in 2008-09 (aged 84.8-88.9). Independent aging was defined as survival to age 85, Mini-Mental State Examination score of 25 or greater, not living in an institution, independent in personal care and hygiene, able to walk outdoors without personal help, and no diagnosis of dementia. The National Swedish Death Registry provided survival data. ResultsThirty-eight percent of the cohort survived to age 85. Seventy-four percent of the participants in 2008-09 were aging independently. In univariable analyses, high leisure-time physical activity predicted survival but not independent aging. Low work-time physical activity was associated more strongly with independent aging (odds ratio (OR)=1.84, 95% confidence interval (CI)=1.18-2.88) than with survival (OR=1.27, 95% CI=1.05-1.52). In multivariable analyses, midlife BMI was negatively associated (OR=0.80/SD, 95% CI=0.65-0.99/SD), and never or former smoking was positively associated (OR=1.66, 95% CI=1.07-2.59), with independent aging. As expected, conventional cardiovascular and lifestyle risk factors were associated with mortality. ConclusionA normal midlife BMI and not smoking were associated with independent aging close to four decades later, indicating that normal weight at midlife has the potential not only to increase survival, but also to preserve independence with aging.

  • 46.
    Franzon, Kristin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Zethelius, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Cederholm, Tommy
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Kilander, Lena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    The impact of muscle function, muscle mass and sarcopenia on independent ageing in very old Swedish men2019Inngår i: BMC Geriatrics, ISSN 1471-2318, E-ISSN 1471-2318, Vol. 19, artikkel-id 153Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background Preserved functions of daily life and cognition are cornerstones of independent aging, which is crucial for maintaining a high quality of life. The aim of this study was to examine the impact of sarcopenia, and its underlying components, on independent ageing in a cohort study of very old men.

    Methods The presence of sarcopenia and independent ageing at a mean age of 87 was investigated in 287 men from the Uppsala Longitudinal Study of Adult Men. Five years later 127 men were re-evaluated for independent ageing. Sarcopenia was defined by two different definitions from the European Working Group on Sarcopenia in Older People. In the first definition sarcopenia was defined as skeletal muscle index < 7.26 kg/m2 and either gait speed ≤0.8 m/s or hand grip strength < 30 kg. In the later up-dated definition, HGS < 27 kg and/or chair stand test > 15 s defines probable sarcopenia, which is confirmed by SMI < 7.0 kg/m2. Independent ageing was defined as a Mini-Mental State Examination score of ≥25 points, absence of diagnosed dementia, community-dwelling, independency in personal care and ability to walk outdoors alone.

    Results Sarcopenia at baseline was observed in 21% (60/287) and 20% (58/287), respectively, due to definition. The prevalence of independent ageing was 83% (239/288) at baseline and 69% (87/127) five years later. None of the sarcopenia diagnoses were associated with independent ageing. In contrast, gait speed was both in cross-sectional (odds ratio (OR) per one standard deviation increase 2.15, 95% confidence interval (CI) 1.47–3.15), and in longitudinal multivariate analyses (OR 1.84, 95% CI 1.19–2.82). In the cross-sectional analysis also higher hand grip strength was associated with independent ageing (OR 1.58, 95% CI 1.12–2.22), while a slower chair stand test was inversely associated (OR 0.61, 95% CI 0.43–0.86). Muscle mass; i.e. skeletal muscle index, was not associated with independent ageing.

    Conclusions For very old men, especially a higher gait speed, but also a higher hand grip strength and a faster chair stand test, were associated with independent ageing, while skeletal muscle index alone, and the composite sarcopenia phenotype measured with two different definitions, were not.

  • 47. Giron, Maria Stella T
    et al.
    Forsell, Yvonne
    Bernsten, Cecilia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Hälso- och sjukvårdsforskning.
    Thorslund, Mats
    Winblad, Bengt
    Fastbom, Johan
    Sleep problems in a very old population: drug use and clinical correlates2002Inngår i: The journals of gerontology. Series A, Biological sciences and medical sciences, ISSN 1079-5006, E-ISSN 1758-535X, Vol. 57, nr 4, s. M236-40Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background. Complaints of disturbed or dissatisfied sleep are common among older people. This study aimed to evaluate the prevalence of sleep problems in very old persons and its relation to physical and mental health and drug use.

    Methods. This is a cross-sectional analysis of sleep problems in a population of old persons living in Stockholm, Sweden. There were 641 subjects aged 81+ years; 77.8% were women, 91.4% were noninstitutionalized, and 68.6% lived alone. All persons underwent a comprehensive medical and psychiatric interview and examination. Sleep problems were assessed using the Clinical Psychopathological Rating Scale (CPRS). Covariates included chronic medical conditions, depression, dementia, pain, self-rated health, activities of daily living, use of hypnotics-sedatives, use of other psychotropic drugs, and use of nonpsychotropic drugs.

    Results. More than one third of subjects were identified with sleep problems. They were more common among women and persons using a higher number of drugs. Poor self-rated health, depression, and pain were related to the presence of sleep problems. Among persons with sleep problems and depression, only 19.2% used antidepressants, and 46.2% used hypnotics-sedatives. Among persons with sleep problems and pain, 63.2% used analgesics, and 47.0% used hypnotics-sedatives. One or more chronic diseases, use of hypnotics-sedatives, use of other psychotropic drugs, and use of nonpsychotropic drugs were also related to sleep problems. After multivariate analysis, factors significantly related to sleep problems were female gender, depression, pain, and hypnotic-sedative use.

    Conclusions. Sleep problems were common in this very old population. These results suggest the importance of carefully assessing an older person's complaints to accurately diagnose and effectively treat sleep problems.

  • 48.
    Grönstedt, Helena
    et al.
    Stockholms Sjukhem R&D Unit, Stockholm, Sweden;Karolinska Univ Hosp, Allied Hlth Profess, Funct Area Occupat Therapy & Physiotherapy, Stockholm, Sweden.
    Vikström, Sofia
    Stockholms Sjukhem R&D Unit, Stockholm, Sweden;Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Occupat Therapy, Stockholm, Sweden.
    Cederholm, Tommy
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism. Uppsala Univ Hosp, Dept Geriatr Med, Uppsala, Sweden;Karolinska Univ Hosp, Theme Aging, Stockholm, Sweden.
    Franzen, Erika
    Stockholms Sjukhem R&D Unit, Stockholm, Sweden;Karolinska Univ Hosp, Allied Hlth Profess, Funct Area Occupat Therapy & Physiotherapy, Stockholm, Sweden;Karolinska Inst, Div Physiotherapy, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden.
    Seiger, Åke
    Stockholms Sjukhem R&D Unit, Stockholm, Sweden;Karolinska Inst, Div Clin Geriatr, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden.
    Wimo, Anders
    Karolinska Inst, Div Neurogeriatr, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden.
    Faxen-Irving, Gerd
    Stockholms Sjukhem R&D Unit, Stockholm, Sweden;Karolinska Inst, Div Clin Geriatr, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden;Karolinska Univ Hosp, Funct Area Clin Nutr, Allied Hlth Professionals, Stockholm, Sweden.
    Boström, Anne-Marie
    Stockholms Sjukhem R&D Unit, Stockholm, Sweden;Karolinska Univ Hosp, Theme Aging, Stockholm, Sweden;Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Nursing, Stockholm, Sweden;Western Norway Univ Appl Sci, Haugesund, Norway.
    A study protocol of Older Person's Exercise and Nutrition Study (OPEN) - a sit-to-stand activity combined with oral protein supplement - effects on physical function and independence: a cluster randomized clinical trial2018Inngår i: BMC Geriatrics, ISSN 1471-2318, E-ISSN 1471-2318, Vol. 18, artikkel-id 138Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Poor nutrition and age per see add to the development of sarcopenia, i.e. loss of muscle mass and strength, which contributes to increased risk of impaired activities of daily living (ADL) and reduced independence. Protein deficiency plays an important role in the development of sarcopenia. In order to increase the muscle mass protein intake should be combined with physical exercise. A daily physical activity, the sit-to-stand exercise, has been proven to decrease older persons' dependence in ADL. Our study aims to evaluate the effects of the sit-to-stand exercise in combination with a protein-rich nutritional supplement, on physical function and independence in frail nursing home residents. The resident's perceptions and experiences of the intervention and the staff's experiences of supporting the resident to complete the intervention will also be explored.

    Methods: The study is a two-arm cluster-randomized controlled trial which will be performed in nursing homes at two municipalities in Sweden. We will recruit 120 residents, age 75 or older and able to stand up from a seated position. Residents (n = 60) randomized to the intervention group will perform the sit-to-stand exercise at four occasions daily and will be offered a protein-rich oral supplement, twice a day. The intervention period will last for 12 weeks and measures of physical function, nutritional status, quality of life and health economy will be performed at baseline and at 12-weeks follow-up. The primary outcome will be the number of chair rises performed in 30 s. The control group will receive standard care. Data will be analysed by intention-to-treat analysis and with mixed effect models. During the last part of the intervention period individual interviews with the residents, on the topic of feasibility with the OPEN concept will be held. Likewise, focus-group-interviews with staff will be performed.

    Discussion: The residents' physical and mental health could be expected to improve. Even the work situation for staff could be positively affected. One innovative feature of the OPEN study is the simple intervention consisting of a basic daily activity that can be performed by several nursing home residents with the support of existing staff and available resources.

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    Gunnarsson, Anna-Karin