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  • 1.
    Benedict, Christian
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Brooks, Samantha J
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Burgos, Jonathan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Kempton, Matthew J
    Nordenskjöld, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Nylander, Ruta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Craft, Suzanne
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Schiöth, Helgi B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Impaired Insulin Sensitivity as Indexed by the HOMA Score Is Associated With Deficits in Verbal Fluency and Temporal Lobe Gray Matter Volume in the Elderly2012In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 35, no 3, p. 488-494Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE

    Impaired insulin sensitivity is linked to cognitive deficits and reduced brain size. However, it is not yet known whether insulin sensitivity involves regional changes in gray matter volume. Against this background, we examined the association between insulin sensitivity, cognitive performance, and regional gray matter volume in 285 cognitively healthy elderly men and women aged 75 years from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study.

    RESEARCH DESIGN AND METHODS

    Insulin sensitivity was calculated from fasting serum insulin and plasma glucose determinations using the homeostasis model assessment of insulin resistance (HOMA-IR) method. Cognitive performance was examined by a categorical verbal fluency. Participants also underwent a magnetic resonance imaging (MRI) brain scan. Multivariate analysis using linear regression was conducted, controlling for potential confounders (sex, education, serum LDL cholesterol, mean arterial blood pressure, and abdominal visceral fat volume).

    RESULTS

    The HOMA-IR was negatively correlated with verbal fluency performance, brain size (S1), and temporal lobe gray matter volume in regions known to be involved in speech production (Brodmann areas 21 and 22, respectively). No such effects were observed when examining diabetic (n = 55) and cognitively impaired (n = 27) elderly subjects as separate analyses.

    CONCLUSIONS

    These cross-sectional findings suggest that both pharmacologic and lifestyle interventions improving insulin signaling may promote brain health in late life but must be confirmed in patient studies.

  • 2.
    Benedict, Christian
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Brooks, Samantha J
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Nordenskjöld, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Burgos, Jonathan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Le Grevès, Madeleine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Schiöth, Helgi B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Association between physical activity and brain health in older adults2013In: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 34, no 1, p. 83-90Article in journal (Refereed)
    Abstract [en]

    In the present cross-sectional study, we examined physical activity (PA) and its possible association with cognitive skills and brain structure in 331 cognitively healthy elderly. Based on the number of self-reported light and hard activities for at least 30 minutes per week, participants were assigned to 4 groups representing different levels of PA. The cognitive skills were assessed by the Mini Mental State Examination score, a verbal fluency task, and the Trail-making test as a measure of visuospatial orientation ability. Participants also underwent a magnetic resonance imaging of the brain. Multiple regression analysis revealed that greater PA was associated with a shorter time to complete the Trail-making test, and higher levels of verbal fluency. Further, the level of self-reported PA was positively correlated with brain volume, white matter, as well as a parietal lobe gray matter volume, situated bilaterally at the precuneus. These present cross-sectional results indicate that PA is a lifestyle factor that is linked to brain structure and function in late life.

  • 3.
    Benedict, Christian
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Cedernaes, Jonathan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Hogenkamp, Pleunie S
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Giedratis, Vilmantas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Lind, Lars
    Lannfelt, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Schiöth, Helgi B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Self-reported sleep disturbance is associated with Alzheimer's disease risk in men2015In: Alzheimer's & Dementia, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 11, no 9, p. 1090-1097Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To study the association between self-reported sleep disturbances and dementia risk.

    METHODS: Self-reported sleep disturbances and established risk factors for dementia were measured in men at ages 50 (n = 1574) and 70 (n = 1029) years. Dementia incidence was determined by reviewing their patient history between ages 50 and 90 years. In addition, plasma levels of β-amyloid (Aβ) peptides 1-40 and 1-42 were measured at ages 70, 77, and 82 years.

    RESULTS: Cox regression demonstrated that men with self-reported sleep disturbances had a higher risk of developing dementia (+33%) and Alzheimer's disease (AD, +51%) than men without self-reported sleep disturbances (both P < .05). Binary logistic regression showed the increased risk for both dementia (+114%) and AD (+192%) were highest when sleep disturbance was reported at age 70 years (both P < .001). No group differences were found in Aβ levels.

    CONCLUSION: Improving sleep quality may help reduce the neurodegenerative risk in older men.

  • 4.
    Benedict, Christian
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Jacobsson, Josefin A
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Rönnemaa, Elina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Sällman Almén, Markus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Brooks, Samantha
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Schultes, Bernd
    Interdisciplinary Obesity Center, Kantonsspital St. Gallen.
    Fredriksson, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Lannfelt, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Schiöth, Helgi B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    The fat mass and obesity gene is linked to reduced verbal fluency in overweight and obese elderly men2011In: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 32, no 6, p. 1159.e1-1159.e5Article in journal (Refereed)
    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.

  • 5. Berg, L
    et al.
    Gustafson, L
    Hansson, G
    Kilander, L
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Klingen, S
    Marcusson, J
    Näsman, B
    Passant, U
    Wahlund, L O
    Wallin, A
    [Harmonization of dementia diagnoses--a necessary quality assurance]2001In: Lakartidningen, ISSN 0023-7205, Vol. 98, no 34, p. 3531-6Article in journal (Refereed)
  • 6.
    Brooks, Samantha J
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Burgos, J
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Kempton, M J
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Nordenskjöld, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Nylander, Ruta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Schiöth, Helgi B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Late-life obesity is associated with smaller global and regional gray matter volumes: a voxel-based morphometric study2013In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 37, no 2, p. 230-236Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: 

    Obesity adversely affects frontal lobe brain structure and function. Here we sought to show that people who are obese versus those who are of normal weight over a 5-year period have differential global and regional brain volumes.

    DESIGN: 

    Using voxel-based morphometry, contrasts were done between those who were recorded as being either obese or of normal weight over two time points in the 5 years prior to the brain scan. In a post-hoc preliminary analysis, we compared scores for obese and normal weight people who completed the trail-making task.

    SUBJECTS: 

    A total of 292 subjects were examined following exclusions (for example, owing to dementia, stroke and cortical infarcts) from the Prospective Investigation of the Vasculature in Uppsala Seniors cohort with a body mass index of normal weight (<25 kg m−2) or obese (30 kg m−2).

    RESULTS: 

    People who were obese had significantly smaller total brain volumes and specifically, significantly reduced total gray matter (GM) volume (GMV) (with no difference in white matter or cerebrospinal fluid). Initial exploratory whole brain uncorrected analysis revealed that people who were obese had significantly smaller GMV in the bilateral supplementary motor area, bilateral dorsolateral prefrontal cortex (DLPFC), left inferior frontal gyrus and left postcentral gyrus. Secondary more stringent corrected analyses revealed a surviving cluster of GMV difference in the left DLPFC. Finally, post-hoc contrasts of scores on the trail-making task, which is linked to DLPFC function, revealed that obese people were significantly slower than those of normal weight.

    CONCLUSION: 

    These findings suggest that in comparison with normal weight, people who are obese have smaller GMV, particularly in the left DLPFC. Our results may provide evidence for a potential working memory mechanism for the cognitive suppression of appetite that may lower the risk of developing obesity in later life.

  • 7.
    Byberg, Liisa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Gedeborg, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Cars, Thomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Berglund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Prediction of fracture risk in men: A cohort study2012In: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 27, no 4, p. 797-807Article in journal (Refereed)
    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. 

  • 8.
    Byberg, Liisa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Warensjö Lemming, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Vessby, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Cancer death is related to high palmitoleic acid in serum and to polymorphisms in the SCD-1 gene in healthy Swedish men2014In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 99, no 3, p. 551-558Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    A high proportion of monounsaturated fatty acids (MUFAs) or a high ratio of MUFAs to saturated fatty acids in plasma, reflecting a high activity of the lipogenic enzyme stearoyl-CoA desaturase-1 (SCD-1), has been shown to be related to cancer death and incidence in some studies.

    OBJECTIVES:

    The objective was to study whether the serum cholesteryl ester proportion of palmitoleic acid [16:1n-7 (16:1ω-3)] and the ratio of palmitoleic to palmitic acid (16:1n-7/16:0), as an estimation of the activity of SCD-1, are related to cancer death and to investigate whether polymorphisms in the SCD-1 gene are related to cancer mortality.

    DESIGN:

    A community-based cohort of 50-y-old men was followed for a maximum of >40 y. Survival analysis was used to relate fatty acid composition in serum, analyzed at baseline by gas-liquid chromatography (n = 1981), and single nucleotide polymorphisms in the SCD-1 gene (n = 986) to cancer death. A 7-d dietary record was completed at age 70 y (n = 880).

    RESULTS:

    The proportions of 16:1n-7 and the ratio of 16:1n-7 to 16:0 were associated with cancer mortality during follow-up in a comparison of the highest with the lowest quartile of 16:1n-7 (adjusted HR: 1.37; 95% CI: 1.04, 1.82). Inherited variance of the SCD-1 gene seemed to be related to cancer death, especially among men with a low proportion of PUFA in the diet in a comparison of the highest with the lowest weighted genetic risk score (HR: 2.14; 95% CI: 1.13, 4.04).

    CONCLUSION:

    The findings are compatible with the hypothesis that there is an association between endogenously synthesized MUFAs and cancer death.

  • 9.
    Byberg, Liisa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Olsson, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Karlström, Brita
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Sjögren, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Reply to WB Grant2017In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 106, no 2, p. 700-701Article in journal (Other academic)
  • 10.
    Byberg, Liisa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Olsson, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Karlström, Brita
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Sjögren, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Reply to Y Mao and H Yu.2017In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 106, no 2, p. 698-699Article in journal (Other academic)
  • 11.
    Cedervall, Ylva
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Åberg, Anna Cristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Declining Physical Capacity But Maintained Aerobic Activity in Early Alzheimer's Disease2012In: American Journal of Alzheimer’s Disease and Other Dementia, ISSN 1533-3175, E-ISSN 1938-2731, Vol. 27, no 3, p. 180-187Article in journal (Refereed)
    Abstract [en]

    The longitudinal influences on physical capacity and habitual aerobic activity level in the early stages of Alzheimer's disease (AD) are unclear. Therefore, changes in physical capacity and aerobic activity level were evaluated. Twenty-five individuals with AD were assessed annually for 2 years, by 10-m walk test, 6-minute walk test, and timed up-and-go (TUG) single/dual tasks. Habitual aerobic activity was assessed by diary registrations. The AD group showed a lower physical capacity than controls at baseline but comparable levels of aerobic activity. During the follow-up period, physical capacity declined in the AD group, but the aerobic activity levels changed only marginally. Our results show that in the early stages of AD, people are capable of maintaining health-promoting aerobic activity levels, despite a decline in their physical capacity. Additionally, it appears that cognitive dysfunction contributes to an impaired physical capacity. The TUG tasks might, therefore, be useful for detecting early signs of cognitive impairment.

  • 12.
    Degerman Gunnarsson, Malin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Basun, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Lannfelt, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Reduction of Phosphorylated Tau during Memantine Treatment of Alzheimer's Disease2007In: Dementia and Geriatric Cognitive Disorders, ISSN 1420-8008, E-ISSN 1421-9824, Vol. 24, no 4, p. 247-252Article in journal (Refereed)
    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.

  • 13.
    Degerman Gunnarsson, Malin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Lannfelt, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Ingelsson, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Basun, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    High Tau Levels in Cerebrospinal Fluid Predict Rapid Decline and Increased Dementia Mortality in Alzheimer's Disease2014In: Dementia and Geriatric Cognitive Disorders, ISSN 1420-8008, E-ISSN 1421-9824, Vol. 37, no 3-4, p. 196-206Article in journal (Refereed)
    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.

  • 14.
    Degerman Gunnarsson, Malin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Lindau, M
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Santillo, A F
    Wall, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Engler, H
    Lannfelt, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Basun, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Re-evaluation of clinical dementia diagnoses with pittsburgh compound B positron emission tomography2013In: Dementia and geriatric cognitive disorders extra, ISSN 1664-5464, Vol. 3, no 1, p. 472-481Article in journal (Refereed)
    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.

  • 15.
    Degerman Gunnarsson, Malin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Lindau, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Wall, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Blennow, K
    Darreh-Shori, T
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Nordberg, A
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Lannfelt, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Basun, H
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Pittsburgh compound-B and Alzheimer's disease biomarkers in CSF, plasma and urine: An exploratory study2010In: Dementia and Geriatric Cognitive Disorders, ISSN 1420-8008, E-ISSN 1421-9824, Vol. 29, no 3, p. 204-212Article in journal (Refereed)
    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.

  • 16.
    Dumanski, Jan P.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Lambert, Jean-Charles
    Univ Lille, INSERM, CHU Lille, Pasteur Lille,U1167,RID AGE Risk Factors & Mol De, F-59000 Lille, France..
    Rasi, Chiara
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Giedraitis, Vilmantas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Davies, Hanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Grenier-Boley, Benjamin
    Univ Lille, INSERM, CHU Lille, Pasteur Lille,U1167,RID AGE Risk Factors & Mol De, F-59000 Lille, France..
    Lindgren, Cecilia M.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.;Broad Inst MIT, Cambridge, MA 02142 USA.;Harvard Univ, Cambridge, MA 02142 USA..
    Campion, Dominique
    Rouen Univ Hosp, INSERM, CNR MAJ, U1079, F-76031 Rouen, France..
    Dufouil, Carole
    Victor Segalen Univ, INSERM, U708, F-33076 Bordeaux, France..
    Pasquier, Florence
    Univ Lille, CNR MAJ, Inserm 1171, F-59000 Lille, France.;CHU Lille, F-59000 Lille, France..
    Amouyel, Philippe
    Univ Lille, INSERM, CHU Lille, Pasteur Lille,U1167,RID AGE Risk Factors & Mol De, F-59000 Lille, France..
    Lannfelt, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Ingelsson, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Forsberg, Lars A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Mosaic Loss of Chromosome Y in Blood Is Associated with Alzheimer Disease2016In: American Journal of Human Genetics, ISSN 0002-9297, E-ISSN 1537-6605, Vol. 98, no 6, p. 1208-1219Article in journal (Refereed)
    Abstract [en]

    Men have a shorter life expectancy compared with women but the underlying factor(s) are not clear. Late-onset, sporadic Alzheimer disease (AD) is a common and lethal neurodegenerative disorder and many germline inherited variants have been found to influence the risk of developing AD. Our previous results show that a fundamentally different genetic variant, i.e., lifetime-acquired loss of chromosome Y (LOY) in blood cells, is associated with all-cause mortality and an increased risk of non-hematological tumors and that LOY could be induced by tobacco smoking. We tested here a hypothesis that men with LOY are more susceptible to AD and show that LOY is associated with AD in three independent studies of different types. In a case-control study, males with AD diagnosis had higher degree of LOY mosaicism (adjusted odds ratio = 2.80, p = 0.0184, AD events = 606). Furthermore, in two prospective studies, men with LOY at blood sampling had greater risk for incident AD diagnosis during follow-up time (hazard ratio [HR] = 6.80, 95% confidence interval [95% CI] = 2.16-21.43, AD events = 140, p = 0.0011). Thus, LOY in blood is associated with risks of both AD and cancer, suggesting a role of LOY in blood cells on disease processes in other tissues, possibly via defective immunosurveillance. As a male-specific risk factor, LOY might explain why males on average live shorter lives than females.

  • 17.
    Ekström, Curt
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Open-angle glaucoma and Alzheimer´s disease: a population-based 30 year follow-up study2016In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 95, no 2, p. E157-E158Article in journal (Other academic)
  • 18.
    Ekström, Curt
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Pseudoexfoliation and Alzheimer´s disease: a population-based 30-year follow-up study2014In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 92, no 4, p. 355-358Article in journal (Refereed)
  • 19.
    Emami Khoonsari, Payam
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine.
    Haggmark, Anna
    KTH Royal Inst Technol, Sch Biotechnol, Affin Prote, Sci Life Lab, Stockholm, Sweden..
    Lönnberg, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Mikus, Maria
    KTH Royal Inst Technol, Sch Biotechnol, Affin Prote, Sci Life Lab, Stockholm, Sweden..
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Lannfelt, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Ingelsson, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Nilsson, Peter
    KTH Royal Inst Technol, Sch Biotechnol, Affin Prote, Sci Life Lab, Stockholm, Sweden..
    Kultima, Kim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine.
    Shevchenko, Ganna
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry. Uppsala Univ, Dept Chem BMC, Analyt Chem, Uppsala, Sweden..
    Analysis of the Cerebrospinal Fluid Proteome in Alzheimer's Disease2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 3, article id e0150672Article in journal (Refereed)
    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.

  • 20.
    Engler, Henry
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Santillo, Alexander Frizell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Wang, Shu Xia
    Lindau, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Savitcheva, Irina
    Nordberg, Agneta
    Lannfelt, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Långström, Bengt
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    In vivo amyloid imaging with PET in frontotemporal dementia2008In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 35, no 1, p. 100-106Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: N-methyl[11C]2-(4'methylaminophenyl)-6-hydroxy-benzothiazole (PIB) is a positron emission tomography (PET) tracer with amyloid binding properties which allows in vivo measurement of cerebral amyloid load in Alzheimer's disease (AD). Frontotemporal dementia (FTD) is a syndrome that can be clinically difficult to distinguish from AD, but in FTD amyloid deposition is not a characteristic pathological finding. PURPOSE: The aim of this study is to investigate PIB retention in FTD. METHODS: Ten patients with the diagnosis of FTD participated. The diagnosis was based on clinical and neuropsychological examination, computed tomography or magnetic resonance imaging scan, and PET with 18 Fluoro-2-deoxy-d-glucose (FDG). The PIB retention, measured in regions of interest, was normalised to a reference region (cerebellum). The results were compared with PIB retention data previously obtained from 17 AD patients with positive PIB retention and eight healthy controls (HC) with negative PIB retention. Statistical analysis was performed with a students t-test with significance level set to 0.00625 after Bonferroni correction. RESULTS: Eight FTD patients showed significantly lower PIB retention compared to AD in frontal (p < 0.0001), parietal (p < 0.0001), temporal (p = 0.0001), and occipital (p = 0.0003) cortices as well as in putamina (p < 0.0001). The PIB uptake in these FTD patients did not differ significantly from the HC in any region. However, two of the 10 FTD patients showed PIB retention similar to AD patients. CONCLUSION: The majority of FTD patients displayed no PIB retention. Thus, PIB could potentially aid in differentiating between FTD and AD.

  • 21.
    Evers, Kathinka
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Lindau, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Insight in frontotemporal dementia: Conceptual analysis and empirical evaluation of the consensus criterion “loss of insight” in frontotemporal dementia2007In: Brain and Cognition, ISSN 0278-2626, E-ISSN 1090-2147, Vol. 63, no 1, p. 13-23Article in journal (Refereed)
    Abstract [en]

    The objective of this study was to suggest a new formulation of the core research diagnostic consensus criterion “loss of insight” in frontotemporal dementia (FTD). Eight patients with FTD (diagnoses made by interviews, medical and neuropsychological examination, CT scan, and regional cerebral glucose metabolism measured by positron emission tomography (PET) participated in the study). The results indicated that insight was present in three out of eight patients, and that insight appears to be a heterogeneous concept. Two types of insight emerged: Emotional insight associated with frontotemporal functions, and cognitive insight, related to posterior cognitive functions. These results suggest that loss of insight should not serve as a core criterion on FTD, but serves well as a supportive criterion of the disease.

  • 22.
    Franzon, Kristin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Sjögren, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. Med Prod Agcy, Uppsala, Sweden.
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Predictors of Independent Aging and Survival: A 16-Year Follow-Up Report in Octogenarian Men2017In: Journal of The American Geriatrics Society, ISSN 0002-8614, E-ISSN 1532-5415, Vol. 65, no 9, p. 1953-1960Article in journal (Refereed)
    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.

  • 23.
    Franzon, Kristin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Zethelius, Bjorn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    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 Cohort2015In: Journal of The American Geriatrics Society, ISSN 0002-8614, E-ISSN 1532-5415, Vol. 63, no 5, p. 877-885Article in journal (Refereed)
    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.

  • 24.
    Froelich-Fabre, Susanne
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Skoglund, Lena
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Ostojic, Jovanka
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Kilander, Lena
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Lindau, Maria
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Glaser, Anna
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Basun, Hans
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Lannfelt, Lars
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Clinical and molecular aspects of frontotemporal dementia.2004In: Neurodegener Dis, ISSN 1660-2854, Vol. 1, no 4-5, p. 218-24Article in journal (Refereed)
  • 25.
    Fällmar, David
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Univ Med Ctr Freiburg, Dept Neuroradiol, Freiburg, Germany.; Univ Geneva, Fac Med, Geneva, Switzerland.; Affidea CDRC Ctr Diagnost Radiol Carouge, Carouge, Switzerland..
    Lilja, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Hermes Med Solut, Stockholm, Sweden.
    Danfors, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Tolboom, Nelleke
    Vrije Univ Amsterdam, Dept Radiol & Nucl Med, Med Ctr, Neurosci Campus, Amsterdam, Netherlands.
    Egger, Karl
    Univ Med Ctr Freiburg, Dept Neuroradiol, Freiburg, Germany.
    Kellner, Elias
    Univ Freiburg, Dept Radiol, Med Ctr, Fac Med,Med Phys, Freiburg, Germany.
    Croon, Philip M
    Vrije Univ Amsterdam, Dept Radiol & Nucl Med, Med Ctr, Neurosci Campus, Amsterdam, Netherlands.
    Verfaillie, Sander C J
    Vrije Univ Amsterdam, Alzheimer Ctr Amsterdam, Dept Neurol, Med Ctr, Amsterdam, Netherlands.
    van Berckel, Bart N M
    Vrije Univ Amsterdam, Dept Radiol & Nucl Med, Med Ctr, Neurosci Campus, Amsterdam, Netherlands.
    Ossenkoppele, Rik
    Vrije Univ Amsterdam, Alzheimer Ctr Amsterdam, Dept Neurol, Med Ctr, Amsterdam, Netherlands.
    Barkhof, Frederik
    Vrije Univ Amsterdam, Dept Radiol & Nucl Med, Med Ctr, Neurosci Campus, Amsterdam, Netherlands.; UCL, Inst Neurol & Healthcare Engn, London, England..
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Arterial spin labeling-based Z-maps have high specificity and positive predictive value for neurodegenerative dementia compared to FDG-PET.2017In: European Radiology, ISSN 0938-7994, E-ISSN 1432-1084, Vol. 27, no 10, p. 4237-4246Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Cerebral perfusion analysis based on arterial spin labeling (ASL) MRI has been proposed as an alternative to FDG-PET in patients with neurodegenerative disease. Z-maps show normal distribution values relating an image to a database of controls. They are routinely used for FDG-PET to demonstrate disease-specific patterns of hypometabolism at the individual level. This study aimed to compare the performance of Z-maps based on ASL to FDG-PET.

    METHODS: Data were combined from two separate sites, each cohort consisting of patients with Alzheimer's disease (n = 18 + 7), frontotemporal dementia (n = 12 + 8) and controls (n = 9 + 29). Subjects underwent pseudocontinuous ASL and FDG-PET. Z-maps were created for each subject and modality. Four experienced physicians visually assessed the 166 Z-maps in random order, blinded to modality and diagnosis.

    RESULTS: Discrimination of patients versus controls using ASL-based Z-maps yielded high specificity (84%) and positive predictive value (80%), but significantly lower sensitivity compared to FDG-PET-based Z-maps (53% vs. 96%, p < 0.001). Among true-positive cases, correct diagnoses were made in 76% (ASL) and 84% (FDG-PET) (p = 0.168).

    CONCLUSION: ASL-based Z-maps can be used for visual assessment of neurodegenerative dementia with high specificity and positive predictive value, but with inferior sensitivity compared to FDG-PET.

    KEY POINTS: • ASL-based Z-maps yielded high specificity and positive predictive value in neurodegenerative dementia. • ASL-based Z-maps had significantly lower sensitivity compared to FDG-PET-based Z-maps. • FDG-PET might be reserved for ASL-negative cases where clinical suspicion persists. • Findings were similar at two study sites.

  • 26.
    Fällmar, David
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lilja, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Danfors, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Iyer, Victor
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Z-score maps from low-dose 18F-FDG PET of the brain in neurodegenerative dementia.2018In: American Journal of Nuclear Medicine and Molecular Imaging, ISSN 2160-8407, Vol. 8, no 4, p. 239-246Article in journal (Refereed)
    Abstract [en]

    Neuroimaging is a central part of diagnostic work-up of patients with suspected neurodegenerative disease. FDG-PET can reveal pathological changes earlier and more reliably than morphological imaging. Diagnostic accuracy can be improved by constructing 3D SSP Z-score maps, showing patterns of significant deficits. During FDG-PET, the subject receives a moderate but not insignificant dose of ionizing radiation, and a dose reduction with retained image quality is desirable. With lower dose, repeated examinations can become a useful tool for monitoring disease progress and potential effects of disease-modifying interventions. The aim of this study was to evaluate Z-maps created from low-dose and normal-dose FDG-PET of the brain, with quantitative and qualitative methods. Nine patients with neurodegenerative disorders were prospectively enrolled and nine age-matched controls were recruited through advertising. All subjects (n=18) underwent two FDG-PET scans on separate occasions; a routine and a low-dose scan. The routine dosage of FDG was 3 MBq/kg, and low dosage was 0.75 MBq/kg. 3D-SSP images showing Z-scores of < -1.96 were created from 10-minute summations. The study was comprised of a quantitative part comparing the Z-scores, and a qualitative part where experienced nuclear medicine specialists visually assessed the images. Regarding the quantitative part, Bland-Altman analysis showed a slight constant bias (0.206). Regarding qualitative discrimination between patients and controls, the performance between normal- and low-dose were equal, both showing 72% sensitivity, 83% specificity and 78% accuracy. In this study, visual assessment of 3D-SSP Z-score maps from low-dose FDG-PET provided diagnostic information highly comparable to normal-dose, with minor quantitative discrepancies.

  • 27.
    Fällmar, David
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lilja, Johan
    Hermes Medical Solutions, Stockholm, Sweden..
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Danfors, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Validation of true low-dose 18F-FDG PET of the brain2016In: American Journal of Nuclear Medicine and Molecular Imaging, ISSN 2160-8407, Vol. 6, no 5, p. 269-276Article in journal (Refereed)
    Abstract [en]

    The dosage of F-18-FDG must be sufficient to ensure adequate PET image quality. For younger patients and research controls, the lowest possible radiation dose should be used. The purpose of this study was to find a protocol for FDG-PET of the brain with reduced radiation dose and preserved quantitative characteristics. Eight patients with neurodegenerative disorders and nine controls (n= 17) underwent FDG-PET/ CT twice on separate occasions, first with normal-dose (3 MBq/ kg), and second with low-dose (0.75 MBq/ kg, 25% of the original). Five additional controls (total n= 22) underwent FDG-PET twice, using normal-dose and ultra-low-dose (0.3 MBq/ kg, 10% of original). All subjects underwent MRI. Ten-minute summation images were spatially normalized and intensity normalized. Regional standard uptake value ratios (SUV-r) were calculated using an automated atlas. SUV-r values from the normal-and low-dose images were compared pairwise. No clinically significant bias was found in any of the three groups. The mean absolute difference in regional SUV-r values was 0.015 (1.32%) in controls and 0.019 (1.67%) in patients. The ultra-low-dose protocol produced a slightly higher mean difference of 0.023 (2.10%). The main conclusion is that 0.75 MBq/ kg (56 MBq for a 75-kg subject) is a sufficient FDG dose for evaluating regional SUV-ratios in brain PET scans in adults with or without neurodegenerative disease, resulting in a reduction of total PET/ CT effective dose from 4.54 to 1.15 mSv. The ultra-low-dose (0.5 mSv) could be useful in research studies requiring serial PET in healthy controls or children.

  • 28.
    Gunnarsson, Malin Degerman
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Ingelsson, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Blennow, Kaj
    Univ Gothenburg, Sahlgrenska Univ Hosp, Inst Neurosci & Physiol, Clin Neurochem Lab, SE-43180 Molndal, Sweden..
    Basun, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Lannfelt, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    High tau levels in cerebrospinal fluid predict nursing home placement and rapid progression in Alzheimer's disease2016In: Alzheimer's Research & Therapy, ISSN 0065-6755, E-ISSN 1758-9193, Vol. 8, article id 22Article in journal (Refereed)
    Abstract [en]

    Background: Increased concentrations of cerebrospinal fluid (CSF) total tau (t-tau) and phosphorylated tau, as well as decreased amyloid-beta 42 peptide, are biomarkers of Alzheimer's disease (AD) pathology, but few studies have shown an association with AD progression rate. We hypothesized that high CSF tau, as a marker of ongoing neurodegeneration, would predict a more aggressive course of AD, using time to nursing home placement (NHP) as the main outcome. Methods: Our sample inlcuded 234 patients with mild cognitive impairment (MCI) due to AD (n = 134) or mild to moderate AD (n = 100) who underwent lumbar puncture at a memory clinic and were followed for 2-11 years (median 4.9 years). Results: Individuals with CSF t-tau in the highest quartile (>= 900 ng/L) had a higher ratio of NHP, both in the total cohort and in patients with MCI only (adjusted HR 2.17 [95 % CI 1.24-3.80]; HR 2.37 [95 % CI 1.10-5.09], respectively), than the lowest quartile. The association between high t-tau levels and future steep deterioration was confirmed in analyses with conversion to moderate dementia (HR 1.66; 95 % CI 1.08-2.56), rapid decline in Mini Mental State Examination score (>= 4-point drop/12 months), and dying in severe dementia as outcomes. Conclusions: To our knowledge, this is the first study to show that high CSF t-tau levels predict early NHP and conversion to moderate dementia in an AD cohort. Selecting patients with high CSF t-tau, indicating more aggressive neurodegeneration and steeper decline, for AD immunotherapy trials might increase the possibility of showing contrast between active treatment and placebo.

  • 29.
    Hagström, Emil
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Nylander, Ruta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Arnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Plasma Parathyroid Hormone Is Associated with Vascular Dementia and Cerebral Hyperintensities in Two Community-Based Cohorts2014In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 99, no 11, p. 4181-4189Article in journal (Refereed)
    Abstract [en]

    Context:

    In diseases with increased PTH such as hyperparathyroidism and chronic renal failure, dementia is common. Little is known of PTH and dementia in the community.

    Objective:

    We sought to investigate relations between PTH, clinical dementia and cerebral micro-vascular disease.

    Setting and Design:

    The Uppsala Longitudinal Study Of Adult Men (ULSAM) was prospective, baseline, 1991-1995; followup, 15.8 years. The Prospective Investigation Of The Vasculature In Uppsala Seniors (PIVUS) was cross-sectional, baseline, 2001. Both settings were community based.

    Participants and Main Outcome Measure:

    In the ULSAM study of 998 men (age 71) the association between PTH and dementia was investigated. In the PIVUS study of 406 men and women (age 70) the relation between PTH and magnetic resonance imaging signs of cerebral small vascular disease was investigated.

    Results:

    During followup, 56 individuals were diagnosed with vascular, 91 with Alzheimer's, and 59 with other dementias. In Cox-regression analyses, higher PTH was associated with vascular dementia (hazard ratio per 1 SD increase of PTH, 1.41; P < .01), but not with other dementias. The top tertile of PTH accounted for 18.5% of the population-attributable risk for vascular dementia, exceeding all other risk factors. In linear regression analysis in PIVUS, PTH was associated with increasing white matter hyperintensities (WMHI), reflecting increasing burden of cerebral small vessel disease (1 SD PTH increase, 0.31 higher category of WMHI; P = .016). All models were adjusted for vascular risk factors and mineral metabolism.

    Conclusions:

    In two community-based samples, PTH predicted clinically diagnosed and neuroimaging indices of vascular dementia and cerebral small vessel disease. Our data suggest a role for PTH in the development of vascular dementia.

  • 30.
    Hagström, Emil
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Plasma parathyroid hormone and the risk of cerebrovascular diseases in the community2012In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 33, no Suppl 1, p. 236-236Article in journal (Other academic)
  • 31.
    Hansen, Tomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Total atherosclerotic burden measured by magnetic resonance imaging is related to five-year decline in cognitive function2018In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 38, no 3, p. 373-377Article in journal (Refereed)
    Abstract [en]

    Objective: The aim of this study was to explore whether total atherosclerotic burden is related to future decline in performance on cognitive tests.

    Methods: The total atherosclerotic burden (TAS) was assessed by whole‐body magnetic resonance angiography (WBMRA) in 305 subjects at age 70 in the study Prospective Investigation of Vasculature in Uppsala Seniors (PIVUS). The mini‐mental state examination (MMSE) and trail making tests (TMT) A and B were evaluated at ages 75 and 80 in 190 of those subjects. No subject with a diagnosis of dementia was included in the sample.

    Results: MMSE did not change during the 5 years of follow‐up, while TMT A and B increased by 4 and 7 s, respectively. TAS at age 70 was significantly related to the individual change in TMT B (P<0·0001) between age 75 and 80, when adjusted for sex, education level, TMT B at age 75 and Framingham score at age 70. No such relationship was seen for the change in TMT A (P = 0·10). The relationship between TAS and the change in MMSE was of borderline significance (P = 0·025).

    Conclusion: A relationship was found between the total atherosclerotic burden and future decline in performance on TMT B, highlighting a role of global atherosclerosis in the cognitive decline seen during ageing.

  • 32.
    Hogenkamp, Pleunie S.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Sjögren, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Late-life alcohol consumption and cognitive function in elderly men2014In: Age (Omaha), ISSN 0161-9152, E-ISSN 1574-4647, Vol. 36, no 1, p. 243-249Article in journal (Refereed)
    Abstract [en]

    Moderate alcohol consumption (one to two drinks per day) has been associated with better cognitive function and lower risk of developing dementia in the elderly. In light of alcohol's well-known neurotoxic properties, more evidence from well-controlled population-based studies is required. The objective of this study was to examine whether self-reported alcohol intake at age 70 is linked to cognitive function (assessed by trail making tests (TMTs) A and B, which are measures of attention, mental speed, and flexibility) in a population-based cohort consisting of 652 cognitively healthy elderly men. Linear regression models were used to assess both cross-sectional (i.e., age 70) and prospective (i.e., age 77) associations between alcohol intake and cognitive function. The analyses were adjusted for education, body mass index, energy intake, self-reported physical activity, smoking, a history of hypertension or diabetes, apolipoprotein E epsilon 4 status, and cholesterol levels at the age of 70. Baseline data were obtained from 1990 to 1996. Self-reported alcohol intake (mean 6.9 +/- 7.1 g/day) was associated with better performance on TMT-B at ages 70 and 77 (beta = -0.87, p < 0.001). In contrast, alcohol intake was not predictive of the difference in performance on these tests between ages 70 and 77. Despite cross-sectional associations with performance in a test of executive functioning, moderate intake of alcohol was not linked to differences in cognitive performance between ages 70 and 77 in the present study. Thus, our findings do not support the view that daily moderate alcohol consumption is a recommendable strategy to slow cognitive aging in elderly populations.

  • 33.
    Kilander, L
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    [Can better antihypertensive treatment prevent dementia? A question under investigation]1999In: Lakartidningen, ISSN 0023-7205, Vol. 96, no 48, p. 5357-60Article in journal (Refereed)
  • 34. Maddock, Jane
    et al.
    Zhou, Ang
    Cavadino, Alana
    Kuźma, Elżbieta
    Bao, Yanchun
    Smart, Melissa C
    Saum, Kai-Uwe
    Schöttker, Ben
    Engmann, Jorgen
    Kjærgaard, Marie
    Karhunen, Ville
    Zhan, Yiqiang
    Lehtimäki, Terho
    Rovio, Suvi P
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Lahti, Jari
    Marques-Vidal, Pedro
    Sen, Abhijit
    Perna, Laura
    Schirmer, Henrik
    Singh-Manoux, Archana
    Auvinen, Juha
    Hutri-Kähönen, Nina
    Kähönen, Mika
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Räikkönen, Katri
    Melhus, Håkan
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Guessous, Idris
    Petrovic, Katja E
    Schmidt, Helena
    Schmidt, Reinhold
    Vollenweider, Peter
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Eriksson, Johan G
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Raitakari, Olli T
    Hägg, Sara
    Pedersen, Nancy L
    Herzig, Karl-Heinz
    Järvelin, Marjo-Riitta
    Veijola, Juha
    Kivimaki, Mika
    Jorde, Rolf
    Brenner, Hermann
    Kumari, Meena
    Power, Chris
    Llewellyn, David J
    Hyppönen, Elina
    Vitamin D and cognitive function: A Mendelian randomisation study.2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 13230Article in journal (Refereed)
    Abstract [en]

    The causal nature of the association between hypovitaminosis D and poor cognitive function in mid- to later-life is uncertain. Using a Mendelian randomisation(MR) approach, we examined the causal relationship between 25(OH)D and cognitive function. Data came from 172,349 participants from 17 cohorts. DHCR7(rs12785878), CYP2R1 rs12794714) and their combined synthesis score were chosen to proxy 25(OH)D. Cognitive tests were standardised into global and memory scores. Analyses were stratified by 25(OH)D tertiles, sex and age. Random effects meta-analyses assessed associations between 25(OH)D and cognitive function. Associations of serum 25(OH)D with global and memory-related cognitive function were non-linear (lower cognitive scores for both low and high 25(OH)D, p curvature ≤ 0.006), with much of the curvature attributed to a single study. DHCR7, CYP2R1, and the synthesis score were associated with small reductions in 25(OH)D per vitamin D-decreasing allele. However, coefficients for associations with global or memory-related cognitive function were non-significant and in opposing directions for DHCR7 and CYP2R1, with no overall association observed for the synthesis score. Coefficients for the synthesis score and global and memory cognition were similar when stratified by 25(OH)D tertiles, sex and age. We found no evidence for serum 25(OH)D concentration as a causal factor for cognitive performance in mid- to later life.

  • 35. Makitalo, Signar
    et al.
    Mellgren, Asa
    Borgh, Ellen
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Skillback, Tobias
    Zetterberg, Henrik
    Gisslen, Magnus
    The cerebrospinal fluid biomarker profile in an HIV-infected subject with Alzheimer's disease2015In: AIDS research and therapy, ISSN 1742-6405, E-ISSN 1742-6405, Vol. 12, article id 23Article in journal (Refereed)
    Abstract [en]

    It is a challenge to differentiate between HIV-associated neurocognitive disorders (HAND) and other types of neurocognitive disease in the ageing HIV-infected population. Here we describe a 63 year old HIV-infected woman who had a history, neuropsychological test result, and PET examination consistent with characteristic Alzheimer's disease (AD). The cerebrospinal fluid (CSF) biomarker profile was analogous to the profile typically found in AD in HIV-negative patients with increased t-tau and p-tau, a decreased level of A beta 42 and normal levels of CSF neurofilament light protein and sAPP alpha and sAPP beta, distinctly different from findings in HIV-associated dementia (HAD). Assessment of CSF biomarkers may be a valuable tool for clinicians to distinguish between HAD and AD.

  • 36.
    Nylander, Ruta
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Small Vessel Disease on Neuroimaging in a 75-Year-Old Cohort (PIVUS): Comparison With Cognitive and Executive Tests.2018In: Frontiers in Aging Neuroscience, ISSN 1663-4365, E-ISSN 1663-4365, Vol. 10, article id 217Article in journal (Refereed)
    Abstract [en]

    Background and Purpose: Signs of small vessel disease (SVD) are commonly seen on magnetic resonance imaging (MRI) of the brain in cognitively healthy elderly individuals, and the clinical relevance of these are often unclear. We have previously described three different MRI manifestations of SVD as well as cerebral perfusion in a longitudinal study of non-demented 75-year-old subjects. The purpose of the present study was to evaluate the relationship of these findings to cognition and executive function at age 75 and changes after 5 years. Methods: In all, 406 subjects from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study were examined with MRI of the brain at age 75 years. Two-hundred and fifty of the subjects were re-examined 5 years later. White matter hyperintensities (WMHs) and lacunar infarcts (LIs) were assessed on both occasions, but microbleeds (MBs) and perfusion only at age 75. Cognitive function was screened by the Mini Mental State Examination (MMSE). Trail Making Test A and B (TMT-A and TMT-B) were performed at baseline and at follow-up at age 80. Results: At baseline, 93% performed >27 points in the MMSE. The TMT-B at age 75 was significantly related to WMH visual scoring after adjustment for sex, education and cerebrovascular disease risk factors (+80 s (95% CI 0.3-161 s), P < 0.05 for grade 2-3 vs. grade 0). Neither MMSE nor TMT-A was significantly related to WMH scoring. There was no relation between any test performance and WMH volume, white matter volume, number of MBs or brain perfusion at age 75. Subjects who had sustained a new LI (n = 26) showed a greater increase of the time to perform TMT-A at the 5-year follow-up (+25 s vs. +4 s in LI-free subjects, P = 0.003). Changes in MMSE or TMT-A and -B test performance between ages 75 and 80 were not related to changes in WMH scoring or volume during the 5 years follow-up, or to brain perfusion at age 75. Conclusion: In this cognitively healthy community-based population, moderate-severe WMHs and incident LIs on brain MRI in individuals aged 75-80 years were associated with a mild impairment of processing speed and executive function.

  • 37.
    Olsson, Erika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Karlström, Brita
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Sjögren, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Vitamin D is not associated with incident dementia or cognitive impairment: an 18-y follow-up study in community-living old men2017In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 105, no 4, p. 936-943Article in journal (Refereed)
    Abstract [en]

    Background: Vitamin D has been implicated as being important for maintaining cognitive function in old age. Results from longitudinal studies examining the association of vitamin D with incident dementia and cognitive impairment have been inconsistent. Objective: We investigated the relation between vitamin D, assessed in 3 different ways, and the risk of dementia. Design: We measured plasma 25-hydroxyvitamin D [25(OH) D] with the use of high-performance liquid chromatography-mass spectrometry, assessed dietary vitamin D intake with the use of 7-d dietary records, and created a vitamin D-synthesis genetic risk score (GRS) at baseline (1991-1995) in a cohort of 1182 Swedish men (mean age: 71 y). In a maximum of 18 y (median: 12 y) of follow-up, 116 men developed Alzheimer disease, 64 men developed vascular dementia, and 250 men developed all-cause dementia. An additional 80 men declined in cognitive function as assessed with the use of the Mini-Mental State Examination. Adjusted HRs and ORs were calculated with the use of Cox and logistic regressions. Results: The mean +/- SD plasma 25(OH) D concentration was 68.7 +/- 19.1 nmol/L. Plasma 25(OH) D, dietary vitamin D intake, and vitamin D-synthesis GRS were not associated with any cognitive outcomes (crude and adjusted HRs and ORs were similar to 1.0 for all continuous exposures). The adjusted HR for all-cause dementia was 0.88 (95% CI: 0.59, 1.31) in men with plasma 25(OH) D concentrations <= 50 compared with >75 nmol/L. The adjusted HR for all-cause dementia was 0.92 (95% CI: 0.63, 1.32) for the lowest compared with highest tertiles of vitamin D intake. The adjusted HR for the continuous GRS for all-cause dementia was 1.04 (95% CI: 0.91, 1.19). Conclusion: In this cohort study, we show that there is no association between baseline vitamin D status and long-term risk of dementia or cognitive impairment over an 18-y period of time.

  • 38.
    Olsson, Erika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Karlström, Brita
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Food, Nutrition and Dietetics.
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Sjögren, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Kostmönster och risk för utveckling av demenssjukdom: en 12 års uppföljning av 70 åriga män2011In: Svenska läkaresällskapets riksstämma, 2011Conference paper (Other academic)
    Abstract [sv]

    Samband mellan kost och demenssjukdom är inte tydligt fastställda. Studiens syfte var att prospektivt undersöka hur tre olika kostmönster relaterar till utvecklingen av demenssjukdom, inkl. Alzheimers sjukdom (AD), eller alla typer av kognitiv störning hos äldre friska män.

  • 39.
    Olsson, Erika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Karlström, Brita
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Sjögren, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Dietary Patterns and Cognitive Dysfunction in a 12-Year Follow-up Study of 70 Year Old Men2015In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 43, no 1, p. 109-119Article in journal (Refereed)
    Abstract [en]

    Background:

    Adherence to dietary patterns has been associated with cognitive decline and dementia, but studies are inconsistent.

    Objective:

    Dietary patterns, i.e., WHO recommendations (Healthy Diet Indicator), a Mediterranean-like diet (modified Mediterranean Diet Score, mMDS), and a low carbohydrate high protein diet (LCHP), were related to incident cognitive dysfunction, as indicated by Alzheimer's disease (AD), all-type dementia, and all-type cognitive impairment, in a cohort of 1,138 elderly Swedish men.

    Methods:

    Dietary patterns were derived from 7-day records. Risk relations were calculated by Cox and logistic regression analyses, adjusted for potential confounders. Sensitivity analysis was performed in a subpopulation (n = 564) with energy intake according to the Goldberg cut-off.

    Results:

    During a mean follow-up of 12 years, 84, 143, and 198 men developed AD, all-type dementia, and all-type cognitive impairment, respectively. There was no association between Healthy Diet Indicator and any of the outcomes. Hazard ratios associated with 1 standard deviation (SD) increment in the LCHP score were 1.16 (95% confidence interval [CI]: 0.95, 1.43) for AD and 1.16 (95% CI: 0.99, 1.37) for all-type dementia. mMDS was not associated with dementia diagnosis. Odds ratio (OR)/1 SD increase for mMDS and all-type cognitive impairment was 0.82 (95% CI: 0.65, 1.05). In the subpopulation OR for mMDS and all-type cognitive impairment was 0.32 (95% CI: 0.11, 0.89).

    Conclusion:

    We found no strong associations with development of cognitive dysfunction for any of the dietary patterns investigated. However, there was a potentially beneficial association for a Mediterranean-like diet on the development of cognitive dysfunction in the subpopulation.

  • 40.
    Olsson, Erika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Karlström, Brita
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Sjögren, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Dietary Patterns And Cognitive Dysfunction In A Prospective Study Of 70-Year-Old Swedish Men2013In: Annals of Nutrition and Metabolism, ISSN 0250-6807, E-ISSN 1421-9697, Vol. 63, no Suppl. 1, p. 862-862Article in journal (Other academic)
  • 41. Religa, Dorota
    et al.
    Fereshtehnejad, Seyed-Mohammad
    Cermakova, Pavla
    Edlund, Ann-Katrin
    Garcia-Ptacek, Sara
    Granqvist, Nicklas
    Hallback, Anne
    Kawe, Kerstin
    Farahmand, Bahman
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Mattsson, Ulla-Britt
    Nagga, Katarina
    Nordstrom, Peter
    Wijk, Helle
    Wimo, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Winblad, Bengt
    Eriksdotter, Maria
    SveDem, the Swedish Dementia Registry - A Tool for Improving the Quality of Diagnostics, Treatment and Care of Dementia Patients in Clinical Practice2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 2, article id e0116538Article in journal (Refereed)
    Abstract [en]

    Background The Swedish Dementia Registry (SveDem) was developed with the aim to improve the quality of diagnostic work-up, treatment and care of patients with dementia disorders in Sweden. Methods SveDem is an internet based quality registry where several indicators can be followed over time. It includes information about the diagnostic work-up, medical treatment and community support (www.svedem.se). The patients are diagnosed and followed-up yearly in specialist units, primary care centres or in nursing homes. Results The database was initiated in May 2007 and covers almost all of Sweden. There were 28 722 patients registered with a mean age of 79.3 years during 2007-2012. Each participating unit obtains continuous online statistics from its own registrations and they can be compared with regional and national data. A report from SveDem is published yearly to informmedical and care professionals as well as political and administrative decision-makers about the current quality of diagnostics, treatment and care of patients with dementia disorders in Sweden. Conclusion SveDem provides knowledge about current dementia care in Sweden and serves as a framework for ensuring the quality of diagnostics, treatment and care across the country. It also reflects changes in quality dementia care over time. Data from SveDem can be used to further develop the national guidelines for dementia and to generate new research hypotheses.

  • 42. Rosén, Christoffer
    et al.
    Farahmand, Bahman
    Skillbäck, Tobias
    Nägga, Katarina
    Mattsson, Niklas
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Religa, Dorota
    Wimo, Anders
    Blennow, Kaj
    Winblad, Bengt
    Zetterberg, Henrik
    Eriksdotter, Maria
    Benchmarking biomarker-based criteria for Alzheimer's disease: Data from the Swedish Dementia Registry, SveDem2015In: Alzheimer's & Dementia, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 11, no 12, p. 1470-1479Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: New research guidelines for the diagnosis of Alzheimer's disease (AD) include biomarker evidence of amyloid-β (Aβ) and tau pathology. The aim of this study was to investigate what proportion of AD patients diagnosed in clinical routine in Sweden that had an AD-indicative cerebrospinal fluid (CSF) biomarker profile.

    METHODS: By cross-referencing a laboratory database with the Swedish Dementia Registry (SveDem), 2357 patients with data on CSF Aβ and tau biomarkers and a clinical diagnosis of AD with dementia were acquired.

    RESULTS: Altogether, 77.2% had pathologic Aβ42 and total tau or phosphorylated tau in CSF. These results were stable across age groups. Female sex and low mini-mental state examination score increased the likelihood of pathologic biomarkers.

    CONCLUSION: About a quarter of clinically diagnosed AD patients did not have an AD-indicative CSF biomarker profile. This discrepancy may partly reflect incorrect (false positive) clinical diagnosis or a lack in sensitivity of the biomarker assays.

  • 43.
    Rönnemaa, E
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Zethelius, B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Sundelöf, J
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Sundström, J
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Degerman-Gunnarsson, M
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Berne, C
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lannfelt, L
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Kilander, L
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Impaired insulin secretion increases the risk of Alzheimer disease2008In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 71, no 14, p. 1046-47Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Subjects with diabetes are reported to have an increased risk of dementia and cognitive impairment. However, the underlying causes remain unknown. We investigated the longitudinal associations between midlife insulin secretion, glucose metabolism, and the subsequent development of Alzheimer disease (AD) and dementia. METHODS: The population-based Uppsala Longitudinal Study of Adult Men started 1970 when the 2,322 participants were 50 years old. Investigation at baseline included determinations of acute insulin response and glucose tolerance using the IV glucose tolerance test and Homeostasis Model Assessment insulin resistance index. During a median follow up of 32 years, 102 participants were diagnosed with AD, 57 with vascular dementia, and 394 with any dementia or cognitive impairment. Associations were analyzed using Cox proportional hazard models. RESULTS: A low insulin response at baseline was associated with a higher cumulative risk of AD (hazard ratio for 1 SD decrease, 1.31; 95% CI, 1.10-1.56) also after adjustment for age, systolic blood pressure, body mass index, serum cholesterol, smoking, education level, and insulin resistance. This association was stronger in subjects without the APOE epsilon4 allele. Impaired glucose tolerance increased the risk of vascular dementia (hazard ratio for 1 SD decrease, 1.45; 95% CI, 1.05-2.00) but not AD. Impaired insulin secretion, glucose intolerance, and estimates of insulin resistance were all associated with higher risk of any dementia and cognitive impairment. CONCLUSIONS: In this longitudinal study, impaired acute insulin response at midlife was associated with an increased risk of Alzheimer disease (AD) up to 35 years later suggesting a causal link between insulin metabolism and the pathogenesis of AD.

  • 44.
    Rönnemaa, Elina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Lannfelt, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Vascular Risk Factors and Dementia: 40-Year Follow-Up of a Population-Based Cohort2011In: Dementia and Geriatric Cognitive Disorders, ISSN 1420-8008, E-ISSN 1421-9824, Vol. 31, no 6, p. 460-466Article in journal (Refereed)
    Abstract [en]

    Aims: Our aim was to evaluate the longitudinal associations of individual and multiple vascular risk factors with the subsequent development of dementia and Alzheimer's disease (AD). Methods: The Uppsala Longitudinal Study of Adult Men started in 1970 when the 2,268 participants were 50 years old. Baseline investigations included determinations of blood pressure, fasting glucose, cholesterol, BMI and smoking status. Over a maximum follow-up of 40 years, 349 participants were diagnosed with dementia, out of which 127 had AD. Analyses were repeated using a re-examination of the cohort at 70 years of age as a baseline. Results: No associations between vascular risk factors and AD were found. For all-type dementia, the association between high systolic blood pressure and dementia was the most consistent. High fasting glucose was associated with increased risk of all-type dementia only when measured at 70 years. Individuals with both an APOE epsilon 4 allele and vascular risk factors had the greatest dementia risk. Conclusion: Vascular risk factors influence the future risk of dementia, in particular vascular and mixed-type rather than AD. The impact of vascular risk factors on dementia in a longitudinal study depends on the age at baseline and the length of follow-up. Copyright

  • 45.
    Rönnemaa, Elina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Vessby, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Lannfelt, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Serum fatty-acid composition and the risk of Alzheimer’s disease: a longitudinal population based study2012In: European Journal of Clinical Nutrition, ISSN 0954-3007, E-ISSN 1476-5640, Vol. 66, no 8, p. 885-890Article in journal (Refereed)
    Abstract [en]

    BACKGROUND/OBJECTIVES:

    It is unknown if a specific fatty-acid composition influences the development of Alzheimer's disease (AD). Nutrition is a possible target for prevention of dementia and especially omega-3-based fatty acids (n-3 FAs) have previously been suggested to be beneficial for cognition. The objective was to ascertain whether serum FAs predicts the risk of incident AD and dementia in a longitudinal population-based cohort.

    SUBJECTS/METHODS:

    Uppsala Longitudinal Study of Adult Men started in 1970. The proportions of FAs in serum cholesteryl esters were estimated in men (n=2009) who were 50 years old at baseline. During a 35 year follow-up time, 213 men had developed dementia, out of which 91 AD. The associations were analyzed with Cox proportional hazards and logistic regression; adjusted for age, education and vascular risk factors.

    RESULTS:

    Subjects with a higher proportion of saturated FAs had a decreased risk of AD in crude and multi-adjusted models (hazard ratio for 1-s.d. increase in palmitic acid 0.72; 95% confidence intervals: 0.59-0.89). These associations persisted even in the group of approximately 85-year-old survivors. n-3 FAs FAs were not associated with decreased risk of AD or dementia.

    CONCLUSIONS:

    In contrast to experimental studies, saturated FAs were inversely associated with risk of AD. No evidence of a protective effect of n-3 FAs against dementia was found. The results remained essentially unchanged if competing risk from mortality was taken into account.

  • 46.
    Santillo, Alexander Frizell
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Gambini, Juan Pablo
    Lannfelt, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Långström, Bengt
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry.
    Ulla-Marja, Luohija
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Engler, Henry
    In vivo imaging of astrocytosis in Alzheimer's disease: an ¹¹C-L-deuteriodeprenyl and PIB PET study2011In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 38, no 12, p. 2202-2208Article in journal (Refereed)
    Abstract [en]

    PURPOSE:

    Astrocytosis is an important feature of the neuropathology of Alzheimer's disease (AD), yet there is currently no way of detecting this phenomenon in vivo.

    METHODS:

    In this study we examine the retention of the positron emission tomography (PET) tracer (11)C-L-deuteriodeprenyl (DED), thought to bind activated astrocytes, in 9 patients with moderate to severe AD compared with 11 healthy controls. As a measure of amyloid load, (11)C-labelled Pittsburgh Compound B (PIB) retention was determined.

    RESULTS:

    Results show a significantly higher (11)C-L-DED retention in the frontal (35.1% increase, p = 0.001), parietal (35.2%, p = 0.001), temporal (30.9%, p = 0.0001) and medial temporal lobes (22.3%, p = 0.001) in AD compared to healthy controls after blood flow correction. DED retention in the sensorimotor and occipital cortices, and in white matter and subcortical structures, did not differ between groups. There was a moderate but statistically significant (r = 0.492, p = 0.01) correlation between DED and PIB retention values.

    CONCLUSION:

    Our conclusion is that DED may serve as an in vivo marker for astrocytosis in AD, providing a window into intermediate processes between amyloidosis and neuronal loss and a means of monitoring immunotherapy.

  • 47.
    Sims, Rebecca
    et al.
    Cardiff Univ, MRC Ctr Neuropsychiat Genet & Gen, Inst Psychol Med & Clin Neurosci, Cardiff, S Glam, Wales..
    van der Lee, Sven J.
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands..
    Naj, Adam C.
    Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, Dept Biostat & Epidemiol, Philadelphia, PA USA.;Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA..
    Bellenguez, Celine
    Risk Factors & Mol Determinants Aging Related Dis, RID AGE, U1167, INSERM, Lille, France.;Inst Pasteur, Lille, France.;Univ Lille, Excellence Lab LabEx DISTALZ, U1167, Lille, France..
    Badarinarayan, Nandini
    Cardiff Univ, MRC Ctr Neuropsychiat Genet & Gen, Inst Psychol Med & Clin Neurosci, Cardiff, S Glam, Wales..
    Jakobsdottir, Johanna
    Iceland Heart Assoc, Kopavogur, Iceland. Univ Miami, John P Hussman Inst Human Gen, Miami, FL USA..
    Kunkle, Brian W.
    Boland, Anne
    Ctr Natl Genotypage, Inst Genom, CEA, Evry, France..
    Raybould, Rachel
    Cardiff Univ, MRC Ctr Neuropsychiat Genet & Gen, Inst Psychol Med & Clin Neurosci, Cardiff, S Glam, Wales..
    Bis, Joshua C.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. Univ Miami, Dept Human Genet, Dr John T Macdonald Fdn, Miami, FL USA..
    Martin, Eden R.
    Grenier-Boley, Benjamin
    Risk Factors & Mol Determinants Aging Related Dis, RID AGE, U1167, INSERM, Lille, France.;Inst Pasteur, Lille, France.;Univ Lille, Excellence Lab LabEx DISTALZ, U1167, Lille, France..
    Heilmann-Heimbach, Stefanie
    Univ Bonn, Inst Human Genet, Bonn, Germany.;Univ Bonn, Life & Brain Ctr, Dept Gen, Bonn, Germany..
    Chouraki, Vincent
    Boston Univ, Sch Med, Boston, MA 02118 USA.;Framingham Heart Dis Epidemiol Study, Framingham, MA USA..
    Kuzma, Amanda B.
    Univ Penn, Sch Med, Dept Pathol & Lab Med, Penn Neurodegenerat Genom Ctr, Philadelphia, PA 19104 USA..
    Sleegers, Kristel
    VIB, Dept Mol Genet, Neurodegenerat Brain Dis Grp, Antwerp, Belgium.;Univ Antwerp, Inst Born Bunge, Antwerp, Belgium..
    Vronskaya, Maria
    Cardiff Univ, MRC Ctr Neuropsychiat Genet & Gen, Inst Psychol Med & Clin Neurosci, Cardiff, S Glam, Wales..
    Ruiz, Agustin
    Inst Catala Neurociencies Aplicades, Res Ctr, Barcelona, Spain.;Inst Catala Neurociencies Aplicades, Memory Clin Fundacio ACE, Barcelona, Spain..
    Graham, Robert R.
    Genentech Inc, Immunol Biomarkers Grp, San Francisco, CA USA..
    Olaso, Robert
    Ctr Natl Genotypage, Inst Genom, CEA, Evry, France..
    Hoffmann, Per
    Univ Bonn, Inst Human Genet, Bonn, Germany.;Univ Bonn, Life & Brain Ctr, Dept Gen, Bonn, Germany.;Univ Basel, Div Med Genet, Univ Hosp, Basel, Switzerland.;Univ Basel, Dept Biomed, Basel, Switzerland..
    Grove, Megan L.
    Univ Texas Hlth Sci Ctr Houston, Human Genet Ctr, Sch Publ Hlth, Houston, TX USA..
    Vardarajan, Badri N.
    Columbia Univ, Dept Neurol, Taub Inst Alzheimers Dis & Aging Brain, New York, NY USA.;Columbia Univ, Gertrude H Sergievsky Ctr, New York, NY USA.;Columbia Univ, Dept Neurol, New York, NY USA..
    Hiltunen, Mikko
    Univ Eastern Finland, Inst Biomed, Kuopio, Finland.;Kuopio Univ Hosp, Dept Neurol, Kuopio, Finland..
    Noethen, Markus M.
    Univ Bonn, Inst Human Genet, Bonn, Germany.;Univ Bonn, Life & Brain Ctr, Dept Gen, Bonn, Germany..
    White, Charles C.
    Brigham & Womens Hosp, Dept Neurol & Psychiat, Inst Neurosci, Program Translat NeuroPsychiatr Gen, Boston, MA USA..
    Hamilton-Nelson, Kara L.
    Epelbaum, Jacques
    Univ Paris 05, INSERM, Ctr Psychiat & Neurosci, UMR 894, Paris, France..
    Maier, Wolfgang
    German Ctr Neurodegenerat Dis DZNE, Bonn, Germany.;Univ Bonn, Dept Psychiat & Psychotherapy, Bonn, Germany..
    Choi, Seung-Hoan
    Boston Univ, Sch Med, Boston, MA 02118 USA.;Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA..
    Beecham, Gary W.
    Dulary, Cecile
    Ctr Natl Genotypage, Inst Genom, CEA, Evry, France..
    Herms, Stefan
    Univ Bonn, Inst Human Genet, Bonn, Germany.;Univ Bonn, Life & Brain Ctr, Dept Gen, Bonn, Germany.;Univ Basel, Div Med Genet, Univ Hosp, Basel, Switzerland.;Univ Basel, Dept Biomed, Basel, Switzerland..
    Smith, Albert V.
    Iceland Heart Assoc, Kopavogur, Iceland. Univ Miami, John P Hussman Inst Human Gen, Miami, FL USA.;Univ Iceland, Fac Med, Reykjavik, Iceland..
    Funk, Cory C.
    Inst Syst Biol, Seattle, WA USA..
    Derbois, Celine
    Ctr Natl Genotypage, Inst Genom, CEA, Evry, France..
    Forstner, Andreas J.
    Univ Bonn, Inst Human Genet, Bonn, Germany.;Univ Bonn, Life & Brain Ctr, Dept Gen, Bonn, Germany..
    Ahmad, Shahzad
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands..
    Li, Hongdong
    Inst Syst Biol, Seattle, WA USA..
    Bacq, Delphine
    Ctr Natl Genotypage, Inst Genom, CEA, Evry, France..
    Harold, Denise
    Dublin City Univ, Sch Biotechnol, Dublin, Ireland..
    Satizabal, Claudia L.
    Boston Univ, Sch Med, Boston, MA 02118 USA.;Framingham Heart Dis Epidemiol Study, Framingham, MA USA..
    Valladares, Otto
    Univ Penn, Sch Med, Dept Pathol & Lab Med, Penn Neurodegenerat Genom Ctr, Philadelphia, PA 19104 USA..
    Squassina, Alessio
    Univ Cagliari, Dept Biomed Sci, Sect Neurosci & Clin Pharmacol, Cagliari, Italy..
    Thomas, Rhodri
    Cardiff Univ, MRC Ctr Neuropsychiat Genet & Gen, Inst Psychol Med & Clin Neurosci, Cardiff, S Glam, Wales..
    Brody, Jennifer A.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. Univ Miami, Dept Human Genet, Dr John T Macdonald Fdn, Miami, FL USA..
    Qu, Liming
    Univ Penn, Sch Med, Dept Pathol & Lab Med, Penn Neurodegenerat Genom Ctr, Philadelphia, PA 19104 USA..
    Sanchez-Juan, Pascual
    Neurol Serv, Santander, Spain.;Univ Cantabria, Marques Valdecilla Univ Hosp, CIBERNED, Santander, Spain.;IFIMAV, Santander, Spain..
    Morgan, Taniesha
    Cardiff Univ, MRC Ctr Neuropsychiat Genet & Gen, Inst Psychol Med & Clin Neurosci, Cardiff, S Glam, Wales..
    Wolters, Frank J.
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands..
    Zhao, Yi
    Univ Penn, Sch Med, Dept Pathol & Lab Med, Penn Neurodegenerat Genom Ctr, Philadelphia, PA 19104 USA..
    Sanchez Garcia, Florentino
    Hosp Univ Doctor Negrin, Dept Immunol, Las Palmas Gran Canaria, Spain..
    Denning, Nicola
    Cardiff Univ, MRC Ctr Neuropsychiat Genet & Gen, Inst Psychol Med & Clin Neurosci, Cardiff, S Glam, Wales..
    Fornage, Myriam
    Univ Texas Hlth Sci Ctr Houston, Brown Fdn Inst Mol Med, Houston, TX 77030 USA..
    Malamon, John
    Univ Penn, Sch Med, Dept Pathol & Lab Med, Penn Neurodegenerat Genom Ctr, Philadelphia, PA 19104 USA..
    Deniz Naranjo, Maria Candida
    Hosp Univ Doctor Negrin, Dept Immunol, Las Palmas Gran Canaria, Spain..
    Majounie, Elisa
    Cardiff Univ, MRC Ctr Neuropsychiat Genet & Gen, Inst Psychol Med & Clin Neurosci, Cardiff, S Glam, Wales..
    Mosley, Thomas H.
    Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA.;Univ Mississippi, Med Ctr, Dept Geriatr, Jackson, MS 39216 USA.;Univ Mississippi, Med Ctr, Dept Gerontol & Neurol, Jackson, MS 39216 USA..
    Dombroski, Beth
    Univ Penn, Sch Med, Dept Pathol & Lab Med, Penn Neurodegenerat Genom Ctr, Philadelphia, PA 19104 USA..
    Wallon, David
    Ctr Hos Rouvray, Sotteville Ies Rouen, France.;Normandy Univ, IRIB, Rouen Univ, U1079,INSERM, Rouen, France..
    Lupton, Michelle K.
    Kings Coll London, Inst Psychiat Psychol & Neurosci, Dept Basic & Clin Neurosci, London, England.;QIMR Berghofer Med Res Inst, Genet Epidemiol, Herston, Qld, Australia..
    Dupuis, Josee
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA..
    Whitehead, Patrice
    Fratiglioni, Laura
    Karolinska Univ Hosp Huddinge, Dept Geriatr Med, Stockholm, Sweden.;Karolinska Inst, Dept Neurobiol, Care Sci & Soc, Aging Res Ctr, Stockholm, Sweden.;Stockholm Univ, Stockholm, Sweden..
    Medway, Christopher
    Univ Nottingham, Queens Med Ctr, Inst Genet, Nottingham, England..
    Jian, Xueqiu
    Univ Texas Hlth Sci Ctr Houston, Brown Fdn Inst Mol Med, Houston, TX 77030 USA..
    Mukherjee, Shubhabrata
    Univ Washington, Dept Med, Seattle, WA USA..
    Keller, Lina
    Karolinska Inst, Dept Neurobiol, Care Sci & Soc, Aging Res Ctr, Stockholm, Sweden.;Stockholm Univ, Stockholm, Sweden..
    Brown, Kristelle
    Univ Nottingham, Queens Med Ctr, Inst Genet, Nottingham, England..
    Lin, Honghuang
    Boston Univ, Sch Med, Dept Med, Sect Computat Biomed, Boston, MA 02118 USA..
    Cantwell, Laura B.
    Univ Penn, Sch Med, Dept Pathol & Lab Med, Penn Neurodegenerat Genom Ctr, Philadelphia, PA 19104 USA..
    Panza, Francesco
    Univ Bari Aldo Moro, Dept Basic Med Neurosci & Sense Organs, Neurodegenerat Dis Unit, Bari, Italy..
    McGuinness, Bernadette
    Queens Univ, Sch Med Dent & Biomed Sci, Ctr Publ Hlth, Belfast, Antrim, North Ireland..
    Moreno-Grau, Sonia
    Inst Catala Neurociencies Aplicades, Res Ctr, Barcelona, Spain.;Inst Catala Neurociencies Aplicades, Memory Clin Fundacio ACE, Barcelona, Spain..
    Burgess, Jeremy D.
    Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA..
    Solfrizzi, Vincenzo
    Univ Bari Aldo Moro, Geriatr Med Memory Unit, Bari, Italy.;Univ Bari Aldo Moro, Rare Dis Ctr, Bari, Italy..
    Proitsi, Petra
    Kings Coll London, Inst Psychiat Psychol & Neurosci, Dept Basic & Clin Neurosci, London, England..
    Adams, Hieab H.
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands..
    Allen, Mariet
    Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA..
    Seripa, Davide
    IRCCS Casa Sollievo Sofferenza, Geriatr Unit, San Giovanni Rotondo, Italy.;IRCCS Casa Sollievo Sofferenza, Dept Med Sci, Gerontol Geriatr Res Lab, San Giovanni Rotondo, Italy..
    Pastor, Pau
    Univ Perugia, Dept Med, Sect Gerontol & Geriatr, Perugia, Italy..
    Cupples, L. Adrienne
    Framingham Heart Dis Epidemiol Study, Framingham, MA USA.;Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA..
    Price, Nathan D.
    Inst Syst Biol, Seattle, WA USA..
    Hannequin, Didier
    Normandy Univ, IRIB, Rouen Univ, U1079,INSERM, Rouen, France.;Rouen Univ Hosp, Dept Neurol, Rouen, France..
    Frank-Garcia, Ana
    Univ Autonoma Madrid, Univ Hosp La Paz, Dept Neurol, Madrid, Spain.;Inst Invest Sanitaria Hosp la Paz IdiPAZ, Madrid, Spain.;Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain..
    Levy, Daniel
    Boston Univ, Sch Med, Boston, MA 02118 USA.;Framingham Heart Dis Epidemiol Study, Framingham, MA USA.;NHLBI, Bldg 10, Bethesda, MD 20892 USA..
    Chakrabarty, Paramita
    Univ Florida, Dept Neurosci, Ctr Translat Res Neurodegenerat Dis, Gainesville, FL 32610 USA..
    Caffarra, Paolo
    Univ Parma, Dept Neurosci, Parma, Italy.;AUSL, Ctr Cognit Disorders, Parma, Italy..
    Giegling, Ina
    Martin Luther Univ Halle Wittenberg, Dept Psychiat, Halle, Germany..
    Beiser, Alexa S.
    Framingham Heart Dis Epidemiol Study, Framingham, MA USA.;Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA..
    Giedraitis, Vilmantas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Hampel, Harald
    AXA Res Fund & UPMC Chair, Paris, France.;Univ Paris 06, Sorbonne Univ, Paris, France.;Hop La Pitie Salpetriere, Inst Memoire & Malad Alzheimer IM2A, Paris, France.;Hop La Pitie Salpetriere, Inst Cerveau & Moelle Epiniere ICM, Dept Neurol, Paris, France..
    Garcia, Melissa E.
    NIA, Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA..
    Wang, Xue
    Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA..
    Lannfelt, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Mecocci, Patrizia
    Univ Perugia, Dept Med, Sect Gerontol & Geriatr, Perugia, Italy..
    Eiriksdottir, Gudny
    Iceland Heart Assoc, Kopavogur, Iceland. Univ Miami, John P Hussman Inst Human Gen, Miami, FL USA..
    Crane, Paul K.
    Univ Washington, Dept Med, Seattle, WA USA..
    Pasquier, Florence
    Ctr Hosp Univ Lille, Epidemiol & Publ Hlth Dept, Lille, France.;CNR Maj, INSERM, UMRS 1171, Lille, France..
    Boccardi, Virginia
    Univ Perugia, Dept Med, Sect Gerontol & Geriatr, Perugia, Italy..
    Henandez, Isabel
    Inst Catala Neurociencies Aplicades, Res Ctr, Barcelona, Spain.;Inst Catala Neurociencies Aplicades, Memory Clin Fundacio ACE, Barcelona, Spain..
    Barber, Robert C.
    Univ North Texas, Hlth Sci Ctr, Dept Pharmacol & Neurosci, Ft Worth, TX USA..
    Scherer, Martin
    Univ Med Ctr Hamburg Eppendorf, Dept Primary Med Care, Hamburg, Germany..
    Tarraga, Lluis
    Inst Catala Neurociencies Aplicades, Res Ctr, Barcelona, Spain.;Inst Catala Neurociencies Aplicades, Memory Clin Fundacio ACE, Barcelona, Spain..
    Adams, Perrie M.
    Univ Texas Southwestern Med Ctr Dallas, Dept Psychiat, Dallas, TX USA..
    Leber, Markus
    Univ Cologne, Dept Psychiat & Psychotherapy, Cologne, Germany..
    Chen, Yuning
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA..
    Albert, Marilyn S.
    Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA..
    Riedel-Heller, Steffi
    Univ Leipzig, Inst Social Med Occupat Hlth & Publ Hlth, Leipzig, Germany..
    Emilsson, Valur
    Iceland Heart Assoc, Kopavogur, Iceland. Univ Miami, John P Hussman Inst Human Gen, Miami, FL USA.;Univ Iceland, Fac Pharmaceut Sci, Reykjavik, Iceland..
    Beekly, Duane
    Univ Washington, Natl Alzheimers Coordinating Ctr, Seattle, WA 98195 USA..
    Braae, Anne
    Univ Nottingham, Sch Life Sci, Nottingham, England.;Univ Nottingham, Sch Med, Nottingham, England..
    Schmidt, Reinhold
    Med Univ Graz, Dept Neurol, Clin Div Neurogeriatr, Graz, Austria..
    Blacker, Deborah
    Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.;Harvard Med Sch, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA USA..
    Masullo, Carlo
    Univ Cattolica Sacro Cuore, Dept Neurol, Rome, Italy..
    Schmidt, Helena
    Med Univ Graz, Inst Mol Biol & Biochem, Graz, Austria..
    Doody, Rachelle S.
    Baylor Coll Med, Alzheimers Dis & Memory Disorders Ctr, Houston, TX 77030 USA..
    Spalletta, Gianfranco
    IRCCS, Santa Lucia Fdn, Expt Neuropsychiat Lab, Dept Clin & Behav Neurol, Rome, Italy..
    Longstreth, W. T., Jr.
    Univ Washington, Dept Neurol, Seattle, WA 98195 USA.;Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA..
    Fairchild, Thomas J.
    Univ North Texas, Hlth Sci Ctr, Off Strategy & Measurement, Ft Worth, TX USA..
    Bossu, Paola
    IRCCS, Santa Lucia Fdn, Expt Neuropsychiat Lab, Dept Clin & Behav Neurol, Rome, Italy..
    Lopez, Oscar L.
    Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA.;Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA..
    Frosch, Matthew P.
    Massachusetts Gen Hosp, CS Kubik Lab Neuropathol, Charlestown, MA USA..
    Sacchinelli, Eleonora
    IRCCS, Santa Lucia Fdn, Expt Neuropsychiat Lab, Dept Clin & Behav Neurol, Rome, Italy..
    Ghetti, Bernardino
    Indiana Univ, Dept Pathol & Lab Med, Indianapolis, IN 46204 USA..
    Yang, Qiong
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA..
    Huebinger, Ryan M.
    Univ Texas Southwestern Med Ctr Dallas, Dept Surg, Dallas, TX USA..
    Jessen, Frank
    German Ctr Neurodegenerat Dis DZNE, Bonn, Germany.;Univ Bonn, Dept Psychiat & Psychotherapy, Bonn, Germany.;Univ Cologne, Dept Psychiat & Psychotherapy, Cologne, Germany..
    Li, Shuo
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA..
    Kamboh, M. Ilyas
    Univ Pittsburgh, Alzheimers Dis Res Ctr, Pittsburgh, PA USA.;Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA USA..
    Morris, John
    Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA.;Washington Univ, Sch Med, Hope Ctr Program Prot Aggregat & Neurodegenerat, St Louis, MO USA..
    Sotolongo-Grau, Oscar
    Inst Catala Neurociencies Aplicades, Res Ctr, Barcelona, Spain.;Inst Catala Neurociencies Aplicades, Memory Clin Fundacio ACE, Barcelona, Spain..
    Katz, Mindy J.
    Albert Einstein Coll Med, Dept Neurol, Bronx, NY 10467 USA..
    Corcoran, Chris
    Utah State Univ, Dept Math & Stat, Logan, UT 84322 USA..
    Dunstan, Melanie
    Cardiff Univ, MRC Ctr Neuropsychiat Genet & Gen, Inst Psychol Med & Clin Neurosci, Cardiff, S Glam, Wales..
    Braddel, Amy
    Cardiff Univ, MRC Ctr Neuropsychiat Genet & Gen, Inst Psychol Med & Clin Neurosci, Cardiff, S Glam, Wales..
    Thomas, Charlene
    Cardiff Univ, MRC Ctr Neuropsychiat Genet & Gen, Inst Psychol Med & Clin Neurosci, Cardiff, S Glam, Wales..
    Meggy, Alun
    Cardiff Univ, MRC Ctr Neuropsychiat Genet & Gen, Inst Psychol Med & Clin Neurosci, Cardiff, S Glam, Wales..
    Marshall, Rachel
    Cardiff Univ, MRC Ctr Neuropsychiat Genet & Gen, Inst Psychol Med & Clin Neurosci, Cardiff, S Glam, Wales..
    Gerrish, Amy
    Cardiff Univ, MRC Ctr Neuropsychiat Genet & Gen, Inst Psychol Med & Clin Neurosci, Cardiff, S Glam, Wales..
    Chapman, Jade
    Cardiff Univ, MRC Ctr Neuropsychiat Genet & Gen, Inst Psychol Med & Clin Neurosci, Cardiff, S Glam, Wales..
    Aguilar, Miquel
    Fundacio Recerca Biomed & Social Mutua Terrassa, Barcelona, Spain.;Hosp Univ Mutua Terrassa, Dept Neurol, Memory Unit, Barcelona, Spain..
    Taylor, Sarah
    Cardiff Univ, MRC Ctr Neuropsychiat Genet & Gen, Inst Psychol Med & Clin Neurosci, Cardiff, S Glam, Wales..
    Hill, Matt
    Cardiff Univ, MRC Ctr Neuropsychiat Genet & Gen, Inst Psychol Med & Clin Neurosci, Cardiff, S Glam, Wales..
    Diez Fairen, Mnica
    Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain.;Fundacio Recerca Biomed & Social Mutua Terrassa, Barcelona, Spain..
    Hodges, Angela
    Kings Coll London, Inst Psychiat Psychol & Neurosci, Dept Old Age Psychiat, London, England..
    Vellas, Bruno
    Univ Toulouse, INSERM, U558, Toulouse, France..
    Soininen, Hilkka
    Kuopio Univ Hosp, Dept Neurol, Kuopio, Finland..
    Kloszewska, Iwona
    Med Univ Lodz, Elderly & Psychiat Disorders Dept, Lodz, Poland..
    Daniilidou, Makrina
    Univ Leicester, Dept Hlth Sci, Psychiat Elderly, Leicester, Leics, England..
    Uphill, James
    UCL Inst Neurol, MRC Prion Unit, Dept Neurodegenerat Dis, London, England..
    Patel, Yogen
    Kings Coll London, Inst Psychiat Psychol & Neurosci, Dept Basic & Clin Neurosci, London, England..
    Hughes, Joseph T.
    Kings Coll London, Inst Psychiat Psychol & Neurosci, Dept Basic & Clin Neurosci, London, England..
    Lord, Jenny
    Univ Nottingham, Queens Med Ctr, Inst Genet, Nottingham, England..
    Turton, James
    Univ Nottingham, Queens Med Ctr, Inst Genet, Nottingham, England..
    Hartmann, Annette M.
    Martin Luther Univ Halle Wittenberg, Dept Psychiat, Halle, Germany..
    Cecchetti, Roberta
    Univ Perugia, Dept Med, Sect Gerontol & Geriatr, Perugia, Italy..
    Fenoglio, Chiara
    Univ Milan, IRCCS Osped Policlin, Fdn Ca Granda, Dept Pathophysiol & Transplantat, Milan, Italy..
    Serpente, Maria
    Univ Milan, IRCCS Osped Policlin, Fdn Ca Granda, Dept Pathophysiol & Transplantat, Milan, Italy..
    Arcaro, Marina
    Univ Milan, IRCCS Osped Policlin, Fdn Ca Granda, Dept Pathophysiol & Transplantat, Milan, Italy..
    Caltagirone, Carlo
    IRCCS, Santa Lucia Fdn, Expt Neuropsychiat Lab, Dept Clin & Behav Neurol, Rome, Italy..
    Orfei, Maria Donata
    IRCCS, Santa Lucia Fdn, Expt Neuropsychiat Lab, Dept Clin & Behav Neurol, Rome, Italy..
    Ciaramella, Antonio
    IRCCS, Santa Lucia Fdn, Expt Neuropsychiat Lab, Dept Clin & Behav Neurol, Rome, Italy..
    Pichler, Sabrina
    Univ Hosp, Dept Psychiat & Psychotherapy, Saarland, Germany..
    Mayhaus, Manuel
    Univ Hosp, Dept Psychiat & Psychotherapy, Saarland, Germany..
    Gu, Wei
    Univ Hosp, Dept Psychiat & Psychotherapy, Saarland, Germany..
    Lleo, Alberto
    Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain.;Autonomous Univ Barcelona, Memory Unit, Dept Neurol, Barcelona, Spain.;Autonomous Univ Barcelona, Hosp Santa Creu & St Pau, St Pau Biomed Res Inst, Barcelona, Spain..
    Forte, Juan
    Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain.;Autonomous Univ Barcelona, Memory Unit, Dept Neurol, Barcelona, Spain.;Autonomous Univ Barcelona, Hosp Santa Creu & St Pau, St Pau Biomed Res Inst, Barcelona, Spain..
    Blesa, Rafael
    Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain.;Autonomous Univ Barcelona, Memory Unit, Dept Neurol, Barcelona, Spain.;Autonomous Univ Barcelona, Hosp Santa Creu & St Pau, St Pau Biomed Res Inst, Barcelona, Spain..
    Barber, Imelda S.
    Univ Nottingham, Sch Life Sci, Nottingham, England.;Univ Nottingham, Sch Med, Nottingham, England..
    Brookes, Keeley
    Univ Nottingham, Sch Life Sci, Nottingham, England.;Univ Nottingham, Sch Med, Nottingham, England..
    Cupidi, Chiara
    ASP Catanzaro, Reg Neurogenet Ctr CRN, Lamezia Terme, Italy..
    Maletta, Raffaele Giovanni
    ASP Catanzaro, Reg Neurogenet Ctr CRN, Lamezia Terme, Italy..
    Carrell, David
    Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA..
    Sorbi, Sandro
    Univ Florence, NEUROFARBA, Dept Neurosci Psychol Drug Res & Child Hlth, Florence, Italy.;IRCCS Don Carlo Gnocchi, Florence, Italy..
    Moebus, Susanne
    Univ Duisburg Essen, Univ Hosp Essen, Inst Med Informat Biometry & Epidemiol, Essen, Germany..
    Urbano, Maria
    IRCCS Casa Sollievo Sofferenza, Geriatr Unit, San Giovanni Rotondo, Italy.;IRCCS Casa Sollievo Sofferenza, Dept Med Sci, Gerontol Geriatr Res Lab, San Giovanni Rotondo, Italy..
    Pilotto, Alberto
    IRCCS Casa Sollievo Sofferenza, Geriatr Unit, San Giovanni Rotondo, Italy.;IRCCS Casa Sollievo Sofferenza, Dept Med Sci, Gerontol Geriatr Res Lab, San Giovanni Rotondo, Italy..
    Kornhuber, Johannes
    Univ Erlangen Nurnberg, Dept Psychiat & Psychotherapy, Erlangen, Germany..
    Bosco, Paolo
    Assoc Oasi Maria Santissima Srl, IRCCS, Troina, Italy..
    Todd, Stephen
    Queens Univ, Sch Med Dent & Biomed Sci, Ctr Publ Hlth, Belfast, Antrim, North Ireland..
    Craig, David
    Queens Univ, Sch Med Dent & Biomed Sci, Ctr Publ Hlth, Belfast, Antrim, North Ireland..
    Johnston, Janet
    Queens Univ, Sch Med Dent & Biomed Sci, Ctr Publ Hlth, Belfast, Antrim, North Ireland..
    Gill, Michael
    St James Hosp, Mercers Inst Res Aging, Dublin, Ireland.;Trinity Coll Dublin, Dublin, Ireland..
    Lawlor, Brian
    St James Hosp, Mercers Inst Res Aging, Dublin, Ireland.;Trinity Coll Dublin, Dublin, Ireland..
    Lynch, Aoibhinn
    St James Hosp, Mercers Inst Res Aging, Dublin, Ireland.;Trinity Coll Dublin, Dublin, Ireland..
    Fox, Nick C.
    UCL, Inst Neurol, Dept Mol Neurosci, London, England..
    Hardy, John
    UCL, Inst Neurol, Dept Mol Neurosci, London, England..
    Albin, Roger L.
    Univ Michigan, Dept Neurol, Ann Arbor, MI USA.;VAAAHS, GRECC, Ann Arbor, MI USA.;Michigan Alzheimer Dis Ctr, Ann Arbor, MI USA..
    Apostolova, Liana G.
    Indiana Univ Sch Med, Indiana Alzheimers Dis Ctr, Indianapolis, IN 46202 USA.;Indiana Univ, Dept Med & Mol Genet, Indianapolis, IN USA.;Indiana Univ, Dept Neurol, Indianapolis, IN USA.;Indiana Univ, Dept Radiol & Imaging Sci, Indianapolis, IN 46204 USA..
    Arnold, Steven E.
    Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA..
    Asthana, Sanjay
    Univ Wisconsin, GRECC, Madison, WI USA.;Univ Wisconsin, Dept Med, Madison, WI USA.;Wisconsin Alzheimers Dis Res Ctr, Madison, WI USA..
    Atwood, Craig S.
    Univ Wisconsin, GRECC, Madison, WI USA.;Univ Wisconsin, Dept Med, Madison, WI USA.;Wisconsin Alzheimers Dis Res Ctr, Madison, WI USA..
    Baldwin, Clinton T.
    Boston Univ, Dept Med, Genet Program, Boston, MA USA..
    Barnes, Lisa L.
    Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA.;Rush Univ, Med Ctr, Dept Behav Sci, Chicago, IL 60612 USA.;Rush Univ, Rush Alzheimers Dis Ctr, Med Ctr, Chicago, IL 60612 USA..
    Barral, Sandra
    Columbia Univ, Dept Neurol, Taub Inst Alzheimers Dis & Aging Brain, New York, NY USA.;Columbia Univ, Gertrude H Sergievsky Ctr, New York, NY USA.;Columbia Univ, Dept Neurol, New York, NY USA..
    Beach, Thomas G.
    Banner Sun Hlth Res Inst, Civin Lab Neuropathol, Phoenix, AZ USA..
    Becker, James T.
    Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA.;Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA.;Univ Pittsburgh, Sch Med, Dept Psychol, Pittsburgh, PA 15261 USA..
    Bigio, Eileen H.
    Northwestern Univ, Feinberg Sch Med, Dept Pathol, Chicago, IL 60611 USA.;Northwestern Univ, Feinberg Sch Med, Cognit Neurol & Alzheimers Dis Ctr, Chicago, IL 60611 USA..
    Bird, Thomas D.
    Univ Washington, Dept Neurol, Seattle, WA 98195 USA.;VA Puget Sound Hlth Care Syst GRECC, Seattle, WA USA..
    Boeve, Bradley F.
    Mayo Clin, Dept Neurol, Rochester, MN USA..
    Bowen, James D.
    Swedish Med Ctr, Seattle, WA USA..
    Boxer, Adam
    Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA..
    Burke, James R.
    Duke Univ, Dept Med, Durham, NC USA..
    Burns, Jeffrey M.
    Univ Kansas, Med Ctr, Alzheimers Dis Ctr, Kansas City, KS 66103 USA..
    Buxbaum, Joseph D.
    Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY USA.;Mt Sinai Sch Med, Dept Neurosci, New York, NY USA.;Mt Sinai Sch Med, Dept Psychiat, New York, NY USA..
    Cairns, Nigel J.
    Washington Univ, Dept Pathol & Immunol, St Louis, MO USA..
    Cao, Chuanhai
    Univ S Florida, USF Hlth Byrd Alzheimers Inst, Tampa, FL USA..
    Carlson, Chris S.
    Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA..
    Carlsson, Cynthia M.
    Univ Wisconsin, Dept Med, Madison, WI USA.;Wisconsin Alzheimers Dis Res Ctr, Madison, WI USA..
    Carney, Regina M.
    Univ Miami, Miller Sch Med, Dept Psychiat & Behav Sci, Miami, FL 33136 USA..
    Carrasquillo, Minerva M.
    Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA..
    Carroll, Steven L.
    Med Univ South Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA..
    Diaz, Carolina Ceballos
    Univ Florida, Dept Neurosci, Ctr Translat Res Neurodegenerat Dis, Gainesville, FL 32610 USA..
    Chui, Helena C.
    Univ Southern Calif, Dept Neurol, Los Angeles, CA USA..
    Clark, David G.
    Med Univ South Carolina, Dept Neurol, Charleston, SC 29425 USA.;Ralph H Johnson VA Med Ctr, Dept Neurol, Charleston, SC USA..
    Cribbs, David H.
    Univ Calif Irvine, Dept Neurol, Irvine, CA 92717 USA..
    Crocco, Elizabeth A.
    Univ Miami, Miller Sch Med, Dept Psychiat & Behav Sci, Miami, FL 33136 USA..
    DeCarli, Charles
    Univ Calif Davis, Dept Neurol, Sacramento, CA 95817 USA..
    Dick, Malcolm
    Univ Calif Irvine, Inst Memory Impairments & Neurol Disorder, Irvine, CA USA..
    Duara, Ranjan
    Mt Sinai Med Ctr, Wien Ctr Alzheimers Dis & Memory Disorders, Miami Beach, FL 33140 USA..
    Evans, Denis A.
    Rush Univ, Med Ctr, Dept Internal Med, Rush Inst Hlth Aging, Chicago, IL 60612 USA..
    Faber, Kelley M.
    Indiana Univ, Dept Med & Mol Genet, Indianapolis, IN USA..
    Fallon, Kenneth B.
    Univ Alabama Birmingham, Dept Pathol, Birmingham, AL USA..
    Fardo, David W.
    Univ Kentucky, Sanders Brown Ctr Aging, Dept Biostat, Lexington, KY 40536 USA..
    Farlow, Martin R.
    Indiana Univ, Dept Neurol, Indianapolis, IN USA..
    Ferris, Steven
    NYU, Dept Psychiat, 550 1St Ave, New York, NY 10016 USA..
    Foroud, Tatiana M.
    Indiana Univ, Dept Med & Mol Genet, Indianapolis, IN USA..
    Galasko, Douglas R.
    Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA..
    Gearing, Marla
    Emory Univ, Dept Pathol & Lab Med, Atlanta, GA 30322 USA.;Emory Univ, Emory Alzheimers Dis Ctr, Atlanta, GA 30322 USA..
    Geschwind, Daniel H.
    Univ Calif Los Angeles, Neurogenet Program, Los Angeles, CA USA..
    Gilbert, John R.
    Graff-Radford, Neill R.
    Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA.;Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA..
    Green, Robert C.
    Brigham & Womens Hosp, Dept Med, Div Genet, 75 Francis St, Boston, MA 02115 USA.;Brigham & Womens Hosp, Partners Ctr Personalized Genet Med, 75 Francis St, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA USA..
    Growdon, John H.
    Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA..
    Hamilton, Ronald L.
    Univ Pittsburgh, Dept Pathol Neuropathol, Pittsburgh, PA USA..
    Harrell, Lindy E.
    Univ Alabama Birmingham, Dept Neurol, Birmingham, AL USA..
    Honig, Lawrence S.
    Columbia Univ, Dept Neurol, Taub Inst Alzheimers Dis & Aging Brain, New York, NY USA..
    Huentelman, Matthew J.
    Translat Genom Res Inst, Neurogenom Div, Phoenix, AZ USA..
    Hulette, Christine M.
    Duke Univ, Dept Pathol, Durham, NC 27706 USA..
    Hyman, Bradley T.
    Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA..
    Jarvik, Gail P.
    Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.;Univ Washington, Dept Med Med Genet, Seattle, WA 98195 USA..
    Abner, Erin
    Univ Kentucky, Sanders Brown Ctr Aging, Coll Publ Hlth, Dept Epidemiol, Lexington, KY 40536 USA..
    Jin, Lee-Way
    Univ Calif Davis, Dept Pathol & Lab Med, Sacramento, CA 95817 USA..
    Jun, Gyungah
    Boston Univ, Dept Med, Genet Program, Boston, MA USA.;Boston Univ, Dept Biostat, Boston, MA 02215 USA.;Boston Univ, Dept Ophthalmol, Boston, MA USA..
    Karydas, Anna
    Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA..
    Kaye, Jeffrey A.
    Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA.;Portland VA Med Ctr, Dept Neurol, Portland, OR USA..
    Kim, Ronald
    Univ Calif Irvine, Dept Pathol & Lab Med, Irvine, CA USA..
    Kowall, Neil W.
    Boston Univ, Dept Neurol, Boston, MA USA.;Boston Univ, Dept Pathol, Boston, MA USA..
    Kramer, Joel H.
    Univ Calif San Francisco, Dept Neuropsychol, San Francisco, CA 94143 USA..
    LaFerla, Frank M.
    Univ Calif Irvine, Dept Neurobiol & Behav, Irvine, CA USA..
    Lah, James J.
    Emory Univ, Dept Neurol, Atlanta, GA USA..
    Leverenz, James B.
    Cleveland Clin, Cleveland Clin Lou Ruvo Ctr Brain Hlth, Cleveland, OH 44106 USA..
    Levey, Allan I.
    Emory Univ, Dept Neurol, Atlanta, GA USA..
    Li, Ge
    Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA.;VA Puget Sound Hlth Care Syst GRECC, Seattle, WA USA..
    Lieberman, Andrew P.
    Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA..
    Lunetta, Kathryn L.
    Boston Univ, Dept Biostat, Boston, MA 02215 USA..
    Lyketsos, Constantine G.
    Johns Hopkins Univ, Dept Psychiat, Baltimore, MD USA..
    Marson, Daniel C.
    Univ Alabama Birmingham, Dept Neurol, Birmingham, AL USA..
    Martiniuk, Frank
    NYU, Dept Med Pulm, New York, NY USA..
    Mash, Deborah C.
    Univ Miami, Dept Neurol, Miami, FL USA..
    Masliah, Eliezer
    Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA.;Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA..
    McCormick, Wayne C.
    Univ Washington, Dept Med, Seattle, WA USA..
    McCurry, Susan M.
    Univ Washington, Sch Nursing, Northwest Res Grp Aging, Seattle, WA 98195 USA..
    McDavid, Andrew N.
    Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA..
    Mckee, Ann C.
    Boston Univ, Dept Neurol, Boston, MA USA.;Boston Univ, Dept Pathol, Boston, MA USA..
    Mesulam, Marsel
    Northwestern Univ, Feinberg Sch Med, Cognit Neurol & Alzheimers Dis Ctr, Chicago, IL 60611 USA.;Northwestern Univ, Feinberg Sch Med, Dept Neurol, Chicago, IL USA..
    Miller, Bruce L.
    Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA..
    Miller, Carol A.
    Univ Southern Calif, Dept Pathol, Los Angeles, CA 90089 USA..
    Miller, Joshua W.
    Univ Calif Davis, Dept Pathol & Lab Med, Sacramento, CA 95817 USA..
    Morris, John C.
    Washington Univ, Dept Pathol & Immunol, St Louis, MO USA.;Washington Univ, Dept Neurol, St Louis, MO USA..
    Murrell, Jill R.
    Indiana Univ, Dept Pathol & Lab Med, Indianapolis, IN 46204 USA.;Indiana Univ, Dept Med & Mol Genet, Indianapolis, IN USA..
    Myers, Amanda J.
    Univ Miami, Miller Sch Med, Dept Psychiat & Behav Sci, Miami, FL 33136 USA..
    O'Bryant, Sid
    Univ North Texas, Hlth Sci Ctr, Div Geriatr, Internal Med, Ft Worth, TX USA..
    Pankratz, Vernon S.
    Univ Calif Davis, Dept Neurol, Sacramento, CA 95817 USA.;Univ New Mexico, Hlth Sci Ctr, Dept Internal Med, Albuquerque, NM 87131 USA..
    Parisi, Joseph E.
    Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA..
    Paulson, Henry L.
    Univ Michigan, Dept Neurol, Ann Arbor, MI USA.;Michigan Alzheimer Dis Ctr, Ann Arbor, MI USA..
    Perry, William
    Peskind, Elaine
    Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA..
    Pierce, Aimee
    Univ Calif Irvine, Dept Neurol, Irvine, CA 92717 USA..
    Poon, Wayne W.
    Univ Calif Irvine, Inst Memory Impairments & Neurol Disorder, Irvine, CA USA..
    Potter, Huntington
    Univ Colorado, Sch Med, Dept Neurol, Aurora, CO USA..
    Quinn, Joseph F.
    Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA.;Portland VA Med Ctr, Dept Neurol, Portland, OR USA..
    Raj, Ashok
    Univ S Florida, USF Hlth Byrd Alzheimers Inst, Tampa, FL USA..
    Raskind, Murray
    Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA..
    Reisberg, Barry
    NYU, Dept Psychiat, 550 1St Ave, New York, NY 10016 USA.;NYU, Alzheimers Dis Ctr, New York, NY USA..
    Reitz, Christiane
    Columbia Univ, Gertrude H Sergievsky Ctr, New York, NY USA.;Columbia Univ, Dept Neurol, New York, NY USA.;Columbia Univ, Dept Epidemiol, New York, NY USA..
    Ringman, John M.
    Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA..
    Roberson, Erik D.
    Univ Alabama Birmingham, Dept Neurol, Birmingham, AL USA..
    Rogaeva, Ekaterina
    Univ Toronto, Tanz Ctr Res Neurodegenerat Dis, Toronto, ON, Canada..
    Rosen, Howard J.
    Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA..
    Rosenberg, Roger N.
    Univ Texas Southwestern Med Ctr Dallas, Dept Neurol, Dallas, TX USA..
    Sager, Mark A.
    Univ Wisconsin, Dept Med, Madison, WI USA..
    Saykin, Andrew J.
    Indiana Univ, Dept Med & Mol Genet, Indianapolis, IN USA.;Indiana Univ, Dept Radiol & Imaging Sci, Indianapolis, IN 46204 USA..
    Schneider, Julie A.
    Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA.;Rush Univ, Rush Alzheimers Dis Ctr, Med Ctr, Chicago, IL 60612 USA.;Rush Univ, Med Ctr, Dept Pathol Neuropathol, Chicago, IL 60612 USA..
    Schneider, Lon S.
    Univ Southern Calif, Dept Neurol, Los Angeles, CA USA.;Univ Southern Calif, Dept Psychiat, Los Angeles, CA USA..
    Seeley, William W.
    Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA..
    Smith, Amanda G.
    Univ S Florida, USF Hlth Byrd Alzheimers Inst, Tampa, FL USA..
    Sonnen, Joshua A.
    Univ Washington, Dept Pathol, Seattle, WA 98195 USA..
    Spina, Salvatore
    Indiana Univ, Dept Pathol & Lab Med, Indianapolis, IN 46204 USA..
    Stern, Robert A.
    Boston Univ, Dept Neurol, Boston, MA USA..
    Swerdlow, Russell H.
    Univ Kansas, Med Ctr, Alzheimers Dis Ctr, Kansas City, KS 66103 USA..
    Tanzi, Rudolph E.
    Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA..
    Thornton-Wells, Tricia A.
    Novartis Inst Biomed Res, Translat Med, Cambridge, MA USA..
    Trojanowski, John Q.
    Univ Penn, Dept Pathol & Lab Med, Perelman Sch Med, Philadelphia, PA USA..
    Troncoso, Juan C.
    Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA..
    Van Deerlin, Vivianna M.
    Univ Penn, Dept Pathol & Lab Med, Perelman Sch Med, Philadelphia, PA USA..
    Van Eldik, Linda J.
    Univ Kentucky, Sanders Brown Ctr Aging, Dept Anat & Neurobiol, Lexington, KY 40536 USA..
    Vinters, Harry V.
    Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA.;Univ Calif Los Angeles, Dept Pathol & Lab Med, Los Angeles, CA USA..
    Vonsattel, Jean Paul
    Columbia Univ, Dept Pathol, Taub Inst Alzheimers Dis & Aging Brain, New York, NY USA..
    Weintraub, Sandra
    Northwestern Univ, Feinberg Sch Med, Cognit Neurol & Alzheimers Dis Ctr, Chicago, IL 60611 USA.;Northwestern Univ, Dept Psychiat, Feinberg Sch Med, Chicago, IL USA..
    Welsh-Bohmer, Kathleen A.
    Duke Univ, Dept Med, Durham, NC USA.;Duke Univ, Dept Psychiat & Behav Sci, Durham, NC USA..
    Wilhelmsen, Kirk C.
    Univ North Carolina Chapel Hill, Dept Genet, Chapel Hill, NC USA..
    Williamson, Jennifer
    Columbia Univ, Dept Neurol, Taub Inst Alzheimers Dis & Aging Brain, New York, NY USA..
    Woltjer, Randall L.
    Emory Univ, Dept Neurol, Atlanta, GA USA..
    Wright, Clinton B.
    Oregon Hlth & Sci Univ, Dept Pathol, Portland, OR 97201 USA..
    Yu, Chang-En
    Univ Miami, Miller Sch Med, Dept Neurol, Evelyn F McKnight Brain Inst, Miami, FL 33136 USA..
    Yu, Lei
    Univ Washington, Dept Med, Seattle, WA USA..
    Garzia, Fabienne
    Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA.;Rush Univ, Rush Alzheimers Dis Ctr, Med Ctr, Chicago, IL 60612 USA..
    Golamaully, Feroze
    Ctr Natl Genotypage, Inst Genom, CEA, Evry, France..
    Septier, Gislain
    Ctr Natl Genotypage, Inst Genom, CEA, Evry, France..
    Engelborghs, Sebastien
    Univ Antwerp, Inst Born Bunge, Antwerp, Belgium.;Hosp Network Antwerp, Dept Neurol, Antwerp, Belgium.;Hosp Network Antwerp, Memory Clin, Antwerp, Belgium..
    Vandenberghe, Rik
    Hosp Network Antwerp, Dept Neurol, Antwerp, Belgium.;Hosp Network Antwerp, Memory Clin, Antwerp, Belgium.;Univ Leuven, Dept Neurol, Lab Cognit Neurol, Leuven, Belgium..
    De Deyn, Peter P.
    Univ Antwerp, Inst Born Bunge, Antwerp, Belgium.;Hosp Network Antwerp, Dept Neurol, Antwerp, Belgium.;Hosp Network Antwerp, Memory Clin, Antwerp, Belgium..
    Munoz Fernadez, Carmen
    Hosp Univ Doctor Negrin, Dept Immunol, Las Palmas Gran Canaria, Spain..
    Aladro Benito, Yoland
    Hosp Univ Doctor Negrin, Dept Immunol, Las Palmas Gran Canaria, Spain..
    Thonberg, Hakan
    Karolinska Univ, Hosp Huddinge, Genet Unit, Dept Geriatr Med, Stockholm, Sweden.;Karolinska Inst, KIADRC, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden..
    Forsell, Charlotte
    Karolinska Univ, Hosp Huddinge, Genet Unit, Dept Geriatr Med, Stockholm, Sweden.;Karolinska Inst, KIADRC, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden..
    Lilius, Lena
    Karolinska Univ, Hosp Huddinge, Genet Unit, Dept Geriatr Med, Stockholm, Sweden.;Karolinska Inst, KIADRC, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden..
    Kinhult-Stahlbom, Anne
    Karolinska Univ, Hosp Huddinge, Genet Unit, Dept Geriatr Med, Stockholm, Sweden.;Karolinska Inst, KIADRC, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden..
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Brundin, RoseMarie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Concari, Letizia
    Univ Parma, Dept Neurosci, Parma, Italy.;AUSL, Ctr Cognit Disorders, Parma, Italy..
    Helisalmi, Seppo
    Kuopio Univ Hosp, Dept Neurol, Kuopio, Finland.;Univ Eastern Finland, Inst Clin Med Neurol, Kuopio, Finland..
    Koivisto, Anne Maria
    Kuopio Univ Hosp, Dept Neurol, Kuopio, Finland.;Univ Eastern Finland, Inst Clin Med Neurol, Kuopio, Finland..
    Haapasalo, Annakaisa
    Kuopio Univ Hosp, Dept Neurol, Kuopio, Finland.;Univ Eastern Finland, Inst Clin Med Neurol, Kuopio, Finland..
    Dermecourt, Vincent
    CHU Lille, Memory Ctr Lille, Ctr Memoire Ressources & Rech, Lille, France..
    Fievet, Nathalie
    Risk Factors & Mol Determinants Aging Related Dis, RID AGE, U1167, INSERM, Lille, France.;Inst Pasteur, Lille, France.;Univ Lille, Excellence Lab LabEx DISTALZ, U1167, Lille, France.;Univ Paris 05, Hop Broca, AP HP, Geriatr Dept,EA 4468, Paris, France..
    Hanon, Olivier
    Boston Univ, Sch Med, Boston, MA 02118 USA.;Univ Paris 05, Hop Broca, AP HP, Geriatr Dept,EA 4468, Paris, France..
    Dufouil, Carole
    Univ Bordeaux, Neuroepidemiol, Bordeaux, France.;INSERM, UMR 897, Neuroepidemiol, Bordeaux, France..
    Brice, Alexis
    Univ Paris 06, UPMC, Sorbonne Univ,CNRS,UMR 7225,UMRS 1127, Inst Cerveau & Moelle Epinisre,INSERM,U1127, Paris, France.;Hop La Pitie Salpetriere, AP HP, Dept Genet, Paris, France..
    Ritchie, Karen
    La Colombiere Hosp, INSERM, U1061, Montpellier, France..
    Dubois, Bruno
    Hop La Pitie Salpetriere, AP HP, Dept Neurol, Inst Memoire & Malad Alzheimer IM2A, Paris, France.;Inst Cerveau & Moelle Epiniere ICM, Inst Neurosci Translationnelles Paris IHU A ICM, Paris, France.;Inst Cerveau & Moelle Epiniere ICM, CNRS, UMRS 975, INSERM, Paris, France.;Univ Paris 06, Hop La Pitie Salpetriere, AP HP, Sorbonne Univ, Paris, France..
    Himali, Jayanadra J.
    Keene, C. Dirk
    Univ Washington, Dept Pathol, Seattle, WA 98195 USA..
    Tschanz, Joann
    Utah State Univ, Dept Math & Stat, Logan, UT 84322 USA..
    Fitzpatrick, Annette L.
    Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.;Univ Washington, Dept Family Med, Seattle, WA 98195 USA..
    Kukull, Walter A.
    Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA..
    Norton, Maria
    Utah State Univ, Dept Math & Stat, Logan, UT 84322 USA..
    Aspelund, Thor
    Iceland Heart Assoc, Kopavogur, Iceland. Univ Miami, John P Hussman Inst Human Gen, Miami, FL USA.;Univ Iceland, Ctr Publ Hlth, Reykjavik, Iceland..
    Larson, Eric B.
    Univ Washington, Dept Med, Seattle, WA USA.;Grp Hlth, Res Inst, Seattle, WA USA..
    Munger, Ron
    Utah State Univ, Dept Math & Stat, Logan, UT 84322 USA..
    Rotter, Jerome I.
    Harbor UCLA Med Ctr, Los Angeles BioMed Res Inst, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA..
    Lipton, Richard B.
    Albert Einstein Coll Med, Dept Neurol, Bronx, NY 10467 USA..
    Bullido, Maria J.
    Inst Invest Sanitaria Hosp la Paz IdiPAZ, Madrid, Spain.;Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain.;UAM, CSIC, Ctr Biol Mol Severo Ochoa, Madrid, Spain..
    Hofman, Albert
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands..
    Montine, Thomas J.
    Univ Washington, Dept Pathol, Seattle, WA 98195 USA..
    Coto, Eliecer
    Univ Cent Asturias, Mol Genet Lab Hosp, Oviedo, Spain..
    Boerwinkle, Eric
    Univ Texas Hlth Sci Ctr Houston, Human Genet Ctr, Sch Publ Hlth, Houston, TX USA.;Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA..
    Petersen, Ronald C.
    Mayo Clin, Dept Neurol, Rochester, MN USA..
    Alvarez, Victoria
    Univ Cent Asturias, Mol Genet Lab Hosp, Oviedo, Spain..
    Rivadeneira, Fernando
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.;Erasmus Univ, Med Ctr, Dept Internal Med, Rotterdam, Netherlands.;Netherlands Consortium Hlth Aging & Natl Genom In, Leiden, Netherlands..
    Reiman, Eric M.
    Translat Genom Res Inst, Neurogenom Div, Phoenix, AZ USA.;Arizona Alzheimers Consortium, Phoenix, AZ USA.;Banner Alzheimers Inst, Phoenix, AZ USA.;Univ Arizona, Dept Psychiat, Phoenix, AZ USA..
    Gallo, Maura
    ASP Catanzaro, Reg Neurogenet Ctr CRN, Lamezia Terme, Italy..
    O'Donnell, Christopher J.
    Framingham Heart Dis Epidemiol Study, Framingham, MA USA..
    Reisch, Joan S.
    Univ Texas Southwestern Med Ctr Dallas, Dept Clin Sci, Dallas, TX 75390 USA..
    Bruni, Amalia Cecilia
    ASP Catanzaro, Reg Neurogenet Ctr CRN, Lamezia Terme, Italy..
    Royall, Donald R.
    Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA.;Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA.;Univ Texas Hlth Sci Ctr San Antonio, Dept Family & Community Med, San Antonio, TX 78229 USA.;Univ Texas Hlth Sci Ctr San Antonio, South Texas Vet Hlth Adm, GRECC, San Antonio, TX 78229 USA..
    Dichgans, Martin
    Klinikum Univ Munchen, Inst Stroke & Dementia Res, Munich, Germany.;German Ctr Neurodegenerat Dis DZNE, Munich, Germany..
    Sano, Mary
    Mt Sinai Sch Med, Dept Psychiat, New York, NY USA..
    Galimberti, Daniela
    Univ Milan, IRCCS Osped Policlin, Fdn Ca Granda, Dept Pathophysiol & Transplantat, Milan, Italy..
    St George-Hyslop, Peter
    Univ Toronto, Tanz Ctr Res Neurodegenerat Dis, Toronto, ON, Canada.;Univ Cambridge, Cambridge Inst Med Res, Cambridge, England..
    Scarpini, Elio
    Univ Milan, IRCCS Osped Policlin, Fdn Ca Granda, Dept Pathophysiol & Transplantat, Milan, Italy..
    Tsuang, Debby W.
    Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA.;Univ Wisconsin, Dept Med, Madison, WI USA.;VA Puget Sound Hlth Care Syst GRECC, Seattle, WA USA..
    Mancuso, Michelangelo
    Univ Pisa, Neurol Inst, Dept Expt & Clin Med, Pisa, Italy..
    Bonuccelli, Ubaldo
    Univ Pisa, Neurol Inst, Dept Expt & Clin Med, Pisa, Italy..
    Winslow, Ashley R.
    Pfizer Worldwide Res & Dev, PharmaTherapeut Clin Res, Cambridge, MA USA..
    Daniele, Antonio
    Univ Cattolica Sacro Cuore, Inst Neurol, Rome, Italy..
    Wu, Chuang-Kuo
    Texas Tech Univ, Hlth Sci Ctr, Dept Neurol, Lubbock, TX 79430 USA.;Texas Tech Univ, Hlth Sci Ctr, Dept Pharmacol & Neurosci, Lubbock, TX 79430 USA..
    Peters, Oliver
    Charite, Dept Psychiat, Berlin, Germany..
    Nacmias, Benedetta
    Univ Florence, NEUROFARBA, Dept Neurosci Psychol Drug Res & Child Hlth, Florence, Italy.;IRCCS Don Carlo Gnocchi, Florence, Italy..
    Riemenschneider, Matthias
    Univ Hosp, Dept Psychiat & Psychotherapy, Saarland, Germany..
    Heun, Reinhard
    Univ Bonn, Dept Psychiat & Psychotherapy, Bonn, Germany..
    Brayne, Carol
    Univ Cambridge, Inst Publ Hlth, Cambridge, England..
    Rubinsztein, David C.
    Univ Cambridge, Cambridge Inst Med Res, Cambridge, England..
    Bras, Jose
    UCL, Inst Neurol, Dept Mol Neurosci, London, England.;Univ Aveiro, Inst Biomed iBiMED, Dept Med Sci, Aveiro, Portugal..
    Guerreiro, Rita
    UCL, Inst Neurol, Dept Mol Neurosci, London, England.;Univ Aveiro, Inst Biomed iBiMED, Dept Med Sci, Aveiro, Portugal..
    Al-Chalabi, Ammar
    Kings Coll London, Inst Psychiat Psychol & Neurosci, London, England..
    Shaw, Christopher E.
    Kings Coll London, Inst Psychiat Psychol & Neurosci, London, England..
    Collinge, John
    UCL Inst Neurol, MRC Prion Unit, Dept Neurodegenerat Dis, London, England..
    Mann, David
    Univ Manchester, Inst Brain Behav & Mental Hlth, Clin & Cognit Neurosci Res Grp, Manchester, Lancs, England..
    Tsolaki, Magda
    Aristotle Univ Thessaloniki, Med Sch, Dept Neurol 3, Thessaloniki, Greece..
    Clarimon, Jordi
    Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain.;Autonomous Univ Barcelona, Memory Unit, Dept Neurol, Barcelona, Spain.;Autonomous Univ Barcelona, Hosp Santa Creu & St Pau, St Pau Biomed Res Inst, Barcelona, Spain..
    Sussams, Rebecca
    Univ Southampton, Sch Med, Div Clin Neurosci, Southampton, Hants, England..
    Lovestone, Simon
    Univ Oxford, Dept Psychiat, Oxford, England..
    O'Donovan, Michael C.
    Cardiff Univ, MRC Ctr Neuropsychiat Genet & Gen, Inst Psychol Med & Clin Neurosci, Cardiff, S Glam, Wales..
    Owen, Michael J.
    Cardiff Univ, MRC Ctr Neuropsychiat Genet & Gen, Inst Psychol Med & Clin Neurosci, Cardiff, S Glam, Wales..
    Behrens, Timothy W.
    Genentech Inc, Immunol Biomarkers Grp, San Francisco, CA USA..
    Mead, Simon
    UCL Inst Neurol, MRC Prion Unit, Dept Neurodegenerat Dis, London, England..
    Goate, Alison M.
    Mt Sinai Sch Med, Dept Neurosci, New York, NY USA..
    Uitterlinden, Andre G.
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.;UCL Inst Neurol, MRC Prion Unit, Dept Neurodegenerat Dis, London, England.;Univ Milan, IRCCS Osped Policlin, Fdn Ca Granda, Dept Pathophysiol & Transplantat, Milan, Italy..
    Holmes, Clive
    VA Puget Sound Hlth Care Syst GRECC, Seattle, WA USA..
    Cruchaga, Carlos
    Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA.;Washington Univ, Sch Med, Hope Ctr Program Prot Aggregat & Neurodegenerat, St Louis, MO USA..
    Ingelsson, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Bennett, David A.
    Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA.;Rush Univ, Rush Alzheimers Dis Ctr, Med Ctr, Chicago, IL 60612 USA..
    Powell, John
    Kings Coll London, Inst Psychiat Psychol & Neurosci, Dept Basic & Clin Neurosci, London, England..
    Golde, Todd E.
    Univ Florida, Dept Neurosci, Ctr Translat Res Neurodegenerat Dis, Gainesville, FL 32610 USA.;Florida Alzheimers Dis Res Ctr, Gainesville, FL USA..
    Graff, Caroline
    Karolinska Univ Hosp Huddinge, Dept Geriatr Med, Stockholm, Sweden.;Karolinska Inst, KIADRC, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden..
    De Jager, Philip L.
    Columbia Univ, Dept Neurol, Med Ctr, Ctr Translat & Syst Neuroimmunol, New York, NY USA..
    Morgan, Kevin
    Univ Nottingham, Queens Med Ctr, Inst Genet, Nottingham, England..
    Ertekin-Taner, Nilufer
    Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA.;Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA..
    Combarros, Onofre
    Neurol Serv, Santander, Spain.;Univ Cantabria, Marques Valdecilla Univ Hosp, CIBERNED, Santander, Spain.;IFIMAV, Santander, Spain..
    Psaty, Bruce M.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. Univ Miami, Dept Human Genet, Dr John T Macdonald Fdn, Miami, FL USA.;Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain.;Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.;Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA..
    Passmore, Peter
    Queens Univ, Sch Med Dent & Biomed Sci, Ctr Publ Hlth, Belfast, Antrim, North Ireland..
    Younkin, Steven G.
    Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA.;Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA..
    Berr, Claudine
    Hop La Pitie Salpetriere, AP HP, Dept Neurol, Inst Memoire & Malad Alzheimer IM2A, Paris, France.;Hosp Gui de Chauliac, Dept Neurol, CMRR Montpellier, Memory Res & Resources Ctr, Montpellier, France.;Montpellier Univ, Dept Neurol, Montpellier, France..
    Gudnason, Vilmundur
    Iceland Heart Assoc, Kopavogur, Iceland. Univ Miami, John P Hussman Inst Human Gen, Miami, FL USA.;Univ Iceland, Fac Med, Reykjavik, Iceland..
    Rujescu, Dan
    Martin Luther Univ Halle Wittenberg, Dept Psychiat, Halle, Germany..
    Dickson, Dennis W.
    Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA..
    Dartigues, Jean-Francois
    CMRR Bordeaux, Memory Res & Resources Ctr, Bordeaux, France..
    DeStefano, Anita L.
    Framingham Heart Dis Epidemiol Study, Framingham, MA USA.;Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA..
    Ortega-Cubero, Sara
    Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain.;Univ Navarra, Sch Med, Ctr Appl Med Res, Neurogenet Lab,Div Neurosci, Pamplona, Spain.;Complejo Asistencial Univ Palencia, Dept Neurol, Palencia, Spain..
    Hakonarson, Hakon
    Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA..
    Campion, Dominique
    Ctr Hos Rouvray, Sotteville Ies Rouen, France.;Normandy Univ, IRIB, Rouen Univ, U1079,INSERM, Rouen, France..
    Boada, Merce
    Inst Catala Neurociencies Aplicades, Res Ctr, Barcelona, Spain.;Inst Catala Neurociencies Aplicades, Memory Clin Fundacio ACE, Barcelona, Spain..
    Kauwe, John Keoni
    Brigham Young Univ, Dept Biol, Provo, UT 84602 USA.;Brigham Young Univ, Dept Neurosci, Provo, UT 84602 USA..
    Farrer, Lindsay A.
    Boston Univ, Sch Med, Boston, MA 02118 USA.;Boston Univ, Dept Med, Genet Program, Boston, MA USA.;Boston Univ, Dept Biostat, Boston, MA 02215 USA.;Boston Univ, Dept Ophthalmol, Boston, MA USA.;Boston Univ, Dept Neurol, Boston, MA USA..
    Van Broeckhoven, Christine
    VIB, Dept Mol Genet, Neurodegenerat Brain Dis Grp, Antwerp, Belgium.;Univ Antwerp, Inst Born Bunge, Antwerp, Belgium..
    Ikram, M. Arfan
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.;Erasmus MC Univ, Med Ctr, Dept Neurol, Rotterdam, Netherlands..
    Jones, Lesley
    Cardiff Univ, MRC Ctr Neuropsychiat Genet & Gen, Inst Psychol Med & Clin Neurosci, Cardiff, S Glam, Wales..
    Haines, Jonathan L.
    Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA..
    Tzourio, Christophe
    Univ Paris 06, UPMC, Sorbonne Univ,CNRS,UMR 7225,UMRS 1127, Inst Cerveau & Moelle Epinisre,INSERM,U1127, Paris, France.;Univ Bordeaux, UMR 897, Neuroepidemiol, Bordeaux, France..
    Launer, Lenore J.
    NIA, Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA..
    Escott-Price, Valentina
    Cardiff Univ, MRC Ctr Neuropsychiat Genet & Gen, Inst Psychol Med & Clin Neurosci, Cardiff, S Glam, Wales..
    Mayeux-, Richard
    Columbia Univ, Dept Neurol, Taub Inst Alzheimers Dis & Aging Brain, New York, NY USA.;Columbia Univ, Gertrude H Sergievsky Ctr, New York, NY USA.;Columbia Univ, Dept Neurol, New York, NY USA..
    Deleuze, Jean-Francois
    Ctr Natl Genotypage, Inst Genom, CEA, Evry, France..
    Amin, Najaf
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands..
    Holmans, Peter A.
    Cardiff Univ, MRC Ctr Neuropsychiat Genet & Gen, Inst Psychol Med & Clin Neurosci, Cardiff, S Glam, Wales..
    Pericak-Vance, Margaret A.
    Amouyel, Philippe
    Risk Factors & Mol Determinants Aging Related Dis, RID AGE, U1167, INSERM, Lille, France.;Inst Pasteur, Lille, France.;Univ Lille, Excellence Lab LabEx DISTALZ, U1167, Lille, France.;Ctr Hosp Univ Lille, Epidemiol & Publ Hlth Dept, Lille, France..
    van Duijn, Cornelia M.
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands..
    Ramirez, Alfredo
    Univ Bonn, Inst Human Genet, Bonn, Germany.;Univ Bonn, Dept Psychiat & Psychotherapy, Bonn, Germany.;Univ Cologne, Dept Psychiat & Psychotherapy, Cologne, Germany..
    Wang, Li-San
    Univ Penn, Sch Med, Dept Pathol & Lab Med, Penn Neurodegenerat Genom Ctr, Philadelphia, PA 19104 USA..
    Lambert, Jean-Charles
    Risk Factors & Mol Determinants Aging Related Dis, RID AGE, U1167, INSERM, Lille, France.;Inst Pasteur, Lille, France..
    Seshadri, Sudha
    Boston Univ, Sch Med, Boston, MA 02118 USA.;Framingham Heart Dis Epidemiol Study, Framingham, MA USA..
    Williams, Julie
    Cardiff Univ, MRC Ctr Neuropsychiat Genet & Gen, Inst Psychol Med & Clin Neurosci, Cardiff, S Glam, Wales..
    Schellenberg, Gerard D.
    Univ Penn, Sch Med, Dept Pathol & Lab Med, Penn Neurodegenerat Genom Ctr, Philadelphia, PA 19104 USA..
    Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease2017In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 49, no 9, p. 1373-+Article in journal (Refereed)
    Abstract [en]

    We identified rare coding variants associated with Alzheimer's disease in a three-stage case-control study of 85,133 subjects. In stage 1, we genotyped 34,174 samples using a whole-exome microarray. In stage 2, we tested associated variants (P < 1 x 10(-4)) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, we used an additional 14,997 samples to test the most significant stage 2 associations (P < 5 x 10(-8)) using imputed genotypes. We observed three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease: a protective variant in PLCG2 (rs72824905: p. Pro522Arg, P = 5.38 x 10(-10), odds ratio (OR) = 0.68, minor allele frequency (MAF) cases = 0.0059, MAFcontrols = 0.0093), a risk variant in ABI3 (rs616338: p. Ser209Phe, P = 4.56 x 10-10, OR = 1.43, MAFcases = 0.011, MAFcontrols = 0.008), and a new genome-wide significant variant in TREM2 (rs143332484: p. Arg62His, P = 1.55 x 10(-14), OR = 1.67, MAFcases = 0.0143, MAFcontrols = 0.0089), a known susceptibility gene for Alzheimer's disease. These protein-altering changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified risk genes in Alzheimer's disease. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to the development of Alzheimer's disease.

  • 48. Sjögren, M
    et al.
    Hesse, C
    Basun, H
    Kol, G
    Thostrup, H
    Kilander, L
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Marcusson, J
    Edman, A
    Wallin, A
    Karlsson, I
    Troell, M
    Wachtmaister, G
    Ekdahl, A
    Olofsson, H
    Sandström, A
    Andreasen, N
    Minthon, L
    Blennow, K
    Tacrine and rate of progression in Alzheimer's disease--relation to ApoE allele genotype.2001In: J Neural Transm, ISSN 0300-9564, Vol. 108, no 4, p. 451-8Article in journal (Refereed)
  • 49.
    Skillback, Tobias
    et al.
    Univ Gothenburg, Sahlgrenska Acad, Dept Neurochem, Clin Neurochem Lab,Inst Neurosci & Physiol, Molndal, Sweden..
    Farahmand, Bahman Y.
    Karolinska Inst, Div Clin Geriatr, Ctr Alzheimer Res, Dept Neurobiol Care Sci & Soc NVS, Huddinge, Sweden..
    Rosen, Christoffer
    Univ Gothenburg, Sahlgrenska Acad, Dept Neurochem, Clin Neurochem Lab,Inst Neurosci & Physiol, Molndal, Sweden..
    Mattsson, Niklas
    Univ Gothenburg, Sahlgrenska Acad, Dept Neurochem, Clin Neurochem Lab,Inst Neurosci & Physiol, Molndal, Sweden.;Univ Calif San Francisco, Dept Vet Affairs Med Ctr, Ctr Imaging Neurodegenerat Dis, San Francisco, CA 94143 USA..
    Nagga, Katarina
    Lund Univ, Dept Clin Sci Malmo, Clin Memory Res Unit, Malmo, Sweden..
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Religa, Dorota
    Karolinska Inst, Div Neurogeriatr, Ctr Alzheimer Res, Dept Neurobiol Care Sci & Soc NVS, Huddinge, Sweden.;Karolinska Univ Hosp, Dept Geriatr Med, Huddinge, Sweden..
    Wimo, Anders
    Karolinska Inst, Div Neurogeriatr, Ctr Alzheimer Res, Dept Neurobiol Care Sci & Soc NVS, Huddinge, Sweden..
    Winblad, Bengt
    Karolinska Inst, Div Neurogeriatr, Ctr Alzheimer Res, Dept Neurobiol Care Sci & Soc NVS, Huddinge, Sweden.;Karolinska Univ Hosp, Dept Geriatr Med, Huddinge, Sweden..
    Schott, Jonathan M.
    UCL Inst Neurol, London WC1N 3BG, England..
    Blennow, Kaj
    Univ Gothenburg, Sahlgrenska Acad, Dept Neurochem, Clin Neurochem Lab,Inst Neurosci & Physiol, Molndal, Sweden..
    Eriksdotter, Maria
    Karolinska Inst, Div Clin Geriatr, Ctr Alzheimer Res, Dept Neurobiol Care Sci & Soc NVS, Huddinge, Sweden.;Karolinska Univ Hosp, Dept Geriatr Med, Huddinge, Sweden..
    Zetterberg, Henrik
    Univ Gothenburg, Sahlgrenska Acad, Dept Neurochem, Clin Neurochem Lab,Inst Neurosci & Physiol, Molndal, Sweden.;UCL Inst Neurol, London WC1N 3BG, England..
    Cerebrospinal fluid tau and amyloid-beta(1-42) in patients with dementia2015In: Brain, ISSN 0006-8950, E-ISSN 1460-2156, Vol. 138, no 9, p. 2716-2731Article in journal (Refereed)
    Abstract [en]

    Progressive cognitive decline in combination with a cerebrospinal fluid biomarker pattern of low levels of amyloid-beta(1-42) and high levels of total tau and phosphorylated tau is typical of Alzheimer's disease. However, several neurodegenerative disorders may overlap with Alzheimer's disease both in regards to clinical symptoms and neuropathology. In a uniquely large cohort of dementia patients, we examined the associations of cerebrospinal fluid biomarkers for Alzheimer's disease molecular pathology with clinical dementia diagnoses and disease severity. We cross-referenced the Swedish Dementia Registry with the clinical laboratory database at the Sahlgrenska University Hospital. The final data set consisted of 5676 unique subjects with a clinical dementia diagnosis and a complete set of measurements for cerebrospinal fluid amyloid-beta(1-42), total tau and phosphorylated tau. In cluster analysis, disregarding clinical diagnosis, the optimal natural separation of this data set was into two clusters, with the majority of patients with early onset Alzheimer's disease (75%) and late onset Alzheimer's disease (73%) assigned to one cluster and the patients with vascular dementia (91%), frontotemporal dementia (94%), Parkinson's disease dementia (94%) and dementia with Lewy bodies (87%) to the other cluster. Frontotemporal dementia had the highest cerebrospinal fluid levels of amyloid-beta(1-42) and the lowest levels of total tau and phosphorylated tau. The highest levels of total tau and phosphorylated tau and the lowest levels of amyloid-beta(1-42) and amyloid-beta(1-42):phosphorylated tau ratios were found in Alzheimer's disease. Low amyloid-beta(1-42), high total tau and high phosphorylated tau correlated with low Mini-Mental State Examination scores in Alzheimer's disease. In Parkinson's disease dementia and vascular dementia low cerebrospinal fluid amyloid-beta(1-42) was associated with low Mini-Mental State Examination score. In the vascular dementia, frontotemporal dementia, dementia with Lewy bodies and Parkinson's disease dementia groups 53%, 34%, 67% and 53% of the subjects, respectively had abnormal amyloid-beta(1-42) levels, 41%, 41%, 28% and 28% had abnormal total tau levels, and 29%, 28%, 25% and 19% had abnormal phosphorylated tau levels. Cerebrospinal fluid biomarkers were strongly associated with specific clinical dementia diagnoses with Alzheimer's disease and frontotemporal dementia showing the greatest difference in biomarker levels. In addition, cerebrospinal fluid amyloid-beta(1-42), total tau, phosphorylated tau and the amyloid-beta(1-42):phosphorylated tau ratio all correlated with poor cognitive performance in Alzheimer's disease, as did cerebrospinal fluid amyloid-beta(1-42) in Parkinson's disease dementia and vascular dementia. The results support the use of cerebrospinal fluid biomarkers to differentiate between dementias in clinical practice, and to estimate disease severity.

  • 50. Skillbäck, T
    et al.
    Farahmand, B
    Bartlett, JW
    Rosén, C
    Mattsson, N
    Nägga, K
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Religa, D
    Wimo, A
    Winblad, B
    Rosengren, L
    Schott, JM
    Blennow, K
    Eriksdotter, M
    Zetterberg, H
    CSF neurofilament light differs in neurodegenerative diseases and predicts severity and survival2014In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 83, no 21, p. 1945-1953Article in journal (Refereed)
    Abstract [en]

    Objectives: We hypothesized that CSF neurofilament light (NFL) levels would be elevated in dementias with subcortical involvement, including vascular dementia (VaD), but less elevated in dementias primarily affecting gray matter structures, such as Alzheimer disease (AD), and that elevated CSF NFL would correlate with disease severity and shorter survival time irrespective of clinical diagnosis.

    Methods: We included 3,356 individuals with dementia who had CSF NFL analyzed in our laboratory between 2005 and 2012. Clinical diagnoses and Mini-Mental State Examination (MMSE) scores were obtained from the Swedish Dementia Registry, and in selected cases (n = 478), date of death from the Swedish Mortality Registry.

    Results: CSF NFL differed among clinical diagnoses, with the highest levels seen in frontotemporal dementia, VaD, and mixed AD and VaD. Early-onset AD (younger than 65 years) had the lowest levels. High CSF NFL correlated with low MMSE score and short survival time irrespective of diagnosis, and was also particularly evident in AD.

    Conclusions: CSF NFL differs among different neurodegenerative diseases and is especially high in dementias engaging subcortical brain regions, such as VaD and mixed AD and VaD, but also in frontotemporal dementia. The association of high CSF NFL levels with disease severity and short survival supports the notion that high CSF NFL levels indicate more aggressive disease processes.

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