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Kilander, Lena
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Publications (10 of 67) Show all publications
Åhman, H. B., Giedraitis, V., Cedervall, Y., Lennhed, B., Berglund, L., McKee, K., . . . Åberg, A. C. (2019). Dual-Task Performance and Neurodegeneration: Correlations Between Timed Up-and-Go Dual-Task Test Outcomes and Alzheimer's Disease Cerebrospinal Fluid Biomarkers. Journal of Alzheimer's Disease, 71, S75-S83
Open this publication in new window or tab >>Dual-Task Performance and Neurodegeneration: Correlations Between Timed Up-and-Go Dual-Task Test Outcomes and Alzheimer's Disease Cerebrospinal Fluid Biomarkers
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2019 (English)In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 71, p. S75-S83Article in journal (Refereed) Published
Abstract [en]

Background: Tools to identify individuals at preclinical stages of dementia disorders are needed to enable early interventions. Alterations in dual-task performance have been detected early in progressive neurodegenerative disorders. Hence, dual-task testing may have the potential to screen for cognitive impairment caused by neurodegeneration. Exploring correlations between dual-task performance and biomarkers of neurodegeneration is therefore of interest. Objective: To investigate correlations between Timed Up-and-Go dual-task (TUGdt) outcomes and Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers amyloid-beta 42 (A beta(42)), total tau (t-tau), and phosphorylated tau (p-tau). Methods: This cross-sectional cohort study included 90 participants (age range 49-84 years) undergoing memory assessment, who were subsequently diagnosed with AD, other dementia disorders, mild cognitive impairment, or subjective cognitive impairment. TUG combined with "Naming Animals" (TUGdt NA) and "Months Backwards" (TUGdt MB), respectively, were used to assess dual-task performance. The number of correct words and time taken to complete the tests were measured. The CSF biomarkers were analysed by ELISA. Spearman's rank correlation was used for analyses between TUGdt outcomes (TUGdt NA and TUGdt MB), and CSF biomarkers, adjusted for age, gender, and educational level. Results: The number of correct words, as well as the number of correct words/10 s during TUGdt NA correlated negatively to CSF t-tau and p-tau. No correlations were found between any time scores and CSF biomarkers. Conclusion: The correlations between TUGdt NA and t-tau and p-tau may indicate that neurodegeneration affects dual-task performance. Longitudinal studies are needed to further explore dual-task testing in screening for cognitive impairment due to neurodegeneration.

Place, publisher, year, edition, pages
IOS PRESS, 2019
Keywords
Alzheimer's disease, attention, biomarkers, cerebrospinal fluid, dementia, executive function, gait, mild cognitive impairment, subjective cognitive impairment
National Category
Geriatrics
Identifiers
urn:nbn:se:uu:diva-395565 (URN)10.3233/JAD-181265 (DOI)000487075000010 ()31104024 (PubMedID)
Funder
Swedish Research Council
Available from: 2019-10-21 Created: 2019-10-21 Last updated: 2019-10-21Bibliographically approved
Kunkle, B. W., Giedraitis, V., Kilander, L., Brundin, R., Lannfelt, L., Ingelsson, M. & Pericak-Vance, M. A. (2019). Genetic meta-analysis of diagnosed Alzheimer's disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing. Nature Genetics, 51(3), 414-430
Open this publication in new window or tab >>Genetic meta-analysis of diagnosed Alzheimer's disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing
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2019 (English)In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 51, no 3, p. 414-430Article in journal (Refereed) Published
Abstract [en]

Risk for late-onset Alzheimer's disease (LOAD), the most prevalent dementia, is partially driven by genetics. To identify LOAD risk loci, we performed a large genome-wide association meta-analysis of clinically diagnosed LOAD (94,437 individuals). We confirm 20 previous LOAD risk loci and identify five new genome-wide loci (IQCK, ACE, ADAM10, ADAMTS1, and WWOX), two of which (ADAM10, ACE) were identified in a recent genome-wide association (GWAS)-by-familial-proxy of Alzheimer's or dementia. Fine-mapping of the human leukocyte antigen (HLA) region confirms the neurological and immune-mediated disease haplotype HLA-DR15 as a risk factor for LOAD. Pathway analysis implicates immunity, lipid metabolism, tau binding proteins, and amyloid precursor protein (APP) metabolism, showing that genetic variants affecting APP and A beta processing are associated not only with early-onset autosomal dominant Alzheimer's disease but also with LOAD. Analyses of risk genes and pathways show enrichment for rare variants (P = 1.32 x 10-7), indicating that additional rare variants remain to be identified. We also identify important genetic correlations between LOAD and traits such as family history of dementia and education.

National Category
Medical Genetics
Identifiers
urn:nbn:se:uu:diva-379343 (URN)10.1038/s41588-019-0358-2 (DOI)000459947200011 ()30820047 (PubMedID)
Note

For complete list of authors see http://dx.doi.org/10.1038/s41588-019-0358-2

Available from: 2019-03-15 Created: 2019-03-15 Last updated: 2019-03-15Bibliographically approved
Emami Khoonsari, P., Shevchenko, G., Herman, S., Remnestal, J., Giedraitis, V., Brundin, R., . . . Kultima, K. (2019). Improved Differential Diagnosis of Alzheimer's Disease by Integrating ELISA and Mass Spectrometry-Based Cerebrospinal Fluid Biomarkers. Journal of Alzheimer's Disease, 67(2), 639-651
Open this publication in new window or tab >>Improved Differential Diagnosis of Alzheimer's Disease by Integrating ELISA and Mass Spectrometry-Based Cerebrospinal Fluid Biomarkers
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2019 (English)In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 67, no 2, p. 639-651Article in journal (Refereed) Published
Abstract [en]

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

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

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

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

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

Place, publisher, year, edition, pages
IOS PRESS, 2019
Keywords
Alzheimer's disease, cerebrospinal fluid, ELISA, mass spectrometry, mild cognitive impairment, proteomics
National Category
Neurology Geriatrics
Identifiers
urn:nbn:se:uu:diva-377711 (URN)10.3233/JAD-180855 (DOI)000457779300016 ()30614806 (PubMedID)
Funder
VINNOVAGun och Bertil Stohnes StiftelseÅke Wiberg FoundationStiftelsen Gamla Tjänarinnor
Available from: 2019-03-08 Created: 2019-03-08 Last updated: 2019-04-29Bibliographically approved
Forsberg, L. A., Halvardson, J., Rychlicka-Buniowska, E., Danielsson, M., Moghadam, B. T., Mattisson, J., . . . Dumanski, J. P. (2019). Mosaic loss of chromosome Y in leukocytes matters [Letter to the editor]. Nature Genetics, 51(1), 4-7
Open this publication in new window or tab >>Mosaic loss of chromosome Y in leukocytes matters
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2019 (English)In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 51, no 1, p. 4-7Article in journal, Letter (Other academic) Published
National Category
Medical Genetics Genetics
Identifiers
urn:nbn:se:uu:diva-373366 (URN)10.1038/s41588-018-0267-9 (DOI)000454108800004 ()30374072 (PubMedID)
Funder
EU, European Research CouncilSwedish Research Council
Available from: 2019-01-15 Created: 2019-01-15 Last updated: 2019-01-15Bibliographically approved
Franzon, K., Zethelius, B., Cederholm, T. & Kilander, L. (2019). The impact of muscle function, muscle mass and sarcopenia on independent ageing in very old Swedish men. BMC Geriatrics, 19, Article ID 153.
Open this publication in new window or tab >>The impact of muscle function, muscle mass and sarcopenia on independent ageing in very old Swedish men
2019 (English)In: BMC Geriatrics, ISSN 1471-2318, E-ISSN 1471-2318, Vol. 19, article id 153Article in journal (Refereed) Published
Abstract [en]

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

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

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

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

Keywords
Sarcopenia, EWGSOP1, EWGSOP2, Muscle mass, Muscle function, Gait speed, Hand grip strength, Chair stand test, Independent ageing
National Category
Geriatrics
Research subject
Geriatrics
Identifiers
urn:nbn:se:uu:diva-380155 (URN)10.1186/s12877-019-1142-y (DOI)000469459000001 ()31142271 (PubMedID)
Available from: 2019-03-25 Created: 2019-03-25 Last updated: 2019-06-20Bibliographically approved
Skillbäck, T., Lautner, R., Mattsson, N., Schott, J. M., Skoog, I., Nagga, K., . . . Zetterberg, H. (2018). Apolipoprotein E genotypes and longevity across dementia disorders. Alzheimer's & Dementia, 14(7), 895-901
Open this publication in new window or tab >>Apolipoprotein E genotypes and longevity across dementia disorders
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2018 (English)In: Alzheimer's & Dementia, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 14, no 7, p. 895-901Article in journal (Refereed) Published
Abstract [en]

Introduction: The ε4 allele of the apolipoprotein E (APOE) gene is a prominent risk factor for Alzheimer's disease (AD), but its implication in other dementias is less well studied.

Methods: We used a data set on 2858 subjects (1098 AD, 260 vascular dementia [VaD], 145 mixed AD and VaD, 90 other dementia diagnoses, and 1265 controls) to examine the association of APOE polymorphisms with clinical dementia diagnoses, biomarker profiles, and longevity.

Results: The ε4 allele was associated with reduced longevity as ε4 versus ε3 homozygotes lived on average 2.6 years shorter (P = .006). In AD, ε4 carriers lived 1.0 years shorter than noncarriers (P = .028). The ε4 allele was more prevalent in AD, mixed AD and VaD, and VaD patients compared to controls, but not in other dementia disorders.

Discussion: The APOE ε4 allele is influential in AD but might also be of importance in VaD and in mixed AD and VaD, diseases in which concomitant AD pathology is common.

Keywords
Apolipoprotein E, Alzheimer's disease, Dementia with Lewy bodies, Vascular dementia, Frontotemporal dementia, Parkinson's disease dementia, Creutzfeldt-Jakob disease
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-361543 (URN)10.1016/j.jalz.2018.02.003 (DOI)000438783200007 ()29548722 (PubMedID)
Available from: 2018-10-01 Created: 2018-10-01 Last updated: 2018-10-01Bibliographically approved
Velickaite, V., Ferreira, D., Cavallin, L., Lind, L., Ahlström, H., Kilander, L., . . . Larsson, E.-M. (2018). Medial temporal lobe atrophy ratings in a large 75-year-old population-based cohort: gender-corrected and education-corrected normative data. European Radiology, 28(4), 1739-1747
Open this publication in new window or tab >>Medial temporal lobe atrophy ratings in a large 75-year-old population-based cohort: gender-corrected and education-corrected normative data
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2018 (English)In: European Radiology, ISSN 0938-7994, E-ISSN 1432-1084, Vol. 28, no 4, p. 1739-1747Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES: To find cut-off values for different medial temporal lobe atrophy (MTA) measures (right, left, average, and highest), accounting for gender and education, investigate the association with cognitive performance, and to compare with decline of cognitive function over 5 years in a large population-based cohort.

METHODS: Three hundred and ninety 75-year-old individuals were examined with magnetic resonance imaging of the brain and cognitive testing. The Scheltens's scale was used to assess visually MTA scores (0-4) in all subjects. Cognitive tests were repeated in 278 of them after 5 years. Normal MTA cut-off values were calculated based on the 10th percentile.

RESULTS: Most 75-year-old individuals had MTA score ≤2. Men had significantly higher MTA scores than women. Scores for left and average MTA were significantly higher in highly educated individuals. Abnormal MTA was associated with worse results in cognitive test and individuals with abnormal right MTA had faster cognitive decline.

CONCLUSION: At age 75, gender and education are confounders for MTA grading. A score of ≥2 is abnormal for low-educated women and a score of ≥2.5 is abnormal for men and high-educated women. Subjects with abnormal right MTA, but normal MMSE scores had developed worse MMSE scores 5 years later.

KEY POINTS: • Gender and education are confounders for MTA grading. • We suggest cut-off values for 75-year-olds, taking gender and education into account. • Males have higher MTA scores than women. • Higher MTA scores are associated with worse cognitive performance.

Keywords
Cognitive test, Dementia, Longitudinal analysis, Medial temporal lobe atrophy (MTA), Population-based, Scheltens’s scale
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-333774 (URN)10.1007/s00330-017-5103-6 (DOI)000426645600044 ()29124383 (PubMedID)
Funder
Stockholm County CouncilThe Karolinska Institutet's Research Foundation
Available from: 2017-11-16 Created: 2017-11-16 Last updated: 2019-03-07Bibliographically approved
Nylander, R., Kilander, L., Ahlström, H., Lind, L. & Larsson, E.-M. (2018). Small Vessel Disease on Neuroimaging in a 75-Year-Old Cohort (PIVUS): Comparison With Cognitive and Executive Tests.. Frontiers in Aging Neuroscience, 10, Article ID 217.
Open this publication in new window or tab >>Small Vessel Disease on Neuroimaging in a 75-Year-Old Cohort (PIVUS): Comparison With Cognitive and Executive Tests.
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2018 (English)In: Frontiers in Aging Neuroscience, ISSN 1663-4365, E-ISSN 1663-4365, Vol. 10, article id 217Article in journal (Refereed) Published
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.

Keywords
cognitive tests, lacunar infarct, magnetic resonance imaging, perfusion, small vessel disease, white matter hyperintensities
National Category
Geriatrics Gerontology, specialising in Medical and Health Sciences Neurology
Identifiers
urn:nbn:se:uu:diva-356786 (URN)10.3389/fnagi.2018.00217 (DOI)000438723000002 ()30061827 (PubMedID)
Available from: 2018-08-07 Created: 2018-08-07 Last updated: 2018-09-27Bibliographically approved
Hansen, T., Kilander, L., Ahlström, H. & Lind, L. (2018). Total atherosclerotic burden measured by magnetic resonance imaging is related to five-year decline in cognitive function. Clinical Physiology and Functional Imaging, 38(3), 373-377
Open this publication in new window or tab >>Total atherosclerotic burden measured by magnetic resonance imaging is related to five-year decline in cognitive function
2018 (English)In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 38, no 3, p. 373-377Article in journal (Refereed) Published
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.

Keywords
Atherosclerosis, dementia, magnetic resonance angiography, mild cognitive impairment, mini-mental state examination, trail making tests
National Category
Physiology
Identifiers
urn:nbn:se:uu:diva-322144 (URN)10.1111/cpf.12423 (DOI)000430103100005 ()28402078 (PubMedID)
Funder
Swedish Research CouncilAstraZeneca
Available from: 2017-05-16 Created: 2017-05-16 Last updated: 2018-06-19Bibliographically approved
Fällmar, D., Lilja, J., Danfors, T., Kilander, L., Iyer, V., Lubberink, M., . . . Sörensen, J. (2018). Z-score maps from low-dose 18F-FDG PET of the brain in neurodegenerative dementia.. American Journal of Nuclear Medicine and Molecular Imaging, 8(4), 239-246
Open this publication in new window or tab >>Z-score maps from low-dose 18F-FDG PET of the brain in neurodegenerative dementia.
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2018 (English)In: American Journal of Nuclear Medicine and Molecular Imaging, ISSN 2160-8407, Vol. 8, no 4, p. 239-246Article in journal (Refereed) Published
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.

Keywords
FDG, PET, methodology, neurodegeneration, neuroimaging, radiation
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-362198 (URN)000444491000001 ()30245916 (PubMedID)
Available from: 2018-10-02 Created: 2018-10-02 Last updated: 2018-11-15Bibliographically approved
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