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Cognitive function in very old men does not correlate to biomarkers of Alzheimer's disease
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. (Molekylär geriatrik/ Rudbecklaboratoriet)ORCID iD: 0000-0003-3423-2021
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 Immunology, Genetics and Pathology, Clinical and experimental pathology. Department of Pathology Uppsala University Hospital, Uppsala, Sweden.. (Irina Alufuzoff)
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2017 (English)In: BMC Geriatrics, E-ISSN 1471-2318, Vol. 17, no 1, article id 208Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: The Alzheimer's disease (AD) brain displays atrophy with amyloid-β (Aβ) and tau deposition, whereas decreased Aβ42 and increased tau are measured in cerebrospinal fluid (CSF). The aim of this study was to relate cognitive performance to the degree of brain atrophy, CSF biomarker levels and neuropathology in a cohort of aged men.

METHODS: Fifty-eight 86-92-year-old men from the Uppsala Longitudinal Study of Adult Men (ULSAM) cohort underwent cognitive testing, brain computed tomography and lumbar puncture. Atrophy was graded with established scales. Concentrations of CSF Aβ42, t-tau and p-tau were measured by ELISA. Thirteen brains were examined post mortem.

RESULTS: Forty-six of the individuals were considered non-demented, whereas twelve were diagnosed with dementia, either at baseline (n = 4) or during follow-up (n = 8). When comparing subjects with and without dementia, there were no differences in the degree of atrophy, although the mini mental state examination (MMSE) scoring correlated weakly with the degree of medial temporal atrophy (MTA) (p = 0.04). Moreover, the CSF biomarker levels did not differ significantly between healthy (n = 27) and demented (n = 8) subjects (median values 715 vs 472 pg/ml for Aβ42, 414 vs 427 pg/ml for t-tau and 63 vs 60 pg/ml for p-tau). Similarly, there were no differences in the biomarker levels between individuals with mild (n = 24) and severe (n = 11) MTA (median values 643 vs 715 pg/ml for Aβ42, 441 vs 401 pg/ml for t-tau and 64 vs 53 pg/ml for p-tau). Finally, the neuropathological changes did not correlate with any of the other measures.

CONCLUSION: In this cohort of aged men only a weak correlation could be seen between cognitive performance and MTA, whereas the various neuroradiological, biochemical and neuropathological measures did not correlate with each other. Thus, AD biomarkers seem to be less informative in subjects of an advanced age.

Place, publisher, year, edition, pages
2017. Vol. 17, no 1, article id 208
Keywords [en]
AD biomarkers, Advanced age, Brain atrophy, CSF biomarkers, Cognitive performance, Neuropathology
National Category
Neurology Geriatrics Radiology, Nuclear Medicine and Medical Imaging Clinical Laboratory Medicine
Research subject
Pathology
Identifiers
URN: urn:nbn:se:uu:diva-329266DOI: 10.1186/s12877-017-0601-6ISI: 000410449900002PubMedID: 28886705OAI: oai:DiVA.org:uu-329266DiVA, id: diva2:1140223
Note

V. Velickaite and V. Giedraitis contributed equally.

Available from: 2017-09-11 Created: 2017-09-11 Last updated: 2024-07-04Bibliographically approved
In thesis
1. Analysis of regional atrophy on brain imaging compared with cognitive function in the elderly and in patients with dementia – cross-sectional and longitudinal evaluation
Open this publication in new window or tab >>Analysis of regional atrophy on brain imaging compared with cognitive function in the elderly and in patients with dementia – cross-sectional and longitudinal evaluation
2019 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

During aging, brain changes are not homogeneous throughout the entire brain, but are related to changes in the morphology of neurons, as well as to changes in the tissue density, and are specific to each region of the brain. Dementia is a broad category of brain disorders with a set of symptoms including memory, visual-spatial and language problems. Most types of dementia are slowly progressing, and by the time the person shows signs of the disorder, processes in the brain are already advanced. Dementia reduces not only the person’s ability to perform everyday activities, it also increases mortality rates significantly. Because of the increasing incidence of dementia, possible prevention and treatment of dementia as early as possible are essential.

The aim of the PhD project is to compare a quantitative and qualitative image analysis of regional cerebral atrophy with cognitive function in the elderly persons.

In paper I, 58 persons participated (84–88 years old) from the ULSAM (Uppsala Longitudinal Study of Adult Men) cohort. They underwent CT of the brain, cognitive testing and LP. This study showed that AD biomarkers seem to be less informative in subjects with an advanced age.

In papers II–IV, the cohort included subjects from the PIVUS (Prospective Investigation of the Vasculature in Uppsala Seniors) study.

Paper II showed that at age 75, gender and education are confounders for MTA rating. Subjects with abnormal right MTA, but normal MMSE scores had developed worse MMSE scores 5 years later.

Paper III showed that automated rating of MTA could be used in clinical practice to support the radiological evaluation. Automated rating of PA and F-GCA should be tested in future studies.

In paper IV, we found a mild age-associated decrease in regional brain volumes in this healthy cohort with well-preserved cognitive and executive functions.

In conclusion, the included studies in this thesis compare regional atrophy grades in the brain on CT and MRI and clinical data and provide knowledge that may be used in future investigations that aim to detect dementia in its early stages.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2019. p. 63
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1546
Keywords
Dementia, Brain Imaging, Visual rating, Volumetry, Cognition
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-378578 (URN)978-91-513-0586-8 (ISBN)
Public defence
2019-04-25, Hedstrandsalen, Akademiska sjukhuset, ingång 70, Uppsala, 09:00 (English)
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Available from: 2019-04-01 Created: 2019-03-07 Last updated: 2019-05-07

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Velickaite, VilmaGiedraitis, VilmantasAlafuzoff, IrinaLannfelt, LarsKilander, LenaLarsson, Elna-MarieIngelsson, Martin

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