Journal Article

DZNE-2025-00317

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Genetic Prοpensity for Different Aspects of Dementia Pathology and Cognitive Decline in a Community Elderly Population.

Sampatakakis, S. N. ; Mourtzi, N. ; Hatzimanolis, A. ; Koutsis, G. ; Charisis, S. ; Gkelmpesi, I. ; Mamalaki, E. ; Ntanasi, E. ; Ramirez, A.DZNE* ; Yannakoulia, M. ; Kosmidis, M. H. ; Dardiotis, E. ; Hadjigeorgiou, G. ; Sakka, P. ; Scarmeas, N.

2025
Molecular Diversity Preservation International Basel

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Please use a persistent id in citations: doi:10.3390/ijms26030910

Abstract: In the present study, we investigated the association of genetic predisposition with specific dimensions of dementia pathophysiology for global and domain-specific cognitive decline in older adults. The sample was drawn from the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD) study, comprising 512 cognitively normal individuals over 64 years of age, with a mean follow-up of 2.9 years. Cognitive function was evaluated through a neuropsychological test battery, while genetic predisposition was assessed based on two distinct Polygenic Risk Scores (PRS) for amyloid-beta 42 (Aβ42) and white matter hyperintensities (WMH). The association of each PRS with the cognitive decline rate was examined using generalized estimating equation models. In the whole sample, higher PRSs Aβ42 (β = -0.042) and WMH (β =-0.029) were associated with a higher rate of global cognitive decline per year, an association which remained significant in age, sex, and education subgroups. Moreover, higher PRSs Aβ42 and WMH were related to significant memory decline only in females, older, and highly educated participants. Thus, while the association of both PRSs with global cognitive decline over time was independent of age, sex, or education, the relationship of the specific PRSs with the memory decline rate appeared to vary depending on these factors.

Keyword(s): Humans (MeSH) ; Female (MeSH) ; Male (MeSH) ; Aged (MeSH) ; Cognitive Dysfunction: genetics (MeSH) ; Dementia: genetics (MeSH) ; Amyloid beta-Peptides: metabolism (MeSH) ; Genetic Predisposition to Disease (MeSH) ; Aged, 80 and over (MeSH) ; Longitudinal Studies (MeSH) ; Neuropsychological Tests (MeSH) ; White Matter: pathology (MeSH) ; White Matter: diagnostic imaging (MeSH) ; Multifactorial Inheritance (MeSH) ; amyloid beta ; cognitive decline ; dementia ; pathophysiology ; polygenic risk score ; white matter hyperintensities ; Amyloid beta-Peptides

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Contributing Institute(s):

1. Patient Studies (Bonn) (Patient Studies (Bonn))

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2025

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Database coverage:
; ; ; Clarivate Analytics Master Journal List ; Current Contents - Physical, Chemical and Earth Sciences ; Ebsco Academic Search ; Essential Science Indicators ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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