TY  - JOUR
AU  - Sampatakakis, Stefanos N
AU  - Mourtzi, Niki
AU  - Hatzimanolis, Alex
AU  - Koutsis, Georgios
AU  - Charisis, Sokratis
AU  - Gkelmpesi, Iliana
AU  - Mamalaki, Eirini
AU  - Ntanasi, Eva
AU  - Ramirez, Alfredo
AU  - Yannakoulia, Mary
AU  - Kosmidis, Mary H
AU  - Dardiotis, Efthimios
AU  - Hadjigeorgiou, Georgios
AU  - Sakka, Paraskevi
AU  - Scarmeas, Nikolaos
TI  - Genetic Prοpensity for Different Aspects of Dementia Pathology and Cognitive Decline in a Community Elderly Population.
JO  - International journal of molecular sciences
VL  - 26
IS  - 3
SN  - 1422-0067
CY  - Basel
PB  - Molecular Diversity Preservation International
M1  - DZNE-2025-00317
SP  - 910
PY  - 2025
AB  - 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.
KW  - Humans
KW  - Female
KW  - Male
KW  - Aged
KW  - Cognitive Dysfunction: genetics
KW  - Dementia: genetics
KW  - Amyloid beta-Peptides: metabolism
KW  - Genetic Predisposition to Disease
KW  - Aged, 80 and over
KW  - Longitudinal Studies
KW  - Neuropsychological Tests
KW  - White Matter: pathology
KW  - White Matter: diagnostic imaging
KW  - Multifactorial Inheritance
KW  - amyloid beta (Other)
KW  - cognitive decline (Other)
KW  - dementia (Other)
KW  - pathophysiology (Other)
KW  - polygenic risk score (Other)
KW  - white matter hyperintensities (Other)
KW  - Amyloid beta-Peptides (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:39940679
DO  - DOI:10.3390/ijms26030910
UR  - https://pub.dzne.de/record/276778
ER  -