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@ARTICLE{Liampas:276181,
author = {Liampas, Ioannis and Siokas, Vasileios and Mourtzi, Niki
and Charisis, Sokratis and Sampatakakis, Stefanos N and
Foukarakis, Ioannis and Hatzimanolis, Alex and Ramirez,
Alfredo and Lambert, Jean-Charles and Yannakoulia, Mary and
Kosmidis, Mary H and Dardiotis, Efthimios and Hadjigeorgiou,
Georgios M and Sakka, Paraskevi and Rouskas, Konstantinos
and Scarmeas, Nikolaos},
title = {{G}enetic {P}redisposition to {H}ippocampal {A}trophy and
{R}isk of {A}mnestic {M}ild {C}ognitive {I}mpairment and
{A}lzheimer's {D}ementia.},
journal = {Geriatrics},
volume = {10},
number = {1},
issn = {2308-3417},
address = {Basel},
publisher = {MDPI},
reportid = {DZNE-2025-00249},
pages = {14},
year = {2025},
abstract = {There is a paucity of evidence on the association between
genetic propensity for hippocampal atrophy with cognitive
outcomes. Therefore, we examined the relationship of the
polygenic risk score for hippocampal atrophy (PRShp) with
the incidence of amnestic mild cognitive impairment (aMCI)
and Alzheimer's disease (AD) as well as the rates of
cognitive decline.Participants were drawn from the
population-based HELIAD cohort. Comprehensive
neuropsychological assessments were performed at baseline
and at follow-up. PRShp was derived from the summary
statistics of a large genome-wide association study for
hippocampal volume. Cox proportional hazards models as well
as generalized estimating equations (GEEs) were used to
evaluate the association of PRShp with the combined
incidence of aMCI/AD and cognitive changes over time,
respectively. All models were adjusted for age, sex,
education, and apolipoprotein E (APOE) genotype.Our analysis
included 618 older adults, among whom 73 developed aMCI/AD
after an average follow-up of 2.96 ± 0.8 years. Each
additional SD of PRShp elevated the relative hazard for
incident aMCI/AD by $46\%.$ Participants at the top quartile
of PRShp had an almost three times higher risk of converting
to aMCI/AD compared to the lowest quartile group. Higher
PRShp scores were also linked to steeper global cognitive
and memory decline. The impact of PRShp was greater among
women and younger adults.Our findings support the
association of PRShp with aMCI/AD incidence and with global
cognitive and memory decline over time. The PRS association
was sex- and age-dependent, suggesting that these factors
should be considered in genetic modelling for AD.},
keywords = {Alzheimer’s disease (Other) / cognitive decline (Other) /
hippocampal atrophy (Other) / polygenic risk score (Other)},
cin = {Patient Studies (Bonn)},
ddc = {610},
cid = {I:(DE-2719)1011101},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:39846584},
doi = {10.3390/geriatrics10010014},
url = {https://pub.dzne.de/record/276181},
}