{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T00:42:29Z","timestamp":1759970549741,"version":"build-2065373602"},"reference-count":73,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,1,22]],"date-time":"2025-01-22T00:00:00Z","timestamp":1737504000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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 (A\u03b242) 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 A\u03b242 (\u03b2 = \u22120.042) and WMH (\u03b2 =\u22120.029) 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 A\u03b242 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.<\/jats:p>","DOI":"10.3390\/ijms26030910","type":"journal-article","created":{"date-parts":[[2025,1,22]],"date-time":"2025-01-22T07:55:32Z","timestamp":1737532532000},"page":"910","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetic Pr\u03bfpensity for Different Aspects of Dementia Pathology and Cognitive Decline in a Community Elderly Population"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-7316-0471","authenticated-orcid":false,"given":"Stefanos N.","family":"Sampatakakis","sequence":"first","affiliation":[{"name":"1st Department of Neurology, Aiginition Hospital, Athens Medical School, National and Kapodistrian University, 11528 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Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6578-393X","authenticated-orcid":false,"given":"Sokratis","family":"Charisis","sequence":"additional","affiliation":[{"name":"Department of Neurology, UT Health San Antonio, San Antonio, TX 78229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iliana","family":"Gkelmpesi","sequence":"additional","affiliation":[{"name":"1st Department of Neurology, Aiginition Hospital, Athens Medical School, National and Kapodistrian University, 11528 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eirini","family":"Mamalaki","sequence":"additional","affiliation":[{"name":"1st Department of Neurology, Aiginition Hospital, Athens Medical School, National and Kapodistrian University, 11528 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva","family":"Ntanasi","sequence":"additional","affiliation":[{"name":"1st Department of Neurology, Aiginition Hospital, Athens Medical School, National and Kapodistrian University, 11528 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4991-763X","authenticated-orcid":false,"given":"Alfredo","family":"Ramirez","sequence":"additional","affiliation":[{"name":"Division of Neurogenetics and Molecular Psychiatry, Department of Psychiatry and Psychotherapy, Medical Faculty, University of Cologne, 50923 Cologne, Germany"},{"name":"Department of Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, 53127 Bonn, Germany"},{"name":"German Center for Neurodegenerative Diseases (DZNE Bonn), 53127 Bonn, Germany"},{"name":"Department of Psychiatry, Glenn Biggs Institute for Alzheimer\u2019s and Neurodegenerative Diseases, San Antonio, TX 78229, USA"},{"name":"Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50923 Cologne, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2171-7337","authenticated-orcid":false,"given":"Mary","family":"Yannakoulia","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Dietetics, Harokopio University, 17676 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8790-1220","authenticated-orcid":false,"given":"Mary H.","family":"Kosmidis","sequence":"additional","affiliation":[{"name":"Laboratory of Neuropsychology and Behavioral Neuroscience, School of Psychology, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2957-641X","authenticated-orcid":false,"given":"Efthimios","family":"Dardiotis","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Hospital of Larissa, Faculty of Medicine, School of Health Sciences, University of Thessaly, 41334 Larissa, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georgios","family":"Hadjigeorgiou","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical School, University of Cyprus, 1678 Nicosia, Cyprus"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paraskevi","family":"Sakka","sequence":"additional","affiliation":[{"name":"Athens Association of Alzheimer\u2019s Disease and Related Disorders, 11636 Marousi, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nikolaos","family":"Scarmeas","sequence":"additional","affiliation":[{"name":"1st Department of Neurology, Aiginition Hospital, Athens Medical School, National and Kapodistrian University, 11528 Athens, Greece"},{"name":"Department of Neurology, The Gertrude H. 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