Genetic Predisposition to Hippocampal Atrophy and Risk of Amnestic Mild Cognitive Impairment and Alzheimer’s Dementia
Ioannis Liampas,
Vasileios Siokas,
Niki Mourtzi,
Sokratis Charisis,
Stefanos N. Sampatakakis,
Ioannis Foukarakis,
Alex Hatzimanolis,
Alfredo Ramirez,
Jean-Charles Lambert,
Mary Yannakoulia,
Mary H. Kosmidis,
Efthimios Dardiotis,
Georgios M. Hadjigeorgiou,
Paraskevi Sakka,
Konstantinos Rouskas,
Nikolaos Scarmeas
Affiliations
Ioannis Liampas
Department of Neurology, University Hospital of Larissa, School of Medicine, University of Thessaly, 41100 Larissa, Greece
Vasileios Siokas
Department of Neurology, University Hospital of Larissa, School of Medicine, University of Thessaly, 41100 Larissa, Greece
Niki Mourtzi
1st Department of Neurology, Aiginition Hospital, National and Kapodistrian University of Athens Medical School, 11528 Athens, Greece
Sokratis Charisis
1st Department of Neurology, Aiginition Hospital, National and Kapodistrian University of Athens Medical School, 11528 Athens, Greece
Stefanos N. Sampatakakis
1st Department of Neurology, Aiginition Hospital, National and Kapodistrian University of Athens Medical School, 11528 Athens, Greece
Ioannis Foukarakis
1st Department of Neurology, Aiginition Hospital, National and Kapodistrian University of Athens Medical School, 11528 Athens, Greece
Alex Hatzimanolis
Department of Psychiatry, Aiginition Hospital, National and Kapodistrian University of Athens Medical School, 11528 Athens, Greece
Alfredo Ramirez
Division of Neurogenetics and Molecular Psychiatry, Department of Psychiatry and Psychotherapy, Medical Faculty, University of Cologne, 50923 Cologne, Germany
Jean-Charles Lambert
U1167-RID-AGE Facteurs de Risque et Déterminants Moléculaires des Maladies Liés au Vieillissement, CHU Lille, Inserm, Institut Pasteur de Lille, Université de Lille, 59000 Lille, France
Mary Yannakoulia
Department of Nutrition and Dietetics, Harokopio University, 17671 Athens, Greece
Mary H. Kosmidis
Lab of Cognitive Neuroscience, School of Psychology, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
Efthimios Dardiotis
Department of Neurology, University Hospital of Larissa, School of Medicine, University of Thessaly, 41100 Larissa, Greece
Georgios M. Hadjigeorgiou
Department of Neurology, Medical School, University of Cyprus, Nicosia 2414, Cyprus
Paraskevi Sakka
Athens Association of Alzheimer’s Disease and Related Disorders, 11636 Maroussi, Greece
Konstantinos Rouskas
Institute of Applied Biosciences, Centre for Research & Technology Hellas, 54124 Thessaloniki, Greece
Nikolaos Scarmeas
1st Department of Neurology, Aiginition Hospital, National and Kapodistrian University of Athens Medical School, 11528 Athens, Greece
Background: 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. Methods: 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. Results: 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. Conclusions: 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.
