Identification of hippocampal volume as a mediator of the association between APOE4 and dementia: Developing topics. (7th December 2020)

• Record Type: Journal Article
• Authors: Brenek, Sixtine; Debette, Stéphanie; Auriacombe, Sophie; Amouyel, Philippe; Chouraki, Vincent; Meirhaeghe, Aline; Damotte, Vincent
• Is Part Of: Alzheimer's & dementia. Volume 16(2020)Supplement 3
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-12-07
• Subjects: Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1002/alz.047425
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: Background: The apolipoprotein E ε4 allele ( APOE4 ), vascular risk factors and neurodegenerative factors are known to be associated with dementia. This study aimed at identifying any mediating effect of those risk factors in the association existing between APOE4 and dementia. Methods: 1, 197 participants from the French Three City Dijon Study without prevalent tumor or dementia were included. Among these participants, 72 developed dementia during the 12 years of follow‐up. Using regression and mediation analyses, we studied whether known risk factors for dementia i.e diabetes mellitus, hypercholesterolemia, hypertension, hippocampal volume or white matter hyperintensities could mediate the association between APOE4 and dementia. Regression models were adjusted for age, sex, education level (and total intracranial volume when imaging metrics were considered). Results: Hippocampal volume was a partial mediator of the association between APOE4 and dementia (mediation ratio = 8.7%, p=0.008). No mediation effect was found for hypercholesterolemia. No mediation analyses could be undertaken for the others factors due to the lack of their association with APOE4 in our sample. Conclusion: In this study, the association between APOE4 and dementia was partially mediated by hippocampal volume, suggesting a deleterious role of APOE4 in the hippocampus. This result warrants further replication in other cohorts, with higher sample sizes.