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Identification of hippocampal volume as a mediator of the association between APOE4 and dementia
Author(s) -
Brenek Sixtine,
Debette Stéphanie,
Auriacombe Sophie,
Amouyel Philippe,
Chouraki Vincent,
Meirhaeghe Aline,
Damotte Vincent
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.047425
Subject(s) - dementia , mediation , association (psychology) , apolipoprotein e , vascular dementia , psychology , medicine , hippocampal formation , hyperintensity , hippocampus , diabetes mellitus , clinical psychology , gerontology , endocrinology , disease , magnetic resonance imaging , psychotherapist , political science , law , radiology
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.