Volumetric alterations in the hippocampal subfields of subjects at increased risk of dementia.

The hippocampus is one of the first regions to demonstrate atrophy during the prodromal stage of Alzheimer's disease. Volumetric analysis of its individual subfields could provide biomarkers with higher sensitivity than whole hippocampal volume during an earlier disease stage. We quantified the hippocampal subfields volume in a large cohort comprising healthy participants (aged 40–59) with dementia family history (FH) and controls (without FH), examined at 2 time points across 2 years. Subfield volumes were quantified using both a T1-weighted and a high-resolution T2 hippocampal magnetic resonance imaging acquisition with Freesurfer. The participants were stratified based on dementia FH, APOE genotype, and CAIDE (Cardiovascular Risk Factors, Aging and Dementia) risk score. Whole hippocampal volume did not differ between the groups. The volume of the molecular layer was lower in participants with an APOE ε4 genotype, but there were no differences between subjects with and without dementia FH or with an increasing CAIDE score. The molecular layer may be the first hippocampal region to demonstrate volumetric alterations in subjects at risk of dementia. • Serial hippocampal subfield volumetry was performed in the PREVENT-Dementia study. • The molecular layer volume was lower in participants with an APOE ε4 genotype. • This finding was recorded in the absence of whole hippocampal atrophy. • The molecular layer might be the first subfield to demonstrate pathological alterations in Alzheimer's disease. • Hippocampal subfield atrophy in Alzheimer's disease might precede whole hippocampal atrophy. [ABSTRACT FROM AUTHOR]