Relating hippocampal subfield microstructure to delayed verbal memory in cognitively intact individuals at genetic risk for developing Alzheimer’s disease

Early intervention to delay Alzheimer’s disease (AD) is critical but detecting at-risk individuals before disease progression is challenging. We evaluate the relationship between hippocampal microstructure and memory in cognitively intact older adults based on the at-risk APOΕ ε4 genotype. Participants (n=41 noncarriers, 33 carriers) > 60 years (mean±SD: carriers 71±6.6; noncarriers 71±6.4) were compared using the diffusion weighted MRI microstructure measures (Neurite Orientation Dispersion and Density Imaging; NODDI), diffusion tensor imaging (DTI), volumetric measures and memory scores. Regression analyses indicated that while volumetric data showed no significant findings, the orientation dispersion (ODI) in the left subiculum was positively associated with verbal memory only in APOΕ ε4 carriers (FDR-corrected p=0.01) but not in noncarriers or for other volumetry or for visual memory. The right hemisphere did not show significant memory correlations. Hippocampal microstructure, rather than volume, may provide early insights into early memory changes in groups at risk for AD.