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

Early intervention to delay the onset of Alzheimers disease (AD) is an important treatment strategy but detecting at-risk individuals before significant disease progression remains challenging. This study evaluates the relationship between hippocampal microstructure and verbal cognition in cognitively intact older adults, focusing on the differences between APOE {varepsilon}4 allele carriers and noncarriers. Participants (n=41 noncarriers, 33 carriers) over 60 years old (mean{+/-}SD: carriers 71{+/-}6.6; noncarriers 71{+/-}6.4 years) underwent diffusion-weighted magnetic resonance imaging (dMRI) and volumetric assessments. We assessed hippocampal structure, including microstructure, using Neurite Orientation Dispersion and Density Imaging (NODDI), diffusion tensor imaging (DTI), and volumetric measures. Regression analyses examined the relationship between these hippocampal measures and verbal and visuospatial cognition, as evaluated by the Rey delayed recall tests i.e., the Auditory Verbal Learning Test (AVLT) and Complex Figure Test (CFT), respectively. Results indicated that while volumetric data showed no significant findings, microstructural measures, particularly orientation dispersion (ODI) in the left subiculum, were positively associated with verbal recall in APOE {varepsilon}4 carriers (FDR-corrected p=0.01). These findings suggest that hippocampal microstructure, rather than volume, may provide early insights into cognitive decline in individuals at genetic risk for AD.