Diffusion MRI-based measures of neurite microstructure associate with future risk of Alzheimers Disease.

Introduction Early detection of Alzheimers disease (AD) is crucial for intervention, but traditional MRI and cognitive assessments may miss presymptomatic changes. Advanced diffusion MRI (dMRI) methods, such as Neurite Orientation Dispersion and Density Imaging (NODDI), show promise in identifying early brain changes. Methods We analyzed 65 cognitively unimpaired older adults (25 APOE E4 carriers, 40 non-carriers) from the ADNI3 dataset. NODDIs neurite density index (NDI) and orientation dispersion index (ODI), volumetric MRI and cognitive performance (MoCA) were analyzed in key brain regions like the hippocampus, fusiform gyrus, and entorhinal cortex. Statistical analyses included linear regression and t tests, with FDR correction. Results NDI differed significantly between carriers and noncarriers and correlated with MoCA scores. ODI differed only in the CA1 hippocampal subfield. Volumetric MRI measures showed no group differences. Discussion ODDI metrics, particularly NDI, could help detect early APOE E4 related microstructural changes, while traditional volumetric MRI measures remain uninformative at early stages.