Association between diffusion MRI-based measures of neurite microstructure and risk of Alzheimer's disease

Early detection of Alzheimer's disease (AD) is crucial for intervention, but traditional MRI and cognitive assessments may miss pre-symptomatic changes. Advanced diffusion MRI (dMRI) methods, such as Neurite Orientation Dispersion and Density Imaging (NODDI), show promise in identifying early brain changes. We analyzed 65 cognitively unimpaired older adults (25 APOE-e4 carriers, 40 non-carriers) from the ADNI3 dataset. NODDI's neurite density index (NDI) and orientation dispersion index (ODI), volumetric MRI and cognition (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. NDI differed significantly between carriers and non-carriers and correlated with MoCA scores. ODI differed only in the CA1 hippocampal subfield. Volumetric MRI measures showed no group differences. Significant APOE-e4 group differences were observed in NDI for the left fusiform gyrus (β = 0.015, p = 0.02), right fusiform gyrus (β = 0.018, p = 0.02), left entorhinal cortex (β = 0.018, p = 0.04), right entorhinal cortex (β = 0.018, p = 0.03), left CA1 (β = 0.03, p = 0.02), and left CA2–3 (β = 0.03, p = 0.02). ODI differences were observed only in left CA1 (β = 0.037, p = 0.008). No volumetric measures differed significantly. MoCA correlated with NDI in bilateral entorhinal cortices (p = 0.001–0.05), left fusiform gyrus (p = 0.02), and right CA2–3 (p = 0.02). NODDI metrics, particularly NDI, could help detect early APOE-e4-related microstructural changes, while traditional volumetric MRI measures remain uninformative at early stages.