Neurite density and free water concentration are associated with synaptic density in the hippocampus as assessed through NODDI and [C‐11]UCB‐J PET

Abstract Background Neurite Orientation Dispersion and Density Imaging (NODDI), derived through multi‐shell diffusion MRI, allows for the estimation of markers pertaining to multiple distinct components neural tissue microstructure. Lower neurite density index (NDI), lower orientation dispersion (ODI), higher volume fraction isotropic water (V iso ), have all been significantly associated with biomarkers AD pathology, as well increase diagnostic model predictability. Recent studies employing [C‐11]UCB‐J PET study synaptic vesicle glycoprotein 2A (SV2A) found strong reductions in individuals AD. Here we explore regional associations between cortical microstructure (indexed by NODDI) (measured PET). We hypothesize that increased NDI ODI, decreased V will associate binding. Method Participants (N=24) included cognitively unimpaired impaired older adults (Table 1) from Wisconsin Alzheimer’s Disease Research Center who underwent MRI. NODDI measures (including NDI, ) were estimated [11‐C]UCB‐J binding was quantified calculating distribution ratios (DVR) using SRTM2 whole cerebellum a reference region. Pearson correlations conducted within Desikan‐Killiany‐derived regions interest (ROI) including hippocampus, entorhinal cortex, parahippocampal gyrus, previously altered metrics population. Result Significant DVR both hippocampus (NDI: r = 0.45, p=0.047; : ‐0.46, p 0.043). A trend identified ODI parahippocampus (r 0.39, 0.098). No significant or trends cortex. Conclusion This preliminary analysis Both correlated indicating dendritic complexity are possibly linked. Future analyses include more participants, determine whether hippocampal addition may predictability, estimate temporal progression loss