Diffusion MRI-based measures of neurite microstructure associate with future risk of Alzheimer’s Disease

INTRODUCTION 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 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.

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.

NODDI metrics, particularly NDI, could help detect early APOE-e4-related microstructural changes, while traditional volumetric MRI measures remain uninformative at early stages. Competing Interest Statement The authors have declared no competing interest. Funding Statement This study did not receive any funding Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Institutional Review Board of Arizona State University gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Footnotes ↵* Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf Figures have been rescaled to suit preview window. Data Availability All data produced are available online at adni.loni.usc.edu