{"doi":"10.1101/2025.04.07.25325401","title":"Diffusion MRI-based measures of neurite microstructure associate with future risk of Alzheimer’s Disease","abstract":"ABSTRACT 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. METHODS 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. RESULTS 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. DISCUSSION NODDI metrics, particularly NDI, could help detect early APOE-e4-related microstructural changes, while traditional volumetric MRI measures remain uninformative at early stages.","journal":"medRxiv","year":2025,"id":557492,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.931,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":580595,"name":"Andrew Hooyman","orcid":"0000-0002-8705-3759","position":1,"is_corresponding":false},{"id":571429,"name":"Jennapher Lingo VanGilder","orcid":"0000-0002-4273-6003","position":2,"is_corresponding":false},{"id":380985,"name":"Sydney Y. Schaefer","orcid":"0000-0002-6976-8419","position":3,"is_corresponding":false},{"id":267702,"name":"Scott C. Beeman","orcid":"0000-0001-6721-1185","position":4,"is_corresponding":false},{"id":229339,"name":"Alzheimer’s Disease Neuroimaging Initiative","orcid":null,"position":5,"is_corresponding":false},{"id":1429572,"name":"Sasha Hakhu","orcid":"0009-0007-0019-6284","position":0,"is_corresponding":true}],"reference_count":70,"raw_metadata":null,"created_at":"2026-07-19T02:55:17.435961Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}