Year: 2026
Type: preprint
Abstract: BACKGROUND: Subjective cognitive decline (SCD) may precede mild cognitive impairment (MCI), but not all individuals with SCD progress to MCI. Identifying which individuals are most likely to convert and over what time frame remains an important goal in Alzheimer's disease research. MRI measures of white matter hyperintensity (WMH) burden and gray matter (GM) atrophy may improve prediction beyond demographic and cognitive predictors, but their incremental value across different time intervals has not been established. METHODS: Data were obtained from four longitudinal cohorts (ADNI, NACC, CIMA-Q, and PREVENT-AD). A total of 1,352 participants with SCD at baseline were included. Machine learning models (logistic regression, random forest, XGBoost) were used to predict conversion from SCD to MCI at 2 years, 3 years, 4 years, and 5-year horizons. Four feature sets were compared: base (age, sex, education, APOE4, hypertension), base and cognition (adding MoCA and Trail Making Test Part B), base and MRI (adding regional WMH and GM volumes), and combined (all features). RESULTS: The base and MRI set achieved the highest Area Under the Curve (AUC) at the 3-year (0.900), 4-year (0.879), and 5-year (0.923) horizons. The combined set achieved the highest AUC at the 2-year horizon only (0.884). MRI features produced larger AUC gains over the base model than cognitive features at the 3, 4, 5-year horizons. Parietal WMH was the most frequently selected MRI predictor. CONCLUSIONS: MRI features, particularly regional WMH and GM volumes, provided greater predictive value than cognitive features at longer prediction horizons. A select number of regional MRI features predicted SCD to MCI conversion with high accuracy up to 5 years in advance.
Source: medRxiv
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: U.S. Department of Defense, Alzheimer's Association, Bristol-Myers Squibb, Eli Lilly and Company, Pfizer, Biogen, University of Southern California, F. Hoffmann-La Roche, Meso Scale Diagnostics, Alzheimer's Disease Neuroimaging Initiative, BioClinica, Novartis Pharmaceuticals Corporation, McGill University, Fondation Brain Canada, Northern California Institute for Research and Education, Réseau en Bio-Imagerie du Quebec, Compute Canada, Réseau québécois de recherche sur le vieillissement, Government of Canada, Alzheimer Society, Eisai, Servier, H. Lundbeck A/S, IXICO, Courtois Foundation, National Institutes of Health, Genentech, Alzheimer Society Research Program, Pfizer Canada, Canadian Institutes of Health Research, Natural Sciences and Engineering Research Council of Canada, Fonds de Recherche du Québec - Santé, National Institute on Aging
Awards: G1012222616, G104586243, G1298807586, Alzheimer's Disease Research Center, G1364373663, G1554142629, G1593117279, G1650819308, G1880935189, G192978874, G2100670906, G2105457377, G2152643862, G2189010064, G2340207221, G2423387114, G2471646051, G2522063444, G2835601961, G2971624992, G29951154, G3131374986, G3146424788, 1Florida Alzheimer's Disease Research Center, G3216574877, G3553156159, G3710456697, G3752451908, G3870774570, G3908963977, G3964029210, G3966393351, G4259465822, G43180419, G4501223628, G4800177743, G505421839, G5207404921, G5209990037, G528601746, G5365730499, G5396387670, G543448746, G559571648, Investigating the impact of loneliness on brain aging and pre-symptomatic Alzheimer's disease progression, G5654639750, G5740349702, G613619302, G6173816828, G6210868510, G6240289386, G6371410416, G639043084, G6412110892, G6437235618, G6441695449, G6447063303, G6576975730, G6719828067, G6760090938, G6792506723, G6876577119, G6899163935, G6948409098, G7026657527, G72415811, G7298697282, Vanderbilt Alzheimer's Disease Research Center, G764699806, G7799614282, G781725486, G8077616060, G8228018387, G8281378126, G839208290, G8620678629, G8760577957, G8852128998, G8895907669, G8897063270, G8957659042, G9000039018, G9000122335, Boston University Alzheimer's Disease Research Center, Yale Alzheimer Disease Research Center, UCSD Shiley-Marcos Alzheimer's Disease Research Center P30, Michigan Alzheimer's Disease Research Center, University of Kansas Alzheimer's Disease Research Center (KU ADRC), Alzheimer Disease Research Center, Alzheimer's Disease Research Center, Oregon Alzheimer's Disease Research Center, Alzheimer's Disease Research Center, UC Davis Alzheimer's Disease Research Center, Johns Hopkins Alzheimer's Disease Research Center, Indiana Alzheimer's Disease Research Center, Cleveland Alzheimers Disease Research Center, New Approaches to Dementia Heterogeneity, Stanford Alzheimer's Disease Research Center, Mount Sinai Alzheimer's Disease Research Center, Mayo Alzheimer's Disease Research Center, University of Washington Alzheimer's Disease Research Center, Duke/UNC Alzheimer's Disease Research Center, Wisconsin Alzheimer's Disease Research Center, Alzheimer's Disease Research Centers, UAB Alzheimer's Disease Research Center, National Alzheimer's Coordinating Center, University of Kentucky Alzheimer's Disease Research Center, NORTHWESTERN Alzheimer's Disease Research Center, Penn Alzheimer's Disease Research Center (ADRC), Alzheimer's Disease Research Center, Massachusetts Alzheimer's Disease Research Center (MADRC), South Texas Alzheimer's Disease Center, Goizueta Alzheimer's Disease Research Center, The Alzheimer's Disease Research Center at the University of California, Irvine, Rush Alzheimer's Disease Research Center
OpenAlex ID: W7212077001