Timing of First Alzheimer's Neuroimaging: A Multicenter Analysis of Genetic, Cognitive, and Social Factors

Abstract

Background. Magnetic resonance imaging (MRI) is central to Alzheimer's disease research and clinical evaluation, yet timing of first MRI after cohort entry varies substantially. In aging cohorts, many participants die before imaging, and treating death as noninformative censoring can distort inference on neuroimaging access and conceal disparities. Objective. To quantify individual-level determinants and center-level heterogeneity in timing of first neuroimaging while accounting for the competing risk of death. Methods. We analyzed National Alzheimer's Coordinating Center Uniform Data Set v3 linked to MRI records from 2015 through March 2025. The study included 20,867 participants aged 50-95 years without dementia at baseline and with known APOE ε4 status. Time from baseline to first post-baseline MRI was the primary event, with death before MRI treated as a competing event. We fit Bayesian multilevel cause-specific accelerated failure time models with Alzheimer's Disease Center random intercepts, using Weibull and log-logistic models for MRI timing and death, respectively. Frequentist accelerated failure time and Cox models were used for sensitivity analyses. Results. APOE ε4 was not credibly associated with timing of first MRI. Older age, lower educational attainment, and non-White race were associated with delayed MRI acquisition. Center-level variation in MRI timing was substantial. Conversely, APOE ε4 homozygosity was associated with earlier death prior to MRI, alongside strong effects of age and cognitive impairment. Conclusions. Timing of first MRI in Alzheimer's research cohorts is driven primarily by demographic, social, and center-level factors rather than genetic risk. Accounting for competing mortality and site heterogeneity is necessary to avoid biased neuroimaging samples and support equitable Alzheimer's research.