APOE and Cognitive impairment: Generalized linear models examined whether baseline IICV predicted incident mild cognitive impairment (MCI)/dementia, cognitive decline, and amyloid and tau positron emission tomography outcomes, adjusting for demographics, intellectual disability, apolipoprotein E ε4, site, assessment interval, and mean cognitive performance, with Bonferroni correction.<h4>Results</h4>Greater IICV predicted incident MCI/dementia (odds ratio = 4.63 to 5.13, p < 0.05), greater amyloid burden, early tau accumulation, and higher tau across Braak stages, independent of mean cognition.