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• A lifestyle composite of smoking, alcohol consumption, diet, physical activity, and social engagement at age 40 was associated with accelerated brain aging in old age. • Brain aging and AD-brain signature in old age were worse among participants with lower age 20 cognitive ability. • Lower cognitive ability predicted better brain outcomes if lifestyle was favorable, but high cognitive ability predicted better brain outcomes regardless of lifestyle. • Favorable early midlife lifestyle may be protective against neurodegeneration and dementia risk especially among adults with lower cognitive ability. • Efforts at prevention could be prioritized earlier in midlife. We examined the influence of lifestyle on brain aging after nearly 30 years, and tested the hypothesis that young adult general cognitive ability (GCA) would moderate these effects. In the community-dwelling Vietnam Era Twin Study of Aging (VETSA), 431 largely non-Hispanic white men completed a test of GCA at mean age 20. We created a modifiable lifestyle behavior composite from data collected at mean age 40. During VETSA, MRI-based measures at mean age 68 included predicted brain age difference (PBAD), Alzheimer's disease (AD) brain signature, and abnormal white matter scores. There were significant main effects of young adult GCA and lifestyle on PBAD and the AD signature (p s ≤ 0.012), and a GCA-by-lifestyle interaction on both (p s ≤ 0.006). Regardless of GCA level, having more favorable lifestyle behaviors predicted less advanced brain age and less AD-like brain aging. Unfavorable lifestyles predicted advanced brain aging in those with lower age 20 GCA, but did not affect brain aging in those with higher age 20 GCA. Targeting early lifestyle modification may promote dementia risk reduction, especially among lower reserve individuals. [ABSTRACT FROM AUTHOR]