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Background: Researchers have used the concept of brain reserve to explain the dissociation between pathological brain damage and cognitive and functional performance. A variety of brain reserve hypotheses exist, and different empirical strategies have been employed to investigate these variants. Objective: The study investigates (i) the relationship between measures of brain burden (atrophy, white matter hyperintensities (WMH)) and measures of reserve (education, creativity, and intelligence); (ii) the relationship between cognitive decline and reserve; (iii) whether measures of reserve mediate the effect of atrophy on estimated cognitive change, and (iv) the association between brain risk factors, education and atrophy. Methods: A cross-sectional study of a sample of 446 individuals 60–64 years of age who underwent MRI scans as part of a large epidemiological study. Measures were taken of …