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 education, intelligence, creativity, cognitive speed, brain volume, WMH, estimated cognitive decline from earlier in life and brain atrophy. Results: No association was found between estimated cognitive decline and brain burden (atrophy, WMH). Risk factors for brain insult were not associated with greater brain atrophy in the less well educated. Neither education, nor any other measure including intelligence or creativity, provided a buffer for cognitive decline in individuals with high levels of brain atrophy. Conclusion: Little support was found for the brain reserve hypothesis.

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