Background: Education may modulate the degree to which the neuropathology of Alzheimer disease (AD) is expressed as impaired cognitive performance.

Methods: We studied 2,051 participants age 65+ years at 27 AD Centers who died and underwent autopsy. All took the Mini-Mental State Examination (MMSE) within 2 years before death. Braak & Braak stage, neuritic plaque density, and Consortium to Establish a Registry for Alzheimer’s Disease and National Institute on Aging (NIA)/Reagan diagnostic classifications quantified AD neuropathologic severity. Multivariate analyses modeled MMSE in relation to education and neuropathologic severity, adjusting for age at death, Lewy body pathology, and vascular dementia.

Results: Higher education was associated with higher MMSE scores when AD neuropathology was absent or mild. But with more advanced neuropathology, differences in MMSE scores among education levels were attenuated. For example, among patients without AD by NIA/Reagan criteria, fitted MMSE scores ranged from 19.6 for patients with less than high school education to 25.9 with education beyond high school. But among patients with neuropathologically advanced AD, the range of scores by education was only 7.1 to 8.6.

Conclusions: We found no evidence of larger education-related differences in cognitive function when Alzheimer disease (AD) neuropathology was more advanced. Higher Mini-Mental State Examination scores among more educated persons with mild or no AD may reflect better test-taking skills or cognitive reserve, but these advantages may ultimately be overwhelmed by AD neuropathology.