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The Mini-mental State Examination (MMSE) is a brief cognitive screening instrument frequently used to track Alzheimer disease (AD) progression. We investigated the structural neuroimaging correlates of MMSE performance in patients with clinical and preclinical AD. We analyzed structural magnetic resonance imaging data from 29 probable AD and 5 MCI patients who later converted to probable AD using an advanced 3D cortical mapping technique. MMSE scores were entered as covariates in a general linear model that predicted the gray matter density at each cortical surface point. The results were corrected for multiple comparisons by permutation testing. The global permutation-corrected significance for the maps linking gray matter loss and cognitive decline was P=0.005 for the left and P=0.012 for the right hemisphere. Strongest correlations between MMSE score and gray matter integrity were seen in the entorhinal, parahippocampal, precuneus, superior parietal, and subgenual cingulate/orbitofrontal cortices. Significant correlations were also seen bilaterally in the temporal, the middle frontal and the left angular and supramarginal gyri. As a global cognitive measure, MMSE depends on the integrity of widely distributed cortical areas in both brain hemispheres with left-sided predominance.