Objective: Cognitive reserve (CR) protects against cognitive decline by utilizing functional connectivity (FC) in the brain, such as the default mode network (DMN). We studied whether CR in individuals with predementia would correlate with better cognition and increased DMN FC in the resting brain. Methods: Fifty-four participants with subjective cognitive decline or mild cognitive impairment completed the Cognitive Reserve Index (CRI) questionnaire, and underwent a comprehensive neuropsychological test battery and resting state functional magnetic resonance imaging. Correlation and regression analyses for clinical variables and seed-to-voxel analyses of CR-related FC in the DMN were conducted. Results: CRI total (β=0.42, p=0.001), education (β=0.39, p=0.001), and leisure time (β=0.33, p=0.009) predicted the Mini- Mental State Examination. The CRI education predicted verbal memory recall (β=0.32, p=0.017), confrontational naming (β=0.57, p<0.001), and phonemic fluency (β=0.43, p=0.004). In the DMN in the resting brain, the CRI total correlated with increased FC, based on the posterior cingulate to both lateral parietal cortices. Conclusion: In individuals with predementia, comprehensive CR correlated with an enhanced network in the DMN in the resting state. These results may support the neural correlate of CR during the initial stage of cognitive decline.
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