Cognitive Reserve in Healthy Aging: Moderation Effect on Structural and Functional Connectivity in the Default Mode Network

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Cognitive reserve (CR) is the mental engagement during tasks that enables reallocation of cogni-tive resources in support of normal cognitive function. It has been shown to compensate for brain structure alterations in pathological and healthy aging. Although previous neuroimaging studies suggest that CR may influence the functional utilization of the brain when coping with tasks, the underlying neural mechanism by which CR directly or indirectly modulates brain activity remains unclear. In this study, we focused on investigating the structural connectivity and functional con-nectivity between the anterior and posterior parts of the default-mode network (apDMN), which has been reported to differentiate during aging and is associated with memory-related behavioral outcomes. We hypothesized that CR would moderate the aging effect on both structural and functional connectivity of the apDMN across lifespan. We employed resting-state functional mag-netic resonance imaging (MRI) and diffusion MRI to assess the functional and structural connec-tivity of the apDMN. The CR index questionnaire (CRIq) was utilized to assess multiple aspects of CR for each subject. Without considering CR effects, our results showed that the functional con-nectivity of the apDMN decreases under aging effect. However, with the intervention of CR prox-ies, the aging effect was moderated and only the subjects with lower level of CR showed signifi-cantly altered age-related brain functional and structural integrity (p < 0.05). This finding suggests that people with lower CR level may be less resistant to aging. Examinations for moderation of CR on age-related change among whole-brain networks with a larger sample size and optimized an-alytic methods would be of great interest in further studies to better elucidate the regional and global effect of CR on brain aging.
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