Do cognitive reserve proxies capture a common neural signature? A systematic review and meta-analysis of task-based fMRI studies

Cognitive reserve (CR) refers to the capacity of the brain to sustain cognitive performance despite age-related changes or pathophysiological conditions. Task-based functional magnetic resonance imaging (tb-fMRI) has been instrumental in exploring its neural correlates. CR is traditionally assessed through socio-behavioral proxies such as education, intelligence quotient, or composite indices. However, these proxies vary considerably in definition and application, posing challenges regarding their validity and consistency across experiments. This systematic review and meta-analysis examined whether these proxies are associated with consistent brain activation patterns in healthy adults. A literature search identified 12 eligible tb-fMRI experiments (n = 802 participants) reporting whole-brain CR-related activation. A coordinate-based meta-analysis using permutation of subject images-signed differential mapping (PSI-SDM) was conducted to assess consistent activation patterns across experiments, complemented by meta-regression analyses to examine whether differences in proxy type accounted for inter-study variability. The PSI-SDM meta-analysis yielded no significant clusters of activation. A qualitative synthesis of individual experiments further highlighted a lack of topographical consistency. These findings indicate that widely used socio-behavioral proxies are not associated with detectable, reproducible convergent patterns in tb-fMRI, revealing a measurement gap in current CR research. This null convergence likely reflects methodological heterogeneity and conceptual inconsistency in the literature, rather than the absence of CR-related neural mechanisms.