Residual reserve index modifies the effect of amyloid pathology on FDG metabolism: implications for efficiency and capacity in cognitive reserve

Cognitive functioning may be protected against AD pathology via cognitive resilience (conferred by cognitive reserve) or brain resilience (conferred by brain reserve or maintenance). The residual approach to measuring cognitive reserve (i.e., using the residual reserve index) aims to capture cognitive resilience, but may be confounded by unmeasured brain factors representing brain resilience. We sought to distinguish between brain and cognitive resilience by comparing the interactions between the residual reserve index and amyloid, tau, and neurodegeneration (AT(N); Jack et al., 2018) biomarkers when predicting executive function. We hypothesized that the residual reserve index would moderate at least one path from an AT(N) biomarker to executive function (consistent with cognitive resilience), as opposed to moderating a path between two AT(N) biomarkers (suggestive of brain resilience).