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

Cathryn McKenzie, Romola Bucks, Michael Weinborn, Pierrick Bourgeat, Olivier Salvado, Brandon Gavett

Research output: Contribution to journalConference article


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).

Participants were 332 older adults from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). AT(N) biomarkers were measured as follows: amyloid = CSF Aβ42/Aβ40; tau = plasma p-tau181; neurodegeneration = FDG metabolism in AD-specific regions. AT(N) biomarkers were measured at consecutive time points and entered in a sequential mediation model testing the indirect effects from amyloid to executive function intercept and slope, via tau and/or FDG metabolism. The residual reserve index was entered as a moderator of paths between AT(N) biomarkers, and between AT(N) biomarkers and executive function.

The only significant interaction was between the residual reserve index and amyloid when predicting FDG metabolism, such that the indirect effect of amyloid → FDG metabolism → executive function intercept and slope varied as a function of the residual reserve index. With lower amyloid pathology, a higher residual reserve index predicted better executive function via lower FDG metabolism. With higher amyloid pathology, a higher residual reserve index predicted better executive function via higher FDG metabolism.

Although the residual reserve index moderated a path between two AT(N) biomarkers, the net effect was consistent with cognitive rather than brain resilience. Our results suggest the residual reserve index captures variation in cognitive reserve; specifically, neural efficiency and neural capacity to upregulate metabolism to enhance cognitive resilience in the face of more severe amyloid pathology.
Original languageEnglish
Pages (from-to)e066376
JournalAlzheimer's & Dementia
Issue numberS7
Publication statusPublished - 20 Dec 2022
EventAlzheimer's Association International Conference 2022 - San Diego, United States
Duration: 31 Jul 20224 Aug 2022

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