Cognitive reserve predicts future executive function decline in older adults with Alzheimer's disease pathology but not age-associated pathology

Cognitive reserve has been described as offering protection against Alzheimer's disease (AD) and other neurodegenerative conditions, but also against age-associated brain changes. Using data from the Alzheimer's Disease Neuroimaging Initiative, we defined cognitive reserve using the residual reserve index: episodic memory performance residualized for 3T MRI-derived brain volumes and demographics. We examined whether cognitive reserve predicted executive function (EF) decline equally across 2 groups of older adults-AD biomarker-positive (n = 468) and -negative (n = 402)-defined by the tau-to-amyloid ratio in cerebrospinal fluid. A significant interaction between the residual reserve index and biomarker group revealed that the effect of cognitive reserve on EF decline was dependent on pathology status. In the biomarker-positive group, higher cognitive reserve predicted EF decline over five years. However, cognitive reserve did not predict EF decline in the biomarker-negative group. These results suggest a certain level of AD pathology may be needed before cognitive reserve exerts its protective effects on future cognition; however, further research that tracks cognitive reserve longitudinally is needed.