biostudies-literatureMcKenzie CNIA NIH HHSU.S. Department of DefenseNational Institutes of HealthCIHR119-127https://www.ebi.ac.uk/biostudies/studies/S-EPMC12903205biostudies-literatureUnknown88Cognitive 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 patholNeurobiology of agingCognitive reserve predicts future executive function decline in older adults with Alzheimer's disease pathology but not age-associated pathology.PMC12903205U01 AG024904Bourgeat PAlzheimer's Disease Neuroimaging InitiativeMcKenzie CWeinborn MBucks RSSalvado OGavett BEfalseCognitive 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 pathol2020-01-01T00:00:00Z2020 Apr2026-07-15T15:34:33.8Z2026-07-06T03:11:23.116ZS-EPMC129032053198027910.1016/j.neurobiolaging.2019.12.022