Objective: Intraindividual variability (IIV) in cognitive performance has been associated with cognitive decline and reductions in white matter integrity, but the predictive utility of IIV-between versus IIV-within domains is unknown. The present study aimed to determine if IIV-within a "frontal-subcortical" domain may be a more robust predictor of changes in general cognitive status and functional independence over time than IIV-between cognitive domains. Method: Mixed linear modeling was used to analyze the relationship between cognitive IIV and cognitive and functional status in 651 controls, 211 people with mild cognitive impairment, and 218 people with Alzheimer's disease over a 5-year period. Results: Both IIV-between and IIV-within a frontal-subcortical domain improved prediction of cognitive and functional declines beyond demographic characteristics, genetic risk, and vascular integrity. IIV-between showed the greatest effect over time and was driven primarily by increases in IIV-within. Conclusions: Cognitive IIV, especially between cognitive domains, may be useful for identifying individuals at risk for cognitive and functional decline. Findings may facilitate investigations into mechanisms underlying declines in global cerebral integrity and aid clinical trials aimed at early detection and treatment.
Key PointsQuestion: Does variability in performance on cognitive tasks predict declines in cognition and functional independence? Findings: Performance variability both within and between cognitive domains predicts declines in cognition and functional independence, but the latter is a more robust predictor than the former. Importance: Performance variability may be used to identify and study those at greatest risk for subsequent decline, with the ultimate aim of improving early detection and treatment.Next Steps: Future research should examine the generalizability and replicability of these findings.