Cognitive intraindividual variability as a biomarker for functional declines in the Texas Alzheimer’s Research and Care Consortium (TARCC) Longitudinal Hispanic Cohort

Abstract

AbstractBackgroundWhile intraindividual variability (IIV) in cognitive performance has been associated with increased risk for cognitive decline, the relative predictive utility of IIV‐across versus IIV‐within different cognitive domains remains unknown. Given that cognitive IIV has also been linked to age‐related reductions in white matter integrity, the current study aimed to determine if IIV‐within a “frontal‐subcortical” domain may be a more robust predictor of functional declines over time than IIV‐across cognitive domains.MethodsParticipants included 651 controls, 211 MCI and 218 AD patients enrolled in the TARCC Hispanic Longitudinal Cohort. Mixed Linear Modeling was used to examine the fixed effects of static predictors (i.e., age, education, gender, ethnicity, APOE genotype, cognitive status) at baseline, and the fixed and random effects of time‐varying covariates (i.e., depression, pulse pressure, IIV‐across domains, and IIV‐within the frontal‐subcortical domain) on changes in functional independence over 5 years.ResultsAge, education and ethnicity moderated the relationship between APOE genotype, baseline cognitive status and declines in functional independence over time. Overall, greater pulse pressure, IIV‐across domains and IIV‐within the frontal‐subcortical domain were all associated with larger decrements in functional independence over time. Although increases in IIV‐across domains were primarily driven by increases in IIV‐within the frontal‐subcortical domain over time, the former emerged as a stronger predictor of functional independence than the latter. Gender and education significantly influenced individual differences in rates of change over time, while the effects of IIV‐across domains and IIV‐within the frontal‐subcortical domain on functional declines differed from person‐to‐person. The addition of cognitive IIV predictors significantly improved model fit with a 1498.3 reduction in ‐2LL (p < 0.001). The final model accounted for 97.8% of the variance in functional independence over time.ConclusionsResults suggest that IIV‐across domains may be a robust biomarker of subsequent declines in functional independence and changes in this metric are primarily driven by increasing variability across tasks dependent on frontal‐subcortical circuitry. Findings also highlight important considerations for the development of future clinical trials aimed at early prevention and treatment, including the significance of demographic and clinical characteristics in moderating the risk of decline in functional independence over time.