Testing covariates of Type 2 diabetes-cognition associations in older adults: moderating or mediating effects?

Abstract

The general goal of this study was to advance our understanding of Type 2 diabetes (T2D)-cognition relationships in older adults by linking and testing comprehensive sets of potential moderators, potential mediators, and multiple cognitive outcomes. We identified in the literature 13 health-related (but T2D-distal) potential covariates, representing four informal domains (i.e., biological vitality, personal affect, subjective health, lifestyle activities). Cross-sectional data from the Victoria Longitudinal Study (age range = 53-90 years; n = 41 T2D and n = 458 control participants) were used. We first examined whether any of the 13 potential covariates influenced T2D-cognition associations, as measured by a comprehensive neuropsychological battery (15 measures). Next, using standard regression-based moderator and mediator analyses, we systematically tested whether the identified covariates would significantly alter observed T2D-cognition relationships. Six potential covariates were found to be sensitive to T2D associations with performance on seven cognitive measures. Three factors (systolic blood pressure, gait-balance composite, subjective health) were significant mediators. Each mediated multiple cognitive outcomes, especially measures of neurocognitive speed, executive functioning, and episodic memory. Our findings offer a relatively comprehensive perspective of T2D-related cognitive deficits, comorbidities, and modulating influences. The implications for future research reach across several fields of study and application. These include (1) neuropsychological research on neural and biological bases of T2D-related cognitive decline, (2) clinical research on intervention and treatment strategies, and (3) larger-scale longitudinal studies examining the potential multilateral and dynamic relationships among T2D status, related comorbidities, and cognitive outcomes.