Insulin Resistance and Future Cognitive Performance and Cognitive Decline in Elderly Patients with Cardiovascular Disease

Background: The role of insulin resistance (IR) in the pathogenesis of cognitive performance is not yet clear. Objective: To examine the associations between IR and cognitive performance and change in cognitive functions two decades later in individuals with cardiovascular disease with and without diabetes. Methods: A subset of 489 surviving patients (mean age at baseline 57.7±6.5 y) with coronary heart disease who previously participated in the secondary prevention Bezafibrate Infarction Prevention (BIP trial; 1990–1997), were included in the current neurocognitive study. Biochemical parameters including IR (using the homeostasis model of assessment; HOMA-IR) were measured at baseline. During 2004–2008, computerized cognitive assessment and atherosclerosis parameters were measured (T1; n = 558; mean age 72.6±6.4 years). A second cognitive assessment was performed during 2011–2013 (T2; n = 351; mean age 77.2±6.4 years). Cognitive function, overall and in specific domains, was assessed. We used linear regression models and linear mixed models to evaluate the differences in cognitive performance and decline, respectively. Results: Controlling for potential confounders, IR (top HOMA-IR quartile versus others) was associated with subsequent poorer cognitive performance overall (β= –4.45±Standard Error (SE) 1.54; p = 0.004) and on tests of memory and executive function among non-diabetic patients (β= –7.16±2.38; p = 0.003 and β= –3.33±1.84; p = 0.073, respectively). Moreover, among non-diabetic patients, IR was related to a greater decline overall (β= –0.17±0.06; p = 0.008), and in memory (β= –0.22±0.10; p = 0.024) and executive function (β= –0.19±0.08; p = 0.012). The observed associations did not differ after excluding subjects with prevalent stroke or dementia. Conclusion: IR is related to subsequent poorer cognitive performance and greater cognitive decline among patients with cardiovascular disease with and without diabetes.