Insulin Resistant States Predict Cognitive Performance and Cognitive Decline in Coronary Heart Disease Patients

Background: Pre-diabetes and underlying insulin resistance are frequent in coronary heart disease (CHD). Their role in the pathogenesis of cognitive performance is not yet clear. We undertook to examine whether the former conditions place individuals at a high risk for late-life low cognitive performance and cognitive decline among CHD patients.

Patients and Methods: We evaluated 351 surviving CHD patients (mean age at baseline 57.9±6.6 y, at reassessment 77±6.4 y, 95.9% males) who had originally participated in a secondary prevention trial (BIP trial; 1990 to 1997), for cognitive function and measures of atherosclerosis (median follow up of 14 yrs) and reassessment for cognitive function (median follow up of 20 yrs). Insulin resistance (using the homeostasis model of assessment; HOMA-IR), blood lipids and low-level inflammatory biomarkers were measured at baseline (1990-1992). Cerebrovascular reactivity, carotid intima media thickness and presence of carotid plaques were determined using carotid Doppler ultrasonography. Cognitive function, overall and in specific domains, was assessed using the NeuroTrax computerized tests. Linear mixed model analysis with random effects was applied to compare cognitive scores and cognitive decline, respectively, in people with insulin resistance vs. none.

Results: Controlling for potential confounders, insulin resistance (upper vs. lower HOMA-IR quartile) was associated with subsequent poorer cognitive performance overall (ß=-3.66± Standard Error (SE) 1.24; p=0.003) and on tests of memory and executive function (ß=-5.22±1.8; p=0.005 and ß=-4.03±1.47; p=0.006, respectively). Moreover, insulin resistance was positively related to a greater decline overall (ß=-0.16±0.06; p=0.006), memory (ß=-0.23±0.09; p=0.010) and in executive function (ß=-0.19±0.07; p=0.011). The observed associations were maintained excluding subjects with prevalent diabetes, stroke and dementia.

Conclusions: Insulin resistance was associated with low cognitive performance and late cognitive decline among CHD patients.