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

J Alzheimers Dis. 2017;57(2):633-643. doi: 10.3233/JAD-161016.


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.

Keywords: Cardiovascular disease; cognitive decline; cognitive impairments; insulin resistance.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Bezafibrate / therapeutic use
  • Cardiovascular Diseases / complications
  • Cardiovascular Diseases / drug therapy
  • Cardiovascular Diseases / physiopathology*
  • Cardiovascular Diseases / psychology*
  • Cognition*
  • Cognitive Dysfunction / complications*
  • Cognitive Dysfunction / physiopathology
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Diabetes Mellitus, Type 2 / psychology
  • Female
  • Follow-Up Studies
  • Humans
  • Hypolipidemic Agents / therapeutic use
  • Insulin Resistance*
  • Linear Models
  • Longitudinal Studies
  • Male
  • Middle Aged


  • Hypolipidemic Agents
  • Bezafibrate