Diabetes, Brain Infarcts, Cognition, and Small Vessels in the Canadian Alliance for Healthy Hearts and Minds Study

J Clin Endocrinol Metab. 2021 Jan 23;106(2):e891-e898. doi: 10.1210/clinem/dgaa815.


Background: Diabetes is a risk factor for cerebrovascular disease and cognitive impairment. The anatomical basis for this is uncertain.

Methods: The Canadian Alliance for Healthy Hearts and Minds collected brain and carotid magnetic resonance imaging (MRI) and 2 cognitive tests (the Digit Symbol Substitution Test and the Montreal Cognitive Assessment test) in a cross-sectional sample of men and women. Brain MRIs identified brain infarcts (BI), lacunar BI, high white matter hyperintensity (WMH), vascular brain injury (VBI; BI or high WMH), and small vessel VBI (lacunar BI or high WMH). Carotid MRIs estimated carotid wall volume, a measure of subclinical atherosclerosis. Cognitive scores were standardized to each site's mean score, and cognitive impairment was identified by 1 or both test scores ≤1 standard deviation below the site's mean score on that test.

Results: The 7733 participants included 495 participants (6.4%) with diabetes, of whom 388 were taking diabetes drugs. After age and sex adjustment, diabetes was independently associated with BI (odds ratio [OR] 1.53, 95% confidence interval [CI] 1.05, 2.24), VBI (OR 1.64, 95% CI 1.26, 2.13), small vessel VBI (OR 1.67, 95% CI 1.28, 2.19), and cognitive impairment (OR 1.47, 95% CI 1.20, 1.80). The association between diabetes and small vessel VBI persisted after adjustment for cerebrovascular disease risk factors and nonlacunar infarcts (OR 1.52, 95% CI 1.15, 2.01), and the association with cognitive impairment persisted after adjustment for small vessel VBI (OR 1.27, 95% CI 1.03, 1.56).

Conclusion: Small vessel disease characterizes much of the relationship between diabetes and VBI. However, additional factors are required to disentangle the relationship between diabetes and cognitive impairment.

Keywords: cognition; diabetes; microvascular; stroke.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Brain / blood supply
  • Brain / diagnostic imaging
  • Brain / pathology
  • Brain Infarction / diagnosis
  • Brain Infarction / epidemiology*
  • Brain Infarction / etiology
  • Canada / epidemiology
  • Cerebrovascular Disorders / diagnosis
  • Cerebrovascular Disorders / epidemiology*
  • Cerebrovascular Disorders / etiology
  • Cognitive Dysfunction / diagnosis
  • Cognitive Dysfunction / epidemiology*
  • Cognitive Dysfunction / etiology
  • Cross-Sectional Studies
  • Diabetes Mellitus / diagnosis
  • Diabetes Mellitus / epidemiology*
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Microcirculation / physiology
  • Middle Aged
  • Neuroimaging
  • Neuropsychological Tests
  • Prevalence
  • Risk Factors