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Diabetes, Brain Infarcts, Cognition, and Small Vessels in the Canadian Alliance for Healthy Hearts and Minds Study
Hertzel C Gerstein1,2,3, Eric E Smith4, Chinthanie Ramasundarahettige1,2
1Population Health Research Institute, Hamilton Health Sciences, Hamilton, Ontario, Canada.
Insights
Diabetes is linked to brain changes and cognitive impairment. Small vessel disease plays a key role in the diabetes-vascular brain injury connection, but more research is needed for cognitive impairment links.
Area of Science:
- Neurology
- Endocrinology
- Cardiology
Background:
- Diabetes mellitus is a known risk factor for cerebrovascular disease and cognitive decline.
- The precise anatomical and pathological links between diabetes and these neurological outcomes remain incompletely understood.
Purpose of the Study:
- To investigate the association between diabetes and markers of cerebrovascular disease and cognitive impairment using neuroimaging and cognitive testing.
- To explore the role of small vessel disease in mediating the relationship between diabetes and brain health.
Main Methods:
- A cross-sectional study of 7733 participants from the Canadian Alliance for Healthy Hearts and Minds cohort.
- Brain and carotid magnetic resonance imaging (MRI) were used to assess brain infarcts, white matter hyperintensity, and carotid wall volume.
- Cognitive function was evaluated using the Digit Symbol Substitution Test and the Montreal Cognitive Assessment test, with impairment defined as scores ≤1 standard deviation below the site mean.
Main Results:
- Diabetes was independently associated with brain infarcts (BI), vascular brain injury (VBI), and small vessel VBI.
- Diabetes was also associated with cognitive impairment.
- The association between diabetes and small vessel VBI remained significant after adjusting for risk factors, and the link with cognitive impairment persisted after accounting for small vessel VBI.
Conclusions:
- Small vessel disease is a significant factor in the relationship between diabetes and vascular brain injury.
- While small vessel disease contributes to the diabetes-cognitive impairment link, other factors likely play a role and require further investigation.
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.