Background: CMB represent hemorrhage-prone small vessel disease (SVD), attributed to hypertensive vasculopathy or cerebral amyloid angiopathy (CAA). CMB are associated with adverse outcomes including prevalent stroke and dementia, but the relation with incident dementia in the community has not been studied.
Objective: To study the association of cerebral microbleeds (CMB) on MRI and incidence of dementia in a community based cohort.
Methods: We evaluated 1296 dementia-free Framingham Original and Offspring Cohort participants (mean age 72years; 54% women) with available brain MRI and incident dementia data (mean follow-up 6.7 years). Using Cox-proportional hazards models we related all CMB and CMB stratified by brain location to incident dementia. Multivariable models were adjusted for age, sex, APOE status, and education, with additional models adjusting for vascular risk factors and MRI markers of ischemic SVD.
Results: CMB were observed in 10.8% of subjects (64% lobar, 36% deep and mixed). Incident dementia was observed in 85 participants (6.6% over study period). We observed a 1.74 times higher risk of dementia in participants with any CMB (HR 1.74, 95% CI 1.00-3.01), and three fold higher risk in those with deep and/or mixed CMB (HR 2.99, 95% CI 1.52-5.90). The associations remained significant after adjusting for vascular risk factors. Although they were attenuated after adjustment for MRI markers of ischemic SVD, they remained significant for participants with deep and/or mixed CMB (HR 2.44, 95% CI 1.22-4.88). Purely lobar CMB were not associated with incident dementia.
Conclusions: CMB were associated with increased risk of incident dementia, and for non-lobar CMB, the associations were independent of vascular risk factors and ischemic markers of small vessel disease. Our findings support a role for hypertensive vasculopathy and the interplay of hypertensive and cerebral amyloid angiopathy in risk of dementia, and highlight the role of CMB as markers of adverse neurological outcomes.