Multiple or mixed cerebral microbleeds and dementia in patients with vascular risk factors

Objective: To investigate whether cerebral microbleeds (CMBs) are independently associated with incident dementia in patients with vascular risk factors. Methods: Using data from a Japanese cohort of participants with vascular risk factors in an observational study from 2001, we evaluated the association between CMBs at baseline and incident dementia. Baseline brain MRI was used to determine small-vessel disease (CMBs, lacunar infarcts, and white matter hyperintensities) and brain atrophy. Cox proportional hazards analyses were performed for predictors of dementia adjusting for age, sex, APOE epsilon 4 allele, educational level, baseline Mini-Mental State Examination score, cerebrovascular events, vascular risk factors, and MRI findings. Results: Of the 524 subjects (mean age 68 +/- 8.3 years, 57.6% male, 12.8 +/- 2.6 years of schooling, 21.6% CMBs), 44 patients with incident dementia (20 Alzheimer disease, 18 vascular dementia, 3 mixed-type, and 3 other) were diagnosed during the median 7.5-year follow-up. In multivariate analysis, the presence of overall CMBs was not associated with an increased risk of incident all-cause dementia (p = 0.15). However, multiple CMBs (>= 2) or mixed (lobar and deep) CMBs were associated with the increased risk of all-cause dementia, whereas strictly lobar CMBs showed no association with any dementia. Conclusions: Multiple CMBs or mixed CMBs independently showed higher risk of all-cause dementia. Our results reinforce the hypothesis that CMBs exert deleterious effects on dementia incidence, suggesting that this association may be mediated by vascular burden.