Cerebral small vessel disease and the risk of dementia: A systematic review and meta-analysis of population-based evidence

Abstract

Introduction: Cerebral small vessel disease is increasingly linked to dementia. Methods: We systematically searched Medline, Embase, and Cochrane databases for prospective population-based studies addressing associations of white matter hyperintensities, covert brain infarcts (i.e., clinically silent infarcts), and cerebral microbleeds with risk of all-dementia or Alzheimer's disease and performed meta-analyses. Results: We identified 11 studies on white matter hyperintensities, covert brain infarcts, or cerebral microbleeds with risk of all-dementia or Alzheimer's disease. Pooled analyses showed an association of white matter hyperintensity volume and a borderline association of covert brain infarcts with risk of all-dementia (hazard ratio: 1.39 [95% confidence interval: 1.00; 1.94], N = 3913, and 1.47 [95% confidence interval: 0.97; 2.22], N = 8296). Microbleeds were not statistically significantly associated with an increased risk of all-dementia (hazard ratio: 1.25 [95% confidence interval: 0.66; 2.38], N = 8739). Discussion: White matter hyperintensities are associated with an increased risk of all-dementia and Alzheimer's disease in the general population. However, studies are warranted to further determine the role of markers of cerebral small vessel disease in dementia.