White matter hyperintensities are associated with an increased risk of stroke, dementia and mortality.

QUESTION Question: Is there an association between white matter hyperintensities (WMHs) and risk of stroke, cognitive decline, dementia and death? Outcomes: Stroke (defi ned as an acute onset focal neurological defi cit of presumed vascular cause lasting at least 24 h or interrupted by death within 24 h); dementia (DSM-III or -IV criteria); Alzheimer’s disease (National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s Disease and Related Disorders Association criteria); vascular dementia (National Institute of Neurological and Communicative Disorders and Stroke and the Association Internationale pour la Recherche et l’Enseignement en Neurosciences criteria); cognitive decline (defi ned as worsening performance on repeated neuropsychological tests) and mortality. METHODS Design: Systematic review and meta-analysis. Data sources: PubMed was searched from 1966 to 23 November 2009. Study selection and analysis: Prospective longitudinal studies that used MRI and assessed the impact of WMHs on risk of incident stroke, cognitive decline, dementia and death were included. Exclusions: white matter lesions evaluated only by CT; MRI carried out at the end of follow-up rather than at baseline; studies of WMHs in infl ammatory or neurodegenerative conditions, autoimmune disorders, monogenic neurodegenerative or cerebrovascular diseases; studies of MRI-defi ned stroke or subjective cognitive decline; studies of cognitive decline in individuals with dementia; or not published in peer-reviewed journal. Meta-analyses were carried out using RevMan version 4.2 software. HRs were pooled using the random effects inverse variance method, and ORs were used as approximations of HRs if the latter were not available. MAIN RESULTS Forty-six studies met inclusion criteria. Twelve studies assessed stroke, 17 dementia, 19 cognitive decline and 10 mortality. WMHs were associated with a signifi cantly increased risk of incident stroke (nine studies; HR 3.5, 95% CI 2.5 to 4.9; p<0.001). WMHs were also signifi cantly associated with an increased risk of incident dementia (nine studies; HR 1.9, 95% CI 1.3 to 2.8; p<0.001). When looking at subtypes of dementia, WMH was associated with an increased risk of incident Alzheimer’s disease (three studies, HR 1.5, 95% CI 1.2 to 1.9). Meta-analysis was not carried out for incident vascular dementia, but all three studies identifi ed showed a signifi cant association. It was also not possible to meta-analyse studies of cognitive decline. Three out of fi ve general population-based studies found that WMHs were associated with an increased risk of low global cognitive test scores, conversion to mild cognitive impairment (MCI) or persistent cognitive impairment at the end of follow-up. One study found that WMHs were associated with incident amnestic MCI in older participants, but not overall incident MCI. The remaining study found that more periventricular hyperintensities predicted a higher rate of annual decline in mini-mental state examination scores. Of the eight studies of cognitive decline in high-risk populations, fi ve found that increasing baseline volume of WMHs was associated with a more marked decline in global cognitive function, while the other three studies found no association. There was a signifi cant association between WMHs with risk of death (HR 2.0, 95% CI 1.6 to 2.7; p<0.001). CONCLUSIONS WMHs are associated with an increased risk of stroke, dementia and death.