Journal
JAMA NEUROLOGY
Volume 76, Issue 1, Pages 81-94Publisher
AMER MEDICAL ASSOC
DOI: 10.1001/jamaneurol.2018.3122
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Funding
- French National Research Agency [ANR-14-CE12-0016]
- Fondation Leducq (Transatlantic Network of Excellence on the Pathogenesis of SVD of the Brain)
- European Union's Horizon 2020 Research and Innovation Programme [640643, 643417, 667375]
- European Research Council
- European Union Joint Programme-Neurodegenerative Disease Research
- Australia, National Health and Medical Research Council
- Austria, Federal Ministry of Science, Research and Economy
- Canada, Canadian Institutes of Health Research
- France, French National Research Agency
- Germany, Federal Ministry of Education and Research
- Netherlands, the Netherlands Organisation for Health Research and Development
- United Kingdom, Medical Research Council
- Initiative of Excellence of Bordeaux University
- National Institute for Health Research Senior Investigator award
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IMPORTANCE Covert vascular brain injury (VBI) is highly prevalent in community-dwelling older persons, but its clinical and therapeutic implications are debated. OBJECTIVE To better understand the clinical significance of VBI to optimize prevention strategies for the most common age-related neurological diseases, stroke and dementia. DATA SOURCE We searched for articles in PubMed between 1966 and December 22, 2017, studying the association of 4 magnetic resonance imaging (MRI) markers of covert VBI (white matter hyperintensities [WMHs] of presumed vascular origin, MRI-defined covert brain infarcts [BIs], cerebral microbleeds [CMBs], and perivascular spaces [PVSs]) with incident stroke, dementia, or death. STUDY SELECTION Data were taken from prospective, longitudinal cohort studies including 50 or more adults. DATA EXTRACTION AND SYNTHESIS We performed inverse variance-weighted meta-analyses with random effects and z score-based meta-analyses for WMH burden. The significance threshold was P < .003 (17 independent tests). We complied with the Meta-analyses of Observational Studies in Epidemiology guidelines. MAIN OUTCOMES AND MEASURES Stroke (hemorrhagic and ischemic), dementia (all and Alzheimer disease), and death. RESULTS Of 2846 articles identified, 94 studies were eligible, with up to 14 529 participants for WMH, 16 012 participants for BI, 15 693 participants for CMB, and 4587 participants for PVS. Extensive WMH burden was associated with higher risk of incident stroke (hazard ratio [HR], 2.45; 95% CI, 1.93-3.12; P < .001), ischemic stroke (HR, 2.39; 95% CI, 1.65-3.47; P < .001), intracerebral hemorrhage (HR, 3.17; 95% CI, 1.54-6.52; P = .002), dementia (HR, 1.84; 95% CI, 1.40-2.43; P < .001), Alzheimer disease (HR, 1.50; 95% CI, 1.22-1.84; P < .001), and death (HR, 2.00; 95% CI, 1.69-2.36; P < .001). Presence of MRI-defined BIs was associated with higher risk of incident stroke (HR, 2.38; 95% CI, 1.87-3.04; P < .001), ischemic stroke (HR, 2.18; 95% CI, 1.67-2.85; P < .001), intracerebral hemorrhage (HR, 3.81; 95% CI, 1.75-8.27; P < .001), and death (HR, 1.64; 95% CI, 1.40-1.91; P < .001). Presence of CMBs was associated with increased risk of stroke (HR, 1.98; 95% CI, 1.55-2.53; P < .001), ischemic stroke (HR, 1.92; 95% CI, 1.40-2.63; P < .001), intracerebral hemorrhage (HR, 3.82; 95% CI, 2.15-6.80; P < .001), and death (HR, 1.53; 95% CI, 1.31-1.80; P < .001). Data on PVS were limited and insufficient to conduct meta-analyses but suggested an association of high PVS burden with increased risk of stroke, dementia, and death; this requires confirmation. CONCLUSIONS AND RELEVANCE We report evidence that MRI markers of VBI have major clinical significance. This research prompts careful evaluation of the benefit-risk ratio for available prevention strategies in individuals with covert VBI.
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