Clinical significance of cerebral microbleeds on MRI: A comprehensive meta-analysis of risk of intracerebral hemorrhage, ischemic stroke, mortality, and dementia in cohort studies (v1)

Abstract

Background: Cerebral microbleeds can confer a high risk of intracerebral hemorrhage, ischemic stroke, death and dementia, but estimated risks remain imprecise and often conflicting. We investigated the association between cerebral microbleeds presence and these outcomes in a large meta-analysis of all published cohorts including: ischemic stroke/TIA, memory clinic, “high risk” elderly populations, and healthy individuals in population-based studies. Methods: Cohorts (with > 100 participants) that assessed cerebral microbleeds presence on MRI, with subsequent follow-up (≥ 3 months) were identified. The association between cerebral microbleeds and each of the outcomes (ischemic stroke, intracerebral hemorrhage, death, and dementia) was quantified using random effects models of (a) unadjusted crude odds ratios and (b) covariate-adjusted hazard rations. Results: We identified 31 cohorts (n = 20,368): 19 ischemic stroke/TIA (n = 7672), 4 memory clinic (n = 1957), 3 high risk elderly (n = 1458) and 5 population-based cohorts (n = 11,722). Cerebral microbleeds were associated with an increased risk of ischemic stroke (OR: 2.14; 95% CI: 1.58–2.89 and adj-HR: 2.09; 95% CI: 1.71–2.57), but the relative increase in future intracerebral hemorrhage risk was greater (OR: 4.65; 95% CI: 2.68–8.08 and adj-HR: 3.93; 95% CI:2.71–5.69). Cerebral microbleeds were an independent predictor of all-cause mortality (adj-HR: 1.36; 95% CI: 1.24–1.48). In three population-based studies, cerebral microbleeds were independently associated with incident dementia (adj-HR: 1.35; 95% CI: 1.00–1.82). Results were overall consistent in analyses stratified by different populations, but with different degrees of heterogeneity. Conclusions: Our meta-analysis shows that cerebral microbleeds predict an increased risk of stroke, death, and dementia and provides up-to-date effect sizes across different clinical settings. These pooled estimates can inform clinical decisions and trials, further supporting cerebral microbleeds role as biomarkers of underlying subclinical brain pathology in research and clinical settings.

Enlarged Perivascular Spaces and Dementia: A Systematic Review

“…Magnetic resonance imaging (MRI) markers of CSVD include white matter hyperintensities (WMH), lacunes, and microbleeds (CMB) [3]. The presence of these CSVD markers have been associated with a higher incidence of dementia and cognitive decline in the elderly [7,8].…”

Microbleed prevalence and burden in anticoagulant‐associated intracerebral bleed

“…There was no difference between VKA-and NOAC-ICH (52% vs. 48%; P = 0.763; Table 1). However, the median CMB number was significantly lower in NOAC-ICH patients (2 [1-3] vs. 7 [4][5][6][7][8][9][10][11]; P < 0.001 (Table 1 and Fig. 1).…”

“…Compared to those who did not receive MRI (Table S1), included patients had higher median BMI (30 vs. 27 kg/m 2 , P = 0.002), were less likely to have hypertension (89% vs. 97%; P = 0.002), hyperlipidemia (52% vs. 65%; P = 0.03), and coronary artery disease (28% vs. 40%; P = 0.04); otherwise there were no significant differences. Patient characteristics according to anticoagulant type are summarized in Table 1 [60-77] years; P = 0.005), had higher CHA 2 DS 2 -VASc score (4 [4][5][6] vs. 4 [3][4][5]); P = 0.017, and were less likely to have lobar ICH location (28% vs. 58%; P = 0.001).…”

“…3 Thus, CMBs are recognized as a potentially useful prognostic of ICH especially in high-risk patients exposed to therapeutic oral anticoagulation. 3,4 Less is known regarding the relationship between oral anticoagulation and the pathogenesis of CMBs. Data regarding Vitamin K antagonists (VKAs) and CMBs generally suggest higher risk, especially among those with highly variable international normalized ratio (INR).…”

Natural genetic variation in Stim1 creates stroke in the spontaneously hypertensive rat

“…3d, e). Microbleeds, which predict future cerebral hemorrhages in humans [19][20][21], were observed in sections of brains in 5 of 9 SHR-A3 rats and major hemorrhages were found in 3 of 9 animals ( Fig. 4a-c) primarily in the cortex, subcortical white matter, and striatum.…”