Rates and determinants of incident lacunes: A systematic review and meta-analysis

Lacunes of presumed vascular origin are a key imaging marker of cerebral small-vessel disease (cSVD), predicting stroke and dementia risk. Their incidence and determinants have not been systematically quantified across different populations, and implications for clinical research remain unclear.

This study aims to estimate the annualized incidence of new lacunes across diverse populations, identify study-level factors contributing to heterogeneity, summarize patient-level risk factors for incident lacunes, and provide empirical data to inform sample size estimation for studies using incident lacunes as an imaging outcome.

Thirty-one studies comprising 12,646 participants and 56,073 person-years were included. The pooled overall incidence was 3.27 per 100 person-years (95% CI, 2.12-4.42), ranging from 1.50 to 8.03 across populations. Rates were highest in cSVD patients (8.03; 95% CI, 3.8-12.27), intermediate in stroke and memory-clinic patients, and lower in community-based, hypertensive, and non-specific artery disease cohorts. Meta-regression showed that baseline lacune prevalence was positively associated with incidence (β = 0.057; 95% CI, 0.006-0.108; P = 0.031). At the individual level, male sex, baseline lacunes, hypertension, and diabetes were associated with higher risk. In cSVD populations, detecting a 30% relative risk reduction required 563, 867, and 1782 participants per arm for 3-, 2-, and 1-year follow-up, respectively.

Incident lacune rates vary substantially across populations and are strongly influenced by baseline lacune burden and vascular risk factors. These findings provide context for population selection and sample size considerations in studies using incident lacunes as an imaging outcome.