Incidence of de novo intracranial aneurysm formation in initially aneurysm-free adults

Background Unruptured intracranial aneurysms occur in approximately 3% of adults and rupture causes aneurysmal subarachnoid haemorrhage. Most evidence is derived from people who already harbour an aneurysm because prevalence reflects both formation and survival to detection. The rate of formation in initially aneurysm-free adults is unclear. We estimated the incidence of de novo formation and secondarily associated factors. Methods In a prospective screening cohort from a Japanese brain health check-up programme (2018–2024), adults ≥18 years with ≥2 brain MR angiography (MRA) visits and no baseline aneurysm were eligible. The outcome was the first appearance of an aneurysm on follow-up MRA, confirmed by two independent readers. Five prespecified factors (age, female sex, ever-smoking, hypertension and first-degree family history) and cumulative cigarette exposure (per 10 pack-years) were examined with multivariable Cox regression. Results Among 10 995 participants (median age, 50 years; 4,711 (42.8%) women), 34 developed a de novo aneurysm over 32 941 person-years. Crude incidence was 1.03/1,000 person-years (95% CI 0.71 to 1.44), and 3 year cumulative incidence was 0.28% (95% CI 0.16 to 0.40). Ever-smoking was associated with formation (adjusted HR, 2.10; 95% CI 1.03 to 4.28), and each 10 pack-years carried an adjusted HR of 1.28 (95% CI 1.13 to 1.46). Conclusions In initially aneurysm-free Japanese adults, de novo aneurysm formation occurred at approximately 1 per 1000 person-years (median 2.9 years), providing a screening-based reference for re-imaging strategy; longer-term risk remains to be established. Cumulative cigarette exposure showed a graded association with formation as an exploratory secondary finding.