Cerebral small vessel disease and its relationship with all-cause mortality risk: Results from the Amsterdam Ageing cohort

Introduction: Cerebral Small-Vessel Disease (CSVD) is a complex condition affecting the brain's vascular network, linked to cognitive and physical decline, cerebrovascular disease, and death. This study assesses the relationship between CSVD (composite and individual features) and all-cause mortality in a large cohort of geriatric outpatients. Methods: Data from 1305 geriatric outpatients (mean age 78 ± 7; 51 % female) in the Amsterdam Ageing cohort were analysed. CSVD presence was based on brain imaging (MRI or CT), defined by a Fazekas score ≥ 2, presence of ≥1 lacunes, or (in MRI) ≥ 3 microbleeds. Mortality data (February 2016 - January 2024) was sourced from the Dutch Municipality Register. The relationship between CSVD and all-cause mortality was evaluated using a Cox proportional-hazards model, adjusting for key confounders. Results: At baseline, 835 (64 %) of the 1305 patients had CSVD. During a median follow-up of 3.1 years (IQR 1.6–4.6 years), all-cause mortality was 40 % (333 patients) in the CSVD group and 26 % (121 patients) in the non-CSVD group, corresponding with incidence rates of 137 and 78 per 1000 patient-years, respectively. The age- and sex-adjusted hazard ratio for mortality in the CSVD group was 1.6 (95 % CI: 1.3–2.0). This association remained significant after adjusting for cardiovascular disease and its risk factors, physical function (gait speed), and cognitive function (MMSE). Conclusion: Radiographic CSVD presence is prevalent and its integration into daily care is important as it is independently linked to increased all-cause mortality in geriatric outpatients.