Smoking cessation duration and risk of Alzheimer's disease: a nationwide cohort study in Korea.

Abstract

Background: Smoking is a modifiable risk factor for Alzheimer's disease, yet the temporal pattern of risk reduction following smoking cessation remains unclear. We investigated whether Alzheimer's disease risk declines according to the duration of sustained smoking cessation in a large nationwide cohort.

Methods: Using the Korean National Health Insurance Service database (2002-2023), we identified 1,403,636 adults with stable longitudinal smoking patterns based on repeated biennial health examinations. Smoking status was classified as never smokers, current smokers, or sustained quitters, with cessation duration categorised into 2-year intervals (< 2, 2-3, 4-5, 6-7, ≥ 8 years). Incident Alzheimer's disease was defined as at least two separate NHIS insurance claims. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals, adjusting for demographic, lifestyle, and metabolic factors.

Results: During a mean follow-up of 10.5 years, 58,519 incident Alzheimer's disease cases were identified. Compared with current smokers, sustained quitters exhibited progressively lower hazards of Alzheimer's disease with increasing duration of abstinence, demonstrating a dose-response pattern. Individuals who had quit for < 2 years showed a risk reduction relative to current smokers (adjusted HR 0.899; 95% CI 0.819-0.986), while those with ≥ 8 years of abstinence had substantially lower risk (adjusted HR 0.582; 95% CI 0.423-0.801). When referenced to never smokers, those with < 2 years of abstinence retained excess risk, whereas cessation for ≥ 2 years was associated with Alzheimer's disease risk approaching that of never smokers.

Conclusions: Sustained smoking cessation was associated with a graded reduction in Alzheimer's disease risk, with approximately 2 years of abstinence needed to approach never-smoker risk.