Abstract
OBJECTIVES: To assess the associations of smoking cessation and post-cessation weight gain with the risk of dementia and cognitive trajectories. DESIGN: Prospective cohort study. SETTING: The U.S. Health and Retirement Study (1995-2020). PARTICIPANTS: A total of 32,802 dementia-free participants were included, with a mean age of 60.5 years (SD 10.7) and 57.1% female. EXPOSURE: Smoking status and body weight were collected biennially via structural interviews. MAIN OUTCOME MEASURES: Dementia was identified using the Langa-Weir algorithm. Cognitive function was assessed using a 27-unit scale. Cox proportional hazard models estimated hazard ratio (HR) of dementia by smoking cessation status, subsequent weight change, and duration of cessation. Among participants who quit during follow-up, linear mixed models assessed cognitive trajectories before and after cessation. RESULTS: Over 25 years of follow-up, 5,868 dementia cases were documented. Compared with current smokers, individuals who quit during follow-up had a lower dementia risk after quitting (HR: 0.82, 95% confidence interval: 0.72-0.93), similar to those who had quit before baseline (0.76, 0.69-0.83) and to never smokers (0.72, 0.66-0.79). The benefits of cessation were largely limited to participants with no or modest weight gain (≤5 kg). By contrast, quitting accompanied by >10 kg weight gain was marginally associated with higher dementia risk (1.31, 0.95-1.80). Dementia risk declined steadily with increasing cessation duration, reaching the level of never smokers after approximately 5-7 years. Cognitive trajectory analyses showed that quitting was associated with long-term slower cognitive decline but no transient change, especially among those with no or modest weight gain. CONCLUSIONS: Smoking cessation was associated with a sustained lower dementia risk and slower cognitive decline, comparable to benefits observed in never smokers and without evidence of a short-term risk increase. However, substantial post-cessation weight gain may attenuate these advantages. Smoking cessation programs should incorporate weight-management strategies to optimize long-term brain health.