Smoking Cessation, Weight Change, and Risk of Dementia: A Prospective Cohort Study

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.

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.

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. SUMMARY BOX What is already known on this topic Smoking cessation is universally prioritized for reducing cardiovascular and cancer risk. Weight gain commonly occurs after quitting and can lead to adverse metabolic outcomes. So far, few studies have examined how cessation timing, duration, and post-cessation weight changes influence long-term dementia risk. What this study adds In this study of 32,802 U.S. middle-aged and older adults, smoking cessation was associated with a steadily declining dementia risk, reaching the level of never smokers after approximately 5-7 years. Substantial post-cessation weight gain may attenuate these advantages, and the lower risk following cessation were largely limited to participants with no or modest weight gain (≤5 kg). Smoking cessation was also associated with long-term slower cognitive decline with no transient change, especially among those with no or modest weight gain. Competing Interest Statement The authors have declared no competing interest. Funding Statement This work was supported by the supported by the Key R&D Program of Zhejiang (2022C03064, to BL). Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study used ONLY openly available human data that were originally located at: https://hrs.isr.umich.edu I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data Availability All data produced in the present study are available upon reasonable request to the authors