Men who quit smoking for a prolonged period drive down their overall risk for dementia compared with recent quitters and continuous smokers, results of a large longitudinal study suggest.
Compared with men who continuously smoked, those who quit for at least 4 years experienced a 14% decrease in dementia risk. This finding suggests a protective effect associated with long-term smoking cessation. Those who never smoked experienced a 19% lower risk for dementia over the same mean follow-up of 7 years.
"We would like to emphasize smoking as a risk factor for dementia," Daein Choi, MD, from the College of Medicine at Seoul National University in Korea, told Medscape Medical News. "Our findings may help physicians encourage their patients to quit smoking."
"We were quite surprised," Choi added, to discover that those who quit smoking had a lower risk than continuous smokers. He and colleagues had expected little change because of the low regenerative capacity of central nervous system neurons.
Women were excluded from the main analysis because of the low smoking rates among Korean women.
The study was published online September 5 in Annals of Clinical and Translational Neurology.
Protective or Risk Factor?
The authors point out that previous studies examining the association between smoking and Alzheimer's disease (AD) have been controversial.
Some early tobacco company–funded research suggested nicotine may improve cognitive function among primates. Clinical research also suggested smoking may confer a protective effect.
However, most of the evidence supporting a link between smoking and an increased dementia risk has focused on Western populations. The current study is the first, the authors note, to look at the effect of smoking cessation in a large Asian population.
For the study, investigators identified 51,849 men aged 60 years or older in the National Health Screening Cohort of the Korean National Health Insurance System.
Participants underwent physical examination and completed questionnaires about smoking and other factors during two assessment periods: 2002-2003 and 2004-2005. After exclusions, the final study cohort included 46,140 participants.
The investigators identified 12,672 continuous smokers, 4175 short-term quitters (cessation less than 4 years), 9268 long-term quitters, and 20,025 never-smokers on the basis of questionnaire responses.
Scores on the Mini-Mental State Examination, Clinical Dementia Rating, and/or Global Deterioration Scale identified cognitive dysfunction. In addition, International Classification of Diseases, 10th Revision, codes flagged the 1644 participants who developed dementia during study follow-up.
The investigators conducted a multivariable analysis that adjusted for patient age, household income, physical activity, drinking habit, body mass index, change in body mass index, blood pressure, fasting serum glucose, total cholesterol, and Charlson Comorbidity Index.
As total tobacco exposure decreased from continual smokers to short-term quitters, long-term quitters, and never-smokers, the risk for developing overall dementia decreased. This trend was statistically significant (P = .001).
Compared with those who smoked continuously through both periods, long-term quitters had a decreased risk for overall dementia (hazard ratio [HR], 0.86), as did the never-smokers (HR, 0.81).
Choi and colleagues also assessed an association between smoking cessation and AD or vascular dementia. Never-smokers had an 18% decreased risk for AD compared with continual smokers (HR, 0.82). Long-term quitters experienced a 15% relative decrease and short-term quitters an 8% decreased risk.
In addition, long-term quitters had a 32% decreased risk for vascular dementia compared with continual smokers (HR, 0.68); those who never smoked had a 29% decreased risk (HR, 0.71) and short-term quitters experienced 19% lower risk (HR, 0.81).
The mean 7-year follow-up may have been insufficient to determine the full effects of smoking on AD risk. In addition, smoking status was based on self-report and the researchers did not account for duration of smoking, which could alter dementia risk.
Strengths of the study include a large population and adjustment for a wide range of potential confounders.
Exclusion of women from the main analysis limits the generalizability of the findings, the researchers note. A secondary analysis looking at dementia and smoking cessation among women was underpowered to detect any significant association.
Longer studies that include other neurologic disorders and use biomarkers to confirm smoking status are warranted, the investigators note. They would also like to perform studies with more women.
"We are planning to investigate the effect of other lifestyle changes, such as physical activity or alcohol consumption, on the development of neurodegenerative disorders," Choi said.
Commenting on the findings for Medscape Medical News, Brendan Kelley, MD, associate professor neurology and neurotherapeutics at UT Southwestern Medical Center in Dallas, said the study has several important strengths, including its large sample size and long-term follow-up.
"Importantly, they asked about how long ago a person had quit smoking. While several large studies have demonstrated that smoking increases the risk of developing dementia, few studies have been able to look at the impact of how long ago participants had quit," he said.
"This study's results are important," Kelley added. "The authors confirmed that smoking is associated with an increased risk of developing dementia, and were the first to report this in a large Asian population study.
"Their study goes even further, finding that long-term quitters had a risk of Alzheimer's disease and vascular dementia that was nearly that of never-smokers. Even short-term quitters, those that quit less than 4 years [previously], had a lower risk compared to continued smokers. These findings add important information to the argument for increased activity of smoking cessation programs," he said.
Providing a geriatrician's perspective on the findings, Marian K. Schuda, MD, medical director, OhioHealth John J. Gerlach Center for Senior Health, Columbus, told Medscape Medical News, "I thought the study was well done."
"The study completely validated the common understanding amongst geriatricians that smoking is a very important risk factor for dementias of all kinds. Going further, it validated that advising people to quit smoking has tremendous benefit for them. That is sometimes difficult for patients to understand, because they say, 'I've smoked for 40 years, what difference does it make, why should I stop?'
"This study demonstrates benefit for those who stop smoking now."
"Dementia is one of those conditions people want to avoid as they age," she added, so this study provides an additional health benefit associated with smoking cessation that physicians can share with patients.
Seoul National University Hospital provided a grant to support the study. Choi, Kelley, and Schuda have disclosed no relevant financial relationships.
Ann Clin Transl Neurol. Published online September 5, 2018. Abstract
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Cite this: Smoking Cessation Lowers Dementia Risk - Medscape - Sep 12, 2018.