Smoking, Death, and Alzheimer Disease: A Case of Competing Risks
Open accessAbstract
If smoking is a risk factor for Alzheimer disease (AD) but a smoker dies of another cause before developing or manifesting AD, smoking-related mortality may mask the relationship between smoking and AD. This phenomenon, referred to as competing risk, complicates efforts to model the effect of smoking on AD. Typical survival regression models assume that censorship from analysis is unrelated to an individual's probability for developing AD (ie, censoring is noninformative). However, if individuals who die before developing AD are younger than those who survive long enough to develop AD, and if they include a higher percentage of smokers than nonsmokers, the incidence of AD will appear to be higher in older individuals and in nonsmokers. Further, age-specific mortality rates are higher in smokers because they die earlier than nonsmokers. Therefore, if we fail to take into account the competing risk of death when we estimate the effect of smoking on AD, we bias the results and are in fact only comparing the incidence of AD in nonsmokers with that in the healthiest smokers. In this study, we demonstrate that the effect of smoking on AD differs in models that are and are not adjusted for competing risks.
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Smokers are at higher risk of premature death before the age at which they might have developed dementia, introducing bias and uncertainty in the smoking-dementia association.
“Smokers are at higher risk of dementia than non-smokers,2 and at a higher risk of premature death before the age at which they might have developed dementia, introducing some bias and uncertainty in the association between smoking and risk of dementia.”
From Dementia prevention, intervention, and care: 2020 report of the Lancet Commission (2020) · cites this paper as [111]
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- Authors
- Chang, C.-C. H., Zhao, Y., Lee, C.-W., & Ganguli, M.
- Affiliations
- University of Pittsburgh (US)
- Corresponding author
- Chang, Chung-Chou H.
- Venue
- Alzheimer Disease & Associated Disorders
- Published
- 2012-10
- Volume
- 26
- Issue
- 4
- Pages
- 300-306
- ISSN
- 0893-0341 (ISSN-L)
- PMC
- PMC3321062
- OpenAlex
- W2066763426
- Cited by
- 85
- References
- 35
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 5 · 2023: 5 · 2022: 10 · 2021: 7 · 2020: 10 · 2019: 4 · 2018: 9 · 2017: 3 · 2016: 1 · 2015: 7 · 2014: 6 · 2013: 3 · 2012: 3
- FWCI
- 2.63
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Alzheimer Disease & Associated Disorders (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (5k24ag022035-08)
- National Institute on Aging (R01AG023651, R01-AG07562, R01AG007562, K24-AG022035)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Epidemiology
- Keywords
- smoking, Alzheimer's disease, competing risks, mortality, survival analysis, censoring, age-specific mortality, incidence estimation
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Female, Humans, Male, Risk Factors, Smoking, Incidence, Proportional Hazards Models
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