title: Alzheimer's disease and smoking: bias in cohort studies.
abstract: The discrepancy between cohort and case-control studies regarding the association between smoking and Alzheimer's disease (AD) has been attributed to the competing risk of early mortality of smokers. A simulation study was conducted to show that the bias favoring smokers acts also on cohort studies. In the model, individuals {grow older} and have smoking habits according to published year-age-gender-specific patterns, with morbidity and mortality according to their demographic and smoking profiles. Those individuals dying of smoking-related causes ("phantoms") remain at risk of AD and of death from other causes. Three scenarios were considered: no association of AD and smoking, increased risk for smokers, and decreased risk for smokers. For each simulation of a cohort study, two incidence density ratios (IDR) were computed: one including the phantoms that developed AD (thus ignoring smoking-related deaths) and another excluding them (thus mimicking real-life studies). For all scenarios, the simulations show that smoking-related death creates a bias, resulting in smokers having an understated risk of AD compared to non-smokers. The speculation that the conflicting results of case-control and cohort studies are solely due to the increased mortality in smokers thus appears unjustified. Other factors must also be considered to explain the discrepancy in results.
authors.affiliation: Department of Epidemiology & Biostatistics, School of Medicine, Case Western Reserve University, Cleveland, OH 44106-4945, USA. sara.debanne@case.edu
authors.forename: Sara M
authors.initials: SM
authors.lastname: Debanne
authors.forename: Roger A
authors.initials: RA
authors.lastname: Bielefeld
authors.forename: Vinay K
authors.initials: VK
authors.lastname: Cheruvu
authors.forename: Thomas
authors.initials: T
authors.lastname: Fritsch
authors.forename: Douglas Y
authors.initials: DY
authors.lastname: Rowland
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000453:epidemiology* / Q000401:mortality; D015982:Bias; D016022:Case-Control Studies; D015331:Cohort Studies; D003198:Computer Simulation; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008390:Markov Chains; D012907:Smoking / Q000453:epidemiology*