Affiliations: [a] Department of Epidemiology & Biostatistics, School of Medicine, Case Western Reserve University, Cleveland, OH, USA | [b] Department of Research Computing, Division of Information Technology Services, Case Western Reserve University, Cleveland, OH, USA | [c] D Y Rowland Associates, 3189 Scarborough Road, Cleveland Heights, OH, USA | [d] University Memory and Aging Center, University Hospitals of Cleveland and, Case Western Reserve University, Cleveland, OH, USA | [e] Department of Neurology, School of Medicine, Case Western Reserve University, Cleveland, OH, USA
Correspondence:
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Address for correspondence: Sara M. Debanne, PhD, Department of Epidemiology and Biostatistics, School of Medicine, Case Western Reserve University, Cleveland, OH 44106-4945, USA. Tel.: +1 216 368 3895; Fax: +1 216 368 3970; E-mail: sara.debanne@case.edu.
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.
