Is Smoking Associated with the Risk of Developing Alzheimer's Disease? Results from Three Canadian Data Sets

doi:10.1016/S1047-2797(00)00061-2

Annals of Epidemiology

Volume 10, Issue 7, October 2000, Pages 409-416

https://doi.org/10.1016/S1047-2797(00)00061-2 Get rights and content

Abstract

PURPOSE: To determine whether smoking is associated with Alzheimer's disease (AD).

METHODS: Analyses were conducted using three Canadian data sets: the University of Western Ontario Dementia Study (200 cases, 163 controls), the Canadian Study of Health and Aging (258 cases, 258 controls), and the patient database from the Clinic for Alzheimer Disease and Related Disorders at the Vancouver Hospital and Health Sciences Centre (566 cases, 277 controls). The association between smoking and AD was investigated using bivariate analyses and multiple logistic regression models adjusted for the potential confounders age, sex, educational level, family history of dementia, head injury, and hypertension.

RESULTS: The results of bivariate analyses were inconsistent across the three data sets, with smoking status a significant protective factor, a significant risk factor, or not associated with AD. The results of multiple logistic regression models, however, were consistent: any association between smoking status and AD disappeared in all three data sets after adjustment for confounders.

CONCLUSIONS: Smoking status was consistently not associated with AD across all three data sets after adjustment for confounders. Failure to adjust for relevant confounders may explain inconsistent reports of the influence of smoking on AD. Any protective effect of smoking may be limited to specific AD subtypes (e.g., early onset AD).

Introduction

Diseases related to aging are growing in importance as populations age. The prevalence of one such disease, Alzheimer's disease (AD), rises exponentially with increasing age (1). AD is a major cause of dementia and is characterized by progressive cognitive impairment and decreased life expectancy (2). AD represents a major economic burden on health care and social services 3, 4 in addition to its personal costs.

The cause of AD remains unknown and no cure or effective treatment is currently available. Many risk factors for AD have been studied. Both genetic and environmental factors have been implicated in AD 5, 6, 7, 8, 9, 10, suggesting that AD may be multifactorial in origin. Tobacco use is one environmental factor that may influence the risk of developing AD. An association between smoking and AD is of particular interest because it is biologically plausible: for example, nicotine may compensate for some of the cholinergic deficits observed in AD 11, 12. Investigation of an association with smoking may provide a theoretical basis for treatment (13) and advance research on the cause of AD.

Despite plausible biological mechanisms, however, epidemiologic evidence of an association between smoking and AD is equivocal. Many studies have found no significant relationship 14, 15, 16, 17. Other researchers have reported a statistically significant decreased 18, 19, 20, 21 or increased risk of AD (22) among smokers.

Inconsistent results may be a reflection of methodological factors. In studies of smoking and AD, common weaknesses include the use of heterogeneous cases (mix of prevalent/incident, early/late onset, familial/sporadic cases), variable case definition, small sample size, exclusion of institutional cases, asymmetric reporting (e.g., proxy-derived information used for cases but self-reported information used for controls), and the use of controls who have not been assessed as free of AD (11). Because there are few established risk factors for AD, studies of AD have often examined tobacco use as only one possibly relevant exposure among many; exposure measures and analytical strategies used thus may not be the most appropriate for assessing the effect of smoking on AD. Analyses have also not always adjusted for the effects of other relevant variables. Failure to adjust for appropriate confounders may have led to inconsistent reports of the effects of smoking on AD, with different results simply reflecting subject heterogeneity.

The association of smoking and AD thus remains to be clarified in epidemiologic studies. Evidence of such a relationship was investigated using three Canadian data sets. Although none of the data sets addressed all of the weaknesses outlined, the data sets selected had various strengths, including detailed measures of tobacco use, cases of recent onset, autopsy confirmation of diagnoses, large sample size, institutional cases, and symmetric reporting. All three data sets used consistent standard diagnostic criteria (23); controls were diagnosed as cognitively intact based on the same clinical assessment as cases. Relevant potential confounders were available for inclusion in the statistical analyses and were comparable across the data sets. This research provides the opportunity to address some of the methodological limitations that have contributed to the inconsistent and inconclusive results found in previous studies of the relationship of smoking with AD.

Section snippets

Data Sets

Analyses were conducted using three Canadian data sets: the University of Western Ontario Dementia Study (UWODS), the Canadian Study of Health and Aging (CSHA), and the patient database of the Clinic for Alzheimer Disease and Related Disorders at the Vancouver Hospital and Health Sciences Centre, University of British Columbia site (UBC). Table 1 provides information on subject characteristics for each of the data sets.

The UWODS was associated with a regional center of expertise in London,

Results

Table 1 summarizes the distribution of study variables for cases and controls in each data set. Subject characteristics varied between cases and controls and across data sets, emphasizing the need to adjust for potential confounders.

Discussion

The association between smoking and AD was inconsistent across the three data sets in bivariate analyses, with smoking status significantly increasing, significantly decreasing, or having no effect on the risk of AD. No significant association remained in any of the data sets, however, after adjustment for confounders in multiple logistic regression models. This lack of agreement across data sets in the bivariate results, in contrast to the concordance in multiple logistic regression results,

Conclusions

Despite pharmacological evidence supporting a plausible biological mechanism, this study provided no evidence to support previous epidemiologic reports of a protective effect of smoking on AD. Inconsistent results in the literature may reflect subject heterogeneity. Previous reports of a reduced risk of AD among smokers may be due to unadjusted confounders: any protective effect may be limited to specific subtypes of AD. These results demonstrate the importance of obtaining data on, and

Acknowledgements

This research was made possible in part by Health Canada through a National Health Research and Development Program Research Training Award to Suzanne Tyas. The Canadian Study of Health and Aging was funded by the Seniors Independence Research Program, administered by the National Health Research and Development Program (Project No. 6606-3954-MC(S)). The study was coordinated through the University of Ottawa and the federal government's Laboratory Centre for Disease Control. The contribution of

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Original reportsIs Smoking Associated with the Risk of Developing Alzheimer's Disease? Results from Three Canadian Data Sets

Abstract

Introduction

Section snippets

Data Sets

Results

Discussion

Conclusions

Acknowledgements

Ann Epidemiol.

Lancet.

Prog Neuropsychopharmacol Biol Psychiatry.

J Clin Epidemiol.

Lancet.

Lancet.

Frequency and distribution of Alzheimer's disease in EuropeA collaborative study of 1980–1990 prevalence findings

Ann Neurol.

Alzheimer Disease

The US economic and social costs of Alzheimer's disease revisited

Am J Public Health.

Net economic costs of dementia in Canada

Can Med Assoc J.

Epidemiology of Alzheimer's disease

Epidemiol Rev.

Research and Alzheimer's diseaseAn epidemiological perspective

Psychol Med.

The epidemiology of dementia and Alzheimer disease

The epidemiology of Alzheimer's diseaseBeyond risk factors

Exploring the etiology of Alzheimer disease using molecular genetics

JAMA.

Genetic epidemiology of Alzheimer disease

Epidemiol Rev.

Are tobacco and alcohol use related to Alzheimer's disease? A critical assessment of the evidence and its implications

Addict Biol.

Smoking, drinking and Alzheimer's diseaseA literature review

Mature Med Can.

Nicotinic system involvement in Alzheimer's and Parkinson's diseases

Drugs Aging.

Relation of smoking and alcohol consumption to incident Alzheimer's disease

Am J Epidemiol.

Original reports
Is Smoking Associated with the Risk of Developing Alzheimer's Disease? Results from Three Canadian Data Sets