Association of Alzheimer's disease and smoking: the case for sibling controls

To study the association between cigarette smoking and Alzheimer's Disease (AD).

Intrafamily case-control, with sibling controls and a variable number of controls per case.

AD cases were identified through the Research Registry of the University Hospitals of the Cleveland/Case Western Reserve University Alzheimer Center.

Study subjects were 86 probable AD cases (index cases) and all of their full siblings, alive or dead, aged > or = 50 years, a total of 238 subjects.

Exposure for each individual was ascertained with a questionnaire answered by several informants. Cognitive status of siblings of the AD cases (impaired or intact) was ascertained by telephone using validated instruments. Diagnosis of dementia in cognitively impaired siblings of index cases was not attempted.

Chi-square analysis tested for departure from a random distribution of disease across smokers and nonsmokers within families. No significant departure was found utilizing all families (P > .40) nor utilizing those families where only the index case was affected (P > .90). Conditional logistic regression evaluated the association within families, controlling for age, sex, and education. Analyses both included and excluded secondary cases of cognitive impairment. No association was found between smoking and disease (OR = 1.26; 95% confidence interval, 0.66-2.42, and OR = 1.42; 95% confidence interval, 0.69-2.89, respectively).

No significant association was found between smoking and cognitive status. Further, analyses based on the comparison of persons with AD with their unaffected siblings also suggest that smoking does not decrease the risk of AD.