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OBJECTIVE:To investigate the hypothesis that differential survival between smokers and non-smokers leading to a decrease in the frequency of the e4 allele of the apolipoprotein E gene may explain the inverse relation between smoking history and early onset Alzheimer's disease. DESIGN:A population based case-control study. SETTING:The four northern provinces of the Netherlands and metropolitan Rotterdam. SUBJECTS:175 patients with early onset Alzheimer's disease and two independent control groups of 159 and 457 subjects. MAIN OUTCOME MEASURES:Frequencies of the apolipoprotein e4 allele and relative risk of early onset Alzheimer's disease. RESULTS:The inverse association between smoking history and early onset Alzheimer's disease could not be explained by a decrease in the frequency of the apolipoprotein e4 allele. Among carriers of this allele with a family history of dementia subjects with a history of smoking had a strongly reduced risk of early onset Alzheimer's disease (odds ratio 0.10 (95% confidence interval 0.01 to 0.87)). CONCLUSIONS:The results suggest that the inverse relation between smoking history and early onset Alzheimer's disease cannot be explained by an increased mortality in carriers of the apolipoprotein e4 allele who smoke. The association is strongly modified by the presence of the apolipoprotein e4 allele as well as by a family history of dementia.

Original publication

DOI

10.1136/bmj.310.6980.627

Type

Journal article

Journal

BMJ (Clinical research ed.)

Publication Date

03/1995

Volume

310

Pages

627 - 631

Addresses

Department of Epidemiology and Biostatistics, Erasmus University Medical School, Rotterdam, Netherlands.

Keywords

Humans, Alzheimer Disease, Apolipoproteins E, Population Surveillance, Odds Ratio, Risk Factors, Case-Control Studies, Smoking, Age of Onset, Gene Frequency, Heterozygote, Alleles, Middle Aged, Netherlands, Female, Male