Interaction between genetic and environmental risk factors for Alzheimer's disease: A reanalysis of case‐control studies

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Abstract
To study the interaction among genetic and environmental risk factors, a reanalysis of case‐control studies of Alzheimer's disease (AD) was conducted based on the original data of all studies carried out to January 1, 1990. Seven studies were included in the present analysis, comprising a total of 814 AD patients and 894 control subjects. When comparing those with a positive and negative family history of dementia, similar odds ratio were found for late maternal age [1.7; 95% confidence interval (0.6–4.8) vs. 2.0 (1.1–3.5)], head trauma [1.7 (0.7–4.2) vs. 1.9 (1.1–3.2)], and history of depression [2.0 (0.2–19.8) vs. 2.1 (0.8–1.7)]. This suggests a model in which these risk factors increase the risk for AD independent of family history of dementia. Among those with a positive family history of dementia, the odds ratios for family history of Down's syndrome [4.2 (0.9–20.0))] and of Parkinson's disease [3.3 (0.4–28.2)] tended to be higher than among those with a negative family history of dementia [2.6 (0.8–8.5) and 2.4 (0.8–7.0), respectively]. However, for both disorders the difference in odds ratio was not statistically significant. For history of cigarette smoking, there was no association to AD for those with no first degree relatives with dementia and an inverse relation with AD for those with a positive family history. Although in all analyses, family history of dementia remained significantly associated with AD in the absence of other factors, the odds ratio associated with family history of dementia tended to be lower for those with a positive smoking history, particularly for those with two or more affected relatives. These findings suggest that smoking may interact specifically with a genetically determined process.