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Controversies in Neurology
May 1998

Is Exposure to Aluminum a Risk Factor for the Development of Alzheimer Disease?—Yes

Author Affiliations

From the Elizabeth Bruyere Health Centre, Ottawa, Ontario



Arch Neurol. 1998;55(5):740-741. doi:10.1001/archneur.55.5.740

THE ANSWER to the question posed by this article's title is a qualified yes. McLachlan1 reviews the evidence for the neurotoxicity of aluminum. Epidemiological studies have correlated the prevalence of Alzheimer disease (AD) and its mortality rate with levels of aluminum in drinking water in different geographical areas. While these ecological studies are inconclusive by design, they are supported by statistical data from both case-control and cohort studies. For example, McLachlan et al2 show a strong association between aluminum concentrations in water and the prevalence of AD. Using autopsy-verified cases of AD, control subjects, and an aluminum concentration cutoff level of 100 µg/L, they determined that the odds ratio for developing AD was 2.6 (95% confidence interval [CI], 1.2-5.7). In addition, they found that the relative risk of developing AD increased with higher aluminum concentration cutoff levels: at a cutoff level of 125 µg/L, the odds ratio was 3.6 (95% CI, 1.4-9.9), and at cutoff levels of 150 and 175 µg/L, the odds ratio rose to 4.4 and 7.6, respectively (95% CI, 0.98-20 and 0.98-61, respectively). The results of this study are significant because they are based on autopsy-verified diagnoses of AD. However, it is not the only article that demonstrates an association between high levels of aluminum in water and the risk of developing AD. Neri and Hewitt3 report a similar association between aluminum and AD using a statistical analysis of data from Canadian hospitals. Comparing areas where aluminum concentrations in drinking water were relatively high (above 200 µg/L) with areas where they were relatively low (<10 µg/L), Neri and Hewitt report a statistically significant, progressively increasing risk trend with increasing aluminum concentrations and a relative risk estimate of 1.46. Using death certificates and questionnaires that assessed mental impairment, Forbes et al4 also correlate high levels of aluminum in drinking water with the risk of AD or mental impairment. The latter results are of particular interest because they were adjusted for a number of other variables that might otherwise have affected the outcome. In an article relating aluminum concentrations in drinking water with death certificates of individuals 85 years and older with AD (International Classification of Diseases, Ninth Revision [ICD-9], code 331.0),5 Forbes and McLachlan6 also illustrate the importance of adjusting for such variables by showing that water quality alters the results. In areas where the aluminum concentration in water was greater than 250 µg/L, they reported an odds ratio of 4.76, before adjusting for other water quality variables, compared with areas where the aluminum concentration was less than or equal to 67 µg/L; this odds ratio increased to 9.95 after such adjustments. This suggests that the bioavailability of aluminum in water is affected by other water constituents. In their quasi-experimental study of miners who were exposed to aluminum dust, Rifat et al7 report a link between aluminum dust exposure and mental impairment.