Effects of Acute Exposure to Aluminum on Cognition in Humans

Abstract

There is epidemiological evidence suggesting an association between aluminum in drinking water and Alzheimer's disease (AD), and between aluminum in dialysate and dialysis dementia. The exact role of aluminum in the pathogenesis of these and other dementias is not clear. This study examined the acute effects of aluminum on cognitive function in patients with AD and related dementias and in age-matched and younger volunteers with normal cognitive function. Whether individuals with AD and/or the APOE ε4 genotype had enhanced gastrointestinal absorption of aluminum was tested, and whether individuals with elevated blood aluminum concentrations exhibited acute cognitive effects was determined. Subjects were randomized to receive a single dose of aluminum orally (Amphojel plus citrate) for 3 d followed by a 3-wk washout, and then 3 d ofmatched placebo administration, or vice versa. Serum aluminum levels were measured and the daily dose of Amphojel was adjusted to a target aluminum level between 50 and 150 μg/L. Neuropsychological tests were administered at baseline and 90 min after the third dose of Amphojel or placebo. There was a large interindividual variation in aluminum serum levels in all study groups after the same initial dose of Amphojel. There were no significant differences in neuropsychological test scores after aluminum ingestion in normal volunteers or in patients with cognitive impairment. There was no association between APOE ε4 genotype and aluminum absorption. The results did not support the hypothesis that aluminum ingested at these doses produces acute effects on cognition or adverse effects, nor did they reveal that AD patients are more vulnerable to such outcomes. Further inquiry is required to explore any possible association between aluminum and cognition, but controlled trials may be limited by safety concerns.

This study was funded by the Physicians' Services Incorporated Foundation, Toronto, Ontario, Canada. Our appreciation is extended to Glenn Fletcher and Ranjit Singh Sandhu, who conducted the aluminum analytical work and assisted during the RCT. The genotyping was carried out by C. Bétard and D. Gauvreau, Project IMAGE/Recherche Alzheimer, Montreal, Quebec, and we are grateful for their input.

Notes

∗An unpublished supplementary study conducted by J. S. Reiach and E. Nieboer (Department of Biochemistry), D. W. Molloy, J. D. Turnbull, MD, and D. C. Strang (Department of Medicine), McMaster University, Hamilton, Ontario, Canada, and C. Bétard and D. Gauvreau, Project IMAGE/Recherche Alzheimer, Montreal, Quebec