American Journal of Epidemiology Vol. 154, No. 3 : 288-290
Copyright © 2001 by The Johns Hopkins University School of Hygiene and Public Health
LETTERS TO THE EDITOR |
RE: ALUMINUM IN DRINKING WATER AND COGNITIVE DECLINE IN ELDERLY SUBJECTS: THE PAQUID COHORT
INSERM Unité 330, case 11 Université Victor Segalen-Bordeaux II 146 rue Léo Saignat 33076 Bordeaux Cedex, France
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INTRODUCTION |
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 TOP INTRODUCTION REFERENCES |
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Although the neurotoxicity of aluminum has been proved (1
), the link between aluminum and the risk of Alzheimer's disease is still debated (2). A related hypothesis has been put forward by Birchall and Chappell (3): silicon in water could be a protective factor against aluminum toxicity.
We recently reported a significant association between the concentration of aluminum in drinking water and the incidence of dementia and Alzheimer's disease (4). These results were based on a cohort of 3,777 elderly subjects followed up for 8 years.
In the present study, we have evaluated in the Paquid cohort the association between aluminum in drinking water and the 8-year evolution of cognitive functions measured by the Mini-Mental State Examination score, a major predictor for dementia. The study has two main methodological interests. First, the evolution of the Mini-Mental State Examination score is not sensitive to diagnostic errors that may be present in the detection of demented or Alzheimer's disease cases. Second, cognitive decline precedes by 3–5 years the occurrence of dementia and is less subject to competitive morbidity or mortality. In addition, this study may give insights into the influence of aluminum in normal cognitive decline and in the dementing process.
The Paquid cohort included 3,777 people aged 65 years or older at baseline and living at home in one of the 75 randomized parishes of the administrative areas of Gironde or Dordogne in southwestern France. Subjects were randomly selected from electoral rolls.
Subjects who agreed to participate underwent a 1-hour home interview with a specially trained psychologist. The Mini-Mental State Examination scores were collected at the first visit in 1988–1989 and 1, 3, 5, and 8 years after the initial visit. The analyses were performed on 3,401 subjects who were nondemented at the initial visit and for whom measurements of water were available. All of these subjects completed the Mini-Mental State Examination at least once and were included in the analysis. They have been followed up between 0 and 8.9 years, with a mean follow-up evaluation of 5.9 years. This sample was described in the previous paper (4).
For each parish, we computed a weighted mean of all measures of aluminum and silica by using the results of chemical analyses of drinking water carried out by the sanitary administration between 1991 and 1994 (4). In order to evaluate the past exposure of subjects, the history of the water distribution network over the previous 10 years (1981–1991) was evaluated.
Analyses were performed using a random effects linear regression model, including subject-specific random intercept and slope to take into account the intrasubject correlation. We also included a random intercept specific to each parish of the cohort in order to control the potential intraparish correlation due to possibly uncontrolled confounding factors. Because the distribution of the Mini-Mental State Examination scores was not normal, we analyzed the square root of the number of errors according to time (5). With this transformed variable, a positive coefficient indicates that the mean Mini-Mental State Examination score decreases when the value of the covariates rises or, for interactions with time, that the decline of the Mini-Mental State Examination score with time is stronger for a high value of the covariate. Besides the variable time that represents the number of years after the initial visit, a binary indicator for the initial visit was introduced to account for the poor score of the subjects at the first interview. Aluminum was introduced as a binary variable with the threshold of 0.1 mg/liter; thus, 86 subjects were considered exposed. This threshold was already used in several studies (6), and we retained this value in our previous analysis (4). Silica was coded as a binary variable with a median of 11.25 mg/liter as the cutoff (4). The other explanatory variables included were age at cohort inception, gender, and educational level in two classes: 1) no education or primary school (ages 6 through 12 years) without diploma and 2) at least primary school with diploma. Parameters were estimated by the MIXED procedure of SAS software (SAS/STAT computer program; SAS Institute, Inc., Cary, North Carolina).
Table 1 presents the estimates of model parameters regarding aluminum and silica for the square root of the number of errors. Exposures to aluminum and silica interacted significantly with time. Therefore, cognitive decline with time was greater in subjects exposed to high levels of aluminum (greater than 0.1 mg/liter) and in those exposed to low levels of silica (lower than 11.25 mg/liter). However, neither aluminum nor silica concentrations had any significant association with the values of the Mini-Mental State Examination scores at inception in the cohort. As it is difficult to interpret the magnitude of the effects in our model from table 1, we have displayed in table 2 the estimated cognitive deterioration for different concentrations of aluminum and silica in drinking water and for two covariate profiles. A woman without a diploma aged 85 years, exposed to low levels of silica and not exposed to aluminum, would on average lose 6.9 points on the Mini-Mental State Examination score between the first follow-up and the 8-year follow-up; however, if exposed to high levels of aluminum, she would lose 9.1 points. In this model a significant intraparish correlation was obtained (p = 0.02). Adjustment for occupation did not modify the results for aluminum or silica (results not shown).
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When subjects diagnosed as demented during the 8-year follow-up were excluded from the analyses (253 subjects excluded), the interaction between aluminum and time was no longer significant (p = 0.67). However, cognitive decline was still dependent on the levels of silica (silica by time, p = 0.02).
This analysis validates our previous results that showed a link between aluminum and silica in drinking water and the risk of dementia (4). This finding was not biased by mis- diagnosis. The analysis of this cohort supports the hypothesis that aluminum concentrations in drinking water may have an effect on cognitive decline. More specifically, it suggests that, when associated with a dementia process, cognitive decline with time is related to high concentrations of aluminum or low concentrations of silica in drinking water. Further work is needed to confirm these results, in particular because of the small number of subjects exposed to high concentrations of aluminum and the possibility of uncontrolled confounding factors.
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REFERENCES |
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TOPINTRODUCTIONREFERENCES |
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- Alfrey AC, Legendre GR, Kaehny WD. The dialysis encephalopathy syndrome: possible aluminum intoxication. N Engl J Med 1976;294:184–8.[Abstract]
- McLachlan DRC. Aluminium and the risk for Alzheimer's disease. Environmetrics 1995;6:233–75.
- Birchall JD, Chappell JS. Aluminium, water chemistry and Alzheimer's disease. (Letter). Lancet 1989;1:953.
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Rondeau V, Commenges D, Jacqmin-Gadda H, et al. Relation between aluminum concentrations in drinking water and Alzheimer's disease: an 8-year follow-up study. Am J Epidemiol 2000;152:59–66.
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Jacqmin-Gadda H, Fabrigoule C, Commenges D, et al. A 5-year longitudinal study of the Mini-Mental State Examination in normal aging. Am J Epidemiol 1997;145:498–506.
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McLachlan DRC, Bergeron MD, Smith JE, et al. Risk for neuropathologically confirmed Alzheimer's disease and residual aluminum in municipal drinking water employing weighted residential histories. Neurology 1996;46:401–5.
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  V. Rondeau, H. Jacqmin-Gadda, D. Commenges, C. Helmer, and J.-F. Dartigues Aluminum and Silica in Drinking Water and the Risk of Alzheimer's Disease or Cognitive Decline: Findings From 15-Year Follow-up of the PAQUID Cohort Am. J. Epidemiol., February 15, 2009; 169(4): 489 - 496. [Abstract] [Full Text] [PDF]
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