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Description of key information


Epidemiological studies of aluminum exposure via drinking water
Overall, many of the studies of aluminium in drinking water and risk of cognitive impairment, dementia and/or AD have had methodological weaknesses. Early studies were ecological, taking into account only the level of cognitive impairment, dementia, or AD in relation to aluminium in drinking water. Most of the case-control and cohort studies took few or no possible confounders or effect modifiers into account in their analyses. The exception to this is the analysis by Rondeau et al. (2000), which is by far the strongest methodologically of the epidemiological studies conducted to date. However, one limitation of this study is a lack of an intermediate exposure category, and therefore the inability to examine the possibility of a dose-response relationship.
Epidemiological investigations of exposure to aluminum in antacids and antiperspirants
Only very weak or no associations have been found between repeated exposures to aluminum in antacids and AD in a number of analytical epidemiological studies ( Graves et al. 1990; Flaten et al. 1991; Lindsay et al. 2002). Positive associations between AD and the use of aluminum containing antiperspirants were reported in two case-control studies, but the interpretation of the results is difficult due to methodological limitations of the studies (e.g., missing data, and misclassification due to varying brands and subtypes of antiperspirant with varying aluminum contents) (Graves et al. 1990;). This positive observation, however, was not supported by a follow-up study on the CSHA21 cohort (Lindsay et al. 2002); the results show that regular use of antiperspirant did not increase the risk of AD.
Aluminium in food
Although the main source of exposure to aluminium for most people probably is food, it is believed that very little is absorbed. There have only been a few epidemiological studies of the effects of aluminium in food in the general population.

Additional information

A number of studies have examined the effects of aluminium in drinking water on cognitive impairment and dementia including AD, as well as other neurological conditions such as Parkinson=s disease and amyotrophic lateral sclerosis. These studies are listed in 

Table 1.

Table 1

Summary of epidemiological studies of aluminium in drinking water and cognitive impairment, dementia and AD.

Study

Design

Subjects

Age range

Outcome measures

Case ascertainment

Association with aluminium

Martyn et al. (1989), UK

Ecological study

445 probable AD, 221 possible AD, 519 other dementia

40-69 years

Probable AD, possible AD, other dementia

Computerized tomographic scanning

Positive for probable AD (statistically significant)

Flaten (1990), Norway

Ecological study

14,727 subjects, 586 demented

 

Dementia

Death certificates

Positive (statistically significant)

Frecker (1991), Canada

Ecological study

568,345 total deaths, 379 demented

 

Dementia

Death certificates

Positive (statistically significant)

Neri & Hewitt (1991), Canada

Ecological study, case-control analysis

2,232 AD or presenile dementia, 2,232 controls

55 years and over

AD, presenile dementia

Hospitalization records

Positive (statistically significant)

Forbes et al. (1991;1992;1994), Canada

Prospective cohort

782 subjects, 400 with some symptoms of mental impairment

45 years at baseline

Impaired mental functioning

Questionnaire completed by the subjects and verified by family members

Positive if aluminium high and fluoride low or high (statistically significant)

Wettstein et al. (1991), Switzerland

Population survey

805 subjects, 99 demented

82-85 years

Mnestic and naming skills

Mnestic and naming subtests of the MMSE.

No statistically significant association

Jacqmin et al. (1994),Jacqmin- Gadda et al. (1996), France

Prospective cohort

3,777 subjects

65 years and over

Cognitive impairment

Score <24 on Mini- Mental State Exam

Positive for aluminium only if silica and pH low (statistically significant)

Forster et al. (1995),Taylor et al. (1995), UK

Case-control

109 PDAT, 109 controls

<65 years

Presenile dementia of the Alzheimer type

Clinical diagnosis

No statistically significant association

McLachlan et al. (1996), Canada

Case-control

119 AD, 51 controls

 

AD

Autopsy

Positive (statistically significant)

Sohn et al. (1996), Korea

Cross-sectional study

558 subjects, 45 cognitively impaired

60 years and over

Cognitive impairment

Mini Mental State test, Korean version

No statistically significant association

Martyn et al. (1997), UK

Case-control

Males only; 106 AD, 441 controls

Born from 1916 to 1945

AD

Computerized tomographic (CT) records, review of hospital case notes

No statistically significant association

Gauthier et al. (2000), Canada

Case-control

68 AD, 68 controls

70 years and over

AD

Clinical diagnosis

Positive (statistically significant) association with organic monomeric Al.; negative for all forms of Al.

Rondeau et al. (2000), France

Prospective cohort

253 demented, 182 AD

65 years and over

AD and dementia

Clinical diagnosis

Positive (statistically significant)

References:

 

  1. Martyn CN, Barker DJ, Osmond C, Harris EC, Edwardson JA, Lacey RF, Geographical relation between Alzheimer's disease and aluminum in drinking water, Lancet 1989 Jan 14;1(8629):59-62.

  2. Flaten TP. Geographical associations between aluminium in drinking water and death rates with dementia (including Alzheimer’s disease), Parkinson’s disease and amyotrophic lateral sclerosis in Norway. Environ Geochem Health. 1990;12:152–167.

  3. Frecker MF. Dementia in Newfoundland: Identification of a geographical isolate? J Epidemiol Comm Health. 1991;45:307–311.

  4. Neri LC, Hewitt D, Aluminium, Alzheimer's disease, and drinking water, Lancet 1991 Aug 10;338(8763):390

  5. Forbes WF, Hayward LM, Agwani N,Dementia, aluminium, and fluoride,Lancet 1991 Dec 21-28;338(8782-8783):1592-3.
  6. Wettstein A, Aeppli J, Gautschi K, Peters M, Failure to find a relationship between mnestic skills of octogenarians and aluminum in drinking water. Int Arch Occup Environ Health, 1991;63(2):97-103.

  7. Jacqmin H, Commenges D, Letenneur L, Barberger-Gateau P, Dartigues JF.,Components of drinking water and risk of cognitive impairment in the elderly,Am J Epidemiol1994 Jan 1;139(1):48-57

  8. Jacqmin-Gadda H, Commenges D, Letenneur L, Dartigues JF,Silica and aluminum in drinking water and cognitive impairment in the elderly,Epidemiology. 1996 May;7(3):281-5.

  9. Forster DP, Newens AJ, Kay DW, Edwardson JA. Risk factors in clinically diagnosed presenile dementia of the Alzheimer type: a case-control study in northern England. J Epidemiol Commun Health. 1995;49:253–258.

  10. Taylor GA, Newens AJ, Edwardson JA, Kay DW, Forster DP.,Alzheimer's disease and the relationship between silicon and aluminium in water supplies in northern England.,J Epidemiol Community Healt.1995 Jun;49(3):323-4

  11. McLachlan DR, Bergeron C, Smith JE, Boomer D, Rifat SL,Risk for neuropathologically confirmed Alzheimer's disease and residual aluminum in municipal drinking water employing weighted residential histories,Neurology.1996 Feb;46(2):401-5.

  12. Sohn SJ, Shin JH, Park YS, Rhee JA, Choi JS. Components of drinking water and risk of cognitive impairment in the rural elderly. Chonnam J Med Sci. 1996;9:189–193

  13. Martyn CN, Coggon DN, Inskip H, Lacey RF, Young WF,Aluminum concentrations in drinking water and risk of Alzheimer's disease,Epidemiology 1997 May;8(3):281-6

  14. Gauthier E, Fortier I, Courchesne F, Pepin P, Mortimer J, Gauvreau D. Aluminium forms in drinking water and risk of Alzheimer’s disease. Environ Res A. 2000;84:234–246

  15. Rondeau V, Commenges D, Jacqmin-Gadda H, Dartigues JF.,Relation between aluminum concentrations in drinking water and Alzheimer's disease: an 8-year follow-up study.,Am J Epidemiol. 2000 Jul 1;152(1):59-66.

Aluminium in antacids and antiperspirants

Graves et al. (1990) conducted a case-control study to investigate the association between exposure to aluminium, from the lifetime use of antiperspirants and antacids, and the risk of AD. Subjects diagnosed with AD were selected from one of two clinics. Selection of cases was limited to those who were married at the time of diagnosis since the spouse served as an informant. Friends of the case and/or informant were selected as controls; when this was not possible, a non-blood relative of the case was identified. The controls were within 10 years of age of the cases and did not suffer from memory loss. Case and control informants were interviewed about the subjects’ antiperspirant/deodorant use and antacid use. Subjects were defined as an antiperspirant/deodorant user if they were reported to have used these products at least once a month for one year prior to the reference year. Frequency, duration, and the name of the most common brands used were also obtained. A subject was considered to have been exposed to antacids if he or she had used antacids daily or almost daily for at least one year prior to the reference year. One hundred and thirty case-control pairs were included in this analysis. The age-adjusted OR for use of aluminium-containing antiperspirants vs. no use of antiperspirant was 1.7 (95% CI: 1.1-2.4). This component of the analysis included only 63 matched pairs as a result of missing information. There was a statistically significant dose-response relationship between the lifetime use of aluminium-containing antiperspirants and the risk of AD, adjusted for age (p = 0.01). The age-adjusted OR for antacid use vs. no use was 3.1 (95% CI: 1.3-7.5). A dose-response gradient was found for any antacid use (p = 0.009), and the adjusted OR for the highest level of exposure was 11.66 (95% CI: 1.28-106.4). However, no association was found when only aluminium-containing antacids were considered (OR=0.8, 95% CI: 0.3-2.1). There are some methodological issues which should be considered in interpreting the results of this study. The necessary use of surrogate informants may have resulted in misclassification of exposure data and a high frequency of missing information. Also the small numbers of subjects in the exposure categories, especially in the subanalyses, may have led to unstable estimates of the ORs.

Flaten et al. (1991) compared the rate of mortality from dementia (as an underlying or contributory cause) of a cohort of 4,179 patients who had surgery for gastro-duodenal ulcer disease between 1911 and 1987 to national rates. It was assumed that the majority of the patients operated on after 1963 were heavy users ofantacids containing aluminium, although no precise exposure information was available. No statistically significant results were seen. The SMR for dementia was 1.10 (95% CI: 0.85 – 1.40, n=64) for all patients, and for those operated on in the period 1967-78 it was 1.25 (95% CI: 0.66 – 2.13, n=13). Limitations of the study include misclassification both in diagnosis and exposure; in addition, the observation period may have been too short to detect an effect. Thus the possibility of an effect cannot be ruled out based on this study.

The Canadian Study of Health and Aging included a prospective analysis of risk factors for AD (Lindsay et al., 2002). The baseline population of this study was comprised of 6,434 subjects aged 65 years or older in 1991. Of these, 4,615 subjects participated in the follow-up study in 1996. The analysis included 194 AD cases, and 3,894 cognitively normal controls. Detailed information regarding a variety of risk factors was obtained through a self-administered questionnaire completed by the subjects at baseline. No association was found between the regular use ofantiperspirants OR=0.77 (95% CI: 0.55-1.08), or antacid use OR=0.91 (95% CI: 0.65-1.26) and the risk of AD.

Aluminium in food

Although the main source of exposure to aluminium for most people probably is food, it is believed that very little is absorbed (Marcus et al., 1992). There have only been a few epidemiological studies of the effects of aluminium in food in the general population. A small study (23 cases, 23 matched controls) reported positive results (Rogers & Simon, 1999). While they reported on some aspects of medical history, there is no indication that they considered possible differences between cases and controls in renal function or vitamin deficiencies relevant to cognitive decline. A comprehensive review of the role of diet in cognitive decline (Solfrizzi et al., 2003) referred to the possibility of a link between aluminium in the diet and AD as “controversial”.

Rogers and Simon (1999) conducted a pilot study to examine dietary differences in individuals with AD and matched controls (n = 46: 23 subjects, 23 controls). The exposure assessment was based on questionnaires to determine past dietary habits. According to the authors, there may be an association between AD and the consumption of foods containing high levels of aluminum food additives. However, the sample size was very small and the association was statistically significant only for one category of food (pancake, waffle and biscuit).

 

References:

  1. Rogers MA, Simon DG. A preliminary study of dietary aluminum intake and risk of Alzheimer’s disease. Age Aging. 1999;28:205–209.

Aluminium in vaccines

Verreault et al. (2001) examined the association between past exposure to conventional vaccines and the risk of AD in order to determine if changes to the immune system could be a factor in the development of this condition. The study population in this investigation consisted of subjects 65 years of age or older who participated in the Canadian Study of Health and Aging, which is a prospective cohort study of dementia. Subjects were screened for dementia at baseline, and cognitively normal subjects completed a risk factor questionnaire which included information about exposure to vaccines. Respondents were asked whether they had ever received vaccinations for tetanus, diphtheria, poliomyelitis, or influeneza. Subjects were screened again for dementia 5 years later. Multivariate logistic regression models were used to determine the association between vaccine exposure and the risk of AD, and to adjust for a variety of other suspected risk factors. One hundred and eighty three subjects, with information about past exposure to vaccines, were diagnosed with probable or possible AD during the 5 year follow up period; 3,682 subjects remained cognitively normal at follow-up. A statistically significant lower risk of AD was demonstrated for subjects who reported at least one vaccination against diptheria/tetanus (OR=0.40, 95% CI: 0.25-0.65), and at least one vaccination against poliomyelitis (OR=0.54, 95% CI: 0.30-0.97). Exposure to influenza vaccine was also associated with a lower risk of AD but did not reach statistical significance (OR= 0.81, 95% CI: 0.55-1.19). These results suggest that past exposure to vaccines may protect against the development of AD.