Epidemiology Supporting Aluminum’s Causal Role in Alzheimer’s Disease

Epidemiological studies comparing the level of aluminum in drinking water to the relative risk of Alzheimer’s disease support the contention that aluminum is a causal factor of Alzheimer’s disease.  Using epidemiology studies to find correlations between aluminum ingestion and Alzheimer’s disease has been made difficult because there are many sources of aluminum in the human diet. Therefore it is surprising that correlations have been found between aluminum in drinking water and AD or dementia in the 7 largest epidemiology studies each involving more than 300 people with AD or dementia.  The reason for this may be because aluminum in drinking water is more easily absorbed by the gastrointestinal tract than aluminum in food. It has been found that 0.3% of the aluminum in drinking water is absorbed, while only 0.1-0.2% of the aluminum in food is absorbed³⁹¹. 

Epidemiology studies are only valid if the number of people with AD and/or dementia in the study is high enough to make the data statistically significant. Therefore the 13 epidemiology studies in the following table are listed in order of number of AD and/or dementia cases evaluated in each study.  Note that there are 7 studies involving 300 or more cases of AD or dementia and all 7 of these studies found a greater risk of AD or dementia due to drinking water with higher aluminum levels. There are 6 studies involving approximately 100 or less cases of AD or dementia. With such a low number of cases it is not surprising that four of these studies (e.g. studies 8, 9, 12, and 13) found no statistically significant (NSS) relationship between aluminum in drinking water and the incidence of AD, dementia, or low cognition. For more details on these four studies see the notes at the end of the table.

Study	No. of Cases AD/Dementia	Total No.  People	Aluminum in DW mcg/liter	Relative Risk of AD/Dem.	Data Source	Country	Year of Publication	Ref.
1	3,736 D	1,224,558	<50	1.00	Death Certs.	Norway	1986-90	81, 692, 693
	9,545 D	2,494,345	50-200	1.17	“	“	“	“
	1,446 D	347,231	>200	1.37	“	“	“	“
2	598 AD	41,800	<67	1.00	Death Certs.	Ontario	1995	694, 695
	2,153 AD	145,000	68-200	0.82-1.01	“	“	“	”
	14 AD	1,000	>336	1.42-4.25	“	“	“	“
3	2,232 D	4,464	<10	1.0	Hospital Records	Ontario	1991	82
			10-100	1.13	“	“	“	“
			100-200	1.26	“	“	“	“
			>200	1.46	“	“	“	“
4	385 AD	680	<100	1.00	Autopsy Verified	Ontario	1995	75
			>100	1.70	“	“	“	“
			>125	3.60	“	“	“	“
			>150	4.40	“	“	“	“
			>175	7.60	“	“	“	“
5	371 D	870	<84.7	1.00	Cognition Tests	Ontario	1994	696
			>84.7	2.27	“	“	“	“
6	364 AD/455 D	1667	<100	1.00	Cognition Tests	France	2000-09	79
		216	>100	2.80/2.26		“	“	“
7	307 AD (<65)	1185	<20	1.00	CT Scans	U.K.	1989	80
			20-70	1.40	“	“	“	“
			80-110	1.60	“	“	“	“
			>110	1.70	“	“	“	“

NNS = Not statistically significant;   AD = Alzheimer’s disease;    D = Dementia

Relative Risk of AD/Dementia: 1.00  = no added risk, 1.20 = 20% increased risk;  2.00 = twice the risk

Notes on Studies 7, 8, 9, 12, and 13

• Studies 7 (1989) and 8 (1997) were both carried out by the same group at South Hampton Hospital and published with the same lead author (e.g. C. N. Martyn)^80,697. The positive correlation between high aluminum levels in drinking water and AD this group reported eight years earlier in study 7 was described and not retracted in study 8. With 200 fewer AD cases in study 8, they were unsuccessful in finding any correlation between high aluminum levels in drinking water and AD⁶⁹⁷.  Seventy percent of the controls in study 8 were people with dementias and neurologic disorders, other than AD. The authors of study 8 point out that aluminum could also influence the course of these diseases in the controls resulting in a systematic error in study 8. In fact, in study 7 they reported a higher relative risk (e.g. 1.1 – 1.2) of dementias, other than AD,  in men 40-64 years of age exposed to aluminum levels in drinking water over 20mcg/liter⁸⁰. 
•  In study 9 only 4 cases of AD had been exposed to greater than 100mcg/liter of aluminum⁴²⁶.
• In study 12 the participants only drank water with less that 100mcg/liter of aluminum⁷⁰¹.
• In study 13 elevated aluminum in drinking water was only ingested for 3 years^79,702.

References

75. McLachlan, D.R.C., et al.; Risk for neuropathologically confirmed Alzheimer’s disease and residual aluminum in municipal drinking water employing weighted residential histories; Neurology, 46:401-5 (1996)

76. Rondeau, V., et al.; 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. 169:489-96 (2009)

77. Gauthier, E., et al.; Aluminum forms in drinking water and risk of Alzheimer’s disease; Environ. Res.; 84, 236-46 (2000)

78. Bondy, S.C.; The neurotoxicity of environmental aluminum is still an issue; Neurotoxicology; 31:575-81 (2010)

79. Flaten, T.P.; Aluminum as a risk factor in Alzheimer’s disease, with emphasis on drinking water; Brain Res. Bull.; May; 55(2):187-96 (2001)

80. Martyn, C.N., et al.; Geographic relation between Alzheimer’s disease and aluminum in drinking water; Lancet, 1:59-62 (1989)

81. Flaten, T.P.;  Geographical associations between aluminum in drinking water and death rates with dementia (including Alzheimer’s disease),Parkinson’s disease and amyotrophic lateral sclerosis in Norway; Environ. Geochem. Health; 12:152-167 (1990)

82. Neri, L.C., and Hewitt, D.; Aluminum, Alzheimer’s disease, and drinking water; Lancet 338:390, (1991)

426. Taylor, G.A., et al.; Alzheimer’s disease and the relationship between silicon and aluminum and water supplies in northern England; J. Epidemiology and Community Health; 49:323-28 (1995)

692. Flaten, T.P.; An investigation of the chemical composition of Norwegian drinking water and its possible relationships with the epidemiology of some diseases. Dept. of Chem.; Norwegian Univ. Sci. and Tech., Trondheim, Norway (1986)

693. Vogt, T.; Water quality and health: Study of a possible relation between aluminum in drinking water and dementia. Sosiale og Okonomiske Studier no. 61. Oslo: Statistics Norway (1986)

694. Forbes, W.F., et al.;  Geochemical risk factors for mental functioning, based upon the Ontario Longitudinal Study of Aging (LSA) V. Comparison of the results, relevant to aluminum water concentrations, obtained from LSA and death certificates mentioning dementia; Can. J. Aging; 14:642-56 (1995)

695. Canadian Study of Health and Aging Group; The incidence of dementia in Canada in 1991; Neurology; July; 55(1):66-73 (2000)

696. Forbes, W.F., and Agwani, N.; Geochemical risk factors for mental functioning, based upon the Ontario Longitudinal Study of Aging (LSA) III. The effects of aluminum-containing compounds; Aging 13:488-98 (1994)

697. Martyn, C.N., et al.; Aluminum concentrations in drinking water and risk of Alzheimer’s disease; Epidemiology; 8:281-86 (1997)

698. Forster, D.P., et al.; Risk factors in clinically diagnosed presenile dementia of the Alzheimer’s type: A case-control study in northern England; J. Epidemiol. Community Health; 49:253-58 (1995)

699. Frecker, M.F.; Dementia in Newfoundland: identification of a geographical isolate?; J. Epidemiol. Community Health; 45:307-11 (1991)

700. Doll, R.; Review: Alzheimer’s disease and environmental aluminum; Age Aging; 22:138-53 (1993)

701. Wettstein, A.; et al.; Failure to find a relationship between mnestic skills of octogenarians and aluminum in drinking water; Int. Arch. Occup. Environ Health 63:97-103 (1991)

702.  Wood, D.J., et al.; Bone mass and dementia in hip fracture patients from areas with different aluminum concentrations in water supplies; Age Aging; 17:415-19 (1988)