Association between aluminum in drinking water and incidence of AD in the Canadian Study of Health and Aging cohort

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Association between aluminum in drinking water and incidence of AD in the Canadian Study of Health and Aging cohort

Postby lumia » Thu Jul 16, 2020 8:48 pm

PMID: 32360354


Neurotoxicology. 2020 Apr 29;S0161-813X(19)30036-1.
doi: 10.1016/j.neuro.2020.04.002. Online ahead of print.
Association between aluminum in drinking water and incident Alzheimer's disease in the Canadian Study of Health and Aging cohort
Nicole Van Dyke 1 , Nagarajkumar Yenugadhati 2 , Nicholas J Birkett 1 , Joan Lindsay 3 , Michelle C Turner 4 , Calvin C Willhite 5 , Daniel Krewski 6

Epidemiological evidence linking aluminum in drinking water and Alzheimer's disease (AD) has been inconsistent, with previous studies often limited by small sample sizes. The present study addresses this issue using data from the Canadian Study of Health and Aging (CSHA), a prospective cohort of 10,263 subjects followed-up from 1991-1992 through 2001-2002. Participants' residential histories were linked to municipal drinking water sources in 35 Canadian municipalities to obtain ecologic pH, aluminum, fluoride, iron and silica concentrations in drinking water. Cox proportional hazards models were used to examine associations between aluminum and incident AD [Hazard Ratios (HRs), 95% confidence intervals (CIs)], adjusting for age, gender, history of stroke, education, and high blood pressure. A total of 240 incident AD cases were identified during follow-up of 3, 638 subjects derived from the CSHA cohort with complete data on all covariates. With categorical aluminum measurements, there was an increasing, but not statistically significant, exposure-response relationship (HR = 1.34, 95% CI 0.88-2.04, in the highest aluminum exposure category; p = 0.13 for linear trend). Similar results were observed using continuous aluminum measurements (HR=1.21, 95% CI 0.97-1.52, at the interquartile range of 333.8 μg/L; p = 0.09 for linear trend). In a subsample genotyped for ApoE-ε4, there was some evidence of an association between aluminum and AD (p = 0.03 for linear trend). Although a clear association between aluminum in drinking water and AD was not found, the linear trend observed in ApoE-ε4 subsample warrants further examination.

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Re: Association between aluminum in drinking water and incidence of AD in the Canadian Study of Health and Aging cohort

Postby Tincup » Fri Jul 17, 2020 2:32 pm

lumia wrote:


Full paper is behind paywall. Though they had silica in the data, didn't look like they used it in the analysis.

laurie wrote:


Wonder if Dennis has a comment?
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Re: Association between aluminum in drinking water and incidence of AD in the Canadian Study of Health and Aging cohort

Postby lumia » Fri Jul 17, 2020 3:47 pm

Tincup wrote: Though they had silica in the data, didn't look like they used it in the analysis.


They only did non-Al analyses to the full cohort. As Si is concerned, there's no way to say it's significant (p=0.67--for comparison, Al is p=0.13 using the same data and model).

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Re: Association between aluminum in drinking water and incidence of AD in the Canadian Study of Health and Aging cohort

Postby laurie » Fri Jul 17, 2020 6:10 pm

Tincup wrote:
lumia wrote:


Full paper is behind paywall. Though they had silica in the data, didn't look like they used it in the analysis.

laurie wrote:


Wonder if Dennis has a comment?


Thanks for the tag Tincup. Dennis and I haven't seen this research. I found the paper and It has been added to his reading list. Interesting that APOE -4 was studied.

Regarding Epidemiology studies and the association between aluminum in drinking water and the risk of Alzheimer's, in my husband's 1st book(Prevent Alzheimer's Autism and Stroke with 7 Supplements, 7 Lifestyle choices and a dissolved mineral) he has an appendix VI which includes a write up on the research in this regard and tables of 13 studies. Tomorrow I will figure out a way to get the appendix uploaded with the tables. For right now here is part of the Appendix.

"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. "
"True prevention is only possible by first discovering the cause of a disease such as Alzheimer's."
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Re: Association between aluminum in drinking water and incidence of AD in the Canadian Study of Health and Aging cohort

Postby Tincup » Fri Jul 17, 2020 7:14 pm

laurie wrote:Tomorrow I will figure out a way to get the appendix uploaded with the tables. For right now here is part of the Appendix.


If you have a PDF or JPG of the table, you can upload it as an attachment. See the Attachment tab next to options below the reply box. Click on Attachments and then Add Files.
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Re: Association between aluminum in drinking water and incidence of AD in the Canadian Study of Health and Aging cohort

Postby lumia » Fri Jul 17, 2020 7:59 pm

Tincup wrote:Full paper is behind paywall.

I found a copy on ResearchGate. Is it appropriate to post a link of it?

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Re: Association between aluminum in drinking water and incidence of AD in the Canadian Study of Health and Aging cohort

Postby Tincup » Fri Jul 17, 2020 8:22 pm

lumia wrote:
Tincup wrote:Full paper is behind paywall.

I found a copy on ResearchGate. Is it appropriate to post a link of it?


I think that is fine.
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Re: Association between aluminum in drinking water and incidence of AD in the Canadian Study of Health and Aging cohort

Postby laurie » Sat Jul 18, 2020 9:58 am

This is from the book Prevent Alzheimer's Autism and Stroke with 7 Supplements and 7 Lifestyle Choices and a Dissolved Mineral
by Dennis N Crouse

Appendix VI

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.

(Find Tables below)
T32New.jpg

T31New.jpg



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/liter(80).
• In study 9 only 4 cases of AD had been exposed to greater than 100mcg/liter of aluminum(426).
• 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).

Conclusion
In Chapter 1 of this book Hill’s criteria was used to show that aluminum is a causal factor for AD. Epidemiological data supports both the strength and consistency of association between aluminum and AD. These two criteria are part of Hill’s nine criteria for causality. From the results of the 7 largest epidemiology studies we can conclude, as did the World Health Organization, that “The positive relationship between aluminum in drinking-water and AD … cannot be totally dismissed”83. Based upon this epidemiological data the World Health Organization recommended a maximum of 100mcg/liter of aluminum in drinking water in 1998 and 200(383) 
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"True prevention is only possible by first discovering the cause of a disease such as Alzheimer's."
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Re: Association between aluminum in drinking water and incidence of AD in the Canadian Study of Health and Aging cohort

Postby laurie » Sat Jul 18, 2020 10:36 am

Dennis read the paper. The time period was 7 years which is a short period of time as it takes a long time for aluminum to accumulate in the brain so this maybe why the association was not a strong as it was in other studies)(see table above). In table 5 of the paper lumia posted it shows that the highest level of aluminum exposure of 72 people found 23 had Alzheimer's. Compared with the lowest level of aluminum exposure that is a 70% greater hazard ratio (greater risk of Alzheimer's). In the table above, study number 6 looked at a period of 10 years.

The finding in the study (posted by lumia) that there was evidence of an association between Aluminum and AD in people with ApoE-e4 is not surprising, People with the APOE4 gene produce more beta amyloid which forms oligomers that react with aluminum to form neurotoxic droplets (Nano droplets) of amyloid oligomers. These neurotoxic droplets are very stable and mobile in the brain and are “freezing” the amyloid in the oligomeric state. These beta amyloid oligomers are 10 times more neurotoxic than amyloid plaque.
Drago, D., et al.; Potential pathogenic role of β-amyloid1-42-aluminum complex in Alzheimer’s disease; Int. J. Biochem. & Cell Biol.; 40:731-46 (2008)
http://europepmc.org/abstract/med/18060826
Denise Drago - Aluminum Modulates Effects of βAmyloid1–42 on Neuronal Calcium Homeostasis and Mitochondria Functioning and Is Altered in a Triple Transgenic Mouse Model of Alzheimer's Disease 2008
http://online.liebertpub.com/doi/abs/10 ... .2008.0761
"True prevention is only possible by first discovering the cause of a disease such as Alzheimer's."
Dennis N Crouse


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