To what extent do increasing incidents of Alzheimer’s disease in the states of California, Illinois, and New York correlate to increased levels of nitrogen oxide release, implying aluminum toxicity?

Aluminum is among one of the most abundant elements present in the environment. It is naturally found in soils as aluminosilicate minerals and plays an important role in plant production and development. However, its potential to affect water in the soil has been found to cause damage to human health. Despite Aluminum being a natural constituent of soil, when the acidity of soil increases, Aluminum becomes soluble, which increases its abundance in the soil. The soluble Aluminium leaches into any water source, which is extracted and used as drinking water. Nitrogen oxides (NOx) are gasses, also a form of primary pollutant, containing nitrogen atoms, that contribute to increased PH levels of the soil, and will be part of this investigation. When NOx increases the acidity, it binds to Aluminum ions and causes the release of Aluminium into water bodies (Agriculture and Food, n.d). Finally, through drinking water, ingesting food, or simply being in contact with the soil and the air, when high levels of Aluminum are ingested in some form, it causes what is known as Aluminium toxicity. Sulfur dioxide is another contributor to soil acidity, however, for this investigation, in particular, only the effects of NOx will be considered, as it has been found to be emitted in higher concentrations in the US as compared to Sulfur dioxide (Tiseo, 2021).

There have been several studies published since the 1920s, around a potential correlation between aluminum toxicity and Alzheimer's disease. A report on increasing incidents of Alzheimer's disease in areas of high levels of Aluminum in drinking water in England and Wales was reported in 1989, for example (Kawahara, Masahiro, and Midori Kato-Negishi, 2011). Another report from Cornwall, in the UK, found that people that had been exposed to Aluminum contaminated water exhibited signs of cerebral impairment (Altmann P, n.d). Another recent study published in The Journal of Alzheimer's disease in 2020, showed researchers were able to identify Aluminum content in brain tissues from donors with Alzheimer's disease (Mold, 2020). All tissues contained Aluminum content, and \(42\%) of them contained significantly high levels of Aluminum. This served as important additional evidence that suggests a potential correlation between aluminum toxicity and the disease. However, there has yet not been enough evidence to confirm a direct cause.

According to the Centers for Disease Control and Prevention, the number of incidents of Alzheimer's disease in the US (5.8 million in 2020), is expected to triple by 2060, serving as an alarm to find answers on how these growing numbers can be slowed down. In the report published by the Alzheimer's Association, California, New York, and Illinois contain one of the highest rates of Alzheimer's incidents as compared to other states¹. This sparked my curiosity to investigate the potential correlation between Alzheimer's disease and the release of NOx in these three states of the US. This exploration is of relevant use for the ongoing search for conclusive answers to this cognitive disease that might potentially be a product of an environmental issue, which calls for urgent solutions to improve the health of US citizens.

The values of NOx in the different states were collected from EPA, the US Environmental Protection Agency. EPA is an official government agency with multiple types of reliable data, which will bring much accuracy to the findings of this exploration. The NOx values have, however, been taken from three different sites in each state. Even though these sites were taken from locations spread across the states, they can bring limitations to the results, not representing the variables with great accuracy to the state as a whole.

As for the numbers of people diagnosed with Alzheimer's Disease (AD), all the numbers were gathered from yearly reports published by an American voluntary health organization called Alzheimer's Association. The data published on the organization's page is claimed to be "accurate, timely and useful", they also explain their data "should not be served as medical guidance or professional advice" ("About This Site", n.d.), which does not relate to the aim of this investigation. Despite their commitment to providing factual information, the numbers found were rounded to the nearest thousand, which can limit precise findings of trends.

The independent variable is the values of NOx, which have been chosen for their contribution to Aluminum toxicity. It is important to note that the values of NOx will be averaged between the three different sites from which they were collected, to obtain one final number for each state for each year, simplifying calculations. The Standard deviations will be calculated as well, as it exposes how close the averaged values are to the original values from each site. The higher the SD value, the more the original values vary, the lower the SD value, the less the original values are spread out. In this case, more compact, less spread data is important as it indicates similar and consistent values in each site, accurately representing its presence in the state as a whole. The dependent variable is the number of incidents of AD in each state. Finally, the controlled variables are the American states from which all the data will derive (California, Illinois and New York) and the years in which the data was collected (2017, 2018, and 2019). No reliable data was found for more years for all variables, therefore, it has been decided upon to maintain a smaller quantity of concrete data.

The correlation between the increase in NOx with the number of incidents of AD will be shown using the Pearson's correlation or the "r-value", which will be calculated using a graphic display calculator. The choice of Pearson's correlation for this investigation lies upon its optimal ability to provide quantitative data, as well as its ability to show the strengths of the relationship between the dependent and independent variables. These will serve as an advantage when interpreting data. R-values that are closer to -1, indicate a negative strong correlation, values that are closer to 1, indicate a strong positive correlation. Diagrams displaying the relationship between the variables for each state will be constructed and presented, containing a trend line to visually represent the correlations.

Based on previous studies on Aluminum toxicity and the potential effect on incidents of AD as well as the ability NOx possesses to increase Aluminum presence in the soil, the hypothesis for this research proposes that: there will be to a high extent, a correlation between NOx values and the incidents of AD, meaning it is expected that positive r-values are found for all three states considered.

Concluding, the results exhibit that incidents of Alzheimer's disease in the state of Illinois and New York do not correlate to the increased levels of nitrogen oxide release, implying no occurrence of aluminum toxicity. The state of California exhibits, however, to a high extent, a correlation between the variables, indicating a significant occurrence of aluminum toxicity. California's outcome confirms what has been found in many previous studies. Where aluminum ingestion has been confirmed to generate adverse cognitive complications, being considered a threat to increased incidents of AD (Rondeau, 2008).

As shown in figure 2, the r-values of New York and Illinois are negative, close to -1 which indicates a strong negative correlation, indicating the variables in fact, change in opposite ways. This is reflected in Figures 4 and 5, where the trendline for the independent variable (NOx) does not touch all data points and is tilted in opposite directions. A reason for this can be explained when considering the values of standard deviation for these particular states. In figure 1, the standard deviation of NOx values in Illinois in 2017 is substantially higher than the average value, indicating the values for each site vary to a great extent. Similarly, the standard deviation of NOx values in New York in 2018, is significantly high relative to the average value, indicating a strong variation of the values of each site. This is consistent with what figures 4 and 5 display, where the only data point that does not lie on the trendline, corresponds to the values of which the standard deviation is extremely high as compared to the average value. When considering the controlled variable, meaning the AD values, they contain numbers that in the long run do show changes however, for Illinois for example, the values increase in the first year but remain constant through the last year. For New York, the initial AD value drops from the first year and remains constant through the last 2 years.

The contradictory results of Illinois and New York regarding what previous studies have shown can be explained by the lack of consideration for another factor: the level of industrialization in the states as well as its size. Highly industrialized states tend to release more polluting gasses, including NOx (US EPA, 2019). The level of industrialization of Illinois and New York is less than California (Crawford,2014), and so is the size of their state. This could explain the inconsistencies of NOx values for the states.

As for California, the r-value is extremely positive, indicating a high correlation, in which the variables change correspondingly with each other. This is shown in figure 3, where the trend lines for both the independent (NOx) and dependent (AD) variables touch all data points and are tilted in the same direction. An indication of this result is found when observing the standard deviation values for the state, in all the years, the values are relatively low as compared to the average values, meaning the data is consistent and similar for NOx values throughout all the sites in the state.

The methodology used for this investigation had a considerable amount of strengths. The use of Pearson's correlation coefficient served to enhance and precisely present the extent of the correlation that was being investigated. Additionally, constructing diagrams that contained a trendline further displayed what the r values presented in the first place, and helped identify trends more easily. Also, the calculation and consideration of standard deviation served as evidence to support the results and assisted in identifying potential errors or indicators of other variables that could have been taken into account.

The data for NOx and AD values had some limitations. The NOx values, since they were collected from three different sites only, did not succeed in accurately representing the different levels of exposures of NOx in the states as a whole, since inconsistencies were found amongst the values from each site. This may have called for values from more than three sites being used, to accurately find an average that accounts for more regions within the states. The source from which the AD values were derived, came from an organization that provided "rounded numbers", which prevented the showing of smaller increases in incidents, hence why there are constant patterns in two out of the three states investigated, affecting the reliability of the final results. Similar to the NOx values, more data from other years would have contributed to potentially a result closer to what was initially expected and found by previous research.

Besides the limitations discussed above, the outcome for California showed a significant level of correlation, which can serve as a signal that similar results are likely to be found within other states. This exploration could then be developed towards investigating all states across the US, to get a broader pool of data that can be used to research more substantially, the correlation between Aluminum toxicity and AD on a broader scale.

To extend and improve this investigation, other variables could have been utilized to change the accuracy of the results. For example, the levels of aluminum in drinking water for each state would most likely lead to different r values. Since NOx is an indirect cause of Aluminum toxicity, it may be difficult to draw conclusions that confirm what previous studies have shown, as the outcome from this investigation does not directly prove that NOx is causing Aluminum Toxicity. Furthermore, the use of AD values specifically found within the regions from which those aluminum levels would come from would consider more closely, the natural relationship between the variables, giving more precise results.

As referred to in the introduction, the study published by The Journal of Alzheimer's disease can serve as an encouragement to act upon reducing Al toxicity. Accounting for the limitations of the variables selected, a more suitable strategy would involve dealing with the direct digestion of Aluminum. According to ATSDR's report published in 2008² Aluminum is ingested mainly through food consumption, especially unprocessed, such as fruits and vegetables grown in Aluminum contaminated soils. A solution to this issue could be through the government's investment in food testing as well as education and campaigns to raise awareness about the different brands and products containing high levels of Aluminum.

This solution can, however, be expensive for the government, creating opportunity costs, as they could allocate those resources onto other severe environmental issues. It may also be ineffective, as US citizens might simply ignore the ads and consume foods that are cheaper and more practical, rather than ecological, more carefully harvested foods. Producers may oppose the testing of their products, fearing a reduction in their revenue, which can generate political unpopularity making the government resistant to conduct food testing. This solution would also be incapable of dealing with indirect causers of aluminum toxicity such as NOx deposition in soils, which do generate knock-on effects that can worsen the issue.

Altmann P, Cunningham J, Dhanesha U, Ballard M, Thompson J, Marsh F. Disturbance of cerebral function in people exposed to drinking water contaminated with aluminium sulphate: a retrospective study of the Camelford water incident. British Medical Journal.

2021 Alzheimer's Disease Facts and Figures. https://www.alz.org/media/Documents/alzheimers-facts-and-figures.pdf.

"Causes of Soil Acidity." Agriculture and Food, https://www.agric.wa.gov.au/soil-acidity/causes-soil-acidity.

Crawford, Mark. "The States Leading the U.S. Manufacturing Resurgence." Area Development, 19 Feb. 2014, https://www.areadevelopment.com/regionalreports/q1-2013/states-leading-us-manufacturing-resurgence-2665542.shtml.

Kawahara, Masahiro, and Midori Kato-Negishi. "Link between Aluminum and the Pathogenesis of Alzheimer's Disease: The Integration of the Aluminum and Amyloid Cascade Hypotheses." International Journal of Alzheimer's Disease, vol. 2011, 2011, pp. 1-17., https://doi.org/10.4061/2011/276393.

Mold, Matthew et al. 'Aluminum and Amyloid-β in Familial Alzheimer's Disease'. 1 Jan. 2020: 1627-1635.

"Nitrogen Oxides Control Regulations | Ground-Level Ozone | New England | US EPA." EPA, Environmental Protection Agency, 10 Oct. 2019, https://www3.epa.gov/region1/airquality/nox.html.

Public Health Statement for Aluminum - Agency for Toxic https://www.atsdr.cdc.gov/ToxProfiles/tp22-c1-b.pdf.

Published by Ian Tiseo, and Aug 20. "U.S. Nitrogen Oxides Emissions 1970-2020." Statista, 20 Aug. 2021, https://www.statista.com/statistics/501284/volume-of-nitrogen-oxides-emissions-us/.

Published by lan Tiseo, and Mar 30. "U.S. Sulfur Dioxide Emissions 1970-2020." Statista, 30 Mar. 2021, https://www.statista.com/statistics/501303/volume-of-sulfur-dioxide-emissions-us/.

Rondeau, Virginie, 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." OUP Academic, Oxford University Press, 8 Dec. 2008, https://academic.oup.com/aje/article/169/4/489/119824?login=true.