Pesticides Exposure and the Risk of Alzheimer’s Disease

Abstract

This literature review discusses the possible connection between pesticide exposure and the risk of developing Alzheimer's disease (AD). After a thorough examination of peer-reviewed articles and a recent literature review, it was revealed that there is an association between the risk of Alzheimer's disease and pesticide exposure, primarily limited to those with a history of occupational pesticide exposure. Only brief evidence of environmental pesticide exposure and risk of Alzheimer's disease was found. While each article touched on the aforementioned topic, the literature also emphasized the importance of supplementary research on specific pesticide classes, as results indicated organophosphates and organochlorines pose the most significant risk in developing Alzheimer's disease.

The literature explicitly calls for further research on this connection, primarily in female populations, as the link between pesticide exposure and risk of Alzheimer's disease in males is more apparent. Further action on this topic could include new research examining pesticide usage in food products, as eating pesticide-altered food is a mechanism of everyday pesticide exposure for both genders, which is not yet explored in literature. If this research is conducted, there is potential for change in overall pesticide usage, policies regarding pesticides, and a possible reduction in cases of Alzheimer's disease.

There is long-standing evidence that, in humans, pesticides can be responsible for acute and long-term health effects. Although there are thousands of studies on pesticides and their link to conditions such as cancers, reproductive health, and Parkinson's disease, data is lacking in regards to pesticide exposure and their relationship to the development of Alzheimer's disease (AD) later in life. Pesticide exposure, even at relatively low doses, may affect brain cells, producing a loss of neurons resulting in cognitive decline, impaired memory or attention, and motor function, all of which are neurobehavioral symptoms that may eventually lead to AD (Baldi et al., 2003, p.409). Databases such as PubMed and ScienceDirect were used to find peer-reviewed articles that applied to this topic between the years 2001 and 2014. MeSH headings included "risk of AD," "risk factors for AD," "occupational pesticide exposure," and "environmental pesticide exposure." The majority of literature that surfaced pertaining to pesticide exposure and its association with an increased risk of AD consisted of cohort, case-control, and ecological studies with a focus on populations where the origin of exposure was through occupational or environmental mechanisms. This paper will discuss the current evidence on the association between daily occupational and environmental pesticide exposure and the risk of developing AD by examining five peer-reviewed articles and one literature review. The presented literature focuses on how the risk of AD may differ between occupational and environmental pesticide exposures, specific types of pesticides and possible elevated risks of AD, as well as explanations representing the lack of data for pesticide exposure and risk of AD in female populations.

The factors that distinguish occupational pesticide exposure from environmental pesticide exposure are defined by the intentional, direct usage of pesticides by a person during their daily occupation, typically in farming and agricultural industries (Quissell, 2018). Conversely, environmental pesticide exposure can include the unintentional contamination of soil, water, air, and vegetation from pesticides (Quissell, 2018). For the purposes of the literature presented, the latter should be considered independently from occupational pesticide exposure.

A prospective cohort study published in The American Journal of Epidemiology reported a significant association between AD and occupational pesticide exposure. The study explained that the French elderly, aged 65 and older, who previously worked in vineyards or agricultural settings, had a relative risk over 2-fold for developing AD (Baldi et al., 2003). It is also important to emphasize that this positive association still occurred after adjusting for smoking and education levels (2003). By the last follow-up session, researchers found cumulative exposure in a total of 228 subjects, with twenty-six cases of AD development in exposed subjects, translating to 30.7 cases per 1,000 person-years (Baldi et al., 2003). According to this study, it is suggested that short term cognitive impairments may occur in occupationally exposed individuals, but AD development is also a possible and more severe result of pesticide exposure, even after long-term work cessation (Baldi et al., 2003).

A more recent case-control study published in The American Academy of Neurology further expanded similar conclusions regarding occupational pesticide exposure and the risk of AD. After self-reported exposure data and cognitive statuses were assessed in residents of Cache County, Utah, researchers concluded that of the 572 pesticide-exposed individuals, over 40% of those exposed to pesticides reported farming as their primary occupation (Hayden et al., 2010). More importantly, 344 of the pesticide-exposed individuals were all diagnosed with AD (2010, p.1526). The results provide some evidence that occupational pesticide exposure and the development of AD are correlated. However, this correlation also poses the argument that pesticide exposure outside of occupational settings and the risk of AD is also possible, as not all of the 344 pesticide-exposed individuals reported an occupational history. This latter statement provides evidence suggesting that pesticides, in general, could be an overall risk factor in developing AD.

Although data seem to be consistent with occupational pesticide exposure and risk of AD, the two studies that evaluated the association between environmental pesticide exposure and the risk of AD differed greatly. In a case-control study conducted in the Saguenay-Lac region of Quebec, Canada, researchers aimed to find an association between environmental pesticide exposure and risk of AD. They based their conclusions on the assessment of pesticide, herbicide, and insecticide spraying activity in residential areas (Gauthier et al., 2001). After controlling for genetic, occupational, and sociodemographic factors, the results failed to show a connection between a significant risk of AD and exposure to any and all pesticides (2001). In a literature review published in Toxicology, some authors considered the outcome of Gauthier et al.'s research (2001) to be compromised because the main measure of environmental exposure was indirectly assessed based on residence and the Agriculture Statistics of Canada for pesticide-spraying activity in these areas (Zaganas et al., 2013).

Conversely, an ecological study conducted in Andalusia, Spain, provides some evidence suggesting that the risk of AD is, in fact, greater in populations living near farms and agricultural lands where pesticide use is high (Parrón, Requena, Hernández, & Alarcón, 2011). Parrón, Requena, Hernández, & Alarcón (2011) explain that pesticides "runoff" or travel into surrounding water, soil, and even air from nearby agricultural land and farms, becoming a harmful substance to those in proximity (p.380). Researchers attribute this concept as one of the mechanisms of environmental pesticide exposure, which is a potential reason why populations living in areas of high pesticide usage have a greater risk of AD (Parrón, Requena, Hernández, & Alarcón, 2011). This data is particularly significant for the association between environmental pesticide exposure and risk of AD because researchers controlled for all occupations relating to agriculture. Therefore, data only represented participants who were exposed to pesticides based on proximity to agricultural practices and farmlands compared to those who lived closer to urban settings. In other words, results suggest that environmental pesticide exposure, independent from occupational exposure, can be associated with a higher risk of AD.

Although Gauthier et al. (2001) did not provide evidence of any association between environmental pesticide exposure and risk of AD, it is beneficial to include in this review because part of the gap in current literature is the actual limit of information on "environmental" pesticide exposure and risk of AD itself. Further research, strictly on environmental pesticide exposure and the risk of AD, is crucial in order to provide a consensus in data. This research should answer if environmental pesticide exposure includes more than the contamination of soil, water, and air, as well as household pesticides. Research should call into question if the duration of environmental pesticide exposure has an effect on the risk of AD if certain classifications of pesticides seem to have a higher risk than others in comparison to widely used occupational pesticides, as well as possible ways to eradicate environmental pesticide exposures.

Part of the difficulty in determining if pesticide exposures are truly associated with a risk in the development of AD is the lack of science-based evidence regarding the harmful effects of specific types of pesticides. Media, news outlets, and even documentaries about the agricultural industry have instilled the idea that the four classes of pesticides are not created equal and some are far worse than others. According to science-based literature, there is some truth to this statement, as research suggests that organophosphates and organochlorines are the two pesticides that have statistically shown a correlation with the risk of developing AD. Before its official ban in 1972, the organochlorine DDT, was one of the most widely used pesticides in U.S. agriculture (Richardson et al., 2014). The knowledge of DDT persistence in the environment and its ability to accumulate in tissues over a long period of time led researchers at The Robert Wood Johnson Medical School at Rutgers University to examine serum levels of patients with AD who previously had an occupational history of DDT exposure (Richardson et al., 2014). Results indicated that serum levels of DDT were significantly elevated in 80% of their patients with AD, which suggests that organochlorines may have a greater effect on the risk of developing AD over other classes of pesticides (2014).

In the Cache County case-control study, questions during the assessment of exposure addressed four specific types of pesticides including organophosphates, carbamates, organochlorines (DDT), and methyl bromides (Hayden et al., 2010). The results identified that of the 572 individuals who reported pesticide exposure, 316 were exposed to organophosphates, 256 were exposed to organochlorines, 25 were exposed to carbamates, and 28 were exposed to methyl bromides (2010). Aside from organophosphates and organochlorines being the two pesticides participants were most exposed to, the data revealed that "participants who were exposed to organophosphates had the highest risk of AD (53% higher)," with organochlorines posing slightly less risk (Hayden et al., 2010, p.1528).

What distinguishes both Richardson et al. (2014) and Hayden et al. (2010) from the previously discussed articles regarding occupational pesticide exposure, is the attention to which types of pesticides can significantly increase the risk of AD, whereas the majority of literature grouped all pesticides together. It is important to draw the connection between these two studies, for their findings furthered the hypothesis that the toxicity of pesticides is variable based on classification. Although these two studies point to clear evidence suggesting exposure to organophosphates and organochlorines pose greater risks in developing AD over other pesticides, further research is necessary to determine levels of toxicity in all classes of pesticides and possible synergistic effects.

Across the literature, the data presented suggests that the majority of pesticide exposure occurs in male-dominated occupational settings, making the association between pesticide exposure and the risk of AD extremely prevalent among males (Hayden et al., 2010). Despite female inclusion at the origin of all studies, researchers made it clear that there is "no significant association of occupational pesticide exposure and risk of AD in females," (Baldi et al., 2003, p.413-14). Focusing on this data trend, it was also seen that apart from male-dominated occupational exposure, males living in high pesticide use areas showed nearly double the risk of presenting with AD over females, revealing that this trend is the same in environmental pesticide exposure (Parrón, Requena, Hernández, & Alarcón, 2011).

The largest gap across literature includes data on female pesticide exposure and the risk of AD. This is ironic considering AD is the most common progressive neurological disease and generally disproportionately affects older female populations (Zaganas et al., 2013). According to Zaganas et al. (2013) literature review, researchers emphasized that across the fourteen studies assessed, a majority of research failed to include reasoning as to why there may be a difference in male versus female pesticide exposure and risk of AD. Researchers attribute some lack of data to the sheer fact that research for AD in general is still underway, whereas data on pesticide exposure and risk of other neurological diseases such as Parkinson's, are more readily available and extensive (Zaganas et al., 2013).

Through close examination of the literature, concrete evidence displayed that the risk of AD increased for those with a history of occupational pesticide exposure. However, the conclusions in studies that examined environmental pesticide exposure and the risk of AD were far less clear. The literature emphasized the danger in specific pesticides such as organophosphates and organochlorines, but the majority of studies failed to draw attention to which pesticides may have caused a more severe connection in the risk of developing AD. Moreover, it was apparent that not only is data on this overall topic still minimal, data on female pesticide exposure and risk of AD is almost non-existent. Baldi et al. (2003) and Gauthier et al. (2001) failed to communicate their speculations as to why there seemed to be no significant association in female populations, while Richardson et al. (2014) disregarded gender, and only classified his participants by occupational exposure. Further research on the link between pesticide exposure and risk of AD must include a way of measuring exposure that can be generalizable across a majority of populations. Initiative in examining pesticide-altered foods provided by the agricultural and food industries is one way to achieve new data solely on environmental pesticide exposure, specific pesticide toxicity classifications, and statistical differences in both genders, as eating pesticide-altered foods is a mechanism of daily pesticide exposure not yet explored in literature.

References

1. Baldi, I., Lebailly, P., Mohammed-Brahim, B., Letenneur, L., Dartigues, J. F., & Brochard, P. (2003). Neurodegenerative diseases and exposure to pesticides in the elderly. American Journal of Epidemiology, 157(5), 409??“414. https://doi.org/10.1093/aje/kwf216
2. Gauthier, E., Fortier, I., Courchesne, F., Pepin, P., Mortimer, J., & Gauvreau, D. (2001). Environmental pesticide exposure as a risk factor for Alzheimer's disease: A case-control study. Environmental Research, 86(1), 37??“45. https://doi.org/10.1006/enrs.2001.4254
3. Hayden, K. M., Norton, M. C., Darcey, D., ??stbye, T., Zandi, P. P., Breitner, J. C. S., & Welsh-Bohmer, K. A. (2010). Occupational exposure to pesticides increases the risk of incident AD: The Cache County Study. Neurology, 74(19), 1524??“1530. https://doi.org/10.1212/WNL.0b013e3181dd4423
4. Parr??n, T., Requena, M., Hern??ndez, A. F., & Alarc??n, R. (2011). Association between environmental exposure to pesticides and neurodegenerative diseases. Toxicology and Applied Pharmacology, 256(3), 379??“385. https://doi.org/10.1016/j.taap.2011.05.006
5. Quissell, K. (2018, March 15). Pesticides. [PowerPoint slides]. Retreived from https://learn.bu.edu/webapps/portal/execute/tabs/tabAction?tab_tab_group_id=_10_1
6. Richardson, J. R., Roy, A., Shalat, S. L., Von Stein, R. T., Hossain, M. M., Buckley, B., ... German, D. C. (2014). Elevated serum pesticide levels and risk for Alzheimer disease. JAMA Neurology, 71(3), 284??“290. https://doi.org/10.1001/jamaneurol.2013.6030
7. Zaganas, I., Kapetanaki, S., Mastorodemos, V., Kanavouras, K., Colosio, C., Wilks, M. F., & Tsatsakis, A. M. (2013). Linking pesticide exposure and dementia: What is the evidence? Toxicology, 307(May), 3??“11. https://doi.org/10.1016/j.tox.2013.02.002

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