Occupational and Environmental Pesticide Exposure and the Risk of Alzheimer’s Disease

This literature review discusses the possible connection between pesticide exposure and the risk of developing Alzheimer's disease (AD). After thorough examination of peer-reviewed and literature review articles, data revealed 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 for supplementary research on specific pesticide classes, as results indicated organophosphates and organochlorines pose the most significant risk in developing Alzheimer's disease. The literature presented distinctly called to action 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 study on this topic may include new research examining pesticide usage in food products, as eating pesticide-altered foods is a mechanism of everyday pesticide exposure in both genders, not yet explored in literature. If this research is conducted, there is potential for change in overall pesticide usage, policies on pesticides, and possible reduction in cases of Alzheimer's disease.

Keywords: pesticides, pesticide exposure, occupational, environmental, Alzheimer's disease, risk factors, neurological disorders

Pesticide Exposure and the Risk of Alzheimer's Disease

There is long-standing evidence that pesticides can be responsible for certain acute and chronic 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 risk of developing Alzheimer's disease (AD). Current findings suggest pesticide exposure may cause the loss of neuron signaling, resulting in cognitive decline, impaired memory/attention, and motor function, all of which are common neurobehavioral symptoms of AD (Baldi et al., 2003, Parrin, Requena, Hernandez, & Alarcin, 2011). 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 increased risk of AD consisted of cohort, case-control, and ecological studies, with a focus on populations where occupational or environmental mechanisms were the origins of exposure. This paper discusses 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 highlights how 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 on pesticide exposure and risk of AD in female populations.

Literature Review

Occupational and Environmental Pesticide Exposures

The factors distinguishing occupational pesticide exposure from environmental pesticide exposure include 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 may include the unintentional contamination of soil, water, air, and vegetation from pesticides (Quissell, 2018). For the purposes of this review, the latter is considered independent 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, explaining that the French elderly, aged 65 and older, who previously worked in vineyards or agricultural settings had over two times the risk of developing AD due to their occupation (Baldi et al., 2003). It is also important to emphasize this positive association still occurred after adjusting for smoking and education levels (2003). By the last follow-up session, researchers found a cumulative exposure for a total of 228 subjects, twenty-six of whom presented with AD, translating to 30.7 cases per 1,000 person-years (Baldi et al., 2003). This study suggests that not only may short-term cognitive impairments occur in occupationally exposed individuals, but AD development is also a possible and more severe result of occupational 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 explained similar conclusions on occupational pesticide exposure and the risk of AD. After assessment of self-reported exposure data and cognitive statuses in residents of Cache County, Utah, researchers concluded that of the 572 pesticide-exposed individuals, over 40% of those exposed reported farming as their primary occupation (Hayden et al., 2010). More importantly, 344 of the pesticide-exposed individuals were all diagnosed with AD (2010). These results provide evidence that there is a correlation between occupational pesticide exposure and development of AD. However, this correlation also poses the argument that pesticide exposure outside of occupational settings and risk of AD is also possible, as not all of the 344 pesticide-exposed individuals reported exposure from only occupational history. This latter statement is evidence suggesting that in general, pesticides could be an overall risk factor in developing AD.

Although data seems consistent in occupational pesticide exposure and risk of AD, the two studies that evaluated the association between environmental pesticide exposure and risk of AD differed immensely. In a case-control study developed in the Saguenay-Lac region of Quebec, Canada, researchers aimed to find an association between environmental pesticide exposure and risk of AD, basing their conclusions on 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 significant risk of AD and exposure to any and all pesticides (2001). In a literature review published in Toxicology, authors consider the outcome of Gauthier et al. (2001) invalid, as the central measure of environmental exposure was indirectly assessed based on residence and the Agriculture Statistics of Canada for pesticide-spraying activity in only a few areas (Zaganas et al., 2013, p.6).

Conversely, an ecological study conducted in Andalusia, Spain, provides some evidence that the risk of AD is in fact greater in populations living near farm and agricultural lands where there is high pesticide usage (Parrin, Requena, Hernndez, & Alarin, 2011). Parin, Requena, Hernndez, & Alarc??n (2011) explain how pesticide residues can travel into surrounding water, soil, and even air from nearby agricultural land and farms, becoming a harmful substance to those in proximity (p.380). This concept is one mechanism of environmental pesticide exposure, and a potential reason why populations living in areas of high pesticide usage have a greater risk of AD (Parr?n, Requena, Hernandez, & Alarcin, 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 exposed to pesticides based on proximity to agricultural practices and farmlands, compared to those who lived closer to urban settings. In other words, results propose that there is an association between environmental pesticide exposure and higher risk of AD, independent from occupational exposure.

Although Gauthier et al. (2001) did not provide evidence of an association between environmental pesticide exposure and risk of AD, it is important to note that this study is an example of the clear-cut gap in current literature on ""environmental pesticide exposure and the risk of AD itself. Further research strictly on environmental pesticide exposure and the risk of ADis crucial to provide a consensus in data. This research should answer if environmental pesticide exposure includes more categories in addition to contamination of soil, water, air, and household pesticides. Research should call into question if duration of environmental pesticide exposure has an effect on the risk of AD, if certain classifications of pesticides have a higher risk than others in comparison to widely used occupational pesticides, as well as possible ways to eradicate environmental pesticide exposures.

Types of Pesticides and Elevated Risk of AD

Part of the difficulty in determining if pesticide exposures are truly associated with risk of AD is the lack of science-based evidence regarding the harmful effects of specific pesticide classes. 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 two specific pesticides, organophosphates and organochlorines, statistically show a correlation in the risk of developing AD (Hayden et al., 2010, Richardson et al., 2014). 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 organochlorines may have a greater effect in the risk of developing AD over other classes of pesticides (2014).

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

Unlike most of the data that grouped all pesticide classes together, both Richardson et al. (2014) and Hayden et al. (2010) called attention to which types of pesticides may significantly increase the risk of AD. It is important to draw the connection between these two studies, for their findings promoted the hypothesis that toxicity levels in pesticides are variable based on classification. Although these two studies point to clear evidence suggesting exposure to organophosphates and organochlorines pose greater risks in developing AD, further research is necessary to determine levels of toxicity across all classes of pesticides and possible synergistic effects.

Pesticide Exposure and AD in Males versus Females

Across the literature, data suggests most 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 participant inclusion at the origin of all studies, researchers clearly emphasized there was no significant association of occupational pesticide exposure and risk of AD in females, (Baldi et al., 2003, p.413-14). Furthermore, it was also determined that males living in areas with high pesticide usage showed nearly double the risk of presenting with AD in comparison to females (Parr?n, Requena, Hernndez, & Alarc?n, 2011). This trend reveals that males seem to have a higher risk in developing AD through both occupational and environmental pesticide exposures.

The largest gap across literature is relevant data on female pesticide exposure and the risk of AD. This is ironic considering AD in general disproportionately affects older female populations (Zaganas et al., 2013). In Zaganas et al's. (2013) literature review, researchers emphasized that of the fourteen studies assessed, the 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 (Zaganas et al., 2013). Researchers attribute some lack of data to the sheer fact that research on AD development itself is still underway, whereas data on other neurological diseases, such as Parkinson's, are more readily available and extensive (Zaganas et al., 2013).

Conclusions and Future Study

Through close examination of the literature, concrete evidence displayed 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. Some literature emphasized the danger in specific pesticides such asorganophosphates and organochlorines, but most 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 overall data on this topic still minimal, but 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 speculations as to why there was no significant association in female populations, while Richardson et al. (2014) disregarded gender, and classified his participants only by occupational exposure. Further research on the link between pesticide exposure and risk of AD must include a way of measuring exposure that is generalizable across a majority of populations. Initiative in examining pesticide-altered foods, provided by 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

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

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

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

Parrin, T., Requena, M., Hernandez, A. F., & Alarcin, 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

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

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

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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