Influence of pesticide exposure on farmers’ cognition: A systematic review

INTRODUCTION

As agriculture developed, pesticide application has become one of the necessary processes for increasing crop productivity.^[1] About 3 billion kilos of pesticides are used every year worldwide to increase productivity and reduce losses caused by pests and diseases.^[2,3] However, the deliberate use of these chemicals in the environment not only pollutes it – including the air, land, and water – but also accumulates pesticides and their metabolites in humans and animals, causing toxic effects.^[1,4]

In this scenario, a large part of the population may be subjected to pesticides, especially in those occupationally exposed to it. Occupational exposure occurs in workers involved in the manufacture, handling, application, and disposal of these products. Thus, farmers are more likely to be exposed to pesticides.^[5]

Farmers’ exposure occurs mainly during the preparation and application of pesticides and cleaning of the spraying equipment. The most common routes of contamination are the respiratory and dermal tracts, but it can also occur orally.^[4,6] Much of the exposure occurs due to a lack of risk perception, low educational attainment, farmers’ lack of training, and defective or absent personal protective equipment (PPE).^[6-8]

Based on exposure time and symptom development speed, pesticide toxicity can be classified as acute or chronic intoxication. Acute toxicity occurs from a single exposure incident. Chronic toxicity occurs from multiple exposure incidents. Low pesticide doses, absorbed in a single exposure, are often insufficient to produce diseases but frequent absorption can cause serious chronic diseases or even death.^[9]

Acute exposure can lead to symptoms such as difficulty breathing, nausea, vomiting, diarrhea, and rashes.^[7] Among the diseases associated with chronic exposure, cancer,^[10,11] reduced fertility, birth defects,^[12,13] and neurodegenerative diseases^[14,15] stand out.

Pesticides are classified into three groups by their origin and chemical group: Natural, inorganic, and synthetic pesticides. The last group includes organochlorides, organophosphates, pyrethroids, and carbamates, among others.^[16]

Organophosphorus compounds (OP) can inhibit the cholinergic enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), crucial for neurotransmission.^[17] Intoxication by this type of anticholinesterase accumulates the neurotransmitter acetylcholine in the synaptic cleft by inhibiting cholinesterase, inducing excessive stimulation of nicotinic and muscarinic receptors in the central and peripheral nervous system and paralyzing cholinergic synaptic transmission.^[18]

The classic signs of acute OP poisoning are diarrhea, polyuria, miosis, muscle weakness, bradycardia, emesis, tearing, salivation, and sweating.^[19] More recently, several studies point to farmers’ neuropsychological impairment associated with exposure to OP pesticides, such as memory and attention problems.^[20-23]

When this relation is observed, it is necessary to know and estimate these individuals’ cognitive status. For this, appropriate tests are used to evaluate overall intellectual performance or individual cognitive functions: attention or processing speed, space-time orientation, visuospatial ability, praxis (voluntary planning of movement), coordination and motor speed, memory, language, communication, reasoning, and executive and other functions related to the frontal lobes of the cerebral cortex.^[21,24]

To date, the literature still lacks a full explanation of the relationship between pesticides and cognitive impairment. Despite the large number of studies involving the theme, their designs and discoveries are heterogeneous.^[24] Thus, this literature review aimed to evaluate if farmers’ exposure to pesticides is associated with cognitive impairment.

MATERIALS AND METHODS

This review was based on the preferred reporting items for systematic reviews and meta-analyses guidelines^[25] and used the participants, interventions, comparators, outcomes, and study design strategy,^[26] enabling us to define:

RESULTS

A total of 2071 articles were first retrieved by the keywords in all chosen databases, of which 695 were duplicates and excluded. Of the remaining 1376 selected articles, 748 were excluded after we read their titles, leaving us with 628 articles. Next, after reading their abstracts, 601 articles were excluded since they failed to fit our defined criteria. Of the 27 eligible studies, 17 were excluded after a full reading of the text. The main reasons for exclusion were including individuals under 18 years of age, lacking farmers in their sample and cognitive tests, and having other study designs. Thus, we elected ten studies to compose this systematic review. Figure 1 shows a flow diagram of the search process.

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Figure 1:

Flow diagram of the selection of systematic review articles.

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DISCUSSION

After analyzing the studies, the findings supported the association of neurobehavioral deficits with work in agriculture. We can observe that farmers had a lower performance in selective attention, information processing, stimulus accuracy,^[29] verbal comprehension, processing speed, discriminative sensitivity,^[21] general memory, alertness and orientation^[27] visual memory, language, and perceptual-motor function and complex attention when compared with control groups.^[20]

The longer the agricultural work period and, consequently, the greater the exposure to pesticides, the more negatively it affects the cognitive performance of the exposed participants compared to the controls.^[35] Research on individuals indirectly exposed to pesticides found an important profile of intoxication since they are close to agricultural areas. Thus, the authors suggest that chronic low-level exposure, whether direct or indirect, also influences cognitive functioning.^[30,31]

Another gap in studying pesticide exposure effects is the susceptibility of the general population to experiencing intoxication. In this review, most studies examined farmers and control groups mostly formed by the general population. However, some studies involved people indirectly exposed to pesticides and observed a degree of cognitive impairment in this group as well. Thus, adding to the knowledge of contamination of water, soil, air, and food by pesticides,^[4] we suggest that the general population is also susceptible to exposure and adverse effects.

The mechanisms by which pesticides produce cognitive impairments are still being described, but it mainly pointed to the cholinergic syndrome. Studies in humans and animals have indicated the central cholinergic system as an important regulator of cognitive functions such as learning and memory.^[37] Thus, OP and carbamates harm cholinergic synapses since they are anticholinesterase compounds. Cognitive deficiencies associated with AChE inhibition can be explained by the overstimulation and persistent activation of muscarinic and nicotinic receptors due to acetylcholine accumulation in the synaptic cleft.^[18]

In relation to cholinesterase, most studies showed decreased activity in individuals exposed to pesticides. While, not all of them were associated with these individuals’ cognitive function, and it was impossible to establish consensus on this variable. However, in agreement with another literature review,^[24] we found that the available studies hardly show similar study designs, making more assertive outcomes on this topic difficult.

Furthermore, it has been a challenge to reliably quantify pesticide exposure levels^[24] since there is often no validated instrument to research the forms and degree of exposure to which farmers are subject, showing heterogeneous data. Thus, it is important to know if there is a profile of intoxication by cholinesterase but only half of the studies in this review included biochemical analyses of these enzymes; of which, more than half found some degree of intoxication in individuals exposed to pesticides.

Regarding individual active ingredients, one study observed an association of glyphosate exposure with visual memory impairment.^[20] Moreover, we observed that a specific class of pesticides can rarely be localized in the studies, and it is impossible to study it in isolation. This is due to the fact that pesticide exposure is evaluated through questionnaires and personal interviews, in which subjects are sometimes incapable of exactly name the used compounds, using mixtures of substances or the pesticides used differ in the sample, making it impossible to establish relations.

CONCLUSION

Despite the limited number of trials available within this study design, we found scientific evidence to support the existence of adverse effects of pesticides on farmers’ cognitive function. Although exposure to pesticides may not be the only factor involved in cognitive impairment, it may be sufficient to trigger it, often in combination with other factors, not yet fully explored in the literature.

We suggest that future studies engage in similar projects, addressing the aspects mentioned above and assessing the specific categories of pesticides most harmful to cognition and the toxicological mechanisms by which they act. Finally, we consider the monitoring of the mode of pesticide application to be important, favoring lower occupational exposure of farmers to pesticides and, consequently, lower cognitive impairment.