Reviewed by A1C Medical Team
Introduction
In the past three decades, increasing attention has turned to environmental factors as the main contributors to neurodegeneration. Previous studies have implicated the role of pesticides in neurological disorders; including Alzheimer’s disease (AD) and Parkinson’s disease (PD). Most evidence, however, originates from occupational exposure studies. Nevertheless, residential exposure is increasingly recognized as a relevant risk factor; especially in settings involving chronic low-dose exposure over long periods.[1] One of the most common settings is golf courses, in which they require intensive chemical management to maintain turf quality and are often integrated into residential developments. Unfortunately, these developments frequently target elderly populations, who are already vulnerable to neurodegenerative diseases. The combination between age as unmodifiable risk factor of neurodegeneration, as well as frequent pesticide exposure raises concerns regarding development of neurodegenerative diseases.
Growing Prevalence of Alzheimer’s Disease
AD is a progressive neurodegenerative disorder, characterized by memory impairment, cognitive decline, and loss of functional independence. AD is considered as the most common cause of dementia worldwide; thus, also represents a growing public health challenge due to population aging. Symptoms of AD vary from difficulty in remembering recent conversation or events to apathy and depression. The symptoms are also progressive within years to the level in which patients with AD can also experience mobility limitations.[2] Within the last thirty years, prevalence of AD and mortality attributed to AD keep increasing along with demographic shifts on life expectancy and aging populations. From 1991 to 2021, prevalence of AD among adults aged at least 65 years old increased by 160%; while global mortality also increased by 115%. This increase was thought to be largely due to expanding older adults. Currently, East and Southeast Asia have the highest prevalence of dementia related to AD with the highest annual incidence in people aged at least 85-year-old (76 per 100,000 people). The Framingham Heart Study also estimated the lifetime risk of 20% in females and 10% in males for Alzheimer’s dementia at, as early as age of 45-year-old. In addition, to date, there is no proven prevention and/or curative therapy for AD. Nevertheless, identifying and addressing modifiable risk factors have been proven to delay the onset of clinical manifestation and further morbidities.[3,4]
Growing Prevalence of Parkinson’s Disease
PD is the second most common neurodegenerative disease characterized by low dopamine levels, attributed to the loss of dopaminergic neurons in the substantia nigra. Similar to AD, PD has also demonstrated the fastest increment in prevalence and disability throughout the years. Between 1990 and 2019, there was a 155.5% increase in the global prevalence of PD with significant increment also in PD-related Disability-Adjusted Life Year (DALY) rates. Study by Li, et al.[5] also showed higher age-standardized prevalence rate of PD in males (157.42 per 100,000) compared to females (12.92 per 100,000). The peaks of incidence were in the 80-84 age group for prevalence and incidence, 90-94 age group for mortality, and 85-89 age group for DALY rates. The most significant increase of age-standardized rate was observed in Norway, while the most rapid increase in age-standardized mortality was seen in the United Arab Emirates.[5] Not only in the elderly population, the incidence and prevalence of early-onset PD (onset before the age of 50) has also demonstrated significant increase in the last three decades. The highest rates of incidence and DALYs were found in the East Asia. Further evaluation of socioeconomic patterns revealed that the highest rates of incidence and prevalence were found in regions with high-middle socio-demographic index; implying that socio-economic had prominent impacts on health outcomes. For instance, middle socio-demographic index regions, which often experience industrialization, tend to experience higher environmental exposure to neurotoxic agents, including pesticides and solvents.[6]
Golf Course Pesticide Use
Types of Pesticides Commonly Used
Golf course turf management relies a lot on a wide array of chemical agents designed to control insects (insecticides), fungi (fungicides), weed (herbicides), and other pests. Throughout the years, the use of these chemical agents, known widely as pesticides, has increased to combat or eliminate undesirable organisms. Any combination of substances which can work as a plant regulator, desiccant, or defoliant can be deemed as pesticides according to the United States Code of Federal Regulations (CFR). There are several modes of entry of pesticides, including contact, systemic, stomach poisons, repellents, and fumigants. In addition, compared with agricultural land, golf courses may receive pesticide application more frequently with greater chemical diversity. Turfgrass aesthetics need higher uniformity and resilience, which may also need more prophylactic treatments, rather than only pest control. As a result, cumulative environmental accumulation may also occur more often.[7]
Although the main goal of applying pesticides is to protect crucial crops, several farmers still use pesticides in higher than recommended dose. For example, organophosphate pesticides can also be used as a neurotoxic agent, especially during World War II. Every year, approximately 44% of 860 million farmers experience pesticide poisoning. Other cases of unintentional acute pesticide poisoning may also reach as high as 385 million cases with around 11,000 fatalities annually.[8] Around 99% of the poisoning incidents happen in the developing countries. This number may be attributed to the inadequate proper training and/or safety equipment related to pesticide utilization in these countries. In addition, pesticides may also cause harm to human and animals through residues in marker food items, aerial application, or contaminated drinking water.[7]
The most commonly used classification of pesticides is created by the World Health Organization (WHO) based on the acute toxicity of each pesticide. Pesticide is classified into acute cutaneous/dermal toxicity and acute oral/mucositis toxicity, measured by its lethal dose (LD50). For acute cutaneous/dermal toxicity, pesticides are considered as extremely toxic if the LD50 is lower than 50 mg/kg, highly toxic if the LD50 is between 50 mg/kg and 200 mg/kg, moderately toxic if the LD50 is between 200 and 2,000 mg/kg, and slightly toxic if the LD50 is higher than 2,000 mg/kg. Meanwhile, for acute oral/mucositis toxicity, pesticides are considered as extremely toxic if the LD50 is lower than 5 mg/kg, highly toxic if the LD50 is between 5 and 50 mg/kg, moderately toxic if the LD50 is between 50 and 2,000 mg/kg, and slightly toxic if the LD50 is higher than 2,000 mg/kg.[9]
Understanding the types and adverse effects of pesticides can increase awareness of the potential risks from these chemical substances. Based on the chemical composition, pesticides are often classified as organochlorines, carbamates, organophosphates, pyrethroids, and neonicotinoids[7,8]:
a) Organochlorines: even though most of them are already forbidden due to their persistent bioaccumulation and side effects on non-target organisms, organochlorines have been recognized as the earliest synthetic peptides. One of the most commonly used organochlorines in the past was dichloro-diphenyl-trichloroethane (DDT). However, due to its persistence in the environment, it has been banned in various regions. Nowadays, the most biodegradable organochlorines, which are still utilized until now, is endosulfan and gamma-hexachlorocyclohexane.
b) Carbamates: work by inhibiting acetylcholinesterase. Acetylcholinesterase itself is a crucial enzyme for transmitting signal between neurons. As a result, inhibiting acetylcholinesterase may disturb nervous function also in non-target organisms, leading to paralysis and death.
c) Organophosphates: similar to carbamates, organophosphates also work by inhibiting acetylcholinesterase. Consequently, acetylcholine will be accumulated at neuron synapses; resulting into overstimulation of nerves and paralysis of the target organisms. Neurotoxicity of organophosphate itself has been linked to a lot of neurodegenerative diseases, especially PD.
d) Pyrethroids: synthetic chemical substances with insecticidal properties. Pyrethroids exhibit similar function as pyrethrins, a natural insecticide from chrysanthemum flowers. Compared to organophosphates, pyrethroids have lower toxicity to humans. Risk of toxicity can be risen if there is a prolonged exposure to pyrethroids. Pyrethroids work by disrupting sodium channels; thus, causing repetitive nerve impulses and paralysis.
e) Neonicotinoids: to some extent, neonicotinoids are considered as newer class of pesticides. Neonicotinoid have strong chemical relation with nicotine; also considered as a highly toxic pesticide. Neonicotinoids work by binding to nicotinic acetylcholine receptors; ultimately resulting into overstimulation and death. Nevertheless, compared to the other classes of pesticides, neonicotinoids demonstrate higher target specificity; thus, minimizing the possible harm to non-target organisms.
Pesticides can also be categorized based on the target of microorganisms, as follows[7]:
a) Fungicides: work by damaging cell membrane of the fungi, inactivating important proteins or enzymes, or disrupting energy production or respiration; thus, inhibiting growth and reproduction of fungi. Fungicides can also be utilized to decrease mycotoxin contamination. Mycotoxins; such as aflatoxins, ochratoxins, fumonisins, trichothecenes, and zearalenone are often found in crops and may cause severe illness in humans and wild animals. Fungicides can be further divided into single-site and multi-site fungicides. Single-site fungicides can disrupt a specific part in fungal metabolic pathway; for example: biosynthesis of protein or ergosterol or mitochondrial respiration. Meanwhile, multi-site fungicides can inhibit multiple parts in fungal metabolic pathway. Another classification of fungicides is based on the chemical structures; divided into organic and bio-fungicides. Organic fungicides are determined based on the availability of carbon atoms on their structures; while bio-fungicides consist of microbial or biochemical products derived from the nature. All of the fungicides above may cause different possible side effects according to each of their structures, as explained in Table 1. [7]
Table 1. List of common possible adverse effects of fungicides administration[7].
| Fungicides | Possible Adverse Effects |
|---|---|
| Azoxystrobin | Acute irritation to eyes, skin, or respiratory tract |
| Mancozeb | Acute irritation to eyes, skin, or respiratory tract |
| Maneb | Acute irritation to eyes, skin, or respiratory tract |
| Thiram | Acute irritation to eyes, skin, or respiratory tract |
| Captan | Acute irritation to eyes, skin, or respiratory tract |
| Copper sulfate | Acute irritation to eyes, skin, or respiratory tract |
| Bordeaux misture | Acute irritation to eyes, skin, or respiratory tract |
| Pentachloronitrobenze | Allergic reactions |
| Sulfur-based fungicides | Acute irritation to eyes, skin, or respiratory tract; diarrhea; irritated dermatitis |
| Ziram | Neural and visual disturbances (in the condition of prolonged inhalation) |
b) Herbicides: also known as weedicides. Herbicides work by inhibiting the growth of weeds, which can interfere the growth of desired crops by competing for light, nutrients, and moistures. Therefore, weedicides can stop the weeds from competing, specifically for water and nutrients. Herbicides can disturb critical metabolic processes of weeds; for instance: production of hormones, photosynthesis, and cell division. Based on the translocation process within the plant, herbicides can be categorized into systemic and non-systemic. Other classifications of herbicides are determined based on the method of administration (soil-applied or foliar) and based on the timing of administration (pre-plant, pre-emergence, or post-emergence). Several herbicides; such as 2,4-dichlorophenoxyacetic acid and Mecoprep may induce neurological (confusion, headache, muscle weakness) and gastrointestinal manifestation (vomiting, diarrhea). One of the most commonly used herbicides, Paraquat, may also cause burnt mouth, chest, throat, diarrhea, headache, fever, and skin ulceration.
c) Nematicides: chemical substances work by controlling non-segmented intervertebrate microscopic worms, which is a huge phytosanitary problem, globally. Nematicides work by inhibiting the feeding of the worms on plant roots; hindering their growth. Fumigant nematicides are biocidal, which can also act on seeds, bacteria, fungi, and other soil organisms. Nematicides can be categorized further into fumigant and non-fumigant. The first fumigant nematicide which can be utilized to control nematodes in crops is methyl bromide, however it can cause phototoxicity and ecological problems. Meanwhile, non-fumigant pesticides are water-soluble liquid or granular substances with nematistatic, contact, or systemic activity against nematodes.
d) Insecticides: chemical substances used to control insect pests (caterpillars, beetles, aphids). Insect vectors; such as ticks and mosquitoes; can also be controlled by insecticides. Insecticides can directly disturb the growth and development of insect pests or directly kill them. Insecticides can cause severe neurological side effects since they mainly target the nervous system of human and insects. Other non-neurological manifestation may also occur in digestive system, cardiovascular system, respiratory system, and endocrine system (Table 2) [7,10].
Table 2. List of insecticides and their possible adverse effects [7,10].
| Insecticides | Possible Adverse Effects |
|---|---|
| Acephate | Headache, excessive salivation, tearing, muscle twitching, nausea, diarrhea, respiratory depression, seizure, fatigue, pinpoint pupils. |
| Aldicarb | Muscle weakness, dizziness, sweating, headache, increased salivation, nausea, abdominal pain, diarrhea, nervous system depression, pulmonary edema. |
| Carbaryl | Muscle weakness, dizziness, sweating, headache, increased salivation, nausea, abdominal pain, diarrhea, nervous system depression, pulmonary edema. |
| Chlorpyrifos | Muscle weakness, dizziness, sweating, headache, increased salivation, nausea, abdominal pain, diarrhea, nervous system depression, pulmonary edema. |
| Methyl Parathion | Muscle weakness, dizziness, sweating, headache, increased salivation, nausea, abdominal pain, diarrhea, nervous system depression, pulmonary edema. |
| Phosmet | Muscle weakness, dizziness, sweating, headache, increased salivation, nausea, abdominal pain, diarrhea, nervous system depression, pulmonary edema. |
| Malathion | Muscle weakness, dizziness, sweating, headache, increased salivation, nausea, abdominal pain, diarrhea, nervous system depression, pulmonary edema. |
| Endosulfan | Itching, burning, skin tingling, tremors, mental confusion, seizure, respiratory depression, coma. |
| Pyrethroids | Abnormal facial sensation, dizziness, salivation, headache, fatigue, vomiting, diarrhea, increased irritability to touch or sound, seizures, numbness. |
e) Rodenticides: chemical compounds which can be utilized to control rodents (rats, squirrels, mice, bats). Rodenticides work by interrupting blood clotting process through inhibition of vitamin K synthesis, resulting into internal bleeding. Rodenticides can also cause dysfunction of nervous system. Rodenticides; such as barium carbonate salt, phosphorus paste, zinc phosphide, white arsenic, and thallium sulphate powders; are usually mixed with bait and put into a strategic place for rodents to ingest. Rodenticides can also cause toxic effects on other non-target organisms, including humans. Zinc phosphide rodenticides can also cause dyspnea, vomiting, fever, seizures, even coma.
f) Biopesticides: defined as pesticides derived from natural sources; inducing a positive shift in pest management. Natural sources that can be used include fungi, bacteria, minerals, and plant extracts. Biopesticides can be used as an alternative to synthetic pesticides. Commonly used biopesticides are ladybugs, Bacillus thuringiensis, Spinosad, resistant crops, and azadirachtin. Biopesticides also work by utilizing semiochemicals, which are chemical signals for communication between organisms. An example of biopesticides is pheromone. Semiochemicals can disturb pest behavior, attract pest into traps, or lure pest away from crops. Another common biopesticide is plant-incorporated protectant, which is a genetically engineered plant which has its own self-defense against pests.
Public Health Implications for Establishment of Golf Courses
There are various factors influencing the impact of pesticides in golf course; starting from more frequent applications to wider chemical diversity. Environmental issue may also arise from the effects of pesticides in reducing conservation of biodiversity, including wildlifes around the golf course. The demand of golf players to play in aesthetically-pleasing golf courses without pests can also increase the use of pesticides. Unfortunately, data of utilization of pesticides in non-agricultural situations are still not well-documented. preliminary study by Kearns, et al. [11] conducted by golf courses in Northern Ireland demonstrated that from the 2,325ha of land area coverage, almost 50% of the area received pesticides treatment. In comparison with agricultural grassland, the overall average pesticide rate on golf courses was higher (2.5 kg/ha on golf courses and 1.7 kg/ha on agricultural grassland). Almost 2.5 tonnes of pesticides were applied into the area with 2.2 kg of pesticide applied into each hectare. Herbicides were the most commonly used pesticides in 90% of the pesticide-coverage area, with the second most frequently used are fungicides. Most of the herbicides (57%) were applied on the fairway with an additional 40% applied to the rough areas of the golf course. Meanwhile, fungicides were given to 21% of all pesticides-coverage area with majority of them were given to control fusarium (Microdochium patch) disease.[11]
To date, direct regulations on the maximum quantity of pesticides used in golf courses have only been established mostly in developed countries. As a result, the establishment of ecofriendly golf courses, which includes lower utilization of pesticides cannot be adequately conducted in all sectors. Establishment of a sustainable golf course certification has been performed in the United Kingdom through the Golf Environment Organization based on the results of self-assessment; field verification; characteristics of the nature (habitat, biodiversity, turfgrass, pollution prevention); characteristics of the resources (water resources, energy, materials); and characteristics of the community involved (volunteer activities, communication methods). In the United States, a private organization called Audubon International established a certification and education program that focuses on the preservation of golf courses environment through environmental planning, reduction and safety of chemical use, habitat and wildlife management, outreach, water quality management, and water conservation.[12]
Nevertheless, there are also other developed countries, such as Korea, which have not established criteria and/or regulations of ecofriendly golf courses. In Korea itself, the number of golf courses increased significantly (more than 30%) within one decade. Similarly, there was also a significant increase (more than 39.5%) in pesticide-coverage area from 2010 to 2019 (from 22,500 ha to 31,400 ha). It is important to be noted that the pesticide-coverage area did not only include the teeing ground or fairway, but also include ponds, clubhouses, and undeveloped regions for environmental conservation. Additionally, exposure of pesticides towards general population was also increased due to an increase as much as 16.6% on the number of golf courses with public non-membership system. There was also an increase of at least 60% in the total quantity of pesticides used from 2010 to 2019. The most commonly used pesticides are fungicides, with a prominent increase of the usage from 56.6% in 2015 to 67.2% in 2017. Moreover, even though Korean-type turfgrass has excellent disease tolerance and low fertilizer requirement, it is still considered as liable to large patch or brown patch. Consequently, fungicides may be applied in large dosage to prevent its exposure to large patch or brown patch. In addition, from 539 golf courses in Korea, the mean quantity of pesticides usage per unit area was 6.97 kg/ha, with total quantity of pesticides sprayed per area nationwide was 5.93 kg/ha. These data indicated that pesticides usage in golf courses contributed massively from all pesticide usage in Korea. Despite all of the facts above, there was still no available references for pesticide usage on Korean golf courses.[13]
Another critical aspect for improving the management of hazardous materials on golf courses is better training regulations on the workers. A study by Arcury-Quandt [14] addressed the necessity for adequate environmental health training curriculum for golf course grounds maintenance workers, especially for the immigrant workers. The training focused on pesticide and chemical knowledge. The results showed that, even in the level of superintendents with experience in golf courses from 10 to 38 years, the subjects still did not demonstrate high level of understanding on federal regulations on hazardous materials. They also did not recognize the fact on how high workers can be exposed to hazardous materials while working on the golf courses. This study also discovered that time, money, and language barrier were the most prominent barriers to videos and hands-on training. In general, workers also had a very little knowledge about pesticides and reported that they only received very little safety training. Therefore, more pesticide safety training programs with educationally, culturally, and linguistically appropriate materials need to be developed for superintendents and workers in golf courses. [14]
Implications of Pesticides on Neurology Problems
Evidences about the neurotoxic adverse effects of pesticides have been increasing within these decades; especially about their roles in neurodegenerative and neurodevelopmental diseases. More recent studies also revealed that pesticides may contribute to brain-gut axis problems, neuroinflammation, and neuropathology related to epigenetic modulation. Discrepancies still exist between the amount of pesticide components identified as toxic to the adult brain and the amount of pesticides considered hazardous to the growing brain with higher susceptibility. Toxicity in the adult brain is usually identified as an acute poisoning event which occurs directly and rapidly after the patient is exposed to the hazardous materials. Meanwhile, developmental neurotoxicity happens in a longer term, even as long as a decade after birth. Pesticides have also been associated with neurodegeneration since it can disturb neurotransmission and also disrupt the functions of ion channels in the nervous system. [15]
Neurotoxicity of Pesticides
A large number of evidences have suggested the involvement of pesticides; particularly organophosphates, pyrethroids, and organochlorinated insecticides; in inducing neurotoxicity. To counter the adverse effects adequately, immediate administration of anticholinergic agent (e.g. atropine) must be done to prevent cholinergic hyperactivation at muscarinic receptor sites. Other agents, such as oximes (obidoxime or pralidoxime) can also restart the blocked enzymes. Combination of atropine and oximes has also been proven to deter clinically significant brain damage associated with pesticides if it can be administered early. [16]
The first well-known pesticide to induce neurotoxicity is organophosphate. The main mechanism of toxicity is by inhibiting acetylcholinesterase in the nervous system; resulting into increased cholinergic activity attributed to the accumulation of acetylcholine in synapses and neuromuscular junctions. After acute intoxication, microglia will be activated and trigger more production of inflammatory cytokine; which include interleukin-1-alpha, interleukin-1-beta, interleukin-6, and TNF-alpha. There neuroinflammatory reactions will subsequently induced neurodegeneration, seizures, and/or behavioral impairments. In comparison to carbamates, a higher incidence of chronic deleterious effects has been reported; including delayed polyneuropathy, cognitive sequelaes, and developmental neurotoxicity. After acute intoxication, distal axonal degeneration may still happen within 7-10 days along with secondary demyelination on peripheral neurons, as well as ascending and descending pathways of the spinal cord. Organophosphate components with low anticholinesterase; such as triorthocresyl phosphate; often induce delayed polyneuropathy. In addition, organophosphate can also affect hippocampus, which is the primary brain region for memory and learning regulation. Delayed and sustained acetylcholinesterase inhibition can also be affected with increased production of oxidative stress due to accumulation of organophosphate, which has hydrophobic characteristic, in the adipose tissue.[15,17]
Common insecticides which are known to be a contributor to neurotoxicity are carbamates and pyrethroids. Carbamates were derived from carbamic acid and can display various levels of acute oral toxicity. Similar to organophosphates, carbamates can also inhibit acetylcholinesterase in the nervous system. However, the link between carbamates and acetylcholinesterase has lower stability compared to the link established between organophosphates and acetylcholinesterase. As a result, gradual hydrolysis can happen, resulting into spontaneous decarbamylation, and eventually reactivates acetylcholinesterase. Therefore, the inhibition of acetylcholinesterase by carbamates is often known as temporary inhibition. Nevertheless, awareness still needs to be increased since accumulation of acetylcholine at muscarinic and nicotinic synapses in the neuromuscular junctions of striae and smooth muscles, as well as in the sympatethic and parasympathetic nervous system, can lead to clinical cholinergic crisis.[15,18] Meanwhile, recent evidence from a pharmacokinetic study revealed that type II pyrethroid deltamethrin can be have a two-fold increase in brain concentration of humans compared to rats. After exposure of type II pyrethroid, neurological complications, especially cognitive dysfunction often occur. Seizure episode may also happen in deltamethrin administration due to the disruption of voltage-gated sodium channels, as well as impaired functions of calcium channels and glutamatergic receptor activation. These mechanisms can also affect gamma-aminobutyric acid and nicotinic acetylcholine receptors. An example of fourth-generation pyrethroid insecticides, called cypermethrin, has also been identified as showing high risk of adverse event by affecting the nerve cell membrane and keeping the gates of sodium ion channel open during repolarization process. As a results, there will be a significant impairment of the signal transferring capability of nervous system; thus, creating repetitive discharges or spontaneous membrane depolarization.[15,19]
More recent studies focus on the neonicotinoid pesticides, which can selectively target niconitic acetylcholine receptors in the neurological systems of insects. Several neonicotinoid pesticides; such as thiamethoxam, clothianidin, and imidacloprid; are banned in the European Union due to their negative impact on pollinator populations. The most commonly proposed neurotoxicity mechanism of neonicotinoids is inadequate transverse through the blood-brain barrier. Generation of oxidative stress, especially after exposure of thiacloprid, also influences neurodevelopment, neurotransmission, as well as trigger more neuroinflammations. This was presented with significantly diminished total antioxidant capacity, elevated malondialdehyde, increased protein carbonyls, and excessive reactive oxygen species. Aside from increased reactive oxygen species, thiacloprid can also produce DNA damage, which will also accelerate various apoptotic pathways.[15,20]
Role of Pesticides in Neurodegenerative Diseases
Pesticides have been studied by previous researches in PD. There are several proposed mechanisms underlying the role of pesticides to PD; including accelerated production of alpha-synuclein fibrils; conformational alteration in alpha-synuclein (especially caused by paraquat, rotenone, and dieldrin); and increased oxidative stress. Along with mitochondrial malfunction, high oxidative stress can contribute to dopaminergic neurodegeneration, which eventually results into PD. Other mechanisms caused by pesticides that may lead to dopaminergic neurodegeneration area acetylcholinesterase inhibition, neuroinflammation, and epigenetic changes.[15] Increased risk of PD has also been associated with lysosomal dysfunction attributed to pesticides. A study on 757 PD patients demonstrated that the most prevalent gene variants found in PD patients exposed to pesticides were the variants associated with lysosomal function, specifically autophagy.[21] Another major mechanism indicated in the progression of PD related to pesticides was neuroinflammation. One of the most common reasons behind secretion of pro-inflammatory cytokines is activated microglia. Microglia can be activated by acute or chronic exposure to pesticides.[22] Neurodegeneration can also happen after oligomerization of amyloid proteins; resulting into misfolded proteins, axonal damage, and neuronal demyelination. These oligomers are triggered by gut dysbiosis, which has been linked with pesticide exposure. Increased Lactobacillaceae and Bacteroides has been associated with increased severity of clinical symptoms in PD. Pesticide-induced dysbiosis has a role on the microbiota-gut-brain axis through local gastrointestinal inflammation and disruption of intestinal barrier; thus, inducing translocation of bacteria and endotoxins into systemic circulation. Consequently, there will be systemic immune activation; leading into blood-brain barrier disturbance, infiltration of peripheral immune cells into the nervous system, and microglial activation.[23]
On the other hand, pesticide usage has also been associated with development of AD. Environmental risk factors themselves are responsible for 30% risk of AD, especially if the exposure is prolonged with lifetime bioaccumulation. The main neuropathological characteristics of AD are neuritic plagues, neuronal degeneration, and neurofibrillary tangles. All of these mechanisms will cause synaptic loss and neuronal cell death, which eventually lead to cognitive dysfunction.[24] Aside from cognitive dysfunction, patients with AD also often exhibit memory deficits, environmental unresponsiveness, as well as difficulty in thinking and language. Interestingly, neurological alterations related to AD can begin much earlier, at least two decades, from the onset of the symptoms. When the brain losses its ability to adapt, gradual cognitive impairment may happen on the individuals.[25] A cross sectional study conducted in Spain discovered that districts high higher utilization of pesticide also showed higher risk and prevalence of AD.[26] Another study performed in 63 AD subjects and 50 healthy controls revealed significantly higher organochlorinated pesticides level in AD subjects with significantly lower antioxidant enzyme activity. The study also found positive correlation between 2,4-dichlorodiphenyldichloroethylene and methylenedioxyamphetamine. Another positive correlation was also observed between gamma-hexachlorocyclohexane and protein carbonyls. All of these findings suggested the link between environmental toxins to neurodegeneration in AD patients.[27]
Conclusion
In conclusion, the increasing global burden of neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease has highlighted the importance of identifying modifiable environmental risk factors beyond aging. Growing evidence suggested that pesticides, widely used in golf course maintenance to preserve turf quality and aesthetics, possess neurotoxic properties that may contribute to neuronal damage through mechanisms such as acetylcholinesterase inhibition, oxidative stress, neuroinflammation, mitochondrial dysfunction, and protein misfolding. Because golf courses often require frequent and diverse pesticide applications and are increasingly integrated into residential developments; many of which target older populations; there is a potential risk of chronic low-dose environmental exposure among nearby residents and workers. Despite these concerns, regulations governing pesticide use in golf courses remain inconsistent across regions, and knowledge gaps persist regarding long-term health impacts. Therefore, greater attention to sustainable turf management, stronger regulatory oversight, improved worker training, and continued research on environmental neurotoxins are essential to minimize potential health risks and to support broader efforts in reducing the growing burden of neurodegenerative diseases in aging populations.
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