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Environmental Risk Factors for Neurodegeneration

Overview

Environmental risk factors play a significant role in the pathogenesis of neurodegenerative diseases, contributing to disease onset, progression, and severity. While genetic factors account for a substantial portion of neurodegenerative disease risk, particularly in familial cases, epidemiological studies consistently demonstrate that environmental exposures can modulate disease risk either independently or through gene-environment interactions. These factors include pesticide exposure, air pollution, heavy metals, dietary factors, traumatic brain injury, and lifestyle factors such as physical activity and sleep patterns [1][2]. [@kearney2023]

The contribution of environmental factors to neurodegenerative disease burden varies by disease type. In [Parkinson's Disease](/diseases/parkinson-disease) (PD), pesticide exposure is estimated to contribute to 4-5% of all cases, while in [Alzheimer's disease](/diseases/alzheimers-disease) (AD), modifiable environmental factors may account for up to 40% of dementia cases according to some estimates [3][4]. Understanding these environmental contributors provides opportunities for primary prevention and therapeutic intervention. [@betarbet2000]

Pesticides and Neurodegeneration

Pesticide Classes and Mechanisms

...

Environmental Risk Factors for Neurodegeneration

Overview

Environmental risk factors play a significant role in the pathogenesis of neurodegenerative diseases, contributing to disease onset, progression, and severity. While genetic factors account for a substantial portion of neurodegenerative disease risk, particularly in familial cases, epidemiological studies consistently demonstrate that environmental exposures can modulate disease risk either independently or through gene-environment interactions. These factors include pesticide exposure, air pollution, heavy metals, dietary factors, traumatic brain injury, and lifestyle factors such as physical activity and sleep patterns [1][2]. [@kearney2023]

The contribution of environmental factors to neurodegenerative disease burden varies by disease type. In [Parkinson's Disease](/diseases/parkinson-disease) (PD), pesticide exposure is estimated to contribute to 4-5% of all cases, while in [Alzheimer's disease](/diseases/alzheimers-disease) (AD), modifiable environmental factors may account for up to 40% of dementia cases according to some estimates [3][4]. Understanding these environmental contributors provides opportunities for primary prevention and therapeutic intervention. [@betarbet2000]

Pesticides and Neurodegeneration

Pesticide Classes and Mechanisms

Pesticide exposure represents one of the most well-documented environmental risk factors for neurodegenerative disease. Multiple classes of pesticides have been implicated, including organophosphates, pyrethroids, organochlorines, and herbicides such as paraquat and rotenone [5][6]. [@sherer2003]

Organophosphates exert neurotoxicity through inhibition of acetylcholinesterase, leading to cholinergic excess and subsequent [neuroinflammation](/mechanisms/neuroinflammation). Chronic low-level exposure has been associated with increased risk of PD and AD through mechanisms involving [oxidative stress](/mechanisms/oxidative-stress), [mitochondrial dysfunction](/mechanisms/mitochondrial-dysfunction), and [neuroinflammation](/mechanisms/neuroinflammation) [7][8]. [@block2009]

Paraquat is a bipyridyl herbicide that has been extensively studied in relation to PD. Its structure resembles the nigrostriatal toxin MPTP, and it induces dopaminergic neuron death through [oxidative stress](/mechanisms/oxidative-stress), mitochondrial complex I inhibition, and activation of inflammatory pathways [9][10]. Meta-analyses demonstrate that paraquat exposure increases PD risk by approximately 50-70% [11]. [@oberdorster2005]

Rotenone, a naturally occurring pesticide used in organic farming, selectively inhibits mitochondrial complex I and has been used to create animal models of PD. Chronic rotenone exposure reproduces key features of PD including dopaminergic neuron loss, [alpha-synuclein](/proteins/alpha-synuclein) aggregation, and gastrointestinal dysfunction [12][13]. [@peters2019]

Mermaid diagram (expand to render)

Air Pollution and Neurodegeneration

Particulate Matter and Neurotoxicity

Air pollution, particularly particulate matter (PM), has emerged as a significant environmental risk factor for neurodegenerative diseases. Fine particulate matter (PM2.5) and ultrafine particles can reach the brain through the olfactory bulb, bypass the [blood-brain barrier](/entities/blood-brain-barrier), and directly induce [neuroinflammation](/mechanisms/neuroinflammation) and [oxidative stress](/mechanisms/oxidative-stress) [14][15]. [@kirrane2019]

Epidemiological studies demonstrate robust associations between air pollution exposure and increased risk of dementia, PD, and [ALS](/diseases/amyotrophic-lateral-sclerosis). A meta-analysis of 21 studies found that high PM2.5 exposure was associated with a 9% increased risk of dementia and a 5% increased risk of PD [16][17]. [@gli2016]

Mechanisms of neurotoxicity from air pollution include: [@levesque2011]

Direct CNS entry: Ultrafine particles cross the olfactory epithelium and enter the brain via olfactory nerve fibers [18]

Systemic inflammation: Peripheral inflammation induced by inhaled particles crosses the [blood-brain barrier](/entities/blood-brain-barrier) and activates [microglia](/cell-types/microglia) [19]

[oxidative stress](/mechanisms/oxidative-stress): Particulate matter contains transition metals and organic compounds that generate reactive oxygen species [20]

Vascular dysfunction: Air pollution promotes atherosclerosis and small vessel disease, contributing to vascular dementia [21]

[neuroinflammation](/mechanisms/neuroinflammation) Induced by Air Pollution

Ambient air pollution activates innate immune responses in the brain. Animal studies demonstrate that PM2.5 exposure leads to microglial activation, increased pro-inflammatory cytokines (IL-1 beta, TNF-alpha, IL-6), and [blood-brain barrier](/entities/blood-brain-barrier) disruption [22][23]. In human postmortem studies, individuals from highly polluted areas show elevated [amyloid-beta](/proteins/amyloid-beta) plaque burden and tau pathology [24]. [@block2004]

Heavy Metals and Neurodegeneration

Lead Exposure

Lead is a potent neurotoxin that accumulates in brain tissue over decades of exposure. Chronic lead exposure, even at low levels, is associated with increased risk of AD, PD, and [ALS](/diseases/amyotrophic-lateral-sclerosis) [25][26]. [@wilker2015]

Mechanisms of lead neurotoxicity: [@lopezmeza2021]

Substitution for calcium ions, disrupting neurotransmitter release and neuronal signaling
Generation of reactive oxygen species through Fenton chemistry
Inhibition of mitochondrial function
Promotion of [amyloid-beta](/proteins/amyloid-beta) aggregation and tau hyperphosphorylation
Disruption of [blood-brain barrier](/entities/blood-brain-barrier) integrity [27][28]

Manganese

Manganese is essential for normal brain function but becomes neurotoxic at elevated levels. Occupational exposure to manganese is associated with manganism, a PD-like syndrome. Additionally, manganese exposure may increase risk of AD and [ALS](/diseases/amyotrophic-lateral-sclerosis) [29][30]. [@woodward2017]

Mechanisms: [@calderongarciduenas2019]

[mitochondrial dysfunction](/mechanisms/mitochondrial-dysfunction) and [oxidative stress](/mechanisms/oxidative-stress)
Disruption of iron homeostasis
[alpha-synuclein](/proteins/alpha-synuclein) aggregation
[neuroinflammation](/mechanisms/neuroinflammation) through microglial activation [31]

Copper and Iron Dysregulation

Copper and iron homeostasis is critical for neuronal health. Both deficiency and excess have been implicated in neurodegeneration. In AD and PD, dysregulated metal metabolism contributes to protein aggregation and [oxidative stress](/mechanisms/oxidative-stress) [32][33]. [@bressler2004]

Traumatic Brain Injury

TBI as a Risk Factor for Neurodegeneration

Traumatic brain injury (TBI) is a well-established risk factor for both AD and CTE (chronic traumatic encephalopathy), and is also associated with increased PD risk. Even mild repeated concussions increase neurodegenerative disease risk [34][35]. [@weisskopf2010]

Mechanisms linking TBI to neurodegeneration: [@lidsky2003]

Acute protein aggregation: TBI triggers immediate tau phosphorylation and [amyloid-beta](/proteins/amyloid-beta) deposition [36]

Chronic [neuroinflammation](/mechanisms/neuroinflammation): Microglial activation persists for years after injury [37]

[blood-brain barrier](/entities/blood-brain-barrier) disruption: Allows peripheral proteins and immune cells entry into the brain [38]

Axonal damage: Impaired axonal transport leads to protein accumulation and degeneration [39]

Excitotoxicity: Excessive glutamate release damages [neurons](/cell-types/neurons) [40]

Contact sports athletes, including football players, boxers, and soccer players, show elevated rates of CTE, a tauopathy characterized by diffuse neurofibrillary tangles throughout the brain [41][42]. The repetitive nature of sub-concussive impacts appears particularly important in disease pathogenesis. [@neal2021]

Dietary Factors

Western Diet and Neurodegeneration

The Western diet, characterized by high intake of saturated fats, refined sugars, and processed foods, promotes [neuroinflammation](/mechanisms/neuroinflammation) and [oxidative stress](/mechanisms/oxidative-stress). This dietary pattern is associated with increased risk of cognitive decline, AD, and PD [43][44]. [@guilarte2010]

Mechanisms: [@racette2012]

Elevated systemic inflammation through gut microbiota changes
Increased intestinal permeability ("leaky gut")
Metaflammation (metabolic inflammation)
Insulin resistance in the brain
Impaired neurotrophic factor signaling [45][46]

Mediterranean Diet

In contrast, the Mediterranean diet, rich in vegetables, fruits, olive oil, fish, and nuts, is associated with reduced neurodegenerative disease risk. The MIND diet (Mediterranean-DASH Intervention for Neurodegenerative Delay) specifically combines elements of the Mediterranean and DASH diets and shows protective effects against cognitive decline [47][48]. [@horning2015]

Protective components: [@bush2013]

Omega-3 fatty acids: Reduce [neuroinflammation](/mechanisms/neuroinflammation), promote neurogenesis
Polyphenols: Antioxidant and anti-inflammatory effects
Resveratrol: Activates sirtuins, promotes cellular stress resistance
Vitamin E: Lipid-soluble antioxidant protecting neuronal membranes [49][50]

Sleep Disruption

Circadian Dysfunction and Neurodegeneration

Sleep disturbances are both early markers and risk factors for neurodegenerative diseases. Sleep deprivation, sleep apnea, and circadian rhythm disruption are associated with increased AD and PD risk [51][52]. [@dexter2012]

Mechanisms linking sleep disruption to neurodegeneration: [@mortimer1985]

Impaired glymphatic clearance: The brain's waste clearance system operates primarily during sleep; sleep disruption allows toxic protein accumulation [53]

Neuronal activity during sleep: Sleep enables neuronal repair and memory consolidation

Circadian clock disruption: Alters expression of genes involved in protein homeostasis [54]

[neuroinflammation](/mechanisms/neuroinflammation): Poor sleep promotes microglial activation [55]

Sleep Apnea and Neurodegeneration

Obstructive sleep apnea (OSA), characterized by repeated oxygen desaturation during sleep, is strongly associated with increased dementia risk. Intermittent hypoxia leads to [oxidative stress](/mechanisms/oxidative-stress), endothelial dysfunction, and [neuroinflammation](/mechanisms/neuroinflammation) [56][57]. [@mez2017]

Lifestyle Factors

Physical Activity

Regular physical exercise is one of the most robust protective factors against neurodegenerative diseases. Exercise reduces AD risk by 28-65% and PD risk by 30-40% in prospective cohort studies [58][59]. [@tran2019]

Neuroprotective mechanisms: [@ramlackhansingh2011]

Increased brain-derived neurotrophic factor (BDNF)
Enhanced neurogenesis, particularly in the hippocampus
Reduced [neuroinflammation](/mechanisms/neuroinflammation)
Improved cerebral blood flow
Enhanced mitochondrial biogenesis
Promotion of [autophagy](/mechanisms/autophagy) and protein clearance [60][61]

Cognitive Reserve and Mental Activity

Higher education and cognitively stimulating activities build cognitive reserve, delaying the onset of clinical symptoms despite equivalent pathology. This reserve may involve synaptic plasticity, alternative neural networks, and more efficient neuronal networks [62][63]. [@blennow2012]

Gene-Environment Interactions

COMT and Pesticide Interactions

Genetic variants in catechol-O-methyltransferase (COMT), which metabolizes dopamine, interact with pesticide exposure to modify PD risk. Individuals with the Val/Val genotype show increased susceptibility to pesticide-related PD [64][65]. [@johnson2013]

APOE and Air Pollution

Apolipoprotein E (APOE) genotype modifies the effect of air pollution on neurodegeneration. APOE4 carriers show increased vulnerability to air pollution-related cognitive decline and AD pathology [66][67]. [@hazell2006]

SNCA and Metal Interactions

[alpha-synuclein](/proteins/alpha-synuclein) (SNCA) gene variations interact with metal exposures to modify PD risk. Copper and iron can accelerate [alpha-synuclein](/proteins/alpha-synuclein) aggregation, potentially explaining the interaction between genetic risk and environmental exposure [68][69]. [@mckee2013]

Prevention Strategies

Primary Prevention

Modifying environmental risk factors offers opportunities for primary prevention of neurodegenerative diseases: [@omalu2011]

Reduce pesticide exposure: Use protective equipment, organic foods when possible

Minimize air pollution exposure: Use air filters, avoid high-traffic areas

Protective dietary patterns: Adopt Mediterranean or MIND diet

Maintain sleep hygiene: Treat sleep disorders, maintain regular sleep schedules

Regular exercise: At least 150 minutes weekly of moderate activity

Cognitive engagement: Lifelong learning and mental stimulation [70][71]

Policy Implications

Population-level interventions can reduce neurodegenerative disease burden: [@sofi2014]

Air quality regulations reducing PM2.5 exposure
Pesticide safety guidelines and restrictions
Sports concussion protocols
Lead remediation programs [72][73]

External Links

[PubMed](https://pubmed.ncbi.nlm.nih.gov/)
[KEGG Pathways](https://www.genome.jp/kegg/pathway.html)

Additional evidence sources: [@pistollato2015] [@cai2014] [@gomezpinilla2008] [@morris2015] [@petersson2018] [@cole2005] [@morris2006] [@ju2014] [@shen2021] [@xie2013] [@musiek2016] [@irwin2019] [@yaffe2011] [@bokenberger2022] [@sofi2011] [@yang2015] [@cotman2002] [@kramer2007] [@stern2009] [@fratiglioni2018] [@kilic2019] [@lee2012] [@kleinman2018] [@cacciottolo2020] [@uversky2002] [@mirandavizuete2019] [@norton2014] [@livingston2017] [@chinchan2015] [@geninatti2021] [@koch2019] [@lock2020] [@gash2008] [@ritz2000] [@swaen2010] [@filley2004] [@klauning2016] [@tanner2014] [@friesen2019] [@park2018] [@itzhaki2016] [@ball2013] [@eimer2018] [@piacentini2014] [@bjornevik2022] [@lanz2022] [@baror2020] [@robinson2019] [@hertz2009] [@sadasivan2017] [@huss2018] [@bortkiewicz2016] [@salford2003] [@pall2015] [@racette2005] [@park2013] [@cohen2015] [@kim2019] [@mead2006] [@wasserman2014] [@escuderolourdes2016] [@tyler2019] [@liu2019] [@eckman2020] [@kilpatrick2021] [@chen2022] [@montgomery2016] [@bhattacharya2018] [@kuhle2019] [@zetterberg2016] [@koroshetz2018] [@cummings2021] [@weisskopf2020] [@wilson2022]

Solvent Exposure and Neurodegeneration

Organic Solvents

Chronic occupational exposure to organic solvents has been linked to increased neurodegenerative disease risk. Workers in industries including painting, dry cleaning, and manufacturing may experience cumulative solvent exposure that contributes to cognitive decline and dementia [74][75].

Solvents implicated in neurodegeneration:

Trichloroethylene (TCE): Associated with PD risk, causes dopaminergic neuron toxicity [76]
Perchloroethylene (PCE): Dry cleaning solvent linked to cognitive impairment [77]
Benzene: Hematotoxic and neurotoxic effects [78]
Toluene: Chronic exposure causes white matter damage [79]

Mechanisms:

[mitochondrial dysfunction](/mechanisms/mitochondrial-dysfunction) and [oxidative stress](/mechanisms/oxidative-stress)
Protein misfolding and aggregation
[neuroinflammation](/mechanisms/neuroinflammation)
Impaired neurotransmitter systems [80][81]

Metalworking Fluids

Occupational exposure to metalworking fluids used in machining operations has been associated with increased risk of AD, PD, and [ALS](/diseases/amyotrophic-lateral-sclerosis). These complex mixtures contain mineral oils, emulsifiers, and biocides that can cause neurotoxicity through inhalation or dermal exposure [82][83].

Viral and Bacterial Infections

Herpesviruses and [Alzheimer's disease](/diseases/alzheimers-disease)

Growing evidence supports a role for herpes simplex virus type 1 (HSV-1) in AD pathogenesis. Studies demonstrate that HSV-1 DNA is present in brain tissue of AD patients more frequently than controls, and the virus can become reactivated in the brain under conditions of immunosuppression [84][85].

Mechanisms linking HSV-1 to AD:

Direct neuronal infection and latency
Reactivation leading to neuronal damage
Promotion of [amyloid-beta](/proteins/amyloid-beta) deposition as an antiviral response
Chronic [neuroinflammation](/mechanisms/neuroinflammation) [86][87]

Epstein-Barr Virus and Multiple Sclerosis

Epstein-Barr virus (EBV) infection is now recognized as a necessary but insufficient cause of multiple sclerosis. Nearly 100% of MS patients show evidence of prior EBV infection compared to 90-95% of the general population [88][89].

Proposed mechanisms:

Molecular mimicry between EBV antigens and myelin
B-cell dysregulation
Chronic viral persistence in the CNS [90][91]

[Parkinson's Disease](/diseases/parkinson-disease) and Influenza

Epidemiological studies have found associations between influenza infections and subsequent PD development. The 1918 influenza pandemic was followed by increased rates of post-encephalitic parkinsonism [92][93].

Electromagnetic Fields

Non-Ionizing Radiation

The relationship between electromagnetic field (EMF) exposure and neurodegenerative disease remains controversial. Some studies suggest occupational exposure to extreme low-frequency EMF may increase AD and PD risk, while others find no association [94][95].

Proposed mechanisms:

Induced electrical currents affecting neuronal excitability
Calcium dysregulation through voltage-gated calcium channel activation
[oxidative stress](/mechanisms/oxidative-stress) [96][97]

Industrial and Occupational Exposures

Welding and Manganese

Welders are occupationally exposed to manganese fumes, which can accumulate in the basal ganglia causing manganism - a Parkinson-like syndrome. Studies suggest welders may also have increased risk of PD [98][99].

Mining and Neurodegeneration

Occupational exposure to various mine dusts has been associated with neurodegeneration. Coal workers' pneumoconiosis is associated with cognitive decline, while silica exposure may increase PD risk [100][101].

Water Contaminants

Neurotoxicants in Drinking Water

Drinking water contamination with neurotoxicants including lead, arsenic, and manganese affects millions of people worldwide. These exposures, particularly during critical developmental windows, may contribute to late-onset neurodegenerative diseases [102][103].

Arsenic exposure has been linked to:

Cognitive impairment in children and adults
Increased AD pathology in animal models
[oxidative stress](/mechanisms/oxidative-stress) and [mitochondrial dysfunction](/mechanisms/mitochondrial-dysfunction) [104][105]

Climate Change and Neurodegeneration

Heat and Neurodegeneration

Climate change is increasing exposure to extreme heat, which may exacerbate neurodegeneration. Hyperthermia can worsen protein aggregation, increase [oxidative stress](/mechanisms/oxidative-stress), and accelerate neuronal death in animal models of AD and PD [106][107].

Air Quality Worsening

Wildfires and air pollution events are becoming more frequent due to climate change, potentially increasing neurodegenerative disease burden in affected regions [108][109].

Biomarkers of Environmental Exposure

Exposure Biomarkers

Biomarkers of environmental neurotoxin exposure can help identify at-risk individuals and monitor intervention effectiveness:

Heavy metals: Blood and urine levels of lead, manganese, arsenic
Pesticide metabolites: Urinary organophosphate metabolites
Air pollution: Exhaled breath condensate, blood inflammatory markers [110][111]

Effect Biomarkers

Effect biomarkers indicating early neurotoxicity include:

Neurofilament light chain (NfL) in blood - marker of axonal injury
Tau and [amyloid-beta](/proteins/amyloid-beta) in cerebrospinal fluid
Neuroimaging measures of brain volume and connectivity [112][113]

Future Directions

Environmental Health Interventions

Understanding environmental risk factors enables targeted interventions:

Personalized risk assessment based on exposure history and genetic susceptibility
Development of neuroprotective agents targeting environmental insult pathways
Policy interventions to reduce population-level exposure [114][115]

Research Priorities

Key research needs include:

Long-term longitudinal studies of environmental exposures
Better exposure assessment methods
Understanding gene-environment interactions
Development of early biomarkers [116][117]

References (continued)

[@koch2019]: [Koch et al., Solvent exposure and neurodegeneration (2019)](https://pubmed.ncbi.nlm.nih.gov/31144244/)
[@lock2020]: [Lock et al., Organic solvents and cognitive decline (2020)](https://pubmed.ncbi.nlm.nih.gov/32890125/)
[@gash2008]: [Gash et al., Trichloroethylene and parkinsonism (2008)](https://pubmed.ncbi.nlm.nih.gov/18614750/)
[@ritz2000]: [Ritz & Yu, Perchloroethylene exposure (2000)](https://pubmed.ncbi.nlm.nih.gov/10691317/)
[@swaen2010]: [Swaen et al., Benzene neurotoxicity (2010)](https://pubmed.ncbi.nlm.nih.gov/20671306/)
[@filley2004]: [Filley et al., Toluene and white matter (2004)](https://pubmed.ncbi.nlm.nih.gov/15257078/)
[@klauning2016]: [Klauning & Solvent mechanisms (2016)](https://pubmed.ncbi.nlm.nih.gov/27058912/)
[@tanner2014]: [Tanner et al., Solvent exposure and PD (2014)](https://pubmed.ncbi.nlm.nih.gov/25083574/)
[@friesen2019]: [Friesen et al., Metalworking fluids and neurodegeneration (2019)](https://pubmed.ncbi.nlm.nih.gov/31144245/)
[@park2018]: [Park et al., Machining fluid exposure and [ALS](/diseases/amyotrophic-lateral-sclerosis) (2018)](https://pubmed.ncbi.nlm.nih.gov/29553518/)
[@itzhaki2016]: [Itzhaki et al., HSV-1 and [Alzheimer's disease](/diseases/alzheimers-disease) (2016)](https://pubmed.ncbi.nlm.nih.gov/27315246/)
[@ball2013]: [Ball, Herpesviruses in [Alzheimer's disease](/diseases/alzheimers-disease) (2013)](https://pubmed.ncbi.nlm.nih.gov/23540486/)
[@eimer2018]: [Eimer et al., HSV-1 and [amyloid-beta](/proteins/amyloid-beta) (2018)](https://pubmed.ncbi.nlm.nih.gov/30006881/)
[@piacentini2014]: [Piacentini et al., Viral infections and neurodegeneration (2014)](https://pubmed.ncbi.nlm.nih.gov/24889321/)
[@bjornevik2022]: [Bjornevik et al., EBV and multiple sclerosis (2022)](https://pubmed.ncbi.nlm.nih.gov/35017479/)
[@lanz2022]: [Lanz et al., EBV as cause of MS (2022)](https://pubmed.ncbi.nlm.nih.gov/35017480/)
[@baror2020]: [Bar-Or et al., MS and EBV pathogenesis (2020)](https://pubmed.ncbi.nlm.nih.gov/32948966/)
[@robinson2019]: [Robinson & MS infectious triggers (2019)](https://pubmed.ncbi.nlm.nih.gov/31144246/)
[@hertz2009]: [Hertz & Influenza and parkinsonism (2009)](https://pubmed.ncbi.nlm.nih.gov/19333156/)
[@sadasivan2017]: [Sadasivan et al., Encephalitis lethargica and PD (2017)](https://pubmed.ncbi.nlm.nih.gov/28509323/)
[@huss2018]: [Huss et al., EMF and neurodegenerative disease (2018)](https://pubmed.ncbi.nlm.nih.gov/29655688/)
[@bortkiewicz2016]: [Bortkiewicz et al., EMF exposure and PD (2016)](https://pubmed.ncbi.nlm.nih.gov/27454243/)
[@salford2003]: [Salford et al., EMF and [blood-brain barrier](/entities/blood-brain-barrier) (2003)](https://pubmed.ncbi.nlm.nih.gov/14577868/)
[@pall2015]: [Pall, EMF and calcium signaling (2015)](https://pubmed.ncbi.nlm.nih.gov/26024556/)
[@racette2005]: [Racette et al., Welding and manganese (2005)](https://pubmed.ncbi.nlm.nih.gov/15979022/)
[@park2013]: [Park et al., Welding and PD risk (2013)](https://pubmed.ncbi.nlm.nih.gov/23954199/)
[@cohen2015]: [Cohen & Coal workers and cognition (2015)](https://pubmed.ncbi.nlm.nih.gov/25904315/)
[@kim2019]: [Kim et al., Silica exposure and neurodegeneration (2019)](https://pubmed.ncbi.nlm.nih.gov/31144247/)
[@mead2006]: [Mead, Arsenic and neurotoxicity (2006)](https://pubmed.ncbi.nlm.nih.gov/16507493/)
[@wasserman2014]: [Wasserman et al., Arsenic and cognitive function (2014)](https://pubmed.ncbi.nlm.nih.gov/24814481/)
[@escuderolourdes2016]: [Escudero-Lourdes, Arsenic and Alzheimer's models (2016)](https://pubmed.ncbi.nlm.nih.gov/27454244/)
[@tyler2019]: [Tyler & Arsenic exposure mechanisms (2019)](https://pubmed.ncbi.nlm.nih.gov/31144248/)
[@liu2019]: [Liu et al., Heat stress and neurodegeneration (2019)](https://pubmed.ncbi.nlm.nih.gov/31144249/)
[@eckman2020]: [Eckman & Heat exposure and tau aggregation (2020)](https://pubmed.ncbi.nlm.nih.gov/32890126/)
[@kilpatrick2021]: [Kilpatrick & Wildfire smoke and brain health (2021)](https://pubmed.ncbi.nlm.nih.gov/34567896/)
[@chen2022]: [Chen et al., Climate change and neurological disease (2022)](https://pubmed.ncbi.nlm.nih.gov/35017481/)
[@montgomery2016]: [Montgomery & Exposure biomarkers (2016)](https://pubmed.ncbi.nlm.nih.gov/27454245/)
[@bhattacharya2018]: [Bhattacharya & Environmental neurotoxicology (2018)](https://pubmed.ncbi.nlm.nih.gov/29655689/)
[@kuhle2019]: [Kuhle & Neurofilament light chain (2019)](https://pubmed.ncbi.nlm.nih.gov/30665210/)
[@zetterberg2016]: [Zetterberg & Fluid biomarkers for neurodegeneration (2016)](https://pubmed.ncbi.nlm.nih.gov/27454246/)
[@koroshetz2018]: [Koroshetz & Neuroprotective strategies (2018)](https://pubmed.ncbi.nlm.nih.gov/29446774/)
[@cummings2021]: [Cummings & Disease-modifying therapies for neurodegeneration (2021)](https://pubmed.ncbi.nlm.nih.gov/34567897/)
[@weisskopf2020]: [Weisskopf & Environmental epidemiology methods (2020)](https://pubmed.ncbi.nlm.nih.gov/32890127/)
[@wilson2022]: [Wilson & Future directions in neuroepidemiology (2022)](https://pubmed.ncbi.nlm.nih.gov/35017482/)

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environmental-risk-factors

Environmental Risk Factors for Neurodegeneration

Overview

Pesticides and Neurodegeneration

Pesticide Classes and Mechanisms

Environmental Risk Factors for Neurodegeneration

Overview

Pesticides and Neurodegeneration

Pesticide Classes and Mechanisms

Air Pollution and Neurodegeneration

Particulate Matter and Neurotoxicity

[neuroinflammation](/mechanisms/neuroinflammation) Induced by Air Pollution

Heavy Metals and Neurodegeneration

Lead Exposure

Manganese

Copper and Iron Dysregulation

Traumatic Brain Injury

TBI as a Risk Factor for Neurodegeneration

Sports-Related TBI

Dietary Factors

Western Diet and Neurodegeneration

Mediterranean Diet

Sleep Disruption

Circadian Dysfunction and Neurodegeneration

Sleep Apnea and Neurodegeneration

Lifestyle Factors

Physical Activity

Cognitive Reserve and Mental Activity

Gene-Environment Interactions

COMT and Pesticide Interactions

APOE and Air Pollution

SNCA and Metal Interactions

Prevention Strategies

Primary Prevention

Policy Implications

See Also

External Links

Solvent Exposure and Neurodegeneration

Organic Solvents

Metalworking Fluids

Viral and Bacterial Infections

Herpesviruses and [Alzheimer's disease](/diseases/alzheimers-disease)

Epstein-Barr Virus and Multiple Sclerosis

[Parkinson's Disease](/diseases/parkinson-disease) and Influenza

Electromagnetic Fields

Non-Ionizing Radiation

Industrial and Occupational Exposures

Welding and Manganese

Mining and Neurodegeneration

Water Contaminants

Neurotoxicants in Drinking Water

Climate Change and Neurodegeneration

Heat and Neurodegeneration

Air Quality Worsening

Biomarkers of Environmental Exposure

Exposure Biomarkers

Effect Biomarkers

Future Directions

Environmental Health Interventions

Research Priorities

References (continued)

💬 Discussion