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  • Adriano dos Santos

Environmental Toxins and Neurodegenerative Diseases: Exploring the Link

As our global population ages and fertility rates decline, leading to a simultaneous decrease in population size and an increase in elderly individuals, the prevalence of neurodegenerative diseases is expected to rise significantly.[1]

Environmental Toxins

The worldwide population of individuals aged 65 and above is growing rapidly, surpassing the number of children under five for the first time in history in 2018.[2] The incidence of neurodegenerative diseases like Alzheimer's and Parkinson's disease is projected to rise in parallel with this demographic shift. The urgency to understand the connection between environmental toxins and neurodegenerative diseases has never been greater.


While genetic factors contribute to disease development, researchers concur that environmental risks also play a pivotal role in accelerating the onset and progression of neurodegenerative diseases.[4] These conditions encompass a diverse range of disorders, each characterized by distinct pathological patterns, clinical presentations, and underlying causes.[5,6] Notably, Alzheimer's disease (AD) and Parkinson's disease (PD), the most prevalent neurodegenerative disorders, have been extensively studied in relation to environmental exposures, particularly heavy metals and pesticides.[7]


Impact of Heavy Metals on Alzheimer's Disease


With over 50 million individuals affected globally, dementia presents a formidable challenge, with projections indicating that this number could escalate to 152 million by 2050.[8] AD, characterized by progressive cognitive impairment and memory dysfunction, has a multifactorial origin that includes environmental elements.[8] Heavy metals like lead, cadmium, and manganese, commonly employed substances, are implicated in AD pathogenesis through mechanisms involving oxidative stress, inflammation, and apoptosis.[5,8]


Lead Exposure


Despite regulatory efforts to curtail lead usage, this toxic metal remains prevalent in industrial applications, including lead-acid storage batteries.[8] Lead sources vary geographically, but electronic waste recycling, lead mining, and smelting are global contributors to high lead levels, leading to inhalation or ingestion exposure pathways. Particularly concerning is childhood lead exposure, as lead dust is often ingested through hand-to-mouth behavior.[8] Longitudinal studies suggest a potential association between early-life lead exposure and accelerated cognitive decline.[4,8] Animal studies have shown that lead-exposed subjects exhibit memory deficits and cognitive decline later in life.[4]


Lead, known for its neurotoxicity, rapidly crosses the blood-brain barrier, instigating neuroinflammation, oxidative stress, endoplasmic reticulum stress, and apoptosis.8 Cross-sectional epidemiological studies support the link between lead exposure and neurodegeneration,[8,10,11] with postmortem brain tissue analyses revealing associations between lead and AD hallmarks such as Aβ accumulation, tau pathology, and inflammation.[4] Inflammatory responses linked to lead poisoning can lead to neuronal demise, involving factors like inducible nitric oxide synthase (iNOS), interleukin-1 beta (IL-1β), and tumor necrosis factor alpha (TNF-α), all contributing to neurotoxicity in AD.[1,4]


Cadmium


Cadmium, while emerging as a neurotoxicant, is less studied in humans.[8] Dietary sources and smoking are the primary exposure routes. Like lead, cadmium can breach the blood-brain barrier, inciting oxidative stress, neuroinflammation, and apoptosis in neurons. A 2023 systematic review found correlations between cognitive decline and increased levels of blood, urine, and dietary cadmium in older adults.[1] Epidemiological studies demonstrated associations between blood cadmium levels and AD-related mortality among older adults.[4,13,14] Meta-analyses indicate elevated cadmium concentrations in AD patients compared to controls,[8,15] and whole blood cadmium was inversely associated with cognitive function in a study of older adults.[8,16]


Manganese Exposure


Despite its essential role in health, excessive manganese exposure leads to neurotoxicity. Beyond occupational contexts, diet is the primary source of manganese, and toxic levels can stem from drinking water, air pollution, and industrial use. Accumulation in the brain can cause neurotoxic effects. Research shows that excess manganese disrupts cellular processes, inducing oxidative stress, mitochondrial dysfunction, and apoptosis. Bioinformatics analyses suggest manganese exposure influences gene expression related to cytokine receptors, apoptosis, and oxidative phosphorylation.[4,18] Studies associate adult manganese levels with cognitive impairment,[8,17] impacting neural function, especially in occupational settings. Accumulation of manganese in the brain and liver contributes to neurotoxicity and hepatic damage.[17]


Parkinson's Disease and Pesticide Connection


Parkinson's disease, the second most common neurodegenerative disorder after AD, affects thousands annually.[21] Motor symptoms, cognitive impairments, and autonomic dysfunction characterize PD. Pesticide exposure, particularly from rural living and occupational contexts, increases the risk of neurodegenerative diseases, including PD.[22] Pesticides like paraquat and maneb/mancozeb are linked to elevated PD risk.[23]


Numerous studies associate insecticide exposure with PD incidence, with paraquat and maneb/mancozeb demonstrating particularly strong correlations.[27] Organochlorine pesticides, neurotoxic and oxidative stress inducers, are frequently implicated.[23] A 2020 study associated PD with specific pesticides like 2,4-D, chlorpyrifos, and paraquat, highlighting geographic patterns and potential exposure pathways.[21]


Role of Astrocytes and Future Directions


Astrocytes, pivotal for brain health due to their antioxidant and metabolic functions, are increasingly scrutinized in the context of neurodegenerative diseases. Their response to environmental toxins is central to understanding their impact on brain health. Disrupted astrocytic metabolism due to toxic exposure contributes to neural degeneration.[29,30] Research suggests that astrocytes play a crucial role in the expression of neural injury and neurodegeneration, shedding light on potential therapeutic targets.[30]


Interventions and the Functional Medicine Approach


Addressing toxicity and enhancing detoxification pathways are fundamental to functional medicine's holistic approach. Probiotic therapies with antimicrobial properties may mitigate heavy metal toxicity. Nutritional strategies, including antioxidant-rich diets and phytonutrient-rich plans, show promise in neuroprotection. Avoiding toxic exposures remains a core tenet, but understanding detoxification processes and total toxic load is crucial.



References

  1. Liu C, Liu Z, Zhang Z, et al. A scientometric analysis and visualization of research on Parkinson’s disease associated with pesticide exposure. Front Public Health. 2020;8:91. doi:3389/fpubh.2020.00091

  2. United Nations Department of Economic and Social Affairs. World Population Prospects 2019: Highlights. Published June 2019. Accessed July 10, 2023. https://population.un.org/wpp/Publications/Files/wpp2019_10KeyFindings.pdf

  3. Mather M, Scommegna P, Kilduff L. Fact sheet: aging in the United States. Population Reference Bureau. Published July 15, 2019. Accessed July 10, 2023. https://www.prb.org/resources/fact-sheet-aging-in-the-united-states/

  4. Huat TJ, Camats-Perna J, Newcombe EA, Valmas N, Kitazawa M, Medeiros R. Metal toxicity links to Alzheimer’s disease and neuroinflammation. J Mol Biol. 2019;431(9):1843-1868. doi:1016/j.jmb.2019.01.018

  5. Cicero CE, Mostile G, Vasta R, et al. Metals and neurodegenerative diseases. A systematic review. Environ Res. 2017;159:82-94. doi:1016/j.envres.2017.07.048

  6. Armstrong RA. What causes neurodegenerative disease? Folia Neuropathol. 2020;58(2):93-112. doi:5114/fn.2020.96707

  7. Gunnarsson LG, Bodin L. Occupational exposures and neurodegenerative diseases—a systematic literature review and meta-analyses. Int J Environ Res Public Health. 2019;16(3):337. doi:3390/ijerph16030337

  8. Bakulski KM, Seo YA, Hickman RC, et al. Heavy metals exposure and Alzheimer’s disease and related dementias. J Alzheimers Dis. 2020;76(4):1215-1242. doi:3233/jad-200282

  9. Cui L, Hou NN, Wu HM, et al. Prevalence of Alzheimer’s disease and Parkinson’s disease in China: an updated systematical analysis. Front Aging Neurosci. 2020;12:603854. doi:3389/fnagi.2020.603854

  10. Zhao Y, Ray A, Portengen L, Vermeulen R, Peters S. Metal exposure and risk of Parkinson disease: a systematic review and meta-analysis. Am J Epidemiol. 2023;192(7):1207-1223. doi:1093/aje/kwad082

  11. Farace C, Fiorito G, Pisano A, et al. Human tissue lead (Pb) levels and amyotrophic lateral sclerosis: a systematic review and meta-analysis of case-control studies. Neurol Sci. 2022;43(10):5851-5859. doi:1007/s10072-022-06237-y

  12. Yang X, Xi L, Guo Z, Liu L, Ping Z. The relationship between cadmium and cognition in the elderly: a systematic review. Ann Hum Biol. 2023;50(1):15-25. doi:1080/03014460.2023.2168755

  13. Min JY, Min KB. Blood cadmium levels and Alzheimer’s disease mortality risk in older US adults. Environ Health. 2016;15(1):69. doi:1186/s12940-016-0155-7

  14. Peng Q, Bakulski KM, Nan B, Park SK. Cadmium and Alzheimer’s disease mortality in US adults: updated evidence with a urinary biomarker and extended follow-up time. Environ Res. 2017;157:44-51. doi:1016/j.envres.2017.05.011

  15. Xu L, Zhang W, Liu X, Zhang C, Wang P, Zhao X. Circulatory levels of toxic metals (aluminum, cadmium, mercury, lead) in patients with Alzheimer’s disease: a quantitative meta-analysis and systematic review. J Alzheimers Dis.2018;62(1):361-372. doi:3233/jad-170811

  16. Li H, Wang Z, Fu Z, et al. Associations between blood cadmium levels and cognitive function in a cross-sectional study of US adults aged 60 years or older. BMJ Open. 2018;8(4):e020533. doi:1136/bmjopen-2017-020533

  17. Balachandran RC, Mukhopadhyay S, McBride D, et al. Brain manganese and the balance between essential roles and neurotoxicity. J Biol Chem. 2020;295(19):6312-6329. doi:1074/jbc.rev119.009453

  18. Ling J, Yang S, Huang Y, Wei D, Cheng W. Identifying key genes, pathways and screening therapeutic agents for manganese-induced Alzheimer disease using bioinformatics analysis. Medicine (Baltimore). 2018;97(22):e10775. doi:1097/md.0000000000010775

  19. Heng YY, Asad I, Coleman B, et al. Heavy metals and neurodevelopment of children in low and middle-income countries: a systematic review. PLoS One. 2022;17(3):e0265536. doi:1371/journal.pone.0265536

  20. Vlasak T, Dujlovic T, Barth A. Manganese exposure and cognitive performance: a meta-analytical approach. Environ Pollut. 2023;332:121884. doi:1016/j.envpol.2023.121884

  21. Hugh-Jones ME, Peele RH, Wilson VL. Parkinson’s disease in Louisiana, 1999-2012: based on hospital primary discharge diagnoses, incidence, and risk in relation to local agricultural crops, pesticides, and aquifer recharge. Int J Environ Res Public Health. 2020;17(5):1584. doi:3390/ijerph17051584

  22. Gunnarsson LG, Bodin L. Occupational exposures and neurodegenerative diseases—a systematic literature review and meta-analyses. Int J Environ Res Public Health. 2019;16(3):337. doi:3390/ijerph16030337

  23. Dardiotis E, Aloizou AM, Sakalakis E, et al. Organochlorine pesticide levels in Greek patients with Parkinson’s disease. Toxicol Rep. 2020;7:596-601. doi:1016/j.toxrep.2020.03.011

  24. Shrestha S, Parks CG, Umbach DM, et al. Pesticide use and incident Parkinson’s disease in a cohort of farmers and their spouses. Environ Res. 2020;191:110186. doi:1016/j.envres.2020.110186

  25. Priyadarshi A, Khuder SA, Schaub EA, Shrivastava S. A meta-analysis of Parkinson’s disease and exposure to pesticides. 2000;21(4):435-440.

  26. Yan D, Zhang Y, Liu L, Shi N, Yan H. Pesticide exposure and risk of Parkinson’s disease: dose-response meta-analysis of observational studies. Regul Toxicol Pharmacol. 2018;96:57-63. doi:1016/j.yrtph.2018.05.005

  27. Pezzoli G, Cereda E. Exposure to pesticides or solvents and risk of Parkinson disease. 2013;80(22):2035-2041. doi:10.1212/wnl.0b013e318294b3c8

  28. Xie A, Gao J, Xu L, Meng D. Shared mechanisms of neurodegeneration in Alzheimer’s disease and Parkinson’s disease. Biomed Res Int. 2014;2014:648740. doi:1155/2014/648740

  29. McCann MS, Maguire-Zeiss KA. Environmental toxicants in the brain: a review of astrocytic metabolic dysfunction. Environ Toxicol Pharmacol. 2021;84:103608. doi:1016/j.etap.2021.103608

  30. Kubik LL, Philbert MA. The role of astrocyte mitochondria in differential regional susceptibility to environmental neurotoxicants: tools for understanding neurodegeneration. Toxicol Sci. 2015;144(1):7-16. doi:1093/toxsci/kfu254

  31. Tang C, Lu Z. Health promoting activities of probiotics. J Food Biochem. 2019;43(8):e12944. doi:1111/jfbc.12944

  32. Daisley BA, Monachese M, Trinder M, et al. Immobilization of cadmium and lead by Lactobacillus rhamnosusGR-1 mitigates apical-to-basolateral heavy metal translocation in a Caco-2 model of the intestinal epithelium. Gut Microbes. 2019;10(3):321-333. doi:1080/19490976.2018.1526581

  33. Abdel-Megeed RM. Probiotics: a promising generation of heavy metal detoxification. Biol Trace Elem Res. 2021;199(6):2406-2413. doi:1007/s12011-020-02350-1

  34. Agnihotri A, Aruoma OI. Alzheimer’s disease and Parkinson’s disease: a nutritional toxicology perspective of the impact of oxidative stress, mitochondrial dysfunction, nutrigenomics and environmental chemicals. J Am Coll Nutr. 2020;39(1):16-27. doi:1080/07315724.2019.1683379

  35. Moore K, Hughes CF, Ward M, Hoey L, McNulty H. Diet, nutrition and the ageing brain: current evidence and new directions. Proc Nutr Soc. 2018;77(2):152-163. doi:1017/s0029665117004177

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