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Behavioural Neurology
Volume 2015, Article ID 620143, 10 pages
http://dx.doi.org/10.1155/2015/620143
Review Article

Toxicant Exposure and Bioaccumulation: A Common and Potentially Reversible Cause of Cognitive Dysfunction and Dementia

1Faculty of Medicine at the University of Calgary, Calgary, AB, Canada T2N 4N1
2Faculty of Medicine at the University of Saskatchewan, Saskatoon, SK, Canada S7N 5E5

Received 25 November 2014; Revised 31 December 2014; Accepted 31 December 2014

Academic Editor: Gianfranco Spalletta

Copyright © 2015 Stephen J. Genuis and Kasie L. Kelln. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. “Alzheimer's incidence accelerates among the oldest old,” in Proceedings of the Alzheimer's Association International Conference on Alzheimer's Disease (ICAD '09), Vienna, Austria, 2009, http://www.medpagetoday.com/MeetingCoverage/ICAD/15075.
  2. 2014 Alzheimer's Disease Facts and Figures, Alzheimer's Association, 2014.
  3. J. Weuve, L. E. Hebert, P. A. Scherr, and D. A. Evans, “Deaths in the United States among persons with Alzheimer's disease (2010–2050),” Alzheimer's & Dementia, vol. 10, no. 2, pp. e40–e46, 2014. View at Publisher · View at Google Scholar · View at Scopus
  4. M. P. J. M. Dijkers, “The value of ‘traditional’ reviews in the era of systematic reviewing,” The American Journal of Physical Medicine and Rehabilitation, vol. 88, no. 5, pp. 423–430, 2009. View at Publisher · View at Google Scholar · View at Scopus
  5. M. T. Baltazar, R. J. Dinis-Oliveira, M. D. L. Bastos, A. M. Tsatsakis, J. A. Duarte, and F. Carvalho, “Pesticides exposure as etiological factors of Parkinson's disease and other neurodegenerative diseases—a mechanistic approach,” Toxicology Letters, vol. 230, pp. 85–103, 2014. View at Publisher · View at Google Scholar · View at Scopus
  6. L. Mah, “Efficacy and safety of the anti-PD-1 monoclonal antibody MK-3475 in 411 patients (pts) with melanoma (MEL),” Journal of Clinical Oncology, vol. 32, no. 5, supplement, 2014, 2014 ASCO Annual Meeting, Abstract no. LBA9000. View at Google Scholar
  7. J. R. Cannon and J. T. Greenamyre, “The role of environmental exposures in neurodegeneration and neurodegenerative diseases,” Toxicological Sciences, vol. 124, no. 2, pp. 225–250, 2011. View at Publisher · View at Google Scholar · View at Scopus
  8. P. Schofield, “Dementia associated with toxic causes and autoimmune disease,” International Psychogeriatrics, vol. 17, no. 1, pp. S129–S147, 2005. View at Publisher · View at Google Scholar · View at Scopus
  9. R. Visvanathan, “Is it truly dementia?” The Lancet, vol. 357, no. 9257, article 684, 2001. View at Publisher · View at Google Scholar · View at Scopus
  10. J. Richardson, A. Roy, S. Shalat et al., “Elevated serum pesticide levels and risk for Alzheimer disease,” Journal of American Medical Association Neurology, vol. 71, pp. E1–E7, 2014. View at Google Scholar
  11. Dichlorodiphenyltrichloroethane (DDT): Centers for Disease Control and Prevention, 2009.
  12. Pesticide Monitoring Program—FY 2008, Food and Drug Administration, 2008.
  13. J. Lu, J. Miao, T. Su, Y. Liu, and R. He, “Formaldehyde induces hyperphosphorylation and polymerization of Tau protein both in vitro and in vivo,” Biochimica et Biophysica Acta (BBA)—General Subjects, vol. 1830, no. 8, pp. 4102–4116, 2013. View at Publisher · View at Google Scholar · View at Scopus
  14. Y. Lu, H. J. He, J. Zhou et al., “Hyperphosphorylation results in tau dysfunction in DNA folding and protection,” Journal of Alzheimer's Disease, vol. 37, no. 3, pp. 551–563, 2013. View at Publisher · View at Google Scholar · View at Scopus
  15. J. D. Rizak, Y. Ma, and X. Hu, “Is formaldehyde the missing link in AD pathology? The differential aggregation of amyloid-beta with APOE isoforms in vitro,” Current Alzheimer Research, vol. 11, no. 5, pp. 461–468, 2014. View at Publisher · View at Google Scholar
  16. M. Yang, J. Lu, J. Miao et al., “Alzheimer's disease and methanol toxicity (part 1): chronic methanol feeding led to memory impairments and tau hyperphosphorylation in mice,” Journal of Alzheimer's disease, vol. 41, no. 4, pp. 1117–1129, 2014. View at Publisher · View at Google Scholar
  17. M. Yang, J. Miao, J. Rizak et al., “Alzheimer's disease and methanol toxicity (part 2): lessons from four rhesus macaques (Macaca mulatta) chronically fed methanol,” Journal of Alzheimer's Disease, vol. 41, no. 4, pp. 1131–1147, 2014. View at Publisher · View at Google Scholar
  18. S. Billioti de Gage, B. Begaud, F. Bazin et al., “Benzodiazepine use and risk of dementia: prospective population based study,” British Medical Journal, vol. 349, Article ID e6231, 2014. View at Google Scholar
  19. N. M. Gatto, V. W. Henderson, H. N. Hodis et al., “Components of air pollution and cognitive function in middle-aged and older adults in Los Angeles,” NeuroToxicology, vol. 40, pp. 1–7, 2014. View at Publisher · View at Google Scholar · View at Scopus
  20. F. Al-Mousa and F. Michelangeli, “Some commonly used brominated flame retardants cause Ca2+-atpase inhibition, beta-amyloid peptide release and apoptosis in SH-SY5Y neuronal cells,” PLoS ONE, vol. 7, no. 4, Article ID e33059, 2012. View at Publisher · View at Google Scholar · View at Scopus
  21. C. F. Jin, M. Haut, and A. Ducatman, “Industrial solvents and psychological effects,” Clinics in Occupational and Environmental Medicine, vol. 4, no. 4, pp. 597–620, 2004. View at Publisher · View at Google Scholar · View at Scopus
  22. E. Mariussen, “Neurotoxic effects of perfluoroalkylated compounds: mechanisms of action and environmental relevance,” Archives of Toxicology, vol. 86, no. 9, pp. 1349–1367, 2012. View at Publisher · View at Google Scholar · View at Scopus
  23. H. A. Tilson, P. Rao, and S. Kodavanti, “The neurotoxicity of polychlorinated biphenyls,” NeuroToxicology, vol. 19, no. 4-5, pp. 517–525, 1998. View at Google Scholar · View at Scopus
  24. H.-A. Rother, “Communicating pesticide neurotoxicity research findings and risks to decision-makers and the public,” NeuroToxicology, vol. 45, pp. 327–337, 2014. View at Publisher · View at Google Scholar · View at Scopus
  25. K.-S. Liu, J.-H. Hao, Y. Zeng, F.-C. Dai, and P.-Q. Gu, “Neurotoxicity and biomarkers of lead exposure: a review,” Chinese Medical Sciences Journal, vol. 28, no. 3, pp. 178–188, 2013. View at Publisher · View at Google Scholar · View at Scopus
  26. B. Walker Jr., “Neurotoxicity in human beings,” Journal of Laboratory and Clinical Medicine, vol. 136, no. 3, pp. 168–180, 2000. View at Publisher · View at Google Scholar · View at Scopus
  27. D. O. Carpenter and R. Nevin, “Environmental causes of violence,” Physiology & Behavior, vol. 99, no. 2, pp. 260–268, 2010. View at Publisher · View at Google Scholar · View at Scopus
  28. S. C. Bondy, “Prolonged exposure to low levels of aluminum leads to changes associated with brain aging and neurodegeneration,” Toxicology, vol. 315, no. 1, pp. 1–7, 2014. View at Publisher · View at Google Scholar · View at Scopus
  29. R. Lucchini and N. Zimmerman, “Lifetime cumulative exposure as a threat for neurodegeneration: need for prevention strategies on a global scale,” NeuroToxicology, vol. 30, no. 6, pp. 1144–1148, 2009. View at Publisher · View at Google Scholar · View at Scopus
  30. K. J. Barnham and A. I. Bush, “Biological metals and metal-targeting compounds in major neurodegenerative diseases,” Chemical Society Reviews, vol. 43, no. 19, pp. 6727–6749, 2014. View at Publisher · View at Google Scholar
  31. G. J. Brewer, “Alzheimer's disease causation by copper toxicity and treatment with zinc,” Frontiers in Aging Neuroscience, vol. 6, article 92, 2014. View at Publisher · View at Google Scholar · View at Scopus
  32. R. Squitti, “Copper subtype of Alzheimer's disease (AD): meta-analyses, genetic studies and predictive value of non-ceruloplasmim copper in mild cognitive impairment conversion to full AD,” Journal of Trace Elements in Medicine and Biology, vol. 28, no. 4, pp. 482–485, 2014. View at Publisher · View at Google Scholar
  33. R. Squitti, M. Siotto, and R. Polimanti, “Low-copper diet as a preventive strategy for Alzheimer's disease,” Neurobiology of Aging, vol. 35, supplement 2, pp. S40–S50, 2014. View at Publisher · View at Google Scholar · View at Scopus
  34. C. Exley and T. Vickers, “Elevated brain aluminium and early onset Alzheimer's disease in an individual occupationally exposed to aluminium: a case report,” Journal of Medical Case Reports, vol. 8, no. 1, article 41, 2014. View at Publisher · View at Google Scholar · View at Scopus
  35. E. van Wijngaarden, J. R. Campbell, and D. A. Cory-Slechta, “Bone lead levels are associated with measures of memory impairment in older adults,” NeuroToxicology, vol. 30, no. 4, pp. 572–580, 2009. View at Publisher · View at Google Scholar · View at Scopus
  36. C. Patterson, J. W. Feightner, A. Garcia, G.-Y. R. Hsiung, C. MacKnight, and A. D. Sadovnick, “Diagnosis and treatment of dementia: 1. Risk assessment and primary prevention of Alzheimer disease,” Canadian Medical Association Journal, vol. 178, no. 5, pp. 548–556, 2008. View at Publisher · View at Google Scholar · View at Scopus
  37. M. L. Bleecker, D. P. Ford, K. N. Lindgren, V. M. Hoese, K. S. Walsh, and C. G. Vaughan, “Differential affects of lead exposure on components of verbal memory,” Occupational and Environmental Medicine, vol. 62, no. 3, pp. 181–187, 2005. View at Publisher · View at Google Scholar · View at Scopus
  38. W. F. Stewart and B. S. Schwartz, “Effects of lead on the adult brain: a 15-year exploration,” The American Journal of Industrial Medicine, vol. 50, no. 10, pp. 729–739, 2007. View at Publisher · View at Google Scholar · View at Scopus
  39. Centers for Disease Control and Prevention: Department of Health and Human Services, Fourth National Report on Human Exposure to Environmental Chemicals: Updated Tables, Centers for Disease Control and Prevention: Department of Health and Human Services, Atlanta, Ga, USA, 2013, http://www.cdc.gov/exposurereport/pdf/FourthReport_UpdatedTables_Mar2013.pdf.
  40. Health Canada, “Second report on human biomonitoring of environmental chemicals in Canada,” 2013, http://occupationalcancer.ca/wp-content/uploads/2013/05/2ndHumanBiomonitoringReport.pdf.
  41. Environmental Working Group, “Toxic Chemicals Found In Minority Cord Blood,” 2009, http://www.ewg.org/news/news-releases/2009/12/02/toxic-chemicals-found-minority-cord-blood.
  42. D. A. Rossignol, S. J. Genuis, and R. E. Frye, “Environmental toxicants and autism spectrum disorders: a systematic review,” Translational Psychiatry, vol. 4, articel e360, 2014. View at Publisher · View at Google Scholar
  43. P. Grandjean and P. Landrigan, “Developmental neurotoxicity of industrial chemicals,” The Lancet, vol. 368, no. 9553, pp. 2167–2178, 2006. View at Publisher · View at Google Scholar · View at Scopus
  44. P. Grandjean and P. J. Landrigan, “Neurobehavioural effects of developmental toxicity,” The Lancet Neurology, vol. 13, no. 3, pp. 330–338, 2014. View at Publisher · View at Google Scholar · View at Scopus
  45. D. Coury, “Pediatric Academic societies annual meeting. April 28-May 1, 2001. Baltimore, Maryland, USA. Abstracts,” Pediatric Research, vol. 49, no. 4, part 2, supplement, 2001. View at Google Scholar
  46. A. Kanthasamy, H. Jin, V. Anantharam et al., “Emerging neurotoxic mechanisms in environmental factors-induced neurodegeneration,” NeuroToxicology, vol. 33, no. 4, pp. 833–837, 2012. View at Publisher · View at Google Scholar · View at Scopus
  47. M. L. Block, A. Elder, R. L. Auten et al., “The outdoor air pollution and brain health workshop,” NeuroToxicology, vol. 33, no. 5, pp. 972–984, 2012. View at Publisher · View at Google Scholar · View at Scopus
  48. J. Reis and G. C. Román, “Environmental neurology: a promising new field of practice and research,” Journal of the Neurological Sciences, vol. 262, no. 1-2, pp. 3–6, 2007. View at Publisher · View at Google Scholar · View at Scopus
  49. E. L. Sabbath, L.-A. Gutierrez, C. A. Okechukwu et al., “Time may not fully attenuate solvent-associated cognitive deficits in highly exposed workers,” Neurology, vol. 82, no. 19, pp. 1716–1723, 2014. View at Publisher · View at Google Scholar
  50. S. J. Genuis, M. E. Sears, G. Schwalfenberg, J. Hope, and R. Bernhoft, “Clinical detoxification: elimination of persistent toxicants from the human body,” The Scientific World Journal, vol. 2013, Article ID 238347, 3 pages, 2013. View at Publisher · View at Google Scholar · View at Scopus
  51. J. Hope, “A review of the mechanism of injury and treatment approaches for illness resulting from exposure to water-damaged buildings, mold, and mycotoxins,” The Scientific World Journal, vol. 2013, Article ID 767482, 20 pages, 2013. View at Publisher · View at Google Scholar · View at Scopus
  52. Drugs.com, “Levonorgestrel and ethinyl estradiol. TABLE I: Mean (SD) Pharmacokinetic parameters of Levonorgestrel and Ethinyl Estradiol tablets over a 21-day dosing period,” 2014, http://www.drugs.com/pro/levonorgestrel-and-ethinyl-estradiol.html.
  53. W. V. Welshons, K. A. Thayer, B. M. Judy, J. A. Taylor, E. M. Curran, and F. S. vom Saal, “Large effects from small exposures. I. Mechanisms for endocrine-disrupting chemicals with estrogenic activity,” Environmental Health Perspectives, vol. 111, no. 8, pp. 994–1006, 2003. View at Publisher · View at Google Scholar · View at Scopus
  54. K. Steenland, S. Tinker, A. Shankar, and A. Ducatman, “Association of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) with uric acid among adults with elevated community exposure to PFOA,” Environmental Health Perspectives, vol. 118, no. 2, pp. 229–233, 2010. View at Publisher · View at Google Scholar · View at Scopus
  55. S. J. Frisbee, A. Shankar, S. S. Knox et al., “Perfluorooctanoic acid, perfluorooctanesulfonate, and serum lipids in children and adolescents: results from the C8 health project,” Archives of Pediatrics and Adolescent Medicine, vol. 164, no. 9, pp. 860–869, 2010. View at Publisher · View at Google Scholar · View at Scopus
  56. E. A. Belyaeva, T. V. Sokolova, L. V. Emelyanova, and I. O. Zakharova, “Mitochondrial electron transport chain in heavy metal-induced neurotoxicity: effects of cadmium, mercury, and copper,” The Scientific World Journal, vol. 2012, Article ID 136063, 14 pages, 2012. View at Publisher · View at Google Scholar · View at Scopus
  57. Y. W. Chen, C. F. Huang, C. Y. Yang, C. C. Yen, K. S. Tsai, and S. H. Liu, “Inorganic mercury causes pancreatic β-cell death via the oxidative stress-induced apoptotic and necrotic pathways,” Toxicology and Applied Pharmacology, vol. 243, no. 3, pp. 323–331, 2010. View at Publisher · View at Google Scholar · View at Scopus
  58. Q. Huang, J. Zhang, F. L. Martin et al., “Perfluorooctanoic acid induces apoptosis through the p53-dependent mitochondrial pathway in human hepatic cells: a proteomic study,” Toxicology Letters, vol. 223, no. 2, pp. 211–220, 2013. View at Publisher · View at Google Scholar · View at Scopus
  59. B. Weiss, “The intersection of neurotoxicology and endocrine disruption,” NeuroToxicology, vol. 33, no. 6, pp. 1410–1419, 2012. View at Publisher · View at Google Scholar · View at Scopus
  60. C. Guerrero-Bosagna and M. K. Skinner, “Environmentally induced epigenetic transgenerational inheritance of phenotype and disease,” Molecular and Cellular Endocrinology, vol. 354, no. 1-2, pp. 3–8, 2012. View at Publisher · View at Google Scholar · View at Scopus
  61. S. Orrenius, P. Nicotera, and B. Zhivotovsky, “Cell death mechanisms and their implications in toxicology,” Toxicological Sciences, vol. 119, no. 1, pp. 3–19, 2011. View at Publisher · View at Google Scholar · View at Scopus
  62. G. S. Bloom, “Amyloid-β and tau: the trigger and bullet in Alzheimer disease pathogenesis,” JAMA Neurology, vol. 71, no. 4, pp. 505–508, 2014. View at Publisher · View at Google Scholar · View at Scopus
  63. S. M. Lasley and M. E. Gilbert, “Rat hippocampal glutamate and GABA release exhibit biphasic effects as a function of chronic lead exposure level,” Toxicological Sciences, vol. 66, no. 1, pp. 139–147, 2002. View at Publisher · View at Google Scholar · View at Scopus
  64. L. S. Kjeldsen, M. Ghisari, and E. C. Bonefeld-Jørgensen, “Currently used pesticides and their mixtures affect the function of sex hormone receptors and aromatase enzyme activity,” Toxicology and Applied Pharmacology, vol. 272, no. 2, pp. 453–464, 2013. View at Publisher · View at Google Scholar · View at Scopus
  65. S. J. Genuis, “The chemical erosion of human health: adverse environmental exposure and in-utero pollution—determinants of congenital disorders and chronic disease,” Journal of Perinatal Medicine, vol. 34, no. 3, pp. 185–195, 2006. View at Publisher · View at Google Scholar · View at Scopus
  66. S. J. Genuis, M. E. Sears, G. Schwalfenberg, J. Hope, and R. Bernhoft, “Clinical detoxification: elimination of persistent toxicants from the human body,” The Scientific World Journal, vol. 2013, Article ID 238347, 3 pages, 2013. View at Publisher · View at Google Scholar · View at Scopus
  67. T. G. Redgrave, P. Wallace, R. J. Jandacek, and P. Tso, “Treatment with a dietary fat substitute decreased Arochlor 1254 contamination in an obese diabetic male,” The Journal of Nutritional Biochemistry, vol. 16, no. 6, pp. 383–384, 2005. View at Publisher · View at Google Scholar · View at Scopus
  68. G. H. Ross and M. C. Sternquist, “Methamphetamine exposure and chronic illness in police officers: significant improvement with sauna-based detoxification therapy,” Toxicology and Industrial Health, vol. 28, no. 8, pp. 758–768, 2012. View at Publisher · View at Google Scholar · View at Scopus
  69. R. J. Jandacek, J. E. Heubi, D. D. Buckley et al., “Reduction of the body burden of PCBs and DDE by dietary intervention in a randomized trial,” Journal of Nutritional Biochemistry, vol. 25, no. 4, pp. 483–488, 2014. View at Publisher · View at Google Scholar · View at Scopus
  70. S. J. Genuis, D. Birkholz, I. Rodushkin, and S. Beesoon, “Blood, urine, and sweat (BUS) study: monitoring and elimination of bioaccumulated toxic elements,” Archives of Environmental Contamination & Toxicology, vol. 61, no. 2, pp. 344–357, 2011. View at Publisher · View at Google Scholar · View at Scopus
  71. R. J. Jandacek and S. J. Genuis, “An assessment of the intestinal lumen as a site for intervention in reducing body burdens of organochlorine compounds,” The Scientific World Journal, vol. 2013, Article ID 205621, 10 pages, 2013. View at Publisher · View at Google Scholar · View at Scopus
  72. P. A. Egner, J. G. Chen, A. T. Zarth et al., “Rapid and sustainable detoxication of airborne pollutants by broccoli sprout beverage: results of a randomized clinical trial in China,” Cancer Prevention Research, vol. 7, no. 8, pp. 813–823, 2014. View at Publisher · View at Google Scholar
  73. S. J. Genuis, “Elimination of persistent toxicants from the human body,” Human and Experimental Toxicology, vol. 30, no. 1, pp. 3–18, 2011. View at Publisher · View at Google Scholar · View at Scopus
  74. S. J. Genuis, Y. Liu, Q. I. T. Genuis, J. W. Martin, and T. Kanda, “Phlebotomy treatment for elimination of perfluoroalkyl acids in a highly exposed family: a retrospective case-series,” PLoS ONE, vol. 9, no. 12, Article ID e114295, 2014. View at Publisher · View at Google Scholar
  75. S. J. Genuis, “Toxic causes of mental illness are overlooked,” NeuroToxicology, vol. 29, no. 6, pp. 1147–1149, 2008. View at Publisher · View at Google Scholar · View at Scopus
  76. J. B. Adams, M. Baral, E. Geis et al., “Safety and efficacy of oral DMSA therapy for children with autism spectrum disorders: part A—medical results,” BMC Clinical Pharmacology, vol. 9, article 16, 2009. View at Publisher · View at Google Scholar · View at Scopus
  77. J. B. Adams, M. Baral, E. Geis et al., “Safety and efficacy of oral DMSA therapy for children with autism spectrum disorders: part B—behavioral results,” BMC Clinical Pharmacology, vol. 9, article 1472, 2009. View at Publisher · View at Google Scholar · View at Scopus
  78. D. E. Bredesen, “Reversal of cognitive decline: a novel therapeutic program,” Aging, vol. 6, no. 9, pp. 707–717, 2014. View at Google Scholar
  79. S. Porru and L. Alessio, “The use of chelating agents in occupational lead poisoning,” Occupational Medicine, vol. 46, no. 1, pp. 41–48, 1996. View at Publisher · View at Google Scholar · View at Scopus
  80. S. Bradberry, T. Sheehan, and A. Vale, “Use of oral dimercaptosuccinic acid (succimer) in adult patients with inorganic lead poisoning,” QJM: An International Journal of Medicine, vol. 102, no. 10, pp. 721–732, 2009. View at Publisher · View at Google Scholar · View at Scopus
  81. S. Bradberry and A. Vale, “Dimercaptosuccinic acid (succimer; DMSA) in inorganic lead poisoning,” Clinical Toxicology, vol. 47, no. 7, pp. 617–631, 2009. View at Publisher · View at Google Scholar · View at Scopus
  82. M. E. Sears, “Chelation: harnessing and enhancing heavy metal detoxification—a review,” The Scientific World Journal, vol. 2013, Article ID 219840, 13 pages, 2013. View at Publisher · View at Google Scholar · View at Scopus
  83. R. P. Wedeen, “Lead poisoning: the evolving definition,” International Journal of Occupational and Environmental Medicine, vol. 2, no. 1, pp. 1–3, 2011. View at Google Scholar · View at Scopus
  84. S. Hernberg, “Lead poisoning in a historical perspective,” American Journal of Industrial Medicine, vol. 38, no. 3, pp. 244–254, 2000. View at Publisher · View at Google Scholar
  85. W. N. Arnold, “The illness of Vincent van Gogh,” Journal of the History of the Neurosciences, vol. 13, no. 1, pp. 22–43, 2004. View at Publisher · View at Google Scholar · View at Scopus
  86. R. J. Shamberger, “Validity of hair mineral testing,” Biological Trace Element Research, vol. 87, no. 1–3, pp. 1–28, 2002. View at Publisher · View at Google Scholar · View at Scopus
  87. Centers for Disease Control and Prevention (CDC), “Very high blood lead levels among adults—United States, 2002–2011,” Morbidity & Mortality Weekly Report, vol. 62, no. 47, pp. 967–971, 2002. View at Google Scholar
  88. J. Liu and G. Lewis, “Environmental toxicity and poor cognitive outcomes in children and adults,” Journal of Environmental Health, vol. 76, no. 6, pp. 130–138, 2014. View at Google Scholar · View at Scopus
  89. L. Mah, M. Kohli, and G. Chan, “Ambient lead exposure is associated with greater risk of conversion to Alzheimer's disease and hippocampal atrophy in individuals with amnestic mild cognitive impairment,” The American Journal of Geriatric Psychiatry, vol. 22, no. 3, pp. S117–S118, 2014. View at Publisher · View at Google Scholar
  90. Centers for Disease Control and Prevention (CDC), “Lead exposure among females of childbearing age—United States, 2004,” Morbidity & Mortality Weekly Report, vol. 56, no. 16, pp. 397–400, 2007. View at Google Scholar · View at Scopus
  91. S. J. Genuis, G. Schwalfenberg, A.-K. J. Siy, and I. Rodushkin, “Toxic element contamination of natural health products and pharmaceutical preparations,” PLoS ONE, vol. 7, no. 11, Article ID e49676, 2012. View at Publisher · View at Google Scholar · View at Scopus
  92. H. Needleman, “Low level lead exposure: history and discovery,” Annals of Epidemiology, vol. 19, no. 4, pp. 235–238, 2009. View at Publisher · View at Google Scholar · View at Scopus
  93. M. Casas, C. Chevrier, E. D. Hond et al., “Exposure to brominated flame retardants, perfluorinated compounds, phthalates and phenols in European birth cohorts: ENRIECO evaluation, first human biomonitoring results, and recommendations,” International Journal of Hygiene and Environmental Health, vol. 216, no. 3, pp. 230–242, 2013. View at Publisher · View at Google Scholar · View at Scopus
  94. S. L. Archibeque-Engle, J. D. Tessari, D. T. Winn, T. J. Keefe, T. M. Nett, and T. Zheng, “Comparison of organochlorine pesticide and polychlorinated biphenyl residues in human breast adipose tissue and serum,” Journal of Toxicology and Environmental Health, vol. 52, no. 4, pp. 285–293, 1997. View at Publisher · View at Google Scholar · View at Scopus
  95. G. W. Yu, J. Laseter, and C. Mylander, “Persistent organic pollutants in serum and several different fat compartments in humans,” Journal of Environmental and Public Health, vol. 2011, Article ID 417980, 8 pages, 2011. View at Publisher · View at Google Scholar · View at Scopus
  96. R. J. Jandacek, N. Anderson, M. Liu, S. Zheng, Q. Yang, and P. Tso, “Effects of yo-yo diet, caloric restriction, and olestra on tissue distribution of hexachlorobenzene,” American Journal of Physiology—Gastrointestinal and Liver Physiology, vol. 288, no. 2, pp. G292–G299, 2005. View at Publisher · View at Google Scholar · View at Scopus
  97. S. M. Rappaport and M. T. Smith, “Environment and disease risks,” Science, vol. 330, no. 6003, pp. 460–461, 2010. View at Publisher · View at Google Scholar · View at Scopus
  98. S. J. Genuis, “Medical practice and community health care in the 21st century: a time of change,” Public Health, vol. 122, no. 7, pp. 671–680, 2008. View at Publisher · View at Google Scholar · View at Scopus
  99. J. R. Roberts and J. R. Reigart, “Environmental health education in the medical school curriculum,” Ambulatory Pediatrics, vol. 1, no. 2, pp. 108–111, 2001. View at Publisher · View at Google Scholar · View at Scopus
  100. K. S. Gehle, J. L. Crawford, and M. T. Hatcher, “Integrating environmental health into medical education,” American Journal of Preventive Medicine, vol. 41, no. 4, pp. S296–S301, 2011. View at Publisher · View at Google Scholar · View at Scopus
  101. K. H. Kilburn, “Why is chemical brain injury ignored? Pondering causes and risks,” Archives of Environmental Health, vol. 58, no. 3, pp. 132–134, 2003. View at Google Scholar · View at Scopus
  102. S. J. Genuis, “Back to the future of healthcare: aetiology-centred medicine,” The New Zealand Medical Journal, vol. 118, no. 1215, Article ID U1467, 2005. View at Google Scholar
  103. S. J. Genuis, “What's out there making us sick?” Journal of Environmental and Public Health, vol. 2012, Article ID 605137, 10 pages, 2012. View at Publisher · View at Google Scholar · View at Scopus
  104. D. Rhodes, A. Spiro III, A. Aro, and H. Hu, “Relationship of bone and blood lead levels to psychiatric symptoms: the normative aging study,” Journal of Occupational and Environmental Medicine, vol. 45, no. 11, pp. 1144–1151, 2003. View at Publisher · View at Google Scholar · View at Scopus
  105. H. S. Hendriks, E. C. Antunes Fernandes, Å. Bergman, M. van den Berg, and R. H. S. Westerink, “PCB-47, PBDE-47, and 6-OH-PBDE-47 differentially modulate human GABAA and alpha4beta2 nicotinic acetylcholine receptors,” Toxicological Sciences, vol. 118, no. 2, pp. 635–642, 2010. View at Publisher · View at Google Scholar · View at Scopus
  106. S. M. Goldman, P. J. Quinlan, G. W. Ross et al., “Solvent exposures and Parkinson disease risk in twins,” Annals of Neurology, vol. 71, no. 6, pp. 776–784, 2012. View at Publisher · View at Google Scholar · View at Scopus
  107. V. Jevtovic-Todorovic, A. R. Absalom, K. Blomgren et al., “Anaesthetic neurotoxicity and neuroplasticity: an expert group report and statement based on the BJA Salzburg Seminar,” British Journal of Anaesthesia, vol. 111, no. 2, pp. 143–151, 2013. View at Publisher · View at Google Scholar · View at Scopus