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      Neurodegenerative Diseases: An Overview of Environmental Risk Factors

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          Abstract

          The population of the United States is aging, and an ever-increasing number of Americans are afflicted with neurodegenerative diseases. Because the pathogenesis of many of these diseases remains unknown, we must consider that environmental factors may play a causal role. This review provides an overview of the epidemiologic evidence for environmental etiologies for neurodegenerative diseases such as Alzheimer disease, Parkinson disease, parkinsonian syndromes (multiple system atrophy and progressive supranuclear palsy), and amyotrophic lateral sclerosis. Epidemiologic evidence for an association between environmental agents’ exposure and neurodegenerative diseases is not conclusive. However, there are indications that there may be causal links, and the need for more research is obvious.

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          Risk factors for Alzheimer's disease: a prospective analysis from the Canadian Study of Health and Aging.

          J. Lindsay (2002)
          A prospective analysis of risk factors for Alzheimer's disease was a major objective of the Canadian Study of Health and Aging, a nationwide, population-based study. Of 6,434 eligible subjects aged 65 years or older in 1991, 4,615 were alive in 1996 and participated in the follow-up study. All participants were cognitively normal in 1991 when they completed a risk factor questionnaire. Their cognitive status was reassessed 5 years later by using a similar two-phase procedure, including a screening interview, followed by a clinical examination when indicated. The analysis included 194 Alzheimer's disease cases and 3,894 cognitively normal controls. Increasing age, fewer years of education, and the apolipoprotein E epsilon4 allele were significantly associated with increased risk of Alzheimer's disease. Use of nonsteroidal anti-inflammatory drugs, wine consumption, coffee consumption, and regular physical activity were associated with a reduced risk of Alzheimer's disease. No statistically significant association was found for family history of dementia, sex, history of depression, estrogen replacement therapy, head trauma, antiperspirant or antacid use, smoking, high blood pressure, heart disease, or stroke. The protective associations warrant further study. In particular, regular physical activity could be an important component of a preventive strategy against Alzheimer's disease and many other conditions.
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            Increased nigral iron content and alterations in other metal ions occurring in brain in Parkinson's disease.

            D T Dexter, F. R. Wells, A Lees … (1989)
            Levels of iron, copper, zinc, manganese, and lead were measured by inductively coupled plasma spectroscopy in parkinsonian and age-matched control brain tissue. There was 31-35% increase in the total iron content of the parkinsonian substantia nigra when compared to control tissue. In contrast, in the globus pallidus total iron levels were decreased by 29% in Parkinson's disease. There was no change in the total iron levels in any other region of the parkinsonian brain. Total copper levels were reduced by 34-45% in the substantia nigra in Parkinson's disease; no difference was found in the other brain areas examined. Zinc levels were increased in substantia nigra in Parkinson's disease by 50-54%, and the zinc content of the caudate nucleus and lateral putamen was also raised by 18-35%. Levels of manganese and lead were unchanged in all areas of the parkinsonian brain studied when compared to control brains, except for a small decrease (20%) in manganese content of the medial putamen. Increased levels of total iron in the substantia nigra may cause the excessive formation of toxic oxygen radicals, leading to dopamine cell death.
            Article 0 comments Cited 205 times – based on 0 reviews     Review now
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              Alterations in the levels of iron, ferritin and other trace metals in Parkinson's disease and other neurodegenerative diseases affecting the basal ganglia.

              Y Agid, Emily A Lees, D W Dexter … (1991)
              Levels of iron, copper, zinc and manganese were measured by inductively coupled plasma spectroscopy in frozen postmortem brain tissue from patients with Parkinson's disease (PD), progressive supranuclear palsy (PSP), multiple system atrophy with strionigral degeneration (MSA), and Huntington's disease (HD) compared with control subjects. Total iron levels were found to be elevated in the areas of basal ganglia showing pathological change in these disorders. In particular, total iron content was increased in substantia nigra in PD, PSP and MSA, but not in HD. Total iron levels in the striatum (putamen and/or caudate nucleus) were increased in PSP, MSA and HD but not in PD. Total iron levels were decreased in the globus pallidus in PD. There were no consistent alterations of manganese levels in basal ganglia structures in any of the diseases studied. Copper levels were decreased in the substantia nigra in PD, and in the cerebellum in PSP, and were elevated in the putamen and possibly substantia nigra in HD. Zinc levels were only increased in PD, in substantia nigra and in caudate nucleus and lateral putamen. Levels of the iron binding protein ferritin were measured in the same patient groups using a radio-immunoassay technique. Increased iron levels in basal ganglia were generally associated with normal or elevated levels of ferritin immunoreactivity, for example, the substantia nigra in PSP and possibly MSA, and in putamen in MSA. The exception was PD where there was a generalized reduction in brain ferritin immunoreactivity, even in the substantia nigra. An increase in total iron content appears to be a response to neurodegeneration in affected basal ganglia regions in a number of movement disorders. However, only in PD was there an increased total iron level, decreased ferritin content, decreased copper content, and an increased zinc concentration in substantia nigra. These findings suggest an alteration of iron handling in the substantia nigra in PD. Depending on the form in which the excess iron load exists in nigra in PD, it may contribute to the neurodegenerative process.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Environ Health Perspect
                Title: Environmental Health Perspectives
                Publisher: National Institute of Environmental Health Sciences
                ISSN (Print): 0091-6765
                Publication date (Print): September 2005
                Publication date (Electronic): 26 May 2005
                Volume: 113
                Issue: 9
                Pages: 1250-1256
                Affiliations
                [1 ] Association of Schools of Public Health, National Center for Environmental Assessment, Office of Research and Development, U.S. Environmental Protection Agency, Washington, DC, USA
                [2 ] Departments of Neurology and Nuclear Medicine, Veterans Affairs Western New York Healthcare System and University at Buffalo, The State University of New York, Buffalo, New York, USA
                [3 ] National Center for Environmental Assessment, Office of Research and Development, U.S. Environmental Protection Agency, Washington, DC, USA
                Author notes
                Address correspondence to R.C. Brown, U.S. EPA, NCEA, 1200 Pennsylvania Ave. NW, Mailcode 8623D, Washington, DC 20460 USA. Telephone: (202) 564-3293. Fax: (202) 565-0079. E-mail: brown.rebecca@epa.gov

                The authors declare they have no competing financial interests.

                Article
                Publisher ID: ehp0113-001250
                DOI: 10.1289/ehp.7567
                PMC ID: 1280411
                PubMed ID: 16140637
                SO-VID: 1f7d5ff2-71c5-495e-85d4-b2b968fd1655
                Copyright © This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original DOI.
                History
                Date received : 1 September 2004
                Date accepted : 5 May 2005
                Categories
                Subject: Research
                Subject: Mini-Monograph

                ScienceOpen disciplines: Public health
                Keywords: parkinson disease,progressive supranuclear palsy,multiple system atrophy,amyotrophic lateral sclerosis,electromagnetic fields,pesticides,alzheimer disease,metals,solvents,neurodegeneration
                Data availability:
                ScienceOpen disciplines: Public health
                Keywords: parkinson disease, progressive supranuclear palsy, multiple system atrophy, amyotrophic lateral sclerosis, electromagnetic fields, pesticides, alzheimer disease, metals, solvents, neurodegeneration

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