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May 1, 1996

Possible environmental, occupational, and other etiologic factors for Parkinson's disease
A case‐control study in Germany

May 1996 issue
46 (5) 1275


In a case-control study, we investigated the possible etiologic relevance to Parkinson's disease (PD) of rural factors such as farming activity, pesticide exposures, well-water drinking, and animal contacts; toxicologic exposures such as wood preservatives, heavy metals, and solvents; general anesthesia; head trauma; and differences in the intrauterine environment. We recruited 380 patients in nine German clinics, 379 neighborhood control subjects, and 376 regional control subjects in the largest case-control study investigating such factors and collected data in structured personal interviews using conditional logistic regression to control for educational status and cigarette smoking. The latter was strongly inversely associated with PD. There were significantly elevated odds ratios (OR) for pesticide use, in particular, for organochlorines and alkylated phosphates, but no association was present between PD and other rural factors. A significantly elevated OR was present for exposure to wood preservatives. Subjective assessment by the probands indicated that exposure to some heavy metals, solvents, exhaust fumes, and carbon monoxide was significantly more frequent among patients than control subjects, but this was not confirmed by a parallel assessment of job histories according to a job exposure matrix. Patients had undergone general anesthesia and suffered severe head trauma more often than control subjects, but a dose-response gradient was not present. Patients reported a significantly larger number of amalgam-filled teeth before their illness than control subjects. The frequency of premature births and birth order did not differ between patients and control subjects. Patients reported significantly more relatives affected with PD than control subjects. These results support a role for environmental and genetic factors in the etiology of PD.

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Langston JW, Ballard P, Tetrud JW, Irwin I. Chronic parkinsonism in humans due to a product of meperidine-analog synthesis. Science 1983;219:979–980.
Sawle GV, Wroe SJ, Lees AJ, Brooks DJ, Frackowiak RSJ. The identification of presymptomatic parkinsonism: clinical and [18F]Dopa positron emission tomography studies in an Irish kindred. Ann Neurol 1992;32:609–617.
Golbe LI, Miller DG, Duvoisin RC. Autosomal dominant Lewy-body Parkinson's disease. Adv Neurol 1990;53:287–292.
Burn DJ, Mark MH, Playford ED, et al. Parkinson's disease in twins studied with 18F-dopa and positron emission tomography. Neurology 1992;42:1894–1900.
Vieregge P, Schiffke KA, Friedrich HJ, Müller B, Ludin HP. Parkinson's disease in twins. Neurology 1992;42:1453–1461.
Vieregge P. Genetic factors in the etiology of idiopathic Parkinson's disease. J Neural Transm 1994;8:1–37.
Kurth JH, Kurth MC, Poduslo SE, Schwankhaus JD. Association of a monoamine oxidase B allele with Parkinson's disease. Ann Neurol 1993;33:368–372.
Barbeau A, Cloutier T, Roy M, Plassé L, Paris S, Poirier J. Ecogenetics of Parkinson's disease: 4-hydroxylation of debrisoquine. Lancet 1985;2:1213–1216.
Barbeau A, Roy M, Cloutier T, Plassé L, Paris S. Environmental and genetic factors in the etiology of Parkinson's disease. Adv Neurol 1986;45:299–306.
Smith CAD, Gough AC, Leigh PN, et al. Debrisoquine hydroxylase gene polymorphism and susceptibility to Parkinson's disease. Lancet 1992;339:1375–1377.
Armstrong M, Daly AK, Cholerton S, Bateman DN, Idle JR. Mutant debrisoquine hydroxylation genes in Parkinson's disease. Lancet 1992;339:1017–1018.
Kondo I, Kanazawa I. Debrisoquine hydroxylase and Parkinson's disease. Adv Neurol 1993;60:338–342.
Steventon GB, Heafield MTE, Waring RH, Williams AC. Xenobiotic metabolism in Parkinson's disease. Neurology 1989;39:883–887.
Waring RH, Steventon GB, Sturman SG, Heafield MTE, Smith MCG, Williams AC. S-methylation in motorneuron disease and Parkinson's disease. Lancet 1989;2:356–357.
Johnson WG, Hodge SE, Duvoisin R. Twin studies and the genetics of Parkinson's disease—a reappraisal. Mov Disord 1990;5:187–194.
Kondo K, Kurland LT, Schull WJ. Parkinson's disease. Genetic analysis and evidence of a multifactorial etiology. Mayo Clinic Proc 1973;48:465–475.
Nicklas WJ, Vyas I, Heikkila RE. Inhibition of NADH-linked oxidation in brain mitochondria by 1-methyl-4-phenylpyridine, a metabolite of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Life Sci 1985;36:2503–2508.
Dexter DT, Carter CJ, Wells FR, et al. Basal lipid peroxidation in substantia nigra is increased in Parkinson's disease. J Neurochem 1989;52:381–389.
Fahn S, Cohen G. The oxidant stress hypothesis in Parkinson's disease: evidence supporting it. Ann Neurol 1992;32:804–812.
Jenner P. Oxidative stress as a cause of Parkinson's disease. Acta Neurol Scand 1991;84(suppl 36):6–15.
Jenner P, Dexter DT, Sian J, Schapira AHV, Marsden CD. Oxidative stress as a cause of nigral cell death in Parkinson's disease and incidental Lewy body disease. Ann Neurol 1992; 32:S82–S87.
Riederer P, Sofic E, Rausch W-D, et al. Transition metals, ferritin, glutathione and ascorbic acid in parkinsonian brains. J Neurochem 1989;52:515–520.
Saggu H, Cooksey J, Dexter D, et al. A selective increase in particulate superoxide dismutase activity in parkinsonian substantia nigra. J Neurochem 1989;53:692–697.
Olanow CW. A radical hypothesis for radical degeneration. Trends Neurosci 1993;16:439–444.
Vieregge P, von Maravic C, Friedrich H-J. Life-style and dietary factors early and late in Parkinson's disease. Can J Neurol Sci 1992;19:170–173.
Golbe LI, Farrell TM, Davis PH. Follow-up study of early-life protective and risk factors in Parkinson's disease. Mov Disord 1990;5:66–70.
Koller W, Vetere-Oldfield B, Gray C, et al. Environmental risk factors in Parkinson's disease. Neurology 1990;40:1218–1221.
Ho SC, Woo J, Lee CM. Epidemiologic study of Parkinson's disease in Hong Kong. Neurology 1989;39:1314–1318.
Jiménez-Jiménez FJ, Mateo D, Gimenez-Roldan S. Exposure to well water and pesticides in Parkinson's disease: a case-control study in the Madrid area. Mov Disord 1992;7:149–152.
Wong GF, Gray CS, Hassanein RS, Koller WC. Environmental risk factors in siblings with Parkinson's disease. Arch Neurol 1991;48:287–289.
Hertzman C, Wiens M, Bowering D, Snow B, Calne D. Parkinson's disease: a case-control study of occupational and environmental risk factors. Am J Indust Med 1990;17:349–355.
Rajput AH, Uitti RJ, Stern W, Laverty W. Early onset Parkinson's disease and childhood environment. Adv Neurol 1986;45:295–297.
Semchuk KM, Love EJ, Lee RG. Parkinson's disease and exposure to rural environmental factors: a population-based case-control study. Can J Neurol Sci 1991;18:279–286.
Semchuk KM, Love EJ, Lee RG. Parkinson's disease and exposure to agricultural work and pesticide chemicals. Neurology 1992;42:1328–1335.
Stern M, Dulaney E, Gruber SB, et al. The epidemiology of Parkinson's disease: a case-control study of young-onset and old-onset patients. Arch Neurol 1991;48:903–907.
Calne S, Schoenberg B, Martin W, Uitti RJ, Spencer P, Calne DB. Familial Parkinson's disease: possible role of environmental factors. Can J Neurol Sci 1987;14:303–307.
Wang W, Fang X, Cheng X, Jiang D, Lin Z. A case-control study on the environmental risk factors of Parkinson's disease in Tianjin, China. Neuroepidemiology 1993;12:209–218.
Tanner CM, Chen B, Peng M, et al. Environmental factors and Parkinson's disease: a case-control study in China. Neurology 1989;39:660–664.
Zayed J, Ducic S, Campanella G, et al. Facteurs environnementeaux dans la maladie de Parkinson. Can J Neurol Sci 1990;17:286–291.
Hart TB. Parkinson's disease and pesticides. Lancet 1987;1:38.
Koller WC. Paraquat and Parkinson's disease [letter]. Neurology 1986;36:1147.
Perry TL, Yong VW, Wall RA, Jones K. Paraquat and two endogenous analogues of the neurotoxic substance MPTP do not damage dopaminergic nigrostriatal neurons in the mouse. Neurosci Lett 1986;69:285–289.
Sanchez-Ramos JR, Hefti F, Weiner WJ. Paraquat and Parkinson's disease. Neurology 1987;37:728.
Hertzman C, Wiens M, Snow B, Kelly S, Calne D. A case-control study of Parkinson's disease in a horticultural region of British Columbia. Mov Disord 1994;9:69–75.
Ohlson C-G, Hogstedt C. Parkinson's disease and occupational exposure to organic solvents, agricultural chemicals and mercury—a case-referent study. Scand J Work Environ Health 1981;7:252–256.
Ngim CH, Devathasan G. Epidemiologic study on the association between body burden mercury level and idiopathic Parkinson's disease. Neuroepidemiology 1989;8:128–141.
Kahn HA. The Dorn study of smoking and mortality among US veterans. Report on eight and one-half years of observation. Natl Cancer Inst Monogr 1966;19:1–125.
Rogot E, Murray JL. Smoking and causes of death among U.S. veterans: 16 years of observation. Public Health Rep 1980;95:213–222.
Hammond EC. Smoking in relation to the death rates of one million men and women. Natl Cancer Inst Monogr 1966;19:127–204.
Doll R, Peto R. Mortality in relation to smoking: 20 years' observations on male British doctors. BMJ 1976;2:1525–1536.
Grandinetti A, Morens DM, Reed D, MacEachern D. Prospective study of cigarette smoking and the risk of developing idiopathic Parkinson's disease. Am J Epidemiol 1994;139:1129–1138.
Nefzger MD, Quadfasel FA, Karl VC. A retrospective study of smoking in Parkinson's disease. Am J Epidemiol 1968;88:149–158.
Kessler II, Diamond EL. Epidemiologic studies of Parkinson's disease. I. Smoking and Parkinson's disease: a survey and explanatory hypothesis. Am J Epidemiol 1971;94:16–25.
Kessler II. Epidemiologic studies of Parkinson's disease. III. A community-based survey. Am J Epidemiol 1972;96:242–254.
Baumann RJ, Jameson HD, McKean HE, Haack DG, Weisberg LM. Cigarette smoking and Parkinson's disease. 1. A comparison of cases with matched neighbours. Neurology 1980;30:839–843.
Marttila RJ, Rinne UK. Smoking and Parkinson's disease. Acta Neurol Scand 1980;62:322–325.
Haack DG, Baumann RJ, McKean HE, Jameson HD, Turbek JA. Nicotine exposure and Parkinson disease. Am J Epidemiol 1981;114:191–200.
Godwin-Austen RB, Lee PN, Marmot MG, Stern GM. Smoking and Parkinson's disease. J Neurol Neurosurg Psychiatry 1982;45:577–581.
Bharucha NE, Stokes L, Schoenberg BS, et al. A case-control study of twin pairs discordant for Parkinson's disease: a search for environmental risk factors. Neurology 1986;36:284–288.
Cazzati G, Capus L, Monti F, Carraro N. Abitudine al fumo e morbo di Parkinson. Riv Neurol (Napoli) 1985;55:79–87.
Hofman A, Collette HJA, Bartelds AIM. Incidence and risk factors of Parkinson's disease in the Netherlands. Neuroepidemiol 1989;8:296–299.
Vieregge P, Friedrich HJ, Rohl A, Ulm G, Heberlein I. Zur multifaktoriellen Atiologie der idiopathischen Parkinson-Krankheit. Eine Fall-Kontroll-Studie. Nervenarzt 1994;65:390–395.
Mayeux R, Tang MX, Marder K, Coté LJ, Stern Y. Smoking and Parkinson's disease. Mov Disord 1994;9:207–212.
Rajput AH, Offord KF', Beard CM, Kurland LT. A case-control study of smoking habits, dementia, and other illnesses in idiopathic Parkinson's disease. Neurology 1987;37:226–232.
Hughes AJ, Daniel SE, Kilford L, Lees A. Accuracy of clinical diagnosis of idiopathic Parkinson's disease: a clinicopathologic study of 100 cases. J Neurol Neurosurg Psychiatry 1992;55:181–184.
Jessen RJ. Statistical Survey techniques. New York: John Wiley and Sons, 1978.
Breslow NE, Day NE. Statistical methods in cancer research. Vol. 1. The analysis of case-control studies. Lyon: IARC Scientific Publication No. 32, International Agency for Research on Cancer, 1982.
Schlesselman JJ. Case-control studies. Design, conduct, analysis. Oxford: Oxford University Press, 1982.
Statistisches Bundesamt, Ed. Statistisches Jahrbuch 1993 für die Bundesrepublik Deutschland. Wiesbaden: Wiesbadener Graphische Betriebe GmbH, 1993.
Fleming L, Mann JB, Bean J, Briggle T, Sanchez-Ramos JR. Parkinson's disease and brain levels of organochlorine pesticides. Ann Neurol 1994;36:100–103.
Secchi GP, Angetti V, Piredda M, et al. Acute and persistent parkinsonism after use of diquat. Neurology 1992;42:261–263.
Eckrich W. Toxicology of wood preservatives. Lecture for the 4th session of the Committee for Environmental and Radiation Protection of the Medical Society of Baden-Württemberg. Engelskirchen, IHG e.V., 1989.
Jorens PG, Schepens PJ. Human pentachlorophenol poisoning. Hum Exp Toxicol 1993;12:479–495.
Semchuk KM, Love EJ, Lee RG. Parkinson's disease: a test of the multifactorial hypothesis. Neurology 1993;43:1173–1180.
Weiner JA, Nylander M, Berglund F. Does mercury from amalgam constitute a health hazard? Sci Total Environ 1990;126:61–74.
Weiner JA, Nylander M. The relationship between mercury concentrations in human organs and different predictor variables. Sci Total Environ 1993;138:101–115.
Eggleston DW, Nylander M. Correlation of dental amalgam with mercury in brain tissue. J Prosthet Dent 1987;58:704–707.
Dexter DT, Wells FR, Lees AJ, et al. Increased nigral iron content and alterations in other metal ions occurring in brain in Parkinson's disease. J Neurochem 1989;52:1830–1836.
Yasui M, Kihira T, Ota K. Calcium, magnesium and aluminum concentrations in Parkinson's disease. Neurotoxicology 1992;13:593–600.
Bouyer J, H?émon D. Retrospective evaluation of occupational exposures in population-based case-control studies. General overview with special attention to job exposure matrices. Int J Epidemiol 1993;22(suppl 2):S57–S64.
Siemiatycki J, Dewar R, Richardson L. Costs and statistical power associated with five methods of collecting occupation exposure information for population-based case-control studies. Am J Epidemiol 1989;130:1236–1246.
Dewar R, Siemiatycki J, Gérin M. Loss of statistical power associated with the use of a job-exposure matrix in occupational case-control studies. Appl Occup Environ Hyg 1991;6:508–515.
Ahrens W, Jöckel K-H, Brochard P, et al. Retrospective assessment of asbestos exposure. I. Case-control analysis in a study of lung cancer: efficiency of job-specific questionnaires and job-exposure matrices. Int J Epidemiol 1993;22(suppl 2):S83–S95.
Van Vliet C, Swaen GMH, Volovics A, et al. Exposure-outcome relationships between organic solvent exposure and neuropsychiatric disorders: results from a Dutch case-control study. Am J Ind Med 1989;16:707–718.
Reinvang I, Borchgrevink HM, Aaserud O, et al. Neuropsychological findings in a nonclinical sample of workers exposed to solvents. J Neurol Neurosurg Psychiatry 1994;57:614–616.
Gregerson P, Klausen H, Elsnab CU. Chronic toxic encephalopathy in solvent exposed painters in Denmark 1976-1980: clinical cases and social consequences after a 5-year follow-up. Am J Ind Med 1987;11:399–417.
Cherry NM, Labrèche FP, McDonald JC. Organic brain damage and occupational solvent exposure. Br J Ind Med 1992;49:776–781.
Brackbill RM, Maizlish N, Fischbach T. Risk of neuropsychiatric disability among painters in the United States. Scand J Work Environ Health 1990;16:182–188.
Fuxe K, Andersson K, Nilsen OG, Toftgard R, Eneroth P, Gustafsson JA. Toluene and telencephalic dopamine: selective reduction of amine turnover in discrete DA nerve terminal systems of the anterior caudate nucleus by low concentrations of toluene. Toxicol Lett 1982;12:115–123.
Uitti RJ, Snow BJ, Shinotoh H, et al. Parkinsonism induced by solvent abuse. Ann Neurol 1994;35:616–619.
Factor SA, Sanchez-Ramos J, Weiner WJ. Trauma as an etiology of parkinsonism: a historical view of the concept. Mov Disord 1988;3:30–36.
Kontouris D, Gehlen W. Zum Problem des posttraumatischen Parkinson Syndroms. In: Gänshirt H, ed. Pathophysiologie, Klinik, und Therapie des Parkinsonismus. Basel: Editiones Roches, 1983;143–149.
Ward CD, Duvoisin R, Ince SE, Nutt JD, Eldridge R, Calne DB. Parkinson's disease in 65 pairs of twins and in a set of quadruplets. Neurology 1983;33:815–824.
Factor SA, Weiner WJ. Prior history of head trauma in Parkinson's disease. Mov Disord 1991;6:225–229.
Williams DB, Annegers JF, Kokmen E, O'Brien PC, Kurland LT. Brain injury and neurologic sequelae: a cohort study of dementia, parkinsonism, and amyotrophic lateral sclerosis. Neurology 1991;41:1554–1557.
Eldridge R, Ince SE. The low concordance rate for Parkinson's disease in twins: a possible explanation. Neurology 1984;34:1354–1356.

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Published In

Volume 46Number 5May 1996
Pages: 1275
PubMed: 8628466

Publication History

Published online: May 1, 1996
Published in print: May 1996


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Affiliations & Disclosures

W. Hellenbrand, MD, MPH
Department of Epidemiology and Social Medicine, Hannover Medical University, Hannover, Germany (Dr. Seidler) (Dr. Nischan)
Institute for Social Medicine, Faculty of Medicine, Otto-von-Guericke University, Magdeburg, Germany (Dr. Hellenbrand) (Dr. Robra)
Department of Neurology, Lübeck Medical University, Lübeck, Germany (Dr. Vieregge)
Neurologic Clinic, Barmen Hospital, Wuppertal, Germany (Dr. Joerg)
Department of Neurology, Ludwig-Maximilians University, Munich, Germany (Dr. Oertel)
Paracelsus-Elena-Clinic, Kassel, Germany (Dr. Ulm)
Department of Neurology, Hamburg-Harburg General Hospital, Hamburg, Germany (Dr. Schneider)


Address correspondence and reprint requests to Dr. W. Hellenbrand, Institute for Social Medicine, Otto-von-Guericke Universität Magdeburg, Leipziger Str. 44, D-39120 Magdeburg, Germany, or Dr. A. Seidler, Department of Epidemiology and Social Medicine, Hannover Medical School, D-30623 Hannover, Germany.

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