Irene Litvan1,2, Peter S J Lees3, Christopher R Cunningham1, Shesh N Rai4, Alexander C Cambon4, David G Standaert5, Connie Marras6, Jorge Juncos7, David Riley8, Stephen Reich9, Deborah Hall10,11, Benzi Kluger11, Yvette Bordelon12, David R Shprecher13. 1. Division of Movement Disorders, Department of Neurology, University of Louisville School of Medicine, Louisville, Kentucy, USA. 2. Movement Disorder Center, Department of Neurosciences, University of California San Diego, San Diego, California, USA. 3. Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA. 4. Department of Bioinformatics and Biostatistics, University of Louisville, Louisville, Kentucky, USA. 5. Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama, USA. 6. Morto and Gloria Shulman Movement Disorders Centre and the Edmond J. Safra Program in Parkinson's Research, Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada. 7. Department of Neurology, Emory University, Atlanta, Georgia, USA. 8. InMotion, Warrensville Heights, Ohio, USA. 9. Department of Neurology, University of Maryland, Baltimore, Maryland, USA. 10. Department of Neurological Sciences, Rush University, Chicago, Illinois, USA. 11. Department of Neurology, University of Colorado, Denver, Colorado, USA. 12. Department of Neurology, University of California Los Angeles, California, USA. 13. Department of Neurology, University of Utah, Salt City, Utah, USA.
Abstract
BACKGROUND: The cause of progressive supranuclear palsy (PSP) is largely unknown. Based on evidence for impaired mitochondrial activity in PSP, we hypothesized that the disease may be related to exposure to environmental toxins, some of which are mitochondrial inhibitors. METHODS: This multicenter case-control study included 284 incident PSP cases of 350 cases and 284 age-, sex-, and race-matched controls primarily from the same geographical areas. All subjects were administered standardized interviews to obtain data on demographics, residential history, and lifetime occupational history. An industrial hygienist and a toxicologist unaware of case status assessed occupational histories to estimate past exposure to metals, pesticides, organic solvents, and other chemicals. RESULTS: Cases and controls were similar on demographic factors. In unadjusted analyses, PSP was associated with lower education, lower income, more smoking pack-years, more years of drinking well water, more years living on a farm, more years living 1 mile from an agricultural region, more transportation jobs, and more jobs with exposure to metals in general. However, in adjusted models, only more years of drinking well water was significantly associated with PSP. There was an inverse association with having a college degree. CONCLUSIONS: We did not find evidence for a specific causative chemical exposure; higher number of years of drinking well water is a risk factor for PSP. This result remained significant after adjusting for income, smoking, education and occupational exposures. This is the first case-control study to demonstrate PSP is associated with environmental factors.
BACKGROUND: The cause of progressive supranuclear palsy (PSP) is largely unknown. Based on evidence for impaired mitochondrial activity in PSP, we hypothesized that the disease may be related to exposure to environmental toxins, some of which are mitochondrial inhibitors. METHODS: This multicenter case-control study included 284 incident PSP cases of 350 cases and 284 age-, sex-, and race-matched controls primarily from the same geographical areas. All subjects were administered standardized interviews to obtain data on demographics, residential history, and lifetime occupational history. An industrial hygienist and a toxicologist unaware of case status assessed occupational histories to estimate past exposure to metals, pesticides, organic solvents, and other chemicals. RESULTS: Cases and controls were similar on demographic factors. In unadjusted analyses, PSP was associated with lower education, lower income, more smoking pack-years, more years of drinking well water, more years living on a farm, more years living 1 mile from an agricultural region, more transportation jobs, and more jobs with exposure to metals in general. However, in adjusted models, only more years of drinking well water was significantly associated with PSP. There was an inverse association with having a college degree. CONCLUSIONS: We did not find evidence for a specific causative chemical exposure; higher number of years of drinking well water is a risk factor for PSP. This result remained significant after adjusting for income, smoking, education and occupational exposures. This is the first case-control study to demonstrate PSP is associated with environmental factors.
Authors: N Vanacore; V Bonifati; G Fabbrini; C Colosimo; R Marconi; D Nicholl; U Bonuccelli; F Stocchi; P Lamberti; G Volpe; G De Michele; I Iavarone; P Bennett; P Vieregge; G Meco Journal: Neurology Date: 2000-01-11 Impact factor: 9.910
Authors: C Tzourio; W A Rocca; M M Breteler; M Baldereschi; J F Dartigues; S Lopez-Pousa; J M Manubens-Bertran; A Alpérovitch Journal: Neurology Date: 1997-11 Impact factor: 9.910
Authors: Dominique Caparros-Lefebvre; Lawrence I Golbe; Vincent Deramecourt; Claude-Alain Maurage; Vincent Huin; Valerie Buée-Scherrer; Helene Obriot; Bernard Sablonnière; Francois Caparros; Luc Buée; Andrew J Lees Journal: Neurology Date: 2015-09-09 Impact factor: 9.910
Authors: J-S Vidal; M Vidailhet; P Derkinderen; T Dubard de Gaillarbois; C Tzourio; A Alpérovitch Journal: J Neurol Neurosurg Psychiatry Date: 2009-11 Impact factor: 10.154
Authors: Adam L Boxer; Jin-Tai Yu; Lawrence I Golbe; Irene Litvan; Anthony E Lang; Günter U Höglinger Journal: Lancet Neurol Date: 2017-06-13 Impact factor: 44.182
Authors: Hee Kyung Park; Sindana Ilango; Christina M Charriez; Harvey Checkoway; David Riley; David G Standaert; Yvette Bordelon; David R Shprecher; Stephen G Reich; Deborah Hall; Benzi Kluger; Connie Marras; Joseph Jankovic; Richard Dubinsky; Irene Litvan Journal: Mov Disord Date: 2018-02-20 Impact factor: 10.338
Authors: Ece Bayram; Connie Marras; David G Standaert; Benzi M Kluger; Yvette M Bordelon; David R Shprecher; Irene Litvan Journal: Mov Disord Date: 2020-03-27 Impact factor: 10.338
Authors: Ali Shoeibi; Irene Litvan; Jorge L Juncos; Yvette Bordelon; David Riley; David Standaert; Stephen G Reich; David Shprecher; Deborah Hall; Connie Marras; Benzi Kluger; Nahid Olfati; Joseph Jankovic Journal: Parkinsonism Relat Disord Date: 2019-10-14 Impact factor: 4.891
Authors: Maria Stamelou; Gesine Respondek; Nikolaos Giagkou; Jennifer L Whitwell; Gabor G Kovacs; Günter U Höglinger Journal: Nat Rev Neurol Date: 2021-08-23 Impact factor: 42.937
Authors: Luca Passamonti; Patricia Vázquez Rodríguez; Young T Hong; Kieren S J Allinson; David Williamson; Robin J Borchert; Saber Sami; Thomas E Cope; W Richard Bevan-Jones; P Simon Jones; Robert Arnold; Ajenthan Surendranathan; Elijah Mak; Li Su; Tim D Fryer; Franklin I Aigbirhio; John T O'Brien; James B Rowe Journal: Brain Date: 2017-03-01 Impact factor: 13.501
Authors: Kristen D Kelley; Harvey Checkoway; Deborah A Hall; Stephen G Reich; Chris Cunningham; Irene Litvan Journal: Front Neurol Date: 2018-06-20 Impact factor: 4.003