Environ Health Perspect. Jan 2009; 117(1): 117–121.
Meeting Report: Consensus Statement—Parkinson’s Disease and the Environment: Collaborative on Health and the Environment and Parkinson’s Action Network (CHE PAN) Conference 26–28 June 2007
1 UCLA School of Medicine, Los Angeles, California, USA
2 Rush University Medical Center, Chicago, Illinois, USA
3 National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA
4 University of Rochester School of Medicine and Dentistry, Rochester, New York, USA
5 The Parkinson’s Institute and Clinical Center, Sunnyvale, California, USA
6 Parkinson’s Disease Research, Education, and Clinical Center, Philadelphia, Pennsylvania, USA
7 California Department of Health Services, Oakland, California, USA
8 U.S. Army Medical Research and Material Command, Fort Detrick, Maryland, USA
9 Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark
10 National Institute of Neurological Disorders and Stroke, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA
11 University of Bari, Bari, Italy
12 Stanford University School of Medicine, Stanford, California, USA
13 University of Rochester School of Medicine, Rochester, New York, USA
14 Mayo Clinic, Rochester, Minnesota, USA
15 Pacific Health Research Institute, Honolulu, Hawaii, USA
16 Science and Environmental Health Network, Ames, Iowa, USA
17 Massachusetts General Hospital, Boston, Massachusetts, USA
18 University of Miami Miller School of Medicine, Miami, Florida, USA
19 New York State Department of Health, Albany, New York, USA
20 National Institutes of Health, Bethesda, Maryland, USA
21 Rollins School of Public Health, Atlanta, Georgia, USA
22 Kaiser Permanente, Oakland, California, USA
23 Harvard School of Public Health, Boston, Massachusetts, USA
Received May 14, 2008; Accepted August 25, 2008.
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Parkinson’s disease (PD) is the second most common neurodegenerative disorder. The likelihood of developing PD increases with age. PD is rare before age 50. The average age of onset is in the mid- to late 60s (Bower et al. 1999
; de Rijk et al. 1995
; Marras and Tanner 2002
; Van den Eeden et al. 2003
). As the U.S. population ages, prevalence of this disabling disorder is expected to rise dramatically (Dorsey et al. 2007
). Unfortunately, few valid data that address changes in PD incidence or prevalence over time are available. In fact, active case-finding efforts in communities detect as many as 10–40% of cases of PD for the first time, suggesting that underestimation of PD prevalence is common (de Pedro-Cuesta 1991
; de Rijk et al. 1997
The symptoms of PD are slowly progressive. Well-recognized clinical features of PD are slowed movements, tremor, rigidity, and difficulties with gait and balance. However, other features commonly occur, including changes in olfaction, autonomic function, cognitive function, affect, sleep, and energy level (Alves et al. 2005
; Burn et al. 2006
; Pfeiffer 1998
; Stern et al. 1994
In PD, specific neuronal populations degenerate. Neurodegeneration occurs in concert with the deposition of aggregates of the protein alpha synuclein in neuronal cell bodies and processes (Spillantini et al. 1998
). The classical focus has been on dopamine-releasing cells in the substantia nigra, because dopamine replacement can partially correct some of the motor features of PD. It has long been known, however, that many other neuronal populations are also affected in PD. Recently, converging epidemiologic and pathologic data suggest that years or even decades before the onset of these classical features of PD, neurons outside of the central nervous system may be injured (Abbott et al. 2005
; Braak et al. 2004
; Langston 2006
; Ross et al. 2008
). If this is correct, current concepts of PD will need revision. Clarification may provide exciting new opportunities for treatment and intervention.
In the 1980s, the observation that intravenous exposure to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) caused parkinsonism in humans offered important insights into environmental triggers (Langston et al. 1983
). Even though relatively uncommon genetic mutations are sufficient to cause some cases of PD, twin studies conclude that the contribution of genetic makeup to the risk of most cases of PD is limited (Tanner et al. 1999
; Wirdefeldt et al. 2004
). Moreover, studies of uncommon genetic forms of PD have shown that changes in the structure of proteins that can lead to neural dysfunction, and death can also be caused independently by some environmental toxicants (Lee 2003
; Purisai et al. 2005
; Uversky et al. 2001
; Vila et al. 2000
). As a result, a general view has evolved that the vast majority of cases of PD are caused by environmental factors interacting with genetic makeup.
People with PD, their families, scientists, health care providers, and the general public are increasingly interested in identifying environmental contributors to PD with an eye toward not only more effective treatments but also prevention. What percentage of cases involves preventable causes? What precautionary interventions would be warranted and effective, and when must they be implemented? Can individuals destined to develop neurologic dysfunction due to PD be identified before typical motor symptoms manifest?
The current scientific literature does not provide conclusive answers to most of these and other relevant questions. But indications from epidemiology, basic neurobiology, and toxicology increasingly support the conclusion that a large portion of the risk of developing PD may be attributable to environmental exposures. Therefore, the risk of PD is theoretically reducible to the extent that some cases may be preventable.
Responding to these questions and concerns, a multidisciplinary group of experts gathered in Sunnyvale, California, USA, 26–28 June 2007, to assess what is known about the contribution of environmental factors to PD. Participants included toxicologists, epidemiologists, geneticists, neuroscientists, and medical practitioners. They were joined by representatives of PD advocacy groups and people with PD to review the state of environmental health science as it pertains to PD.
The purposes of the meeting were as follows:
- To review findings from diverse research disciplines concerning environmental factors that alone or in combination with genetic variables provide a biologic basis of PD
- To identify conclusions that could be drawn with confidence from existing data
- To identify plausible but uncertain conclusions
- To identify research gaps and needs and to describe features of a coherent research agenda.
Participants recognized the existence of various syndromes that may share some clinical and neurobiologic features with classic PD. Sometimes the term “parkinsonism” is used to refer to these syndromes. They often involve more extensive (or less specific) brain injury than is typically seen in classic PD and can be degenerative or nondegenerative (e.g., carbon monoxide–induced parkinsonism, carbon tetrachloride–induced parkinsonism, vascular parkinsonism). However, boundaries between PD and parkinsonism are evolving concepts. For this reason, participants were not asked to discuss and come to a consensus definition of PD.
Participants did not attempt to rank specific pathogenic mechanisms with respect to their relative importance in PD causation. Nonetheless, various combinations of alpha synuclein deposition, mitochondrial dysfunction, proteosome dysfunction, oxidative stress, and inflammation arose in discussions of potential contributors in causal pathways.
Participants were also not asked to address and did not consider a) an exhaustive list of toxicants that have been associated with PD (examples of toxicants not considered include organic solvents, electromagnetic fields); or b) factors that may influence the progression of PD (as differentiated from causes of onset of PD).
Over the course of the meeting, the following core points of consensus were identified, which we offer in this summary to acquaint scientists, medical professionals, public health advocates, and policy makers with the current state of understanding in the field, as seen by conference participants, and to help in identifying fruitful research strategies.