0
Original Contribution |

Pesticides and Risk of Parkinson Disease:  A Population-Based Case-Control Study FREE

Jordan A. Firestone, MD, PhD, MPH; Terri Smith-Weller, MN, COHN; Gary Franklin, MD, MPH; Phillip Swanson, MD, PhD; W. T. Longstreth Jr, MD, MPH; Harvey Checkoway, PhD
[+] Author Affiliations

Author Affiliations: Departments of Neurology (Drs Firestone, Franklin, Swanson, and Longstreth), Environmental and Occupational Health Sciences (Ms Smith-Weller and Drs Franklin and Checkoway), and Epidemiology (Drs Longstreth and Checkoway), University of Washington, Seattle.


Arch Neurol. 2005;62(1):91-95. doi:10.1001/archneur.62.1.91.
Text Size: A A A
Published online

Background  Pesticide exposures are suspected risk factors for Parkinson disease (PD), but epidemiological observations have been inconsistent.

Objective  To investigate associations between pesticide exposures and idiopathic PD.

Design  Population-based case-control study.

Setting  Group Health Cooperative, a health care system in western Washington State, and the University of Washington.

Participants  Two hundred fifty incident PD case patients and 388 healthy control subjects (age- and sex-matched). We assessed self-reported pesticide exposures using a structured interview. Odds ratios (ORs) and 95% confidence intervals (CIs) were determined using logistic regression models, controlling for age, sex, and smoking.

Results  Odds ratios for occupational exposures were not significant but suggested a gradient that paralleled occupational exposures (pesticide worker: OR, 2.07; 95% CI, 0.67-6.38; crop farmer: OR, 1.65; 95% CI, 0.84-3.27; animal and crop farmer: OR, 1.10; 95% CI, 0.60-2.00; and dairy farmer: OR, 0.88; 95% CI, 0.46-1.70). Odds ratios for organophosphates paralleled the World Health Organization hazard classifications, with parathion much higher than diazinon or malathion. We also found elevated ORs from herbicides (OR, 1.41; 95% CI, 0.51-3.88) and paraquat (OR, 1.67; 95% CI, 0.22-12.76). We found no evidence of risk from home-based pesticide exposures. We found significantly increased ORs from lifelong well water consumption (OR, 1.81; 95% CI, 1.02-3.21).

Conclusions  The findings for occupational pesticide exposures are consistent with a growing body of information linking pesticide exposures with PD. However, the lack of significant associations, absence of associations with home-based exposures, and weak associations with rural exposures suggest that pesticides did not play a substantial etiologic role in this population.

Interactions between genetic susceptibilities and environmental exposures are the focus of current research regarding the cause of idiopathic Parkinson disease (PD).14 Pesticide exposure may be an important environmental risk factor for PD.5,6 Toxicological studies in vitro79 and in vivo10,11 have demonstrated specific neurodegenerative effects from exposure to certain pesticides, and human case reports have suggested causal relations between pesticide exposures and PD.12,13

Epidemiological evidence linking PD with pesticides has been inconsistent. Some studies1418 detected increased risk from surrogates for pesticide exposures, such as well water consumption or living in rural agricultural regions, whereas others1921 have not. More consistent results have been seen with occupational exposures, including farming activities and application of herbicides or insecticides.1618,2124 The potential association between home-based pesticide exposures and PD is concerning, as environmental sampling shows that such exposures can be substantial.25

We report findings from an ongoing population-based case-control study of PD in western Washington State. We reviewed subjects’ histories of occupational and home-based pesticide exposures and estimated the risks for PD from these exposures.

SUBJECTS

The methods have been previously described.26 Briefly, all newly diagnosed, idiopathic PD case patients were identified between 1992 and 2002 at the Group Health Cooperative (GHC) in western Washington State or the University of Washington. To ensure complete ascertainment, subjects were identified using a combination of provider referrals and computerized databases containing diagnostic coding and pharmacy information. A trained neurologist (G.F., P.S., or W.T.L.) confirmed PD diagnoses by medical chart review, requiring at least 2 of the 4 cardinal signs of PD (bradykinesia, resting tremor, cogwheel rigidity, and postural reflex impairment), one of which had to be bradykinesia or resting tremor. Exclusion criteria were use of certain medications (eg, phenothiazines, haloperidol, or metoclopramide hydrochloride) for which adverse effects include parkinsonism during the 12 months preceding diagnosis, prior history of multiple cerebrovascular events, or another explanation for parkinsonism (eg, brain injury, brain tumor, or encephalitis). Control subjects were randomly selected GHC enrollees with no history of PD or other progressive neurological disorder. They were frequency-matched to cases by age (in 10-year categories), sex, GHC clinic location, and original year of GHC enrollment. Subjects were not matched by historical exposures, occupation, or residential locale. Human subjects committees at the University of Washington and the GHC Center for Health Studies reviewed and approved the study.

EXPOSURES

During a structured interview, subjects provided information on demographics, medical and occupational history (job duration, ≥6 months), occupational and home-based pesticide use, drinking water source, residential history, and smoking history. The same nurse practitioner conducted all interviews at subjects’ homes. Occupational pesticide exposures were identified from a checklist of common chemical agents and home-based pesticide exposures from a checklist of commercial brand name products. Affirmative answers to occupational exposures were based on having personally worked on machines that sprayed chemicals, applied pesticide sprays or powders by hand, or worked in an area that had recently been sprayed with pesticide chemicals. For home-based exposures, subjects had to report personal use of the products in or around their homes. Subjects reported first and last year of use and frequency of exposure (number of exposed days per year).

DATA ANALYSES

Pesticides were grouped according to active ingredients’ chemical class (eg, organophosphates) and primary use category (eg, insecticides).27 All products, including those containing mixtures of ingredients from more than 1 chemical class, were grouped into the “any pesticide” category. Exposures were only counted when a period of exposure (first and last year) was reported; duration was determined as the inclusive time span. All negative or incomplete responses were considered as “not exposed.”

To avoid counting exposures after disease onset, when subclinical symptoms of PD could have affected the chance of exposure by interfering with cases’ mobility, exposures during the 5 years before the interview date were discounted. Controls’ exposure histories were discounted similarly. Analyses with and without this 5-year discount period were nearly identical; therefore, only the discounted results were shown. Cumulative exposures were categorized as ordinal variables (low/high or low/medium/ high), based on the product of duration and frequency of use. Analyses were limited to agents reported by at least 5 subjects, although paraquat was also included because of a priori interest.18,28

Relative risks were estimated with adjusted odds ratios (ORs) using unconditional logistic regression models (Stata 7.0; StataCorp LP, College Station, Tex). Models included known PD risk factors of age, sex, and smoking status (never vs ever smoked >100 cigarettes) to control for potential confounding. The crude and adjusted ORs were nearly identical throughout; therefore, only adjusted results were shown. Analyses of occupational exposures were limited to men only, as few women reported occupations outside the home. For home-based exposures, values shown were for the entire population, as subanalyses by sex showed similar results for men and women, and results of formal tests based on a multiplicative model for interaction between exposure and sex were not significant. Significance was set a priori at α = .05 using 2-tailed tests.

Several sensitivity analyses were done to test our methodological assumptions. None of the results from four separate sensitivity analyses (omitting the 32 cases identified from the University of Washington, focusing on subjects aged <50 years at diagnosis, discounting prediagnosis exposures for 10 years, and examining men and women separately) differed from the reported results in the magnitude of observed associations or their statistical significance.

STUDY POPULATION

The demographic characteristics of the study population are summarized in Table 1. These characteristics are representative of GHC enrollees, who in turn reflect the demographics of western Washington State. The time spent on each interview (mean, 60 minutes) did not differ significantly between groups. Of those who met study criteria, participation rates were 73% for cases and 66% for controls, resulting in a final study population of 250 cases and 388 controls. The possibility of selection bias could not be assessed, as privacy issues prevented access to detailed information about nonparticipants. The only significant difference between groups was their smoking status, as previously reported.26

Table Graphic Jump LocationTable 1. Demographic Characteristics of the Study Population*
OCCUPATIONAL PESTICIDE EXPOSURES

Associations with various occupational exposures are summarized in Table 2. Although none of the ORs was significant, we observed a range of risk estimates that paralleled the predicted level of exposure: pesticide worker (OR, 2.07; 95% confidence interval [CI], 0.67-6.38) greater than crop farmer (OR, 1.65; 95% CI, 0.84-3.27) greater than combined animal and crop farmer (OR, 1.10; 95% CI, 0.60-2.00) greater than dairy farmer (OR, 0.88; 95% CI, 0.46-1.70). Among the organophosphates, parathion had the highest OR (OR, 8.08; 95% CI, 0.92-70.85), whereas ORs for diazinon (OR, 1.04; 95% CI, 0.35-3.06) and malathion (OR, 1.01; 95% CI, 0.37-2.72) were not increased. Other agents with modestly increased ORs were herbicides (OR, 1.41; 95% CI, 0.51-3.88) and paraquat (OR, 1.67; 95% CI, 0.22-12.76). No significant trend was seen with duration of employment or with duration or cumulative exposure to pesticides (data not shown).

Table Graphic Jump LocationTable 2. Occupational Exposures and Risk of Parkinson Disease in Men
HOME-BASED PESTICIDE EXPOSURES

The ORs associated with various home-based exposures are shown in Table 3. We found no significant associations with home-based pesticide exposures, although ORs were slightly increased for living at least 5 years on a farm during childhood (OR, 1.21; 95% CI, 0.82-1.79) or within 1 mile of an agricultural area sprayed with pesticides (OR, 1.31; 95% CI, 0.84-2.03). Well water use throughout life was associated with significantly increased risk (OR, 1.81; 95% CI, 1.02-3.21). No significant trend was seen with duration or cumulative exposure to home-based pesticides, and ORs for living at other locations with the potential for pesticide exposure were not elevated (data not shown).

Table Graphic Jump LocationTable 3. Home-Based Exposures and Risk of Parkinson Disease in All Subjects

In this large population-based case-control study of incident PD from western Washington State, our findings do not provide strong support for the hypothesis that pesticide exposure is a risk factor for PD. Although some previous reports1424 have demonstrated increased risk from agricultural exposures to pesticides, our study differs in that it examines a predominantly urban population, not particularly enriched for agricultural exposures.

Our results suggest the possibility that occupational exposures increase risk for PD in persons whose work involves pesticide use (Table 2), with an apparent gradient of risk for occupational titles that parallels the predicted level of pesticide exposure (pesticide worker > crop farmer > combined animal and crop farmer > dairy farmer). Among individual agents, the highest OR was seen with parathion, an organophosphate carrying the World Health Organization’s highest hazard classification.29 This seems particularly relevant, as organophosphates rely on direct neurotoxic effects for their efficacy, and parkinsonian effects have been reported with organophosphate intoxication.12,13

We were particularly interested in herbicide exposures, as previous reports have demonstrated increased risks from exposures to herbicides16,18,21,22 and specifically from paraquat.18,28 Although the numbers of subjects reporting occupational exposure to herbicides (n = 17) and paraquat (n = 4) were small and the ORs were not significant, the results suggest moderately increased risk from occupational exposure to these agents. The recent description of rotenone intoxication as a model of PD is also notable,10 although we did not collect data specifically on rotenone exposure. We attempted to refine our risk estimates by examining duration of exposure and cumulative exposure; however, no significant trends were seen.

Our results related to home-based pesticide exposures (Table 3) were somewhat surprising because, although the ORs were not significant, ORs below 1.0 suggested home use of pesticides was protective. The contrast between decreased ORs from home-based exposures and increased ORs from occupational exposures may reflect essential differences between patterns and intensity of these exposures. It is also possible that an increased awareness among the PD community of the pesticide hypothesis has biased the data because of differential recall. Typically, recall bias produces artificially increased risk estimates. However, because home-based use of pesticides may be viewed as a self-imposed hazard, differential underreporting by cases may have artificially lowered risk estimates. Also, when each stratum contains few subjects, as with occupational exposures, misclassification can easily be nondifferential, increasing the chance of biased exposure estimates.

To minimize recall bias, subjects were blinded to the study hypotheses. To minimize interview bias, the interviewer was not told the subjects’ case-control status, although complete blinding is not possible for a disease like PD that has obvious outward manifestations. The fact that the interview duration did not differ significantly between cases and controls provides reassurance that interview bias did not occur.

Well water use14 and farm residence30 have been associated with increased risk for young-onset PD, although reports from studies17,21 of PD in more typical older populations like ours indicate that these may not be independent risk factors. In our population, only the subgroup who had used well water throughout life had significantly increased ORs, suggesting a cumulative dose effect. Our data on residential locale indicate no significant increase in risk for PD associated with ever having lived on a farm, although a higher OR was seen for subjects who lived on a farm before age 25 than for those who lived on a farm at age 25 or older, consistent with the concept of a critical window of exposure during a period of rapid neural development. Of course, well water use and farm residence are only surrogates for pesticide exposure. Therefore, it is relevant that we observed a similarly elevated OR for subjects who reported living within 1 mile of an agricultural area sprayed with pesticides, consistent with recent exposure assessments that have demonstrated a gradient of pesticide exposures within agricultural communities surrounding pesticide application areas.31

The fact that our results replicated the commonly observed inverse association between smoking and PD provides reassuring internal validity to our study.26 However, the nondifferential misclassification that can result from inaccurate self-report may have decreased our chance of identifying significant risks from other exposures. Another potential source of misclassification for home-based exposures is that we did not capture information about residential treatments by commercial applicators, instead only including information about subjects’ personal use. To account for the possibility of reverse causation, in which cases may have been less likely to use pesticides because of preclinical motor dysfunction, we discounted exposure histories for the 5 years before diagnosis. Unfortunately, we have no environmental monitoring data to confirm individual exposure patterns, which can vary considerably even between workers within a single occupational category.32 Despite its limitations, the case-control study design is the standard approach used to study uncommon diseases such as PD.

The growing consensus is that PD is not a single disorder but instead reflects a common pathologic end point resulting from the interaction of various environmental and genetic risk factors. Therefore, the attributable risk from any single factor is likely to be small and is likely to differ depending on specific population characteristics. Confounding the evaluation of pesticides is the complexity and ubiquity of exposures, producing misclassification that can mask true associations. Contemporary work on aggregate assessments of pesticide exposures33,34 may provide a useful model to improve future risk estimates. It is increasingly clear that using an epidemiological approach to identify etiologic factors with small attributable risk for PD will require large study populations. Such studies can best be accomplished with interdisciplinary, multicenter collaborations.

Correspondence: Jordan A. Firestone, MD, PhD, MPH, Department of Neurology, University of Washington, PO Box 359739, Seattle, WA 98104 (jfire@u.washington.edu).

Accepted for Publication: April 16, 2004.

Author Contributions:Study concept and design: (Fire-stone and Checkoway); acquisition of data: (Smith-Weller, Swanson, and Checkoway); analysis and interpretation of data: (Firestone, Franklin, Longstreth, and Checkoway); drafting of the manuscript: (Firestone); critical revision of the manuscript for important intellectual content: (Firestone, Smith-Weller, Franklin, Swanson, Longstreth, and Checkoway); statistical analysis: (Firestone, Franklin, and Longstreth); obtained funding: (Firestone and Checkoway); administrative, technical, and material support: (Smith-Weller and Swanson); study supervision: (Firestone and Checkoway).

Funding/Support: This study was supported by grants K23 ES10756, P42 ES04696, R01 ES10750, and P30 ES07033 from the National Institute of Environmental Health Sciences, Research Triangle Park, NC.

Tanner  CMOttman  RGoldman  SM  et al.  Parkinson disease in twins: an etiologic study. JAMA 1999;281341- 346
PubMed
Costa  LG The emerging field of ecogenetics. Neurotoxicology 2000;2185- 89
PubMed
Di Monte  DALavasani  MManning-Bog  AB Environmental factors in Parkinson’s disease. Neurotoxicology 2002;23487- 502
PubMed
Stoessl  AJ Etiology of Parkinson’s disease. Can J Neurol Sci 1999;26(suppl)S5- S12
PubMed
Lockwood  AH Pesticides and parkinsonism: is there an etiological link? Curr Opin Neurol 2000;13687- 690
PubMed
Priyadarshi  AKhuder  SASchaub  EAShrivastava  S A meta-analysis of Parkinson’s disease and exposure to pesticides. Neurotoxicology 2000;21435- 440
PubMed
Yang  WLSun  AY Paraquat-induced cell death in PC12 cells. Neurochem Res 1998;231387- 1394
PubMed
Chun  HSGibson  GEDeGiorgio  LAZhang  HKidd  VJSon  JH Dopaminergic cell death induced by MPP+, oxidant and specific neurotoxicants shares the common molecular mechanism. J Neurochem 2001;761010- 1021
PubMed
Uversky  VNLi  JBower  KFink  AL Synergistic effects of pesticides and metals on the fibrillation of α-synuclein: implications for Parkinson’s disease. Neurotoxicology 2002;23527- 536
PubMed
Betarbet  RSherer  TBMacKenzie  GGarcia-Osuna  MPanov  AVGreenamyre  JT Chronic systemic pesticide exposure reproduces features of Parkinson’s disease. Nat Neurosci 2000;31301- 1306
PubMed
McCormack  ALThiruchelvam  MManning-Bog  AB  et al.  Environmental risk factors and Parkinson’s disease: selective degeneration of nigral dopaminergic neurons caused by the herbicide paraquat. Neurobiol Dis 2002;10119- 127
PubMed
Bhatt  MHElias  MAMankodi  AK Acute and reversible parkinsonism due to organophosphate pesticide intoxication: five cases. Neurology 1999;521467- 1471
PubMed
Meco  GBonifati  VVanacore  NFabrizio  E Parkinsonism after chronic exposure to the fungicide maneb (manganese ethylene-bis-dithiocarbamate). Scand J Work Environ Health 1994;20301- 305
PubMed
Rajput  AHUitti  RJStern  WLaverty  W Early onset Parkinson’s disease in Saskatchewan: environmental considerations for etiology. Can J Neurol Sci 1986;13312- 316
PubMed
Barbeau  ARoy  MBernier  GCampanella  GParis  S Ecogenetics of Parkinson’s disease: prevalence and environmental aspects in rural areas. Can J Neurol Sci 1987;1436- 41
PubMed
Ho  SCWoo  JLee  CM Epidemiologic study of Parkinson’s disease in Hong Kong. Neurology 1989;391314- 1318
PubMed
Koller  WVetere-Overfield  BGray  C  et al.  Environmental risk factors in Parkinson’s disease. Neurology 1990;401218- 1221
PubMed
Liou  HHTsai  MCChen  CJ  et al.  Environmental risk factors and Parkinson’s disease: a case-control study in Taiwan. Neurology 1997;481583- 1588
PubMed
Tanner  CMChen  BWang  W  et al.  Environmental factors and Parkinson’s disease: a case-control study in China. Neurology 1989;39660- 664
PubMed
Semchuk  KMLove  EJLee  RG Parkinson’s disease and exposure to rural environmental factors: a population based case-control study. Can J Neurol Sci 1991;18279- 286
PubMed
Gorell  JMJohnson  CCRybicki  BAPeterson  ELRichardson  RJ The risk of Parkinson’s disease with exposure to pesticides, farming, well water, and rural living. Neurology 1998;501346- 1350
PubMed
Semchuk  KMLove  EJLee  RG Parkinson’s disease and exposure to agricultural work and pesticide chemicals. Neurology 1992;421328- 1335
PubMed
Hertzman  CWiens  MSnow  BKelly  SCalne  D A case-control study of Parkinson’s disease in a horticultural region of British Columbia. Mov Disord 1994;969- 75
PubMed
Baldi  ILebailly  PMohammed-Brahim  BLetenneur  LDartigues  JFBrochard  P Neurodegenerative diseases and exposure to pesticides in the elderly. Am J Epidemiol 2003;157409- 414
PubMed
Fenske  RABlack  KGElkner  KPLee  CLMethner  MMSoto  R Potential exposure and health risks of infants following indoor residential pesticide applications. Am J Public Health 1990;80689- 693
PubMed
Checkoway  HPowers  KSmith-Weller  TFranklin  GMLongstreth  WT  JrSwanson  PD Parkinson’s disease risks associated with cigarette smoking, alcohol consumption, and caffeine intake. Am J Epidemiol 2002;155732- 738
PubMed
Klasco  RK POISINDEX System.  Greenwood Village, Colo: Thomson MICROMEDEX; 2001
Hertzman  CWiens  MBowering  DSnow  BCalne  D Parkinson’s disease: a case-control study of occupational and environmental risk factors. Am J Ind Med 1990;17349- 355
PubMed
International Programme on Chemical Safety The WHO Recommended Classification of Pesticides by Hazard and Guidelines to Classification 2000-2002.  Geneva Switzerland: World Health Organization; 2002
Rajput  AHUitti  RJStern  W  et al.  Geography, drinking water chemistry, pesticides and herbicides and the etiology of Parkinson’s disease. Can J Neurol Sci 1987;14414- 418
PubMed
Lu  CFenske  RASimcox  NJKalman  D Pesticide exposure of children in an agricultural community: evidence of household proximity to farmland and take home exposure pathways. Environ Res 2000;84290- 302
PubMed
Alavanja  MCSandler  DPMcDonnell  CJ  et al.  Characteristics of pesticide use in a pesticide applicator cohort: the Agricultural Health Study. Environ Res 1999;80172- 179
PubMed
Hubal  EASheldon  LSZufall  MJBurke  JMThomas  KW The challenge of assessing children’s residential exposure to pesticides. J Expo Anal Environ Epidemiol 2000;10638- 649
PubMed
Powell  S New challenges: residential pesticide exposure assessment in the California Department of Pesticide Regulation, USA. Ann Occup Hyg 2001;45(suppl 1)S119- S123
PubMed

Figures

Tables

Table Graphic Jump LocationTable 1. Demographic Characteristics of the Study Population*
Table Graphic Jump LocationTable 2. Occupational Exposures and Risk of Parkinson Disease in Men
Table Graphic Jump LocationTable 3. Home-Based Exposures and Risk of Parkinson Disease in All Subjects

References

Tanner  CMOttman  RGoldman  SM  et al.  Parkinson disease in twins: an etiologic study. JAMA 1999;281341- 346
PubMed
Costa  LG The emerging field of ecogenetics. Neurotoxicology 2000;2185- 89
PubMed
Di Monte  DALavasani  MManning-Bog  AB Environmental factors in Parkinson’s disease. Neurotoxicology 2002;23487- 502
PubMed
Stoessl  AJ Etiology of Parkinson’s disease. Can J Neurol Sci 1999;26(suppl)S5- S12
PubMed
Lockwood  AH Pesticides and parkinsonism: is there an etiological link? Curr Opin Neurol 2000;13687- 690
PubMed
Priyadarshi  AKhuder  SASchaub  EAShrivastava  S A meta-analysis of Parkinson’s disease and exposure to pesticides. Neurotoxicology 2000;21435- 440
PubMed
Yang  WLSun  AY Paraquat-induced cell death in PC12 cells. Neurochem Res 1998;231387- 1394
PubMed
Chun  HSGibson  GEDeGiorgio  LAZhang  HKidd  VJSon  JH Dopaminergic cell death induced by MPP+, oxidant and specific neurotoxicants shares the common molecular mechanism. J Neurochem 2001;761010- 1021
PubMed
Uversky  VNLi  JBower  KFink  AL Synergistic effects of pesticides and metals on the fibrillation of α-synuclein: implications for Parkinson’s disease. Neurotoxicology 2002;23527- 536
PubMed
Betarbet  RSherer  TBMacKenzie  GGarcia-Osuna  MPanov  AVGreenamyre  JT Chronic systemic pesticide exposure reproduces features of Parkinson’s disease. Nat Neurosci 2000;31301- 1306
PubMed
McCormack  ALThiruchelvam  MManning-Bog  AB  et al.  Environmental risk factors and Parkinson’s disease: selective degeneration of nigral dopaminergic neurons caused by the herbicide paraquat. Neurobiol Dis 2002;10119- 127
PubMed
Bhatt  MHElias  MAMankodi  AK Acute and reversible parkinsonism due to organophosphate pesticide intoxication: five cases. Neurology 1999;521467- 1471
PubMed
Meco  GBonifati  VVanacore  NFabrizio  E Parkinsonism after chronic exposure to the fungicide maneb (manganese ethylene-bis-dithiocarbamate). Scand J Work Environ Health 1994;20301- 305
PubMed
Rajput  AHUitti  RJStern  WLaverty  W Early onset Parkinson’s disease in Saskatchewan: environmental considerations for etiology. Can J Neurol Sci 1986;13312- 316
PubMed
Barbeau  ARoy  MBernier  GCampanella  GParis  S Ecogenetics of Parkinson’s disease: prevalence and environmental aspects in rural areas. Can J Neurol Sci 1987;1436- 41
PubMed
Ho  SCWoo  JLee  CM Epidemiologic study of Parkinson’s disease in Hong Kong. Neurology 1989;391314- 1318
PubMed
Koller  WVetere-Overfield  BGray  C  et al.  Environmental risk factors in Parkinson’s disease. Neurology 1990;401218- 1221
PubMed
Liou  HHTsai  MCChen  CJ  et al.  Environmental risk factors and Parkinson’s disease: a case-control study in Taiwan. Neurology 1997;481583- 1588
PubMed
Tanner  CMChen  BWang  W  et al.  Environmental factors and Parkinson’s disease: a case-control study in China. Neurology 1989;39660- 664
PubMed
Semchuk  KMLove  EJLee  RG Parkinson’s disease and exposure to rural environmental factors: a population based case-control study. Can J Neurol Sci 1991;18279- 286
PubMed
Gorell  JMJohnson  CCRybicki  BAPeterson  ELRichardson  RJ The risk of Parkinson’s disease with exposure to pesticides, farming, well water, and rural living. Neurology 1998;501346- 1350
PubMed
Semchuk  KMLove  EJLee  RG Parkinson’s disease and exposure to agricultural work and pesticide chemicals. Neurology 1992;421328- 1335
PubMed
Hertzman  CWiens  MSnow  BKelly  SCalne  D A case-control study of Parkinson’s disease in a horticultural region of British Columbia. Mov Disord 1994;969- 75
PubMed
Baldi  ILebailly  PMohammed-Brahim  BLetenneur  LDartigues  JFBrochard  P Neurodegenerative diseases and exposure to pesticides in the elderly. Am J Epidemiol 2003;157409- 414
PubMed
Fenske  RABlack  KGElkner  KPLee  CLMethner  MMSoto  R Potential exposure and health risks of infants following indoor residential pesticide applications. Am J Public Health 1990;80689- 693
PubMed
Checkoway  HPowers  KSmith-Weller  TFranklin  GMLongstreth  WT  JrSwanson  PD Parkinson’s disease risks associated with cigarette smoking, alcohol consumption, and caffeine intake. Am J Epidemiol 2002;155732- 738
PubMed
Klasco  RK POISINDEX System.  Greenwood Village, Colo: Thomson MICROMEDEX; 2001
Hertzman  CWiens  MBowering  DSnow  BCalne  D Parkinson’s disease: a case-control study of occupational and environmental risk factors. Am J Ind Med 1990;17349- 355
PubMed
International Programme on Chemical Safety The WHO Recommended Classification of Pesticides by Hazard and Guidelines to Classification 2000-2002.  Geneva Switzerland: World Health Organization; 2002
Rajput  AHUitti  RJStern  W  et al.  Geography, drinking water chemistry, pesticides and herbicides and the etiology of Parkinson’s disease. Can J Neurol Sci 1987;14414- 418
PubMed
Lu  CFenske  RASimcox  NJKalman  D Pesticide exposure of children in an agricultural community: evidence of household proximity to farmland and take home exposure pathways. Environ Res 2000;84290- 302
PubMed
Alavanja  MCSandler  DPMcDonnell  CJ  et al.  Characteristics of pesticide use in a pesticide applicator cohort: the Agricultural Health Study. Environ Res 1999;80172- 179
PubMed
Hubal  EASheldon  LSZufall  MJBurke  JMThomas  KW The challenge of assessing children’s residential exposure to pesticides. J Expo Anal Environ Epidemiol 2000;10638- 649
PubMed
Powell  S New challenges: residential pesticide exposure assessment in the California Department of Pesticide Regulation, USA. Ann Occup Hyg 2001;45(suppl 1)S119- S123
PubMed

Correspondence

CME
Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).
Submit a Comment

Multimedia

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Topics
PubMed Articles
JAMAevidence.com

The Rational Clinical Examination
Make the Diagnosis: Parkinsonism

The Rational Clinical Examination
Original Article: Does This Patient Have Parkinson Disease?