[Show abstract][Hide abstract] ABSTRACT: Pesticides have been associated with Parkinson's disease (PD), and protective gloves and workplace hygiene can reduce pesticide exposure. We assessed whether use of gloves and workplace hygiene modified associations between pesticides and PD. The Farming and Movement Evaluation (FAME) study is a nested case–control study within the Agricultural Health Study. Use of protective gloves, other PPE, and hygiene practices were determined by questionnaire (69 cases and 237 controls were included). We considered interactions of gloves and hygiene with ever-use of pesticides for all pesticides with ≥ 5 exposed and unexposed cases and controls in each glove-use stratum (paraquat, permethrin, rotenone, and trifluralin). 61% of respondents consistently used protective gloves and 87% consistently used ≥ 2 hygiene practices. Protective glove use modified the associations of paraquat and permethrin with PD: neither pesticide was associated with PD among protective glove users, while both pesticides were associated with PD among non-users (paraquat OR 3.9 [95% CI 1.3, 11.7], interaction p = 0.15; permethrin OR 4.3 [95% CI 1.2, 15.6] interaction p = 0.05). Rotenone was associated with PD regardless of glove use. Trifluralin was associated with PD among participants who used < 2 hygiene practices (OR 5.5 [95% CI 1.1, 27.1]) but was not associated with PD among participants who used 2 or more practices (interaction p = 0.02). Although sample size was limited in the FAME study, protective glove use and hygiene practices appeared to be important modifiers of the association between pesticides and PD and may reduce risk of PD associated with certain pesticides.
Environment International 11/2014; 75. DOI:10.1016/j.envint.2014.11.002 · 5.66 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Dietary fat intake may modify Parkinson's disease (PD) risk directly or by altering the response to environmental neurotoxicants including pesticides.
We conducted a case-control study of PD nested in the Agricultural Health Study (AHS), a cohort of pesticide applicators and spouses. We evaluated diet and pesticide use before diagnosis in 89 PD cases, confirmed by movement disorder specialists, or a corresponding date in 336 frequency-matched controls. Associations were evaluated using multivariate logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs).
In the AHS, PD was inversely associated with N-3 polyunsaturated fatty acids (PUFAs) (OR 0.4, 95% CI 0.2-0.8 for highest vs. lowest tertile) and the N-3 precursor α-linolenic acid (0.4, 0.2-0.8). In a meta-analysis of nine studies, including the present one, PD was inversely associated with α-linolenic acid (0.81, 0.68-0.96). In the AHS, associations of PD with the pesticides paraquat and rotenone were modified by fat intake. The OR for paraquat was 4.2 (1.5-12) in individuals with PUFA intake below the median but 1.2 (0.4-3.4) in those with higher intake (p-interaction = 0.10). The OR for rotenone was 5.8 (2.3-15) in those with saturated fat intake above the median but 1.5 (0.5-4.2) in those with lower intake (p-interaction = 0.02).
PUFA intake was consistently associated with lower PD risk, and dietary fats modified the association of PD risk with pesticide exposure. If confirmed, these findings suggest that a diet high in PUFAs and low in saturated fats might reduce risk of PD.
[Show abstract][Hide abstract] ABSTRACT: Several case reports have linked solvent exposure to Parkinson disease (PD), but few studies have assessed associations with specific agents using an analytic epidemiologic design. We tested the hypothesis that exposure to specific solvents is associated with PD risk using a discordant twin pair design.
Ninety-nine twin pairs discordant for PD ascertained from the National Academy of Sciences/National Research Council World War II Veteran Twins Cohort were interviewed regarding lifetime occupations and hobbies using detailed job task-specific questionnaires. Exposures to 6 specific solvents selected a priori were estimated by expert raters unaware of case status.
Ever exposure to trichloroethylene (TCE) was associated with significantly increased risk of PD (odds ratio [OR], 6.1; 95% confidence interval [CI] 1.2-33; p = 0.034), and exposure to perchloroethylene (PERC) and carbon tetrachloride (CCl(4) ) tended toward significance (respectively: OR, 10.5; 95% CI, 0.97-113; p = 0.053; OR, 2.3; 95% CI, 0.9-6.1; p = 0.088). Results were similar for estimates of exposure duration and cumulative lifetime exposure.
Exposure to specific solvents may increase risk of PD. TCE is the most common organic contaminant in groundwater, and PERC and CCl(4) are also ubiquitous in the environment. Our findings require replication in other populations with well-characterized exposures, but the potential public health implications are substantial.
Annals of Neurology 06/2012; 71(6):776-84. DOI:10.1002/ana.22629 · 11.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To test the hypothesis that variability in SNCA Rep1, a polymorphic dinucleotide microsatellite in the promoter region of the gene encoding α-synuclein, modifies the association between head injury and Parkinson's disease (PD) risk.
Participants in the Farming and Movement Evaluation (FAME) and the Study of Environmental Association and Risk of Parkinsonism using Case-Control Historical Interviews (SEARCH), 2 independent case-control studies, were genotyped for Rep1 and interviewed regarding head injuries with loss of consciousness or concussion prior to Parkinson's disease (PD) diagnosis. Logistic regression modeling adjusted for potential confounding variables and tested interaction between Rep1 genotype and head injury.
Consistent with prior reports, relative to medium-length Rep1, short Rep1 genotype was associated with reduced PD risk (pooled odds ratio [OR], 0.7; 95% confidence interval [CI], 0.5-0.9), and long Rep1 with increased risk (pooled OR, 1.4; 95% CI, 0.95-2.2). Overall, head injury was not significantly associated with PD (pooled OR, 1.3; 95% CI, 0.9-1.8). However, head injury was strongly associated with PD in those with long Rep1 (FAME OR, 5.4; 95% CI, 1.5-19; SEARCH OR, 2.3; 95% CI, 0.6-9.2; pooled OR, 3.5; 95% CI 1.4-9.2, p-interaction = 0.02). Individuals with both head injury and long Rep1 were diagnosed 4.9 years earlier than those with neither risk factor (p = 0.03).
While head injury alone was not associated with PD risk, our data suggest head injury may initiate and/or accelerate neurodegeneration when levels of synuclein are high, as in those with Rep1 expansion. Given the high population frequency of head injury, independent verification of these results is essential.
Annals of Neurology 01/2012; 71(1):40-8. DOI:10.1002/ana.22499 · 11.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Mitochondrial dysfunction and oxidative stress are pathophysiologic mechanisms implicated in experimental models and genetic forms of Parkinson's disease (PD). Certain pesticides may affect these mechanisms, but no pesticide has been definitively associated with PD in humans.
Our goal was to determine whether pesticides that cause mitochondrial dysfunction or oxidative stress are associated with PD or clinical features of parkinsonism in humans.
We assessed lifetime use of pesticides selected by mechanism in a case-control study nested in the Agricultural Health Study (AHS). PD was diagnosed by movement disorders specialists. Controls were a stratified random sample of all AHS participants frequency-matched to cases by age, sex, and state at approximately three controls:one case.
In 110 PD cases and 358 controls, PD was associated with use of a group of pesticides that inhibit mitochondrial complex I [odds ratio (OR)=1.7; 95% confidence interval (CI), 1.0-2.8] including rotenone (OR=2.5; 95% CI, 1.3-4.7) and with use of a group of pesticides that cause oxidative stress (OR = 2.0; 95% CI, 1.2-3.6), including paraquat (OR=2.5; 95% CI, 1.4-4.7).
PD was positively associated with two groups of pesticides defined by mechanisms implicated experimentally-those that impair mitochondrial function and those that increase oxidative stress-supporting a role for these mechanisms in PD pathophysiology.
Environmental Health Perspectives 01/2011; 119(6):866-72. DOI:10.1289/ehp.1002839 · 7.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We examined risk of parkinsonism in occupations (agriculture, education, health care, welding, and mining) and toxicant exposures (solvents and pesticides) putatively associated with parkinsonism.
To investigate occupations, specific job tasks, or exposures and risk of parkinsonism and clinical subtypes.
Eight movement disorders centers in North America.
Inclusion criteria were parkinsonism (>or=2 cardinal signs), diagnosis within 8 years of recruitment (to minimize survival bias), and ability to participate in detailed telephone interviews. Control subjects were primarily nonblood relatives or acquaintances of patients.
This multicenter case-control study compared lifelong occupational and job task histories to determine associations with parkinsonism and certain clinical subtypes (postural instability and gait difficulty and age at diagnosis <or=50 years).
Findings in 519 cases and 511 controls were analyzed. Work in agriculture, education, health care, or welding was not associated with increased risk of parkinsonism. Unexpected increased risks associated with legal, construction and extraction, or religious occupations were not maintained after adjustment for duration. Risk of parkinsonism increased with pesticide use (odds ratio, 1.90; 95% confidence interval, 1.12-3.21), use of any of 8 pesticides mechanistically associated with experimental parkinsonism (2.20; 1.02-4.75), and use of 2,4-dichlorophenoxyacetic acid (2.59; 1.03-6.48). None of the specific occupations, job tasks, or task-related exposures were associated with younger age at diagnosis (<or=50 years). Ever working in business and finance, legal occupations, construction and extraction, or transportation and material moving was associated with postural instability and gait difficulty subtype of parkinsonism. Tobacco use was inversely associated with parkinsonism risk.
The association of disease risk with pesticides support a toxicant-induced cause of parkinsonism.
Archives of neurology 09/2009; 66(9):1106-13. DOI:10.1001/archneurol.2009.195 · 7.01 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To identify the motor and non-motor factors that are associated with health related quality of life (HR-QOL) in a subgroup of Parkinson's disease (PD) patients with Levodopa therapy in early clinical stages.
391 Levodopa exposed patients were evaluated during the baseline assessment of a clinical trial in China. HR-QOL was measured by the Short Form 36 (SF-36). Motor and non-motor variables were determined during a structured interview and by clinical examination by movement disorder specialists. Multiple regression analyses were used to determine which variables were associated with low levels of HR-QOL.
Even if excluding non-motor variables from the regression model, motor factors, particularly motor deficits (measured by motor score of UPDRS), rigidity (measured by item 22 of UPDRS), and disease severity (measured by Hoehn&Yahr scale), explained only 18.9% of the variance of total SF-36 score. Whereas, when non-motor variables were included in the model, especially depression (measured by CES-D), sleep disturbances (measured by PSQ-I), and fatigue (measured by FSS), 61.7% of the variance of SF-36 score could be explained. Two motor variables, UPDRS motor score and Hoehn&Yahr score, were also contributed to the model, however, the 95% confidence intervals (CIs) of these two motor factors were wide and included the null value (CIs -0.282, 0.019 for UPDRS motor score, and CIs -4.043, 0.856 for Hoehn&Yahr score). Neither, did higher daily levodopa dose contribute significantly to both models predicting SF-36 score.
In our sample patients with levodopa therapy, motor disability and severity of parkinsonism contributed to a lesser extent to patients' self-report distress, within the first 5 years of disease onset. The clinical factors that showed the highest predictive value for worsen HR-QOL were non-motor symptoms, such as depression, sleep disorders, and fatigue. Great effort should be made to recognize and treat those conditions, thus improving all aspects of PD and giving these patients as a good HR-QOL as possible.