Cigarette smoking and Parkinson's disease: a case-control study in a population characterized by a high prevalence of pesticide exposure.

Epidemiological studies have been consistent in showing that cigarette smoking is inversely associated with Parkinson's disease (PD), whereas pesticide use is positively associated with PD. However, the relationship between PD and cigarette smoking remains poorly understood. Our objective was to study the relationship between cigarette smoking and PD in a population characterized by a high prevalence of pesticide exposure. This case-control study was carried out among subjects enrolled in the Mutualite Sociale Agricole, the French health insurance organization for workers connected to the agricultural world. We included 247 cases and 676 controls matched on age, sex, and region of residency. Information on smoking was obtained through in-person interviews. Pesticide exposure was assessed using a case-by-case expert evaluation procedure. We found an inverse relationship between ever cigarette smoking and PD (odds ratio [OR] = 0.6; 95% confidence interval [CI] = 0.4-0.9). The strength of this association increased with the number of pack-years. This relationship was present even when smoking was considered as long as 40 years before PD onset. An inverse association was also present among subjects professionally exposed to pesticides (OR = 0.5; 95% CI = 0.3-0.8) and was independent of the duration of exposure among men. We confirm the inverse association between cigarette smoking and PD in a population characterized by a high prevalence of professional pesticide exposure. The relationship between PD and cigarette smoking was not significantly modified or confounded by exposure to pesticides.     

Pesticide exposure and risk for Parkinson's disease

OBJECTIVE: Chronic, low-dose exposure to pesticides is suspected to increase the risk for Parkinson's disease (PD), but data are inconclusive. METHODS: We prospectively examined whether individuals exposed to pesticides have higher risk for PD than those not exposed. The study population comprised participants in the Cancer Prevention Study II Nutrition Cohort, a longitudinal investigation of US men and women initiated in 1992 by the American Cancer Society. Follow-up surveys were conducted in 1997, 1999, and 2001. The 143,325 individuals who returned the 2001 survey and did not have a diagnosis or symptoms of PD at baseline (1992) were included in the analyses. RESULTS: Exposure to pesticides was reported by 7,864 participants (5.7%), including 1,956 farmers, ranchers, or fishermen. Individuals exposed to pesticides had a 70% higher incidence of PD than those not exposed (adjusted relative risk, 1.7; 95% confidence interval, 1.2-2.3; p = 0.002). The relative risk for pesticide exposure was similar in farmers and nonfarmers. No relation was found between risk for PD and exposure to asbestos, chemical/acids/solvents, coal or stone dust, or eight other occupational exposures. INTERPRETATION: These data support the hypothesis that exposure to pesticides may increase risk for PD. Future studies should seek to identify the specific chemicals responsible for this association.     

Exposure to well water and pesticides in Parkinson's disease: a case-control study in the Madrid area.

Past exposure to well water and pesticides was assessed in 128 unselected Parkinson's disease (PD) patients and 256 age and sex-matched controls. All were residents in a defined urban area of Madrid, Spain. In keeping with other reports, we found that exposure to well water might be a factor associated with the likelihood of developing PD, though only prolonged exposures of 30 years or longer were significantly different between PD and controls (p less than 0.02). In contrast, past exposure to pesticides did not appear to be associated with an increased risk of developing PD. Prolonged well water drinking antedating the development of PD was not associated with early onset of the disease, nor did such cases progress to greater disability. Future case-control studies addressing prolonged well water consumption as a risk factor in PD should look for differences in the content of substances other than pesticides in the water as determined by the source of water to which patients may have been specifically exposed.     

Absence of effect of seven functional mutations in the CYP2D6 gene in Parkinson's disease.

The reduction or loss of cytochrome P450 enzyme activity as a result of mutations in the CYP2D6 gene has been suggested as a risk factor for Parkinson's disease (PD). Conflicting results among reported studies of the prevalence of mutations among patients with PD suggested a more comprehensive genotyping and an analysis of the interactions with other suspected risk factors and family history. We determined the frequency of seven CYP2D6 mutations among 109 patients with PD and 110 control subjects. Family history of PD, age of onset, exposure to pesticides or herbicides, and well-water consumption were obtained for all cases. There was no significant difference in frequency between patients with PD and control subjects for any mutant allele and no significant association with family history, onset age, or environmental exposures. We sought to increase the power of our study by combining reports from the literature, choosing allele frequencies as the most informative measure. Although we found variability in reported allele frequencies for control subjects that made a meta-analysis problematic, summing all reports demonstrated no difference in CYP2D6 mutation frequency between patients with PD and control subjects. This comprehensive study of CYP2D6 mutations demonstrates that other genes or shared environmental exposures account for the familial risk of PD.     

Number of children and risk of Parkinson's disease.

We investigated the association between number of children and Parkinson's disease (PD) in two independent studies. In a case-control study, we identified all subjects who developed PD in Olmsted County, MN, from 1976 through 1995, and matched them individually by age (+/-1 year) and sex to population controls (193 cases and 193 controls). The replication study was a population-based cohort study of 6,341 subjects from Rotterdam, the Netherlands (2,610 men). In the Olmsted County study, men who fathered at least one child had an increased risk of PD (unadjusted OR, 2.7; 95% CI, 1.2-6.1; P = 0.02), and the risk increased with increasing number of children. The findings in women were not significant. In the Rotterdam Study, the risk of PD increased significantly with increasing number of children in men (test for linear trend, unadjusted; P = 0.04), but not in women. The findings from both studies remained consistent in direction but reduced in magnitude of the association, and lost significance after simultaneous adjustment for education, cigarette smoking, alcohol consumption, and coffee consumption. The independent replication in two distinct populations and using different epidemiologic study designs may suggest a link between the number of children and PD restricted to men.     

A pilot study of occupational and environmental risk factors for Parkinson's disease.

Increasingly, the etiology of Parkinson's disease (PD) has been linked to exposures to environmental toxicants. This epidemiologic pilot study used a self-administered questionnaire among 34 PD cases and 22 other neurology clinic control patients. All subjects were at least 40 years old. Risk factors investigated included occupation, well-water use, pesticide use, metal exposures, medical history, smoking, alcohol consumption, and drug use. Twenty-six percent of the male PD cases reported having been employed in farming versus eleven percent for male controls (OR = 3.1, 95% C.I. = 0.3 to 35). Sixteen percent of male cases versus none of the controls reported employment as welders. No clear trends involving exposure to either occupational or home pesticides emerged. In assessing occupational exposures to metals, aluminum and copper exposures tended to be more common among male cases than male controls. Additionally, as reported in other studies, smoking showed an inverse relationship with PD. Although the findings reported here are provocative, these results are statistically imprecise and must be interpreted cautiously because of the small number of subjects included in the study.     

Height as a potential indicator of early life events predicting Parkinson's disease: a case-control study.

Aim of this study was to investigate the relationship between height in young adult age and Parkinson's disease (PD) risk. We included 266 persons affected by idiopathic PD. Patients were matched by age and sex to 266 controls by a random selection from the municipality of residence. We collected information about height preceding PD from official documents where these characteristics referred to young adult age (nearly 30 years). We compared height in cases and controls by calculating differences in mean distribution and by chi(2) analyses. Crude and adjusted odds ratios (OR) and 95% confidence intervals (CI) were calculated by logistic regression models. Mean height was significantly lower in persons affected by PD compared to controls (P = 0.03). Difference was significant only in men (P = 0.001). Logistic regression models showed an inverse association between height and PD (OR 0.35; CI 0.16, 0.79; P < 0.01 comparing individuals in the highest percentiles of height with those in the lowest). Our results indicate an association between height and PD in men. Considering that dopamine sensitivity in the hypothalamic-pituitary axis is related to adult height, our findings suggest a relationship between PD and factors modulating somatic growth early in life.     

A case-control study on cigarette,alcohol, and coffee consumption preceding Parkinson's disease

OBJECTIVE: To investigate the association between cigarette smoking, alcohol drinking, coffee consumption and Parkinson's disease (PD). METHODS: We selected subjects affected by idiopathic PD, with a Mini-Mental State Examination of > or =24, and controls matched 1 to 1 with cases by age (+/- 2 years) and sex. Controls were randomly selected from the resident list of the same municipality of residence of the cases. We assessed cigarette smoking, alcohol drinking, and coffee consumption preceding the onset of PD or the corresponding time for controls using a structured questionnaire, which also evaluated the duration and dose of exposure. Using conditional logistic regression analysis, we calculated adjusted OR and 95% CI. RESULTS: We interviewed 150 PD patients and 150 matched controls. Cigarette smoking (ever vs. never smokers OR = 0.66, 95% CI = 0.41-1.05, p = 0.08) did not show a statistically significant association with PD. We observed an inverse association between alcohol drinking (ever vs. never OR = 0.61, 95% CI = 0.39-0.97, p = 0.037) and coffee consumption (ever vs. never OR = 0.16, 95% CI 0.05-0.46, p = 0.0001) and PD. These associations remained significant after adjustment for other covariates: OR for ever vs. never alcohol consumption was 0.62 (95% CI = 0.43-0.89, p = 0.009) and that for coffee drinking 0.19 (95% CI = 0.07-0.52, p = 0.001). Heavy coffee consumption confirmed the inverse association between coffee and PD (more than 81 cup/year vs. none: OR = 0.20, 95% CI = 0.08-0.47, p < or = 0.0001). CONCLUSIONS: Consistent with previous studies, our results suggest an inverse association between coffee drinking, alcohol consumption and PD. The multiple inverse association observed may indicate a complex interaction between genetic and environmental factors.     

Diabetes preceding Parkinson's disease onset. A case–control study

ObjectiveTo assess the association between diabetes preceding Parkinson's disease (PD) and PD.MethodsPD individuals were matched to PD free individuals randomly selected from people in the same municipality as the cases. Occurrence of diabetes preceding PD onset among cases and controls was assessed through a structured questionnaire. Information regarding current and past medical treatment and other variables was also collected. We used univariate and multivariate logistic models to calculate crude and adjusted odds ratios (OR). Covariates are adjusted for included education, smoking habit, alcohol and coffee consumption.Results318 PD individuals (165 women, 153 men) and 318 matched controls were included in the study. PD patients had a mean age at interview of 66.7 years. Mean age at PD onset was 60.8 years and mean PD duration 5.9 years. We found an inverse association between PD and diabetes preceding PD onset in all groups stratified by gender, age at PD onset, body mass index (BMI), smoking habit, alcohol and coffee consumption. Multivariate analysis yielded the same findings after controlling for the variables (adjusted OR 0.4; 95% CI, 0.2–0.8).ConclusionsOur findings provide additional support for a potential link between diabetes and PD.     

S18Y polymorphism in the UCH-L1 gene and Parkinson's disease: evidence for an age-dependent relationship.

We studied the relationship between Parkinson's disease (PD) and the S18Y polymorphism in the UCH-L1 gene and the effect on this relationship of age at onset, smoking, and pesticides. Patients requested free health coverage for PD to the Mutualité Sociale Agricole (MSA), the French health insurance organization for people whose work is related to agriculture. Controls requested reimbursement of health expenses to the MSA. A maximum of three controls were matched to each case. Analyses included participants with both parents born in Europe. There were no differences in S18Y genotypes between patients (n = 209; 67% SS, 32% SY, 1% YY) and controls (n = 488; 66% SS, 30% SY, 4% YY). The relationship between PD and S18Y was modified by age at onset (P = 0.03). The Y allele was inversely associated with PD for patients with onset before 61 years (odds ratio [OR] = 0.53; 95% confidence interval [CI], 0.29-0.99); there was no association for older patients (62-68 years: OR = 1.21; 95% CI, 0.67-2.20; >68 years: OR = 1.24; 95% CI, 0.67-2.31). Among patients, Y carriers had a later onset than noncarriers (P = 0.04). These findings were not modified or confounded by smoking and pesticides. In this community-based case-control study, carriers of the Y allele were at decreased risk of developing PD at a young age, independently of pesticides and smoking.     

A case-control study of Parkinson's disease in urban population of southern Israel

BACKGROUND: In recent years, an increased prevalence of Parkinson's disease (PD) in southern Israel was observed. The aim of this study was to determine which exposures are associated with PD in the urban population of this region. METHODS: Ninety-three PD patients living in towns were compared to 93 age and sex matched controls. A previously validated questionnaire, including demographic data, education, data on exposures, previous diseases, family history and habits, was administered. RESULTS: In multivariate logistic regression analysis, it was found that history of work in construction sites was the strongest predictor of PD risk, followed by exposure to pesticides. In contrast, there was a negative association with smoking and history of mechanical factory employment. When the same statistical analysis was limited to association of PD with smoking, pesticides and construction work, the latter was found to be the strongest risk factor. CONCLUSION: The risk factors for PD in this population are work on a construction site and exposure to pesticides.     

Head trauma and Parkinson’s disease: results from an Italian case-control study

We evaluated the possible association between head trauma and Parkinson’s disease (PD). The FRAGAMP (Fattori di Rischio Ambientali e Genetici Associati alla Malattia di Parkinson) study is a large Italian multicenter case-control study carried out to evaluate the possible role of environmental and genetic factors in PD. Cases and controls were enrolled from six movement disorders centers located in the Central-Southern Italy. A standardized questionnaire was administered to record demographic, epidemiological, and clinical data. Positive history of head trauma was considered only if the head trauma preceded the onset of PD. All cases and controls underwent a standard neurological examination. Adjusted ORs and 95% CI were estimated using multivariate analysis (logistic regression). Four hundred ninety-two PD patients (292 men and 200 women) and 459 controls (160 men and 299 women) were enrolled in the study. A positive history for head trauma was reported by 106 (21.5%) PD patients and by 62 (13.5%) healthy controls. Multivariate analysis (OR adjusted by age, sex, family history, coffee smoking, and alcohol consumption) showed a significant positive association between PD and head trauma with an adjusted OR of 1.50 (95%CI 1.04–2.17; p value 0.03). In agreement with literature data, our study supports the positive association between head trauma and PD.     

Plantation work and risk of Parkinson disease in a population-based longitudinal study

CONTEXT: Parkinson disease (PD) has an unknown cause; however, convincing evidence is emerging that indicates pesticides can selectively injure the dopaminergic system in laboratory animals. Retrospective studies in humans demonstrate a link between exposure to agricultural lifestyle factors and PD. OBJECTIVE: To determine whether working on a plantation in Hawaii and exposure to pesticides are associated with an increased risk of PD decades later. DESIGN AND SETTING: Prospective cohort study based on the island of Oahu, Hawaii, with 30 years of follow-up. Years of work on a plantation were assessed by questionnaire at study enrollment in 1965. Self-reported information on pesticide exposure was collected at a separate examination 6 years later. PARTICIPANTS: Participants were 7986 Japanese American men born between 1900 and 1919 who were enrolled in the longitudinal Honolulu Heart Program. MAIN OUTCOME MEASURES: Incident PD was determined by medical record review or by an examination conducted by a study neurologist at a later date. RESULTS: During follow-up, 116 men developed PD. Age-adjusted incidence increased significantly among men who worked more than 10 years on a plantation. The relative risk of PD was 1.0 (95% confidence interval, 0.6-1.6), 1.7 (95% confidence interval, 0.8-3.7), and 1.9 (95% confidence interval, 1.0-3.5) for men who worked on a plantation 1 to 10 years, 11 to 20 years, and more than 20 years compared with men who never did plantation work (P =.006, test for trend). Age-adjusted incidence of PD was higher in men exposed to pesticides than in men not exposed to pesticides although this was not statistically significant (P =.10, test for trend). CONCLUSION: These longitudinal observations regarding plantation work in Hawaii support case-control studies suggesting that exposure to pesticides increases the risk of PD.     

Lrrk2 S1647T and BDNF V66M interact with environmental factors to increase risk of Parkinson's disease

Parkinson's disease (PD) is a complex neurodegenerative disorder contributed by both environmental and genetic factors. The inconsistent findings in genetic association studies may be due to unrecognized interactions with other genetic or environmental factors. Therefore, we assessed the combined effects of genetic variants of three candidate genes of familial PD and environmental exposure on risk of PD in Taiwanese population. A total of 744 study subjects, 453 PD cases and 291 ethnicity-matched controls, were included. The genetic variants on the PINK1, BDNF, and LRRK2 genes were sequenced accordingly. We used a regression approach based on a generalized linear model to evaluate single-locus genotype effects and detection of gene-environment interaction by incorporating interaction terms in the model. We found a significant difference of LRRK2 G2385R and R1628P between PD patients and controls, which confirmed our previous findings. A logistic regression model which included gene-environment interactions was applied. Notably, we identified the variant of LRRK2 T4939A (S1647T) (TT, OR?=?-0.36, p?=?0.03) is associated with increased PD risk, after considering the interaction effects with environmental factors in the model. Additionally, two novel interactions were detected: pesticide exposure with BDNF (OR?=?-0.85, p?=?0.01) and to a lesser extent, with PINK1 (OR?=?1.99, p?=?0.07). Our findings reinforced the importance that PD risk is modulated by both genetic and environmental exposures. LRRK2 S1647T may be another risk factor for PD development in our ethnicity while considering the joint interaction effects with environmental factors.     

Pesticides and risk of Parkinson disease: a population-based case-control study

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.     

Prospective study of phobic anxiety and risk of Parkinson's disease.

Anxiety disorders are common in Parkinson's disease (PD). However, the risk of PD among people with anxiety has not been examined in a prospective cohort study. We examined this relation prospectively within the Health Professionals Follow-Up Study, a cohort of US male health professionals. In 1988, anxiety was assessed using the Crown-Crisp phobic anxiety index in 35,815 men without PD, stroke, or cancer at baseline. There were 189 incident cases of PD during 12 years of follow-up. After adjusting for age, smoking, and caffeine intake, the relative risk of PD among men with the highest level of anxiety (Crown-Crisp index scores of 4 and above) was 1.5 (95% CI = 1.0-2.1; P-trend = 0.01) compared to men with the lowest level of anxiety. This positive association persisted after excluding cases of PD with onset in the first 2 years of follow-up. Use of anxiolytic medication was also associated with an elevated risk of PD (RR= 1.6; 95% CI = 0.9-3.1), but adjusting for this potential confounder did not materially affect the association between anxiety and risk of PD. Our results suggest that anxiety is a risk factor for PD. Whether this association is causal or the result of shared underlying biology remains a question.     

MDR1 variants and risk of Parkinson disease

The multidrug resistance protein 1 (MDR1 or ABCB1) gene encodes a P-glycoprotein that protects the brain against neurotoxicants. Certain MDR1 genetic variants are known to compromise the function of this transporter and may thus be associated with Parkinson disease (PD). We therefore conducted a large case-control study investigating the potential relationship between MDR1 variants and PD. We determined the frequency of three MDR1 variants in 599 European PD patients and controls and further stratified the population by ethnicity, age at onset, and exposure to pesticides. We detected no relevant association in either the entire sample, or when separately investigating by ethnic origin or age at onset. However, the distribution of c.3435C/T differed significantly between PD patients exposed to pesticides compared to those non-exposed (odds ratio = 4.74; confidence interval = [1.009; 22.306]); p = 0.047), suggesting that common MDR1 variants might influence the risk to develop PD in conjunction with exposure to pesticides.     

The epidemiology of Parkinson's disease. A case-control study of young-onset and old-onset patients

While the cause of Parkinson's disease (PD) remains unknown, recent evidence suggests that certain external factors, ie, environmental agents, may act as neurotoxins, initiating the chain of oxidative reactions that ultimately destroy neurons in the substantia nigra. Young-onset PD might result from greater exposure to a putative neurotoxin. This hypothesis has rekindled interest in the epidemiology of PD. We therefore conducted a detailed analysis of various environmental exposures and early life experiences in 80 patients with old-onset PD (at an age older than 60 years), 69 young-onset patients (younger than 40 years), and 149 age- and sex-matched control subjects. Contrary to previous reports, we were unable to implicate well water or exposure to herbicides, pesticides, or industrial toxins as significant PD risk factors. A residential history of rural living was reported by more patient cases than control subjects and was marginally significant. On the other hand, at least one episode of head trauma "severe enough to cause vertigo, dizziness, blurred or double vision, seizures or convulsions, transient memory loss, personality changes, or paralysis" occurred significantly more often prior to disease onset in patients with both young-onset and old-onset PD than in control subjects (odds ratio = 2.7). When adjusted for head trauma and rural living, smoking was inversely associated with PD, as has been previously reported (odds ratio = 0.5). There were no significant differences in early life experiences or environmental exposures between young-onset and old-onset patients. We suggest that the risk of developing PD is influenced by a variety of factors.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comorbid cancer in Parkinson's disease

The aim of this article was to evaluate cancer occurrence before and after diagnosis of Parkinson's disease (PD). We investigated 692 patients newly diagnosed with PD and 761 age‐ and sex‐matched control subjects identified during two periods (1994–1995 and 2000–2003) within Kaiser Permanente Medical Care Program of Northern California. Primary cancers were searched and dated, and all participants were followed up until the end of membership, death, or December 31, 2008. We used unconditional logistic regression to evaluate the PD–cancer association before the date of PD diagnosis or the index date and Cox proportional hazards regression to evaluate the PD–cancer association after the index date. Nearly 20% (140 of 692) of the PD patients and 25% (188 of 761) of the non‐PD controls had ever had a cancer diagnosis. Before the index date, the prevalence of cancer was not significantly lower in patients with PD (8.1% PD vs. 9.2% controls; OR = 0.83; 95% CI 0.54–1.3). After the index date, the risk of developing a cancer did not differ between PD cases and controls (relative risk [RR] = 0.94; 95% CI 0.70–1.3). Among specific cancers, melanoma was more common among PD cases (before PD, OR = 1.5; 95% CI 0.40–5.2; after PD, RR = 1.6; 95% CI 0.71–3.6), but independent of dopaminergic therapy. Cancer occurrence is not significantly lower among patients with PD. The positive association between PD and subsequent melanoma merits further investigation, as it does not seem to be attributable to dopaminergic therapy, pigmentation, or confounding by smoking. © 2010 Movement Disorder Society.     

Body mass index does not change before Parkinson's disease onset

Background and purpose:  Previous studies on the association between Parkinson's disease (PD) and body mass index (BMI) have reported conflicting results. We investigated the relationship between PD and BMI by a case–control study.
Methods:  PD patients were randomly matched to healthy individuals by sex and age. BMI distribution in cases has been compared with BMI of controls and odd ratios (ORs) with 95% CI were calculated.
Results:  We included 318 PD patients and 318 controls. We observed no association between PD and BMI. BMI distribution in cases and controls was similar also when we adjusted for diabetes, hypercholesterolemia and the time elapsed between PD onset and the interview (OR = 0.99; CI = 0.94–1.03; P  = 0.51).
Conclusions:  These results did not confirm the previously reported association between PD and BMI. Population characteristics and methodological issues may partially account for the differences observed between the present study and the others.