Olfaction, dyskinesia and profile of weight change in Parkinson's disease: Identifying neurodegenerative phenotypes

ObjectivesTo study the relationship between olfaction and body weight profile in Parkinson's disease.MethodsProspective assessment of 99 PD patients for clinical parameters, olfaction using UPSIT and current and previous body weight. Patients were categorised as weight losers (WL) and non-weight losers (NWL) depending on change of weight from previous years. Olfaction was categorised into two groups at the cut-off of the median level of UPSIT scores. Data was analysed to study the relationship of olfaction on weight change.ResultsThirty-nine were weight losers (WL) and 60 non-weight losers (NWL). WL were significantly older (p = 0.02), females (p = 0.03) and had more severe impairment of olfaction, UPSIT 15 ± 4 vs 19 ± 5; p < 0.004. Patients with more severe olfaction (anosmic) impairment were older (p = 0.001) and had significantly lower weight, 75 vs 83 kg, p = 0.01. There was no difference in the proportion of smokers, medication usage, difficult swallowing or calorie consumption in any group. Weight losers and severe olfaction loss were associated with more severe H&;Y stage. Patients below the median-UPSIT (anosmic) had lost weight during the previous years whereas those above the median (hyposmic) had gained weight. Regression analysis revealed UPSIT at the median level to be the most significant variable (p < 0.001) for weight loss. There was continuous loss of olfaction with increasing disease severity. Higher olfactory loss was associated with higher risk of dyskinesia.ConclusionEarly assessment of olfaction may identify patients of different phenotypes for weight change and risk of dyskinesia during the course of the disease.     

Smoking and tea consumption delay onset of Parkinson's disease

Cigarette smoking, coffee and tea drinking may protect against Parkinson's disease (PD). These factors were assessed, retrospectively, to measure their effect on the age of PD onset. The study population consisted of 278 consecutive PD patients. Smoking > or =10 pack-years delayed age of PD onset by 3.2 years (p<0.05). Consumption of tea more than 3 cups per day delayed age of motor symptoms onset by 7.7 years (p<0.01). Coffee consumption exceeding 3 cups per day advanced the age of PD onset by 4.8 years (p=0.03). Thus, tea consumption and smoking can delay the age of PD onset, while coffee drinking may have the opposite effect.     

Parkinson's disease and aging: Same or different process?

Parkinson's disease (PD), which probably commences in the olfactory bulb and nuclei of IX and X, may represent accelerated normal aging or a disease specific process. The olfactory and motor disorders are associated in PD, so that smell loss should reflect the underlying disease course. Information on age‐associated decline can be obtained by single measurement from cross‐sectional analysis of patients and controls of different ages, because the observed between‐subject picture may reflect a similar within‐subject pattern. University of Pennsylvania Smell Identification Test (UPSIT) scores were examined for aging effects in 263 controls and 266 PD patients. Three models were applied that are (a) simple linear regression and (b) quadratic term in age: (i) assuming two parallel curves and (ii) allowing for two separate curves. Both groups declined with age. All three models were fitted successfully to the cross‐sectional data and none suggested that the lower mean UPSIT score in patients compared to controls was a premature ageing effect. The mean PD‐UPSIT score even at the age of 40, was lower than the control mean at the upper life‐span limit, implied that the decline in olfaction in PD is faster than simple aging. Extrapolation back in time suggested onset before birth, which is unlikely and implies that at some point there is a more rapid decline than observed in this sample. On the basis of olfactory measurement, our data are consistent with the proposal that PD starts as an acute event, followed by further disease progression more rapid than simple aging. © 2007 Movement Disorder Society     

Differential effect of environmental risk factors on postural instability gait difficulties and tremor dominant Parkinson's disease

Both environmental and genetic factors contribute to the development of Parkinson's disease (PD). We have examined environmental risk factors in a Norwegian population of incident PD patients and controls, the Norwegian ParkWest study. All five neurological wards in the study area of Western Norway participated in the study. A 4‐step diagnostic procedure was used to establish a representative cohort of patients with incident PD at a high level of diagnostic accuracy. 212 incident PD patients and 175 age‐ and gender‐matched controls were included. PD patients and controls were asked for information on occupation, education, exposure to pesticides, tobacco, alcohol, and caffeine. Agricultural work was associated with a higher risk of PD (OR 1.75 (1.03–3.0) P = 0.009). There were no differences as to other occupations. Smoking (OR 0.63 (0.42–0.95) P = 0.016) and alcohol use (OR 0.55 P = 0.008) were associated with a lower risk for PD. Interestingly, this inverse association was only seen in postural instability gait difficulties (PIGD) PD (P = 0.046 for smoking, P = 0.07 for alcohol consumption), and not in tremor dominant (TD) PD which was similar to controls. Consumption of coffee was lower in PD patients (3.3 ± 1.8 cups per day vs. 3.8 ± 2.0 in controls P = 0.02). In the regression model including intake of alcohol, coffee, and smoke, only coffee (P = 0.007) and alcohol intake (P = 0.021) remained significant whereas smoking was no longer significant. Thus, it seems as though only coffee intake reduces the risk of PD in general while associations to alcohol and smoking differ between PIGD and TD‐PD patients. © 2010 Movement Disorder Society     

Association of coffee consumption and striatal volume in patients with Parkinson's disease and healthy controls

Background

Mounting studies have demonstrated that coffee consumption significantly reduces the risk of developing Parkinson's disease (PD). However, there have been few investigations about the role of chronic coffee consumption in nigrostriatal structural neurodegeneration in PD. We aimed to investigate whether chronic coffee consumption is associated with the change in striatal volume in PD.

Methods

In this study, 130 de novo patients with PD and 69 healthy controls were enrolled from the Parkinson's Progression Markers Initiative cohort. Patients with PD and healthy controls were, respectively, divided into three subgroups, including current, ever, and never coffee consumers. Then, striatal volume was compared across the three subgroups. Correlation analyses were performed to assess the relationship between cups consumed per day and striatal volume. Furthermore, we included the factors that may have influenced nigrostriatal dopaminergic neurons in multiple linear regression analyses to identify significant contributing factors to striatal volume in each investigated striatal region.

Results

Current coffee consumers had decreased striatal volume compared with ever consumers in controls but not patients with PD. Furthermore, the correlation analyses revealed that cups per day were negatively correlated with striatal volume in current consumers of patients with PD and controls. In addition, multiple linear regression analyses showed that current coffee consumption remained as an independent predictor of a decrease in striatal volume in controls.

Conclusions

Our study showed that chronic coffee consumption was negatively correlated with striatal volume. In addition, our study showed that chronic coffee consumption was associated with the change in striatal volume in current—rather than ever coffee consumers, which suggests that the chronic effects of caffeine on striatal morphology may fade and even compensate after quitting coffee. Our study provides evidence for the effect of chronic coffee consumption on striatal volume in human brain in vivo.     

Olfactory impairment in Parkinson's disease and white matter abnormalities in central olfactory areas: A voxel‐based diffusion tensor imaging study

Olfactory dysfunction is known to occur before the appearance of the classical motor signs in Parkinson's disease (PD) and diffusion tensor imaging (DTI) studies in PD have reported fractional anisotropy (FA) reductions in the early disease stages. We aimed to investigate the relationship between olfactory dysfunction and white matter (WM) FA of central olfactory areas in early PD. Twenty‐four patients at Hoehn and Yahr stages I and II and 24 healthy controls matched by age, gender and years of education participated in this study. DTI was acquired at a 3 Tesla scanner and odor identification was assessed using the University of Pennsylvania Smell Identification Test (UPSIT). We performed FA voxelwise group comparisons in the central olfactory structures using tract‐based spatial statistics (TBSS) and correlation analyses between FA values in these central olfactory areas and UPSIT scores. Patients with severe microsmia (UPSIT between 19 and 25) and anosmia (UPSIT lower or equal to 18) had lower FA values than PD patients with mild/moderate or no olfactory dysfunction (UPSIT between 26 and 40) and healthy controls in the WM adjacent to gyrus rectus. In addition, patients with anosmia had reduced FA in the WM surrounding primary olfactory areas in comparison with healthy controls. FA values in the WM adjacent to primary olfactory cortex and right gyrus rectus correlated with UPSIT scores in the PD group. This study demonstrates, for the first time, that microstructural WM reductions are present in the central olfactory system of early stage PD patients and that these reductions are associated with reduced ability to smell. © 2010 Movement Disorder Society     

Alcohol consumption and the incidence of Parkinson's disease

Cigarette smoking and caffeine consumption are associated with a decreased incidence of Parkinson's disease (PD). This inverse association may result from neuroprotective effects of cigarette smoke and caffeine, or from a disinclination of future PD patients to engage in habituating behaviors. We investigated the association between consumption of alcoholic beverages, another potentially habituating behavior, and risk of PD in two large prospective cohorts Nurses' Health Study, and Health Professionals' Follow-up Study. We detected 415 new cases of PD during follow-up. Compared with nondrinkers at baseline, the relative rate (95% confidence interval) was 1.0 (0.8-1.3) for drinkers of less than 5 gm/day, 1.0 (0.8-1.4) for 5 to less than 15 gm/day, 1.1 (0.8-1.6) for 15 to less than 30 gm/day, and 0.7 (0.5-1.2) for 30 gm/day or more (p for trend = 0.45). Consumption of wine or liquor was not associated with the incidence of PD. Compared with those who consumed beer less than once per month, the relative rate (95% confidence interval) was 0.7 (0.5-0.9) for one to three drinks of beer per month, and 0.7 (0.5, 0.9) for one or more drinks of beer per week. The risk of PD was similar in individuals who usually consume moderate amounts of alcohol and in abstainers.     

Familial aggregation of early- and late-onset Parkinson's disease

The role of heredity in early- versus late-onset Parkinson's disease (PD) is controversial. We estimated the degree of increased risk of PD in first-degree relatives of 221 PD probands with age of onset 50 years or younger and 266 PD probands with age of onset older than 50 years compared with the first-degree relatives of 409 control probands. Risk of PD was similar among first-degree relatives of early-onset PD probands (risk ratio [RR], 2.9; 95% confidence interval [CI], 1.6-5.0; p = 0.0002) and late-onset PD probands (RR, 2.7; 95% CI, 1.6-4.4; p = 0.0002) when each was compared with first-degree relatives of controls. However, siblings of early-onset PD probands were at markedly increased risk of PD compared with siblings of controls (RR, 7.9; 95% CI, 2.5-25.5; p = 0.0005), whereas parents of early-onset PD probands were not at significantly increased risk compared with parents of controls (RR, 1.7; 95% CI, 0.9-3.3; p = 0.2). In late-onset families, both siblings (RR, 3.6; 95% CI, 1.3-10.3; p = 0.02) and parents (RR, 2.5; 95% CI, 1.4-4.6; p = 0.003) were at increased risk compared with control relatives. This pattern is consistent with an autosomal recessive contribution to the inheritance of early but not late-onset PD. Genetic factors are important in both early- and late-onset PD, but specific genes and mode of inheritance may differ between the two groups.     

Parkinson's disease, smoking and family history

There is growing evidence that both genetic and environmental factors play a role in the etiology of Parkinson's disease (PD). The hypothesis of an interaction between genetic and environmental risk factors has been little explored, and never using a population-based case-control study design. Our objective was to investigate the possible interaction between smoking and family history in the etiology of PD, as a part of a collaborative population-based case-control study. We included 149 nondemented PD patients ascertained in three European prevalence surveys using a two-phase design. Each patient was matched by age (±2 years), gender, and center to three controls drawn from the same populations (n=375). Presence of PD among first-degree relatives and smoking history were assessed through an interview for 127 cased and 306 controls. In the overall sample we found suggestive evidence that family history and eversmoking interact in determining the risk of PD (P=0.09), with individuals exposed to both risk factors having the highest risk (OR=10.0; 95% CI=2.0–49.6). Analyses were repeated after stratification into two age-groups (cutoff: 75 years). In older patients, the joint exposure to both risk factors was associated with a significant increase in the risk of PD (OR=17.6; 95% CI=1.9–160.5). Among younger subjects, the OR for joint exposure was not significant. In conclusion, our findings suggest that smoking and family history interact synergistically on a multiplicative scale in determining the risk of PD in individuals older than 75 years. Received: 28 January 2000 / Received in revised form: 1 May 2000 / Accepted: 28 May 2000     

Alcohol and risk of Parkinson's disease in a large, prospective cohort of men and women

Addictive behaviors, such as cigarette smoking and coffee drinking, have been associated with a reduced risk of Parkinson's disease (PD). Whether alcohol consumption is also associated with PD risk is less certain. We prospectively followed 132,403 participants in the Cancer Prevention Study II Nutrition Cohort from 1992 to 2005. Alcohol intake was assessed at baseline. Incident cases of PD (n = 605; 389 male and 216 female) were confirmed by treating physicians and medical record review. Relative risks (RRs) were estimated using proportional hazards models, adjusting for age, smoking, and other risk factors. Alcohol consumption was not significantly associated with PD risk. After adjustment for age, smoking, and other risk factors, the RR comparing men consuming 30 or more grams of alcohol per day (highest category) to nondrinker men was 1.29 (95% confidence interval [CI]: 0.90, 1.86; P trend: 0.40), and the RR comparing women consuming 15 or more grams of alcohol (highest category) per day to nondrinker women was 0.77 (95% CI: 0.41, 1.45; P trend: 0.87). Consumption of beer, wine, or liquor was also not associated with PD risk. The results of this large, prospective study do not support an association between alcohol intake and risk of PD.     

Coffee and tea consumption and the risk of Parkinson's disease.

Several prospective studies have assessed the association between coffee consumption and Parkinson's disease (PD) risk, but the results are inconsistent. We examined the association of coffee and tea consumption with the risk of incident PD among 29,335 Finnish subjects aged 25 to 74 years without a history of PD at baseline. During a mean follow-up of 12.9 years, 102 men and 98 women developed an incident PD. The multivariate-adjusted (age, body mass index, systolic blood pressure, total cholesterol, education, leisure-time physical activity, smoking, alcohol and tea consumption, and history of diabetes) hazard ratios (HRs) of PD associated with the amount of coffee consumed daily (0, 1-4, and > or = 5 cups) were 1.00, 0.55, and 0.41 (P for trend = 0.063) in men, 1.00, 0.50, and 0.39 (P for trend = 0.073) in women, and 1.00, 0.53, and 0.40 (P for trend = 0.005) in men and women combined (adjusted also for sex), respectively. In both sexes combined, the multivariate-adjusted HRs of PD for subjects drinking > or = 3 cups of tea daily compared with tea nondrinkers was 0.41 (95% CI 0.20-0.83). These results suggest that coffee drinking is associated with a lower risk of PD. More tea drinking is associated with a lower risk of PD.     

Parkinson's disease and environmental factors. Matched case-control study in the Limousin region, France

The study included 140 patients with Parkinson's disease (PD) and 280 non-Parkinson age-matched controls to evaluate environmental risk factors associated with PD. The effect of exposure to environmental and dietary factors was determined using conditional logistic regression. This multivariate analysis showed that PD in first-degree relatives and tea drinking were the main risk factors for PD. Smoking appeared to be a protective factor. Exposure to toxic compounds was not a significant risk factor. Further research is needed to validate that tea consumption increases the risk of PD.     

Motor and non-motor correlates of olfactory dysfunction in Parkinson's disease

Hyposmia is highly prevalent in the motor phase of Parkinson's disease (PD) and is an established pre-motor sign of PD that may precede the onset of motor symptoms by as long as 5 years. The data presented here are part of an ongoing study to determine the relationship of the olfactory deficit in PD with both motor and non-motor features of the disease. The study population so far includes 96 patients with a clinical diagnosis of PD (UK PD Society Brain Bank criteria; mean age 64.9 years; mean disease duration 4.8 years). Olfactory testing was performed using the 40-item UPSIT. We analyzed the relationship between UPSIT scores and measures of motor (disease duration, stage and severity) and non-motor (cognitive function, depression, anxiety and sleep) function. In 60 PD patients, [(123)I]FP-CIT SPECT scans were available to assess the relationship between UPSIT scores and striatal dopamine transporter (DAT) binding. Preliminary analyses revealed correlations of the olfactory deficit in PD with both motor and non-motor features, as well as with striatal DAT binding. These data suggest that the olfactory deficit in PD is not stationary by the time the motor phase is entered, but continues to progress over time. Hyposmia may therefore be useful as a marker of disease progression, at least in the early disease stages.     

Prospective study of caffeine consumption and risk of Parkinson's disease in men and women.

Results of case-control studies and of a prospective investigation in men suggest that consumption of coffee could protect against the risk of Parkinson's disease, but the active constituent is not clear. To address the hypothesis that caffeine is protective against Parkinson's disease, we examined the relationship of coffee and caffeine consumption to the risk of this disease among participants in two ongoing cohorts, the Health Professionals' Follow-Up Study (HPFS) and the Nurses' Health Study (NHS). The study population comprised 47,351 men and 88,565 women who were free of Parkinson's disease, stroke, or cancer at baseline. A comprehensive life style and dietary questionnaire was completed by the participants at baseline and updated every two to four years. During the follow-up (10 years in men, 16 years in women), we documented a total of 288 incident cases of Parkinson's disease. Among men, after adjustment for age and smoking, the relative risk of Parkinson's disease was 0.42 (95% CI: 0.23-0.78; p for trend < 0.001) for men in the top one-fifth of caffeine intake compared to those in the bottom one-fifth. An inverse association was also observed with consumption of coffee (p for trend = 0.004), caffeine from noncoffee sources (p for trend < 0.001), and tea (p for trend = 0.02) but not decaffeinated coffee. Among women, the relationship between caffeine or coffee intake and risk of Parkinson's disease was U-shaped, with the lowest risk observed at moderate intakes (1-3 cups of coffee/day, or the third quintile of caffeine consumption). These results support a possible protective effect of moderate doses of caffeine on risk of Parkinson's disease.     

Increased risk of essential tremor in first-degree relatives of patients with Parkinson's disease.

We conducted a historical cohort study of 981 first-degree relatives of 162 patients with Parkinson's disease (PD) and of 838 first-degree relatives of 147 controls representative of the population of Olmsted County, Minnesota. In addition, we studied 2,684 first-degree relatives of 411 patients with PD referred to the Mayo Clinic. Relatives were interviewed and screened for tremor either directly or through a proxy, and those who screened positive were examined or copies of their medical records were obtained to confirm the diagnosis of essential tremor (ET). We also obtained ET information from a medical records-linkage system (family study method). In the population-based sample, the risk of ET was significantly increased for relatives of patients with onset of PD相似文献   

Risk of Alzheimer's disease in relatives of Parkinson's disease patients with and without dementia

OBJECTIVE: To determine whether first-degree relatives of PD patients with dementia were at increased risk for the development of AD compared with first-degree relatives of nondemented PD patients and nondemented normal subjects from the community. METHODS: A structured family history interview was administered to 146 nondemented PD patients, 120 patients with PD and dementia, and 903 normal subjects from the community to ascertain the presence of AD among parents and siblings of these subjects. Cox proportional hazards models with double censoring techniques for missing information were used to model the risk of AD among relatives. RESULTS: No increase in risk of AD was found among parents of patients with PD and dementia or parents of nondemented PD patients compared with parents of normal subjects. However, siblings of demented PD patients were three times as likely (relative risk [RR] = 3.2, 95% confidence interval [CI] = 1.1 to 9.4, p < 0.04) as siblings of normal subjects to develop AD. When only siblings >65 years of age were considered, there was a fivefold increase in risk of AD among siblings of demented PD patients compared with siblings of normal subjects (RR = 4.9, 95% CI = 1.1 to 21.4, p < 0.03). The risk of AD was also increased for female relatives, regardless of whether the woman was a relative of a demented PD patient, a nondemented PD patient, or a normal subject. Ethnicity and APOE genotype did not affect dementia status among relatives. CONCLUSIONS: The increased risk of AD in siblings of demented PD patients compared with siblings of normal subjects supports the possibility of familial aggregation of AD and PD with dementia.     

Odor identification deficits are associated with increased risk of neuropsychiatric complications in patients with Parkinson's disease

Olfactory deficits appear early in the course of Parkinson's disease (PD) but their prognostic significance is not known. The goal of this study was to determine whether the severity of olfactory impairment is associated with subsequent risk of developing complications of PD. One hundred patients with PD self‐administered the University of Pennsylvania Smell Identification Test (UPSIT). Testing was done, on average, 3.6 years from the time of initial diagnosis. The incidence of neuropsychiatric features of PD, including cognitive decline and visual hallucinations, was ascertained through chart review after an average of 6.8 years of follow‐up. Incidence of motor outcomes including falls and dyskinesias was also obtained. There was a significant trend for increased risk of neuropsychiatric complications across declining quartiles of olfactory test scores. In addition, subjects in the lowest quartile of olfactory performance had a significantly higher adjusted risk of hallucinations (HR = 4.70, 95% CI 1.64, 13.42) and cognitive decline (HR = 3.10, 95% CI 1.05, 9.21) than those in the reference quartile. There was no association between olfactory dysfunction and dyskinesias, and a very modest association with risk of falls. These findings suggest that severity of olfactory impairment early in the disease course may be a useful marker for the risk of neuropsychiatric complications of PD. © 2010 Movement Disorder Society     

Caffeine and risk of Parkinson's disease in a large cohort of men and women

Caffeine consumption has been associated with a reduced risk of Parkinson's disease (PD). The association is strong and consistent in men, but uncertain in women, possibly because of an interaction with hormone replacement therapy (HRT). We sought to confirm these findings using data on PD incidence in the Cancer Prevention Study II Nutrition Cohort (CPS II-Nutrition), a large, prospective study of men and women. We conducted a prospective study of caffeine intake and risk of PD within the CPS II Nutrition Cohort. Intakes of coffee and other sources of caffeine were assessed at baseline. Incident cases of PD (n = 317; 197 men and 120 women) were confirmed by treating physicians and medical record review. Relative risks (RRs) were estimated using proportional hazards models, adjusting for age, smoking, and alcohol consumption. After adjustment for age, smoking, and alcohol intake, high caffeine consumption was associated with a reduced risk of PD. The RR comparing the 5th to the 1st quintile of caffeine intake was 0.43 (95% confidence interval [CI]: 0.26, 0.71; P trend = <0.002) in men, and 0.61 (95% CI: 0.34, 1.09; P trend = 0.05) in women. Among women, this association was stronger among never users of HRT (RR = 0.32) than among ever users (RR = 0.81; P interaction = 0.15). Consumption of decaffeinated coffee was not associated with PD risk. Findings from this large, prospective study of men and women are consistent with a protective effect of caffeine intake on PD incidence, with an attenuating influence of HRT in women. ? 2012 Movement Disorder Society.     

Nongenetic causes of Parkinson's disease

Study of the nongenetic causes of Parkinson's disease (PD) was encouraged by discovery of a cluster of parkinsonism produced by neurotoxic pyridine 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the 1980s. Since that time, epidemiologic investigations have suggested risk factors, though their results do not establish causality. Pesticide exposure has been associated with increased risk in many studies. Other proposed risks include rural residence and certain occupations. Cigarette smoking, use of coffee/caffeine, and non-steroidal antiinflammatory drugs (NSAIDs) all appear to lower risk of PD, while dietary lipid and milk consumption, high caloric intake, and head trauma may increase risk. The cause of PD is likely multifactorial. Underlying genetic susceptibility and combinations of risk and protective factors likely all contribute. The combined research effort by epidemiologists, geneticists, and basic scientists will be needed to clarify the cause(s) of PD.     

Dose-dependent protective effect of coffee, tea, and smoking in Parkinson's disease: a study in ethnic Chinese

INTRODUCTION: Few studies have examined the relationship of coffee and tea in Parkinson's disease (PD). The potential protective effect of coffee intake and risk of PD has not been studied in a Chinese population. There is a high prevalence of caffeine takers among Chinese in our population. OBJECTIVE: We undertook a case control study to examine the relationship between coffee and tea drinking, cigarette smoking, and other enviromental factors and risk of PD among ethnic Chinese in our population. METHODS AND RESULTS: 300 PD and 500 population controls were initially screened. Two hundred case control pairs matched for age, gender, and race were finally included in the analysis. Univariate analysis revealed significant association of PD with coffee drinking (p<0.0005), tea drinking (p=0.019), alcohol drinking (p=0.001), cigarette smoking (p<0.0005), and exposure to heavy metals (p=0.006). Conditional logistic regression analysis demonstrated that amount of coffee drunk (OR 0.787, 95%CI 0.664-0.932, p=0.006), amount of tea drunk (OR 0.724, 95%CI 0.559-0.937, p=0.014), number of cigarettes smoked (OR 0.384, 95%CI 0.204-0.722, p=0.003), history of heavy metal and toxin exposure (OR 11.837, 95%CI 1.075-130.366, p=0.044), and heart disease (OR 5.518, 95%CI 1.377-22.116, p=0.016) to be significant factors associated with PD. One unit of coffee and tea (3 cups/day for 10 years) would lead to a 22% and 28% risk reduction of PD. One unit of cigarette smoke (3 packs/day for 10 years) reduced the risk of PD by 62%. CONCLUSIONS: We demonstrated a dose-dependent protective effect of PD in coffee and tea drinkers and smokers in an ethnic Chinese population. A history of exposure to heavy metals increased the risk of PD, supporting the multifactorial etiologies of the disease.