Lower Risk Of Parkinson's Disease Research Articles

Dietary nicotine intake and risk of Parkinson disease: a prospective study

Tobacco use was observed to be associated with a lower risk of Parkinson disease (PD) in previous epidemiologic studies, with nicotine as a potential candidate. The association between dietary nicotine and PD risk has, however, not been examined in prospective studies yet. We aimed to examine prospectively the association between dietary nicotine intake and subsequent PD risk among never-smokers. The current study was based on never-smoker participants from 2 large prospective cohorts: the Nurses' Health Study (n=31,615) and the Health Professionals Follow-up Study (n=19,523). The studies contained information on dietary nicotine intake from 1986 from validated FFQs. Dietary nicotine intake was calculated based on consumption of peppers, tomatoes, processed tomatoes, potatoes, and tea. Incident cases of PD were identified via questionnaires and subsequently confirmed by reviewing medical records. We used Cox proportional hazard models to calculate cohort-specific HRs, and used fixed-effects models to calculate the pooled HR. During 26 y of follow-up, we identified 601 incident PD cases (296 women and 305 men). After adjusting for potential covariates, the pooled HR for the highest compared with the lowest quintile of dietary nicotine intake was 0.70 (95% CI: 0.51, 0.94). The significant inverse association was, however, only observed in women (adjusted HR: 0.64; 95% CI: 0.42, 0.96), not in men (adjusted HR: 0.77; 95% CI: 0.50, 1.20). Further adjusting for environmental tobacco smoke exposure, family history of PD, and use of ibuprofen generated similar significant results in women. Consistently, greater consumption of peppers was associated with lower risk of PD (adjusted HR for ≥5 times/wk compared with ≤3 times/mo: 0.49; 95% CI: 0.25, 0.94) in women but not in men (adjusted HR: 1.04; 95% CI: 0.57, 1.90). Women with greater dietary nicotine intake had a lower risk of PD than those with lower intake.

Diet Quality and Risk of Parkinson Disease: A Prospective Study and a Meta-Analysis

Abstract Objectives Several dietary components have been shown to be neuroprotective against risk of neurodegeneration. We thus examined the associations between diet quality and risk of Parkinson disease (PD) in a prospective cohort study and a meta-analysis. Methods Included in the cohort study were 3653 participants (1519 men and 2134 women; mean age: 81.5 years) in the Geisinger Rural Aging Study longitudinal cohort in Pennsylvania. Diet quality was assessed using a validated dietary screening tool containing 25 food- and behavior-specific questions in 2009 (baseline). Potential PD cases were identified using electronic health records based on ICD10 code (G20) and PD-related treatments. Incident PD cases were defined as being diagnosed after 1 year of follow-up and receiving PD-related medication treatments. Hazard ratios (HRs) and 95% confidence intervals (CIs) across diet quality tertiles were calculated using cox proportional hazards models after adjusting for age, sex, race, educational level, smoking, oral health, obesity and living arrangement. We further performed a meta-analysis by pooling our study with four published papers on this topic. Random-effects model was utilized to calculate the pooled risk ratios and 95% CIs. Results During a mean of 6.94 years of follow-up, 47 incident PD cases were documented. Having high diet quality at baseline was associated with lower PD risk (p-trend = 0.02). The adjusted HR was 0.39 (95% CI: 0.17–0.89) for the highest vs the lowest diet quality tertiles. The meta-analysis including 140,617 individuals also showed that adherence to a healthy dietary pattern was associated with lower risk of incident PD (pooled risk ratio = 0.64; 95% CI: 0.49–0.83). Conclusions Having high diet quality was associated with lower future risk of PD. Funding Sources United States Department of Agriculture, Agricultural Research Service agreement.

Editors' note: Use of β2-adrenoreceptor agonist and antagonist drugs and risk of Parkinson disease

According to epidemiologic data, use of β2-adrenoreceptor agonists has been associated with a significant, and dose-dependent, lower risk of Parkinson disease (PD). Similarly, β2 antagonists have been associated with a higher risk of developing α-synucleinopathy. In an attempt to corroborate these findings, Drs. Hopfner et al. examined population-based data from the Danish health registries. The investigators observed that β2 antagonist use was strongly associated with PD risk, whereas β2 agonists strongly correlated with a lower PD risk. However, potential confounders to these results are the following novel observations: First, driving the effect of β2 antagonists and later PD is the use of propranolol, which the investigators believe may have been used (perhaps incorrectly) to treat essential tremor (ET). Thus, the authors contend that early PD may have been misdiagnosed as ET in these cases. Second, the most common indication for inhaled β2 agonist use in an older population is chronic obstructive pulmonary disease due to tobacco use. As cigarette use has been associated with a reduced risk of PD, it may be that smoking is the actual factor related to the development of PD and not β2 agonist use. Supporting this claim are the findings that COPD diagnosis and use of inhaled anticholinergics were also inversely and independently related to PD. That said, the use of a β2 agonist remains a significant negative predictor of PD in the fully adjusted model, as was noted by Drs. Scherzer et al. in their comment. Drs. Scherzer et al. also maintain that other large studies (which adjusted for tobacco use) have corroborated the β2 agonist hypothesis. The original authors stand by their conclusions that a relationship cannot be decisively confirmed in the present data set given that biomarkers of long-term smoking significantly interact with their outcomes, and that a dose-response and temporal relationship between β2AR remains ambiguous. According to epidemiologic data, use of β2-adrenoreceptor agonists has been associated with a significant, and dose-dependent, lower risk of Parkinson disease (PD). Similarly, β2 antagonists have been associated with a higher risk of developing α-synucleinopathy. In an attempt to corroborate these findings, Drs. Hopfner et al. examined population-based data from the Danish health registries. The investigators observed that β2 antagonist use was strongly associated with PD risk, whereas β2 agonists strongly correlated with a lower PD risk. However, potential confounders to these results are the following novel observations: First, driving the effect of β2 antagonists and later PD is the use of propranolol, which the investigators believe may have been used (perhaps incorrectly) to treat essential tremor (ET). Thus, the authors contend that early PD may have been misdiagnosed as ET in these cases. Second, the most common indication for inhaled β2 agonist use in an older population is chronic obstructive pulmonary disease due to tobacco use. As cigarette use has been associated with a reduced risk of PD, it may be that smoking is the actual factor related to the development of PD and not β2 agonist use. Supporting this claim are the findings that COPD diagnosis and use of inhaled anticholinergics were also inversely and independently related to PD. That said, the use of a β2 agonist remains a significant negative predictor of PD in the fully adjusted model, as was noted by Drs. Scherzer et al. in their comment. Drs. Scherzer et al. also maintain that other large studies (which adjusted for tobacco use) have corroborated the β2 agonist hypothesis. The original authors stand by their conclusions that a relationship cannot be decisively confirmed in the present data set given that biomarkers of long-term smoking significantly interact with their outcomes, and that a dose-response and temporal relationship between β2AR remains ambiguous.

Tobacco smoking and the risk of Parkinson disease: A 65-year follow-up of 30,000 male British doctors.

ObjectiveTo investigate the causal relevance of current tobacco smoking for the risk of Parkinson disease (PD).MethodsWe compared the risks of death from PD with smoking habits in 30,000 male doctors in the British Doctors cohort study in 1951 and in survivors who had been resurveyed periodically for 5 decades. Cause-specific mortality was monitored for 65 years and included 283 deaths from PD. The relative risks (RRs) of PD (and 95% confidence intervals [CIs]) were estimated using Cox models for smoking habits (smoking status, amount smoked, and years since quitting) at baseline or updated habits at resurvey.ResultsThe prevalence of current smoking declined progressively during follow-up from 67% to 8% between 1951 and 1998. The crude rates of PD death were lower in current smokers than in never smokers at baseline (30 vs 46/100,000 persons-years). After adjustment for age at risk, current smokers at baseline had a 30% lower risk of PD (RR 0.71; 95% CI 0.60–0.84), and continuing smokers classified using updated smoking habits at resurvey had a 40% lower risk (RR 0.60; 95% CI 0.46–0.77) of PD compared with never smokers. The risks of PD were inversely associated with the amount of tobacco smoked. The protective effect of current smoking vs never smoking for PD was attenuated by increasing duration since quitting smoking.ConclusionsIn contrast to previous suggestions, the present report demonstrates a causally protective effect of current smoking on the risk of PD, which may provide insights into the etiology of PD.

Sex differences in smoking, alcohol consumption, and risk of Parkinson's disease: A nationwide cohort study

ObjectiveWe assessed the influence of sex on the effects of smoking and alcohol consumption on the risk of Parkinson's disease (PD). MethodsThis population-based cohort study examined data of 6,795,816 Koreans aged ≥40 years from the Korean National Health Insurance Service database who completed a national program for general health check-up at 2009. For a maximum 9 years’ observation period, incident PD was tracked, and hazard ratios and 95% confidence intervals (CIs) were computed using the Cox proportional hazard models, adjusted for potential confounding factors for each sex group. We tested interactions on the addictive scale by estimating the relative excess risk due to interaction (RERI). Results3,400,538 men and 3,395,278 women generated 24,365,694 and 24,754,154 person-years, respectively. A total of 13,223 men (0.39%) and 14,818 women (0.44%) developed PD during follow-up. Current smoking and alcohol independently reduced the risk of PD in both sexes. Current male smokers tended to have a lower risk of PD than current female smokers at equal smoking intensity (P < 0.0001 for interaction) and duration (P < 0.0001 for interaction). In contrast, at equal alcohol intakes, PD risk tended to be lower in female drinkers than in male drinkers (P < 0.0001 for interaction). A superadditive interaction between smoking and alcohol was found in current male smokers (RERI, 0.19; 95% CI, 0.04 to 0.34; P = 0.015) and female ex-smokers (RERI, 0.42; 95% CI, 0.09 to 0.76; P = 0.014). ConclusionOur data suggest sex-related differences in individual and joint impacts of smoking and alcohol intake on the risk of PD.

Peripheral immune biomarkers and neurodegenerative diseases: A prospective cohort study with 20 years of follow-up.

To assess the associations of several blood immune biomarkers with the future risks of amyotrophic lateral sclerosis and Parkinson disease in a prospective cohort study with 20 years of follow-up. The Swedish Apolipoprotein-Related Mortality Risk study is a longitudinal cohort study including 812,073 participants with repeated blood biomarker measurements between 1985 and 1996 and a follow-up until 2011. Using a Cox model, we first estimated hazard ratios of amyotrophic lateral sclerosis and Parkinson disease in relation to leukocytes, immunoglobulin G, haptoglobin, and uric acid. We further described the temporal changes of these biomarkers during the 20 years prior to the diagnosis of these diseases. A total of 585 incident cases of amyotrophic lateral sclerosis and 3,769 incident cases of Parkinson disease were identified during the follow-up. Increasing concentrations of leukocytes, haptoglobin, and uric acid were associated with a lower risk of Parkinson disease. No statistically significant association was, however, noted between the studied biomarkers and amyotrophic lateral sclerosis. Parkinson disease patients appeared to have lower levels of leukocytes and haptoglobin between 20 and 10 years before diagnosis and lower levels of uric acid during the 20 years before diagnosis, compared to controls, although statistically significant differences were only noted during parts of the respective time intervals after multivariable adjustment. No clear differences were noted between patients with amyotrophic lateral sclerosis and controls. If verified in studies of independent populations, our findings may suggest a different role of systemic inflammation on the risk of Parkinson disease compared to amyotrophic lateral sclerosis. ANN NEUROL 2019;86:913-926.

Transplant and risk of Parkinson disease

IntroductionThe pathophysiology of Parkinson's disease (PD) remains unclear, but growing evidence supports a role of neuroinflammation. The purpose of this study was to investigate the association between tissue transplantation and PD risk, given the importance of immunosuppressants in post-transplant management. MethodsWe performed a case-control study among Medicare beneficiaries age 66–90 using claims from 2004 to 2009. We used International Classification of Diseases, Ninth Edition (ICD-9) and Current Procedural Terminology (CPT) codes to identify PD (89,790 incident cases, 118,095 population-based controls) and history of tissue transplant (kidney, heart, liver, lung, and bone marrow). We investigated risk of PD in relation to tissue transplant in logistic regression models, adjusting for age, sex, race, smoking, and overall use of medical care. ResultsBeneficiaries who had received a tissue transplant at least five years prior to PD diagnosis or reference had a lower risk of PD (odds ratio [OR] 0.63, 95% confidence interval [CI] 0.53, 0.75) than those without tissue transplant. This inverse association was observed for kidney (OR 0.63, 95% CI 0.47, 0.84), heart (OR 0.58, 95% CI 0.40, 0.83), lung (OR 0.41, 95% CI 0.21, 0.77), and bone marrow (OR 0.57, 95% 0.38, 0.85) transplants. Associations were attenuated, but remained, following adjustment for indications for the respective type of transplant. Liver transplant was not associated with PD risk. ConclusionsPatients undergoing tissue transplant may have a lower risk of developing PD than the general population. Further studies are needed to determine if this association is causal and if immunosuppressants mediate this association.

Plasma urate and risk of Parkinson's disease: A mendelian randomization study.

Urate is a potent antioxidant, and high plasma urate has been associated with lower incidence of Parkinson's disease (PD) in epidemiological studies. We tested the hypothesis that high concentrations of plasma urate are associated with low incidence of PD. We performed observational and genetic analyses using plasma urate and the urate SLC2A9 rs7442295 and ABCG2 rs2231142 genotype in >102,000 individuals from the CGPS (Copenhagen General Population Study). Information on PD and mortality was from national patient and death registries. Incidences of PD were calculated using Cox regression, Fine and Gray competing-risks regression, and instrumental variable analyses. In total, 398 individuals were diagnosed with PD, of which 285 were incident cases. The multivariable adjusted hazard ratio for PD was 0.56 (95% confidence interval [CI], 0.41-0.77) for the highest versus the lowest tertile of plasma urate (p for trend across 3 groups, 8 × 10-5 ). Each one-allele increase in the combined allele score was associated with 19μmol/l (95% CI, 18.5-19.9) higher plasma urate. In observational analyses, a 50μmol/l higher plasma urate was associated with a hazard ratio of 0.85 (0.77-0.92) for PD; in instrumental variable analyses, 50μmol/l higher plasma urate was associated with an odds ratio of 1.20 (0.85-1.71) for PD. High plasma urate was associated with lower risk of PD in observational analyses; however, in instrumental variable analysis, high plasma urate was not associated with low risk of PD. Thus, our data do not support a causal relationship between high plasma urate and low risk of PD. Ann Neurol 2018;84:178-190.

Higher serum cholesterol and decreased Parkinson's disease risk: A statin-free cohort study.

Higher levels of serum cholesterol are well-established risk factors for coronary artery disease and stroke. The role of serum cholesterol in neurodegeneration is not clear. We evaluated the association between serum cholesterol levels over time and the risk of Parkinson's disease (PD) among statin-free individuals. A population-based cohort study of 261,638 statin-free individuals (aged 40-79 years at their first serum cholesterol test, 42.7% men), with repeated measures of total, low, and high-density lipoprotein cholesterol was performed from 1999 to 2012. Individuals were followed from their first cholesterol test until PD incidence, death, or end of study. The PD incidence was assessed using a validated antiparkinsonian-drug tracing approach. Cox models stratified by sex and age with time-dependent cholesterol variables were applied to estimate PD hazard ratios. A total of 764 (3.3% patients aged 65 + years) incident PD cases were detected during a mean follow-up of 7.9 (±3.6) years. Among men, the middle and upper tertiles of total and low-density lipoprotein cholesterol compared to the lowest were significantly associated with a lower PD risk. Age-pooled hazard ratios (95% confidence interval) for middle and upper tertiles were 0.82 (0.66-1.01) and 0.71 (0.55-0.93), respectively, for total cholesterol, and 0.80 (0.65-0.98) and 0.72 (0.54-0.95) respectively, for low-density lipoprotein cholesterol. Among women, the association between total and low-density lipoprotein cholesterol levels with PD risk was not significant. Null results were found for both sexes for high-density lipoprotein cholesterol. Higher levels of total and low-density lipoprotein cholesterol among men over time indicated a decreased PD risk. The potential role of cholesterol in disease protection warrants further investigation. © 2018 International Parkinson and Movement Disorder Society.

Immunosuppressants and risk of Parkinson disease.

We performed a population‐based case–control study of United States Medicare beneficiaries age 60–90 in 2009 with prescription data (48,295 incident Parkinson disease cases and 52,324 controls) to examine the risk of Parkinson disease in relation to use of immunosuppressants. Inosine monophosphate dehydrogenase inhibitors (relative risk = 0.64; 95% confidence interval 0.51–0.79) and corticosteroids (relative risk = 0.80; 95% confidence interval 0.77–0.83) were both associated with a lower risk of Parkinson disease. Inverse associations for both remained after applying a 12‐month exposure lag. Overall, this study provides evidence that use of corticosteroids and inosine monophosphate dehydrogenase inhibitors might lower the risk of Parkinson disease.

Interaction between caffeine and polymorphisms of glutamate ionotropic receptor NMDA type subunit 2A (GRIN2A) and cytochrome P450 1A2 (CYP1A2) on Parkinson's disease risk.

Caffeine intake has been inversely associated with Parkinson's disease (PD) risk. This relationship may be modified by polymorphisms of glutamate ionotropic receptor NMDA type subunit 2A (GRIN2A) and cytochrome P450 1A2 (CYP1A2), but the results of previous studies have been inconsistent. We examined the interaction of caffeine intake with GRIN2A-rs4998386 and CYP1A2-rs762551 polymorphisms in influencing PD risk among 829 incident cases of PD and 2,754 matched controls selected among participants in the following 3 large prospective ongoing cohorts: the Nurses' Health Study, the Health Professionals' Follow-up Study, and the Cancer Prevention Study II Nutrition Cohort. Matching factors included cohort, birth year, source of DNA, date of DNA collection, and race. Relative risks and 95% confidence intervals were estimated using conditional logistic models. Interactions were tested both on the multiplicative scale and on the additive scale. Overall, caffeine intake was associated with a lower PD risk (adjusted relative risk for highest versus lowest tertile = 0.70; 95% confidence interval, 0.57-0.86; p < .001). In analyses stratified by the GRIN2A-rs4998386 genotype, the multivariable-adjusted relative risk of PD comparing the highest to the lowest tertile of caffeine was 0.69 (95% confidence interval, 0.55-0.88; p < .01) among individuals homozygous for the C allele, and 0.85 (95% confidence interval, 0.55-1.32; p = .47; pRERI = .43) among carriers for the T allele. Interactions between caffeine and GRIN2A were not significant in either the multiplicative or additive scales. We also did not observe significant interactions for CYP1A2-rs762551 and incident PD risk. Our findings do not support the hypothesis of an interaction between the GRIN2A-rs4998386 or CYP1A2-rs762551 polymorphism and caffeine intake in determining PD risk. © 2018 International Parkinson and Movement Disorder Society.

Passive smoking and Parkinson's disease in California Teachers

IntroductionTobacco smoking is consistently inversely associated with Parkinson's disease (PD) in men and women; recently this has been related to reverse causation, prompting questions as to whether similar patterns exist for passive smoke exposure. We used baseline and follow-up data from the California Teachers Study, a prospective cohort of women, to investigate whether timing, location and cumulative measures of intensity and duration of passive smoke exposure are associated with PD risk. MethodsUsing a nested case-control approach, we included 224 diagnostically validated cases (158 with no history of personal smoking) and selected 3230 age- and race-matched controls (1973 with no history of personal smoking). We estimated odds ratios(ORs) and 95% confidence intervals(CI) by fitting adjusted multivariable unconditional logistic regression models. ResultsAmong lifelong non-smokers, passive smoke exposure combined across all settings and accumulated over a lifetime was not associated with PD risk (OR = 1.18, 95% CI 0.60, 2.30). Workplace exposure was also not associated with risk. Household exposure during adulthood but not childhood was inversely associated with PD (OR = 0.59, 95% CI 0.40, 0.87). Exposure to passive smoke in other social settings was positively associated with PD (OR = 1.62, 95% CI 1.11, 2.36). These contradictory results may be attributable to chance due to multiple comparisons in subgroup analyses. No pattern emerged to suggest that increasing years of passive smoke exposure, smokiness of the setting, or combined smokiness by exposure years was associated with lower PD risk. ConclusionResults do not convincingly support a protective effect of passive smoking in PD.

Caffeine as symptomatic treatment for Parkinson disease (Café-PD): A randomized trial.

To assess effects of caffeine on Parkinson disease (PD). In this multicenter parallel-group controlled trial, patients with PD with 1-8 years disease duration, Hoehn & Yahr stages I-III, on stable symptomatic therapy were randomized to caffeine 200 mg BID vs matching placebo capsules for 6-18 months. The primary research question was whether objective motor scores would differ at 6 months (Movement Disorder Society-sponsored Unified Parkinson's Disease Rating Scale [MDS-UPDRS]-III, Class I evidence). Secondary outcomes included safety and tolerability, motor symptoms (MDS-UPDRS-II), motor fluctuations, sleep, nonmotor symptoms (MDS-UPDRS-I), cognition (Montreal Cognitive Assessment), and quality of life. Sixty patients received caffeine and 61 placebo. Caffeine was well-tolerated with similar prevalence of side effects as placebo. There was no improvement in motor parkinsonism (the primary outcome) with caffeine treatment compared to placebo (difference between groups -0.48 [95% confidence interval -3.21 to 2.25] points on MDS-UPDRS-III). Similarly, on secondary outcomes, there was no change in motor signs or motor symptoms (MDS-UPDRS-II) at any time point, and no difference on quality of life. There was a slight improvement in somnolence over the first 6 months, which attenuated over time. There was a slight increase in dyskinesia with caffeine (MDS-UPDRS-4.1+4.2 = 0.25 points higher), and caffeine was associated with worse cognitive testing scores (average Montreal Cognitive Assessment = 0.66 [0.01, 1.32] worse than placebo). Caffeine did not provide clinically important improvement of motor manifestations of PD (Class I evidence). Epidemiologic links between caffeine and lower PD risk do not appear to be explained by symptomatic effects. NCT01738178. This study provides Class I evidence that for patients with PD, caffeine does not significantly improve motor manifestations.

Dietary antioxidants and risk of Parkinson's disease in two population-based cohorts.

ABSTRACT Background: A neuroprotective effect of dietary antioxidants on Parkinson's disease (PD) risk has been suggested, but epidemiological evidence is limited. Objectives: To examine the associations between intake of dietary antioxidant vitamins and total antioxidant capacity and risk of PD. Methods: We prospectively assessed the relationships of dietary antioxidant vitamins C and E, ß‐carotene, and total antioxidant capacity with PD risk in two population‐based cohorts (38,937 women and 45,837 men). Results: During a mean 14.9‐year follow‐up period, 1,329 PD cases were identified. Dietary intake of ß‐carotene was associated with a lower risk of PD (hazard ratio: 0.86; 95% confidence interval: 0.78‐0.95; P trend < 0.01 for women and hazard ratio: 0.91; 95% confidence interval: 0.84‐0.99; P trend = 0.05 for men). An inverse association between dietary vitamin E and PD risk was found in women (hazard ratio: 0.87; 95% confidence interval: 0.79‐0.96; P trend = 0.02). Dietary intake of vitamin C was inversely associated with PD risk in women at borderline significance (hazard ratio: 0.91; 95% confidence interval: 0.83‐1.00; P trend = 0.04). There was no association between dietary total antioxidant capacity and PD risk in either women (hazard ratio: 0.93; 95% confidence interval: 0.84‐1.02; P trend = 0.35) or men (hazard ratio: 1.00; 95% confidence interval: 0.93‐1.07; P trend = 0.97). Conclusion: Intake of dietary vitamin E and ß‐carotene was associated with a lower risk of PD. © 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Occupational and recreational physical activity and Parkinson’s disease in Denmark

Objectives This study aimed to examine whether occupational and physical activity (PA) at different ages contribute to Parkinson's disease (PD) risk in a large population-based case-control study in Denmark. Methods We identified 1828 PD patients from the Danish National Hospital Register and recruited 1909 gender and year of birth matched controls from the Danish Central Population Register. Occupational and leisure-time PA were determined from a job exposure matrix based on occupational history and self-reported leisure-time information. Results No association was found for occupational PA alone in men, but higher leisure-time PA (≥5 hours/week of strenuous activities) in young adulthood (15-25 years) was associated with a lower PD risk (adjusted odds ratio (OR adj) 0.75, 95% confidence interval (95% CI) 0.62-0.90); men who engaged in high occupational and high leisure-time PA in young adulthood had the lowest PD risk (OR adj0.58, 95% CI 0.41-0.81). Among women, inverse associations were found for occupation PA before age 50 (highest vs lowest, OR adj0.75, 95% CI 0.55-1.06) and strenuous leisure-time PA after age 50 (OR adj0.65, 95% CI 0.87-0.99); no clear pattern was seen for leisure and occupational PA combined. Conclusions We observed gender-specific inverse associations between occupational and leisure-time PA and PD risk; however, we cannot preclude reverse causation especially in older ages since PD has a long prodromal stage that might lead to a reduction of PA years before motor symptom onset and PD diagnosis.

Tobacco Use, Oral Health, and Risk of Parkinson's Disease.

Few studies have investigated the associations between use of Swedish moist snuff (snus), associated poor oral health, and risk of Parkinson's disease (PD). We followed 20,175 participants who were free of PD in 1973-1974 in Uppsala, Sweden, until the end of 2012. We used Cox proportional hazards regression models to estimate hazard ratios and corresponding 95% confidence intervals for the associations between tobacco use, oral health indicators, and PD risk. We found that tobacco use was associated with a lower risk of PD in males. Compared with males who never used any tobacco daily, pure ever tobacco smokers, pure ever snus users, and combined users had adjusted hazard ratios of 0.68 (95% confidence interval (CI): 0.49, 0.93; n=83), 0.51 (95% CI: 0.27, 0.95; n=11), and 0.21 (95% CI: 0.07, 0.67; n=3), respectively. No association was observed for number of teeth, dental plaque, or detectable oral mucosal lesions and PD risk, although there was a suggestive association with Candida-related oral mucosal lesions in males (hazard ratio=1.56, 95% CI: 0.92, 2.65; P=0.098). Use of snus is associated with a lower risk of PD in males, while poor oral health seems not to be associated with PD occurrence.

Genetic analysis of FGF20 in Chinese patients with Parkinson's disease.

Sequence variants in fibroblast growth factor 20 (FGF20) have been reported to be associated with Parkinson's disease (PD). We genotyped the rs591323 variant in a total of 2220 Han Chinese subjects, including 1051 patients with sporadic PD and 1169 controls, to investigate the association between rs591323 and the risk of PD. In addition, we also conducted a stratified analysis according to age at onset of PD and compared the clinical characteristics of AA+AG subjects with GG subjects. In this study, we confirmed that the A allele of rs591323 in FGF20 reduces the risk of developing sporadic PD (P=0.013). Additionally, subjects with the AA+AG genotype have a reduced risk compared to individuals with the GG genotype (P=0.024). This association was significant among females (P=0.036), but was not significant among males (P=0.266). Furthermore, no significant association was observed among either the early-onset PD group (P=0.051) or the late-onset PD group (P=0.187). Moreover, we demonstrated that the AA+AG subjects could not be distinguished from the GG subjects based on their clinical features. Our study is the first to demonstrate that FGF20 (rs591323) is associated with a lower risk of PD in a Southern Han Chinese population from mainland China.

Association of UV radiation with Parkinson disease incidence: A nationwide French ecologic study

BackgroundVitamin D is thought to contribute to brain health, but it is unclear whether low vitamin D levels are associated with increased incidence of Parkinson's disease (PD). Using ultraviolet B (UV-B) as a surrogate for vitamin D levels, we conducted a nationwide ecologic study in France in order to examine the association of UV-B with PD incidence. MethodsWe used French national drug claims databases to identify PD cases using a validated algorithm. UV-B data from the solar radiation database were derived from satellite images. We estimated PD incidence (2010–2012) at the canton level (small administrative French unit) and used multilevel Poisson regression to examine its association with UV-B (2005 annual average), after adjustment for age, sex, deprivation index, density of neurologists, smoking, proportion of agricultural land, and vitamin D supplementation. ResultsAnalyses are based on 69,010 incident PD patients. The association between UV-B and PD incidence was quadratic (P<0.001) and modified by age (P<0.001). Below 70y, incidence was higher in the bottom quintile (relative risk, RRQ1:45-49y=1.18, 95% CI=1.08–1.29) compared with the middle UV-B quintile, and lower in the top quintile (RRQ5:45-49y=0.85 [0.77–0.94]). An opposite pattern was observed in older subjects (RRQ1:85-89y=0.92 [0.89–0.96]; RRQ5:85-89y=1.06 [1.02–1.11]). Analysis based on continuous UV-B yielded similar conclusions. ConclusionsIn this nationwide study, there was an age-dependent quadratic association between UV-B and PD incidence. This study suggests that reasonable UV-B exposure is associated with lower PD risk in younger persons and that future studies should examine dose-response relations and take age into account.

Moist smokeless tobacco (Snus) use and risk of Parkinson's disease.

Cigarette smoking is associated with a lower risk of Parkinson's disease. It is unclear what constituent of tobacco smoke may lower the risk. Use of Swedish moist smokeless tobacco (snus) can serve as a model to disentangle what constituent of tobacco smoke may lower the risk. The aim of this study was to determine whether snus use was associated with a lower risk of Parkinson's disease. Individual participant data were collected from seven prospective cohort studies, including 348 601 men. We used survival analysis with multivariable Cox regression to estimate study-specific relative risk of Parkinson's disease due to snus use, and random-effects models to pool estimates in a meta-analysis. The primary analyses were restricted to never-smokers to eliminate the potential confounding effect of tobacco smoking. During a mean follow-up time of 16.1 years, 1199 incident Parkinson's disease cases were identified. Among men who never smoked, ever-snus users had about 60% lower Parkinson's disease risk compared with never-snus users [pooled hazard ratio (HR) 0.41, 95% confidence interval (CI) 0.28-0.61]. The inverse association between snus use and Parkinson's disease risk was more pronounced in current (pooled HR 0.38, 95% CI 0.23-0.63), moderate-heavy amount (pooled HR 0.41, 95% CI 0.19-0.90) and long-term snus users (pooled HR 0.44, 95% CI 0.24-0.83). Non-smoking men who used snus had a substantially lower risk of Parkinson's disease. Results also indicated an inverse dose-response relationship between snus use and Parkinson's disease risk. Our findings suggest that nicotine or other components of tobacco leaves may influence the development of Parkinson's disease.

Appendectomy and risk of Parkinson's disease: A nationwide cohort study with more than 10 years of follow-up.

The appendix may be a key site for the initiation of Parkinson's disease (PD) pathology. We examined the hypothesis that appendectomy is associated with lower PD risk. We used Danish medical and administrative registries to construct a cohort of all patients in Denmark with an operation code of appendectomy during 1980-2010 (n = 265,758) and a matched general population comparison cohort (n = 1,328,790). Using Cox regression, we computed hazard ratios and corresponding 95% confidence intervals for PD, adjusting for potential confounders and stratifying on age at appendectomy (≤45 years / > 45 years), sex, and follow-up time. During follow-up ( > 10 years), PD incidence was 0.19 and 0.15 per 1,000 person-years at risk in the appendectomy cohort and in the general population comparison cohort, respectively, yielding a slightly increased risk of PD (adjusted hazard ratio = 1.14; 95% confidence interval 1.03-1.27). Findings were consistent after more than 20 years of follow-up and when stratified on age of appendectomy and sex. Appendectomy was associated with a small increase in PD risk 10 or more years after surgery. © 2016 International Parkinson and Movement Disorder Society.