Incident Parkinson's Disease Cases Research Articles

Application of a Simple Parkinson's Disease Risk Score in a Longitudinal Population-Based Cohort.

BackgroundIdentifying individuals at risk of developing Parkinson's disease (PD) is critical to define target populations for future neuroprotective trials.ObjectiveThe objective of this study was to apply the PREDICT‐PD algorithm of risk indicators for PD in a prospective community‐based study (the Bruneck study), representative of the general elderly population.MethodsPREDICT‐PD risk scores were calculated based on risk factor assessments obtained at baseline (2005, n = 574 participants). Cases of incident PD were identified at 5‐year and 10‐year follow‐ups. Participants with PD or secondary parkinsonism at baseline were excluded (n = 35). We analyzed the association of log‐transformed risk scores with the presence of well‐established markers as surrogates for PD risk at baseline and with incident PD at follow‐up.ResultsA total of 20 participants with incident PD were identified during follow‐up (11 after 5 years and 9 after 10 years). Baseline PREDICT‐PD risk scores were associated with incident PD with odds ratios of 2.09 (95% confidence interval, 1.35–3.25; P = 0.001) after 5 years and of 1.95 (1.36–2.79; P < 0.001) after 10 years of follow‐up per doubling of risk scores. In addition, higher PREDICT‐PD scores were significantly correlated with established PD risk markers (olfactory dysfunction, signs of rapid eye movement sleep behavior disorder and motor deficits) and significantly associated with higher probability for prodromal PD according to the Movement Disorder Society research criteria at baseline.ConclusionsThe PREDICT‐PD score was associated with an increased risk for incident PD in our sample and may represent a useful first screening step in future algorithms aiming to identify cases of prodromal PD. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

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.

Alcohol Consumption and Risk of Parkinson's Disease: Data From a Large Prospective European Cohort.

BackgroundParkinson's disease (PD) etiology is not well understood. Reported inverse associations with smoking and coffee consumption prompted the investigation of alcohol consumption as a risk factor, for which evidence is inconclusive.ObjectiveTo assess the associations between alcohol consumption and PD risk.MethodsWithin NeuroEPIC4PD, a prospective European population‐based cohort, 694 incident PD cases were ascertained from 209,998 PD‐free participants. Average alcohol consumption at different time points was self‐reported at recruitment. Cox regression hazard ratios were estimated for alcohol consumption and PD occurrence.ResultsNo associations between baseline or lifetime total alcohol consumption and PD risk were observed. Men with moderate lifetime consumption (5–29.9 g/day) were at ~50% higher risk compared with light consumption (0.1–4.9 g/day), but no linear exposure–response trend was observed. Analyses by beverage type also revealed no associations with PD.ConclusionOur data reinforce previous findings from prospective studies showing no association between alcohol consumption and PD risk. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Fractures in the prodromal period of Parkinson disease.

To examine the association between fractures and Parkinson disease (PD) during the 5-year prodromal phase as compared to controls. We performed a population-based case-control study of Medicare beneficiaries in the United States from 2004 to 2009. We identified 89,632 incident PD cases and 117,760 comparable controls 66-90 years of age in 2009. PD case status was the outcome, and noncranial fracture the independent variable. We used logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for association between fracture and PD in yearly time intervals prior to PD diagnosis/control reference date, after adjusting for covariates. There were 39,606 total fractures (25.4% cases, 14.3% controls) over the 5 years prior to the PD diagnosis/control reference date. PD was positively associated with fractures even after adjusting for age, sex, race/ethnicity, Charlson comorbidity index, alcohol use, tobacco use, and osteoporosis. The association between PD and fracture was evident at yearly time windows prior to PD diagnosis/control reference date. The association between PD and each type of fracture strengthened as the PD diagnosis/control reference date approached (all time interaction p values ≤0.02). Among beneficiaries with a mechanism of injury, the majority were attributed to falls (74.6% cases, 72.8% controls). Fractures occur more commonly during the prodromal period of PD compared to controls, especially as diagnosis date approached, suggesting that patients with PD may experience unrecognized motor and nonmotor symptoms.

Identifying incident Parkinson's disease using administrative diagnostic codes: a validation study

BackgroundAdministrative databases that capture diagnostic codes are increasingly being used worldwide for research because they can save time and reduce costs. However, assessing validity is necessary before defining diseases using only diagnostic codes in research applications. ObjectiveOur objective was to assess the validity of using diagnostic codes to identify incident Parkinson's disease (PD) cases in Olmsted County, Minnesota using an established standard for comparison (1976–2005). MethodsCases were identified solely using computer programs applied to administrative diagnostic code indexes from the Rochester Epidemiology Project (REP). Two codes >30 days apart or one code on the death certificate constituted PD. The standard was a clinical diagnosis by movement disorders specialists based on medical record review. Validity was assessed using positive predictive value (PPV) and sensitivity. Numbers of incident cases and incidence rates were compared between the two ascertainment methods by sex. ResultsThe codes only method over-counted the number of incident PD cases by 73% (804 versus 464), and this over-counting generally increased with calendar year. Sensitivity was 80% (95% CI [76%, 84%]) and PPV was 46% (95% CI [34%, 50%]). Disease status misclassification accounted for two-thirds of falsely identified cases, where individuals were found to not have PD (43%) or even parkinsonism (23%) after medical record review. The codes only method also over-estimated the incidence rate time trend for men and women by approximately two-fold. ConclusionIn our context, using administrative diagnostic codes only to identify incident PD cases is not recommended unless more accurate algorithms are developed.

Smoking Cessation, Weight Change, and Risk of Parkinson's Disease: Analysis of National Cohort Data.

Background and PurposeTo determine whether the postcessation weight gain modifies the protective effect of smoking on the development of Parkinson's disease (PD).MethodsThis nationwide cohort study included 3,908,687 Korean males aged ≥40 years who underwent at least 2 health checkups biennially between 2009 and 2015. They were grouped into current smokers; quitters with body mass index (BMI) increase, maintenance, and decrease; and never smokers. The occurrence of incident PD was tracked, and Cox proportional-hazard models were used to adjust for potential confounding factors. We also analyzed the impact of weight change regardless of smoking status in the study population.ResultsThere were 6,871 incident PD cases observed during the 13,059,208 person-years of follow-up. The overall risk of PD was significantly lower in quitters than in never smokers [hazard ratio (HR)=0.78, 95% confidence interval (CI)=0.70–0.86]. The risk of PD was still lower in quitters with BMI increase (HR=0.80, 95% CI=0.65–0.98) and in those with BMI maintenance (HR=0.77, 95% CI=0.68–0.87). This tendency was also observed in quitters with BMI decrease (HR=0.76, 95% CI=0.55–1.06), although it was not as robust as in the other two groups. With respect to weight change alone, BMI increase (HR=1.10, 95% CI=1.02–1.18) but not BMI decrease (HR=1.06, 95% CI=0.98–1.14) significantly increased the PD risk compared to BMI maintenance.ConclusionsPostcessation weight gain in males did not offset the protective impact of smoking on PD development, although overall weight gain predicted an increased risk of PD.

Midbrain hyperechogenicity, hyposmia, mild parkinsonian signs and risk for incident Parkinson's disease over 10 years: A prospective population-based study

IntroductionAssociations of substantia nigra (SN) hyperechogenicity on transcranial sonography, olfactory dysfunction, and mild parkinsonian signs (MPS) with incident Parkinson's disease (PD) have only been studied over limited periods of follow-up and their long-term predictive properties are unclear. We aimed to prospectively assess the risk for incident PD over 10 years in community-dwelling elderly individuals with these risk markers. MethodsSN-hyperechogenicity, olfactory function, and MPS were assessed in the prospective population-based Bruneck Study (2005 in-person assessment; n = 574, aged 55–94 years). Cases of incident PD were identified at 5-year and 10-year follow-up visits. We estimated relative risks of baseline markers for incident cases. ResultsAfter excluding 35 cases with PD or secondary parkinsonism at baseline, a total of 20 cases of incident PD were identified from the remaining 539 participants (11 at 5 years and 9 at 10 years). Relative risks for incident PD over the 10-year follow-up period were 7.43 (2.71–20.39), 3.60 (1.48–8.78), and 5.52 (2.43–12.57) for baseline SN-hyperechogenicity, hyposmia, and mild parkinsonian signs, respectively. While risk of hyposmia for incident PD was similar for the two sequential 5-year periods studied, relative risks of SN-hyperechogenicity and MPS were higher for the first five years as compared to later. ConclusionOur findings extend the established risk relationship of SN-hyperechogenicity, hyposmia, and MPS with incident PD beyond 5 years of follow-up.

Alcohol intake and Parkinson's disease risk in the million women study.

BACKGROUNDAlcohol intake may be associated with a lower risk of Parkinson's disease (PD), but findings from previous studies have been inconclusive.OBJECTIVETo determine the association between alcohol intake and PD risk in the Million Women Study, a large, prospective study of women in the UK.METHODSBetween 1996 and 2001, approximately 1.3 million women in the UK, mean age 56 (standard deviation, 5) years, were recruited into the Million Women Study. Information on alcohol intake, lifestyle factors, and medical history was collected at recruitment by questionnaire. Information on incident cases of PD was ascertained by record linkage to national hospital admission records and death registrations. We estimated multivariable‐adjusted relative risks and corresponding 95% confidence intervals using Cox proportional hazards models according to categories of alcohol intake.RESULTSDuring an average of 17.9 years of follow‐up, 11,009 women had a new record of PD among 1,309,267 women. In drinkers, the multivariable‐adjusted relative risk comparing women who drank more than 14 drinks of alcohol per week with women who drank 1 to 2 drinks of alcohol per week was 0.99 (95% confidence interval: 0.90, 1.10). Results did not materially change after excluding the first 10 years of follow‐up (relative riskadjusted = 1.01; 95% confidence interval: 0.90, 1.13). There were no significant trends in alcohol‐related PD risk among never smokers. Additionally, examining this association by type of alcohol intake also yielded null findings.CONCLUSIONThese results do not support an association between alcohol intake and PD risk in women. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

The characteristics and treatment patterns of patients with Parkinson's disease in the United States and United Kingdom: A retrospective cohort study.

The objective of the study was to describe treatment patterns in patients newly diagnosed with Parkinson's disease (PD) in the United States (US) and the United Kingdom (UK). This retrospective cohort study used the US IBM MarketScan database (2012-2017) and the UK Clinical Practice Research Datalink (CPRD) (2004-2015) database to describe treatment patterns in incident PD cases. Patients fulfilling the case definition of PD, ≥30 years, with a 2-year baseline period prior to the index date (date of PD diagnosis), and ≥90 days of follow-up were included in the study. Treatment was classified as monotherapy (one PD medication for ≥60 continuous days), polytherapy (at least two PD medications concurrently for ≥60 days), or untreated (no PD medication prescription). Treatment patterns described included type of medication, duration and outcome of treatment. There were 11,280 patients in IBM MarketScan and 7775 patients in CPRD who fulfilled the study criteria. The proportion of treated patients was 62.4% (US) and 78.6% (UK). The majority of patients were prescribed monotherapy as first-line treatment (US: 85.2%, UK: 68.5%). Levodopa was the most frequently prescribed first-line medication (US: 70.1%, UK: 29.0%). There were 57.9% in the US and 23.8% in the UK who remained on the first monotherapy treatment till the end of the study. The study has highlighted the current treatment practices in the US and UK, and underscored differences in the two regions impacted by treatment policies and guidelines.

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.

Lipids, Apolipoproteins, and the Risk of Parkinson Disease.

A complete picture of the associations of the most common lipid fractions, including total cholesterol (TC), LDL-C (low-density lipoprotein cholesterol), HDL-C (high-density lipoprotein cholesterol), triglycerides, and apolipoproteins, with the risk of Parkinson disease (PD), is lacking. To assess the associations of lipids and apolipoproteins with the future risk of PD. In the AMORIS (Apolipoprotein-Related Mortality Risk) Study, we enrolled ≈600 000 participants during 1985 to 1996 in Stockholm, Sweden, with repeated measurements of TC, LDL-C, HDL-C, triglycerides, ApoB (apolipoprotein B), and ApoA-I (apolipoprotein A-I). The cohort was followed until the end of 2011, and incident cases of PD were identified through the Swedish Patient Register. We first used Cox models to estimate the associations of these biomarkers with later risk of PD. We further applied a Mendelian randomization analysis for TC, LDL-C, and triglycerides using the GWAS (Genome-wide association study) summary statistics from the public PD GWAS data and 23andMe PD cohorts with >800 000 individuals. One SD increase of TC was associated with a lower hazard of PD (hazard ratio, 0.90; 95% CI, 0.87-0.94). Similar associations were observed for LDL-C (hazard ratio, 0.93; 95% CI, 0.88-0.98), triglycerides (hazard ratio, 0.94; 95% CI, 0.90-0.97), and ApoB (hazard ratio, 0.91; 95% CI, 0.85-0.97). A clear dose-response relation was also noted when using these biomarkers as categorical variables. A causal inverse association of TC, LDL-C, and triglycerides with PD risk was further suggested by the Mendelian randomization analysis. Our findings reinforce that higher levels of TC, LDL-C, and triglycerides are associated with a lower future risk of PD and further suggest that these associations may be causal. The findings for ApoB in relation to PD risk are novel, and whether such association is causal needs to be examined.

β2-adrenoreceptor medications and risk of Parkinson disease.

A recent study observed a 2-fold greater risk of Parkinson disease (PD) in relation to the β2-adrenoreceptor antagonist propranolol and a markedly lower risk of PD for the β2-adrenoreceptor agonist salbutamol. We examined whether confounding by clinical indication for these medications, that is, tremor and smoking-related pulmonary conditions, explained these associations. In a large, population-based case-control study of United States Medicare beneficiaries in 2009 with diagnosis codes, procedure codes, and prescription data (48,295 incident PD cases, 52,324 controls), we examined the risk of PD in relation to use of selected β antagonists (propranolol, carvedilol, metoprolol), the β2 agonist salbutamol, and other medications used for the same clinical indications (primidone, inhaled corticosteroids). We adjusted for demographics, smoking, and overall use of medical care. We then examined the effect of also adjusting for clinical indication and applying medication exposure lagging. Propranolol appeared to increase PD risk (odds ratio [OR] = 3.62, 95% confidence interval [CI] = 3.31-3.96). When we adjusted for tremor or abnormal involuntary movement prior to the PD diagnosis/reference date and lagged propranolol exposure, the association was 0.97 (95% CI = 0.80-1.18). Primidone, also used for tremor, was similarly sensitive to this adjustment and lagging. β Antagonists not indicated for tremor appeared to reduce PD risk (carvedilol: OR = 0.77, 95% CI = 0.73-0.81; metoprolol: OR = 0.94, 95% CI = 0.91-0.97) and were insensitive to adjustment for indications and lagging. Neither salbutamol nor inhaled corticosteroids were consistently associated with PD risk. β2-adrenoreceptor agonists and antagonists do not appear to alter PD risk. Ann Neurol 2018;84:691-701.

Plasticity-related gene 3 (LPPR1) and age at diagnosis of Parkinson disease.

ObjectiveTo identify modifiers of age at diagnosis of Parkinson disease (PD).MethodsGenome-wide association study (GWAS) included 1,950 individuals with PD from the NeuroGenetics Research Consortium (NGRC) study. Replication was conducted in the Parkinson's, Genes and Environment study, including 209 prevalent (PAGEP) and 517 incident (PAGEI) PD cases. Cox regression was used to test association with age at diagnosis. Individuals without neurologic disease were used to rule out confounding. Gene-level analysis and functional annotation were conducted using Functional Mapping and Annotation of GWAS platform (FUMA).ResultsThe GWAS revealed 2 linked but seemingly independent association signals that mapped to LPPR1 on chromosome 9. LPPR1 was significant in gene-based analysis (p = 1E-8). The top signal (rs17763929, hazard ratio [HR] = 1.88, p = 5E-8) replicated in PAGEP (HR = 1.87, p = 0.01) but not in PAGEI. The second signal (rs73656147) was robust with no evidence of heterogeneity (HR = 1.95, p = 3E-6 in NGRC; HR = 2.14, p = 1E-3 in PAGEP + PAGEI, and HR = 2.00, p = 9E-9 in meta-analysis of NGRC + PAGEP + PAGEI). The associations were with age at diagnosis, not confounded by age in patients or in the general population. The PD-associated regions included variants with Combined Annotation Dependent Depletion (CADD) scores = 10–19 (top 1%–10% most deleterious mutations in the genome), a missense with predicted destabilizing effect on LPPR1, an expression quantitative trait locus (eQTL) for GRIN3A (false discovery rate [FDR] = 4E-4), and variants that overlap with enhancers in LPPR1 and interact with promoters of LPPR1 and 9 other brain-expressed genes (Hi-C FDR < 1E-6).ConclusionsThrough association with age at diagnosis, we uncovered LPPR1 as a modifier gene for PD. LPPR1 expression promotes neuronal regeneration after injury in animal models. Present data provide a strong foundation for mechanistic studies to test LPPR1 as a driver of response to damage and a therapeutic target for enhancing neuroregeneration and slowing disease progression.

Occupational stress and risk for Parkinson's disease: A nationwide cohort study.

ABSTRACT Background: Stress has been suggested as a contributing factor in the etiology of Parkinson's Disease (PD), but epidemiological evidence is sparse. Objective: The objective of this study was to explore the association between occupational stress according to the job demands‐control model and the risk for PD. Methods: We conducted a population‐based cohort study with 2,544,748 Swedes born 1920 to 1950 who had an occupation reported in the population and housing censuses in 1980 or, if missing, in 1970. Job demands and control were measured using a job‐exposure matrix. Incident PD cases were identified using Swedish national health registers from 1987 to 2010. Data were analyzed with Cox regression with age as the underlying time scale, adjusting for sex, education, and chronic obstructive pulmonary disease as a proxy for smoking. Results: During a mean follow‐up time of 21.3 years, 21,544 incident PD cases were identified. High demands were associated with increased PD risk among men, most evident in men with high education. High control was associated with increased PD risk among the low educated. This association was more pronounced in women. High‐strain jobs (high demands and low control) was only associated with increased PDrisk among men with high education, whereas active jobs (high demands and high control) were associated with increased PD risk among men with low education. Interpretation: High job demands appear to increase PD risk in men, especially in men with high education, whereas high job control increases PD risk among low educated, more strongly in women. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Metabolic syndrome and risk of Parkinson disease: A nationwide cohort study.

BackgroundThe association of metabolic syndrome (MetS) with the development of Parkinson disease (PD) is currently unclear. We sought to determine whether MetS and its components are associated with the risk of incident PD using large-scale cohort data for the whole South Korean population.Methods and findingsHealth checkup data of 17,163,560 individuals aged ≥40 years provided by the National Health Insurance Service (NHIS) of South Korea between January 1, 2009, and December 31, 2012, were included, and participants were followed up until December 31, 2015. The mean follow-up duration was 5.3 years. The hazard ratio (HR) and 95% confidence interval (CI) of PD were estimated using a Cox proportional hazards model adjusted for potential confounders. We identified 44,205 incident PD cases during follow-up. Individuals with MetS (n = 5,848,508) showed an increased risk of PD development compared with individuals without MetS (n = 11,315,052), even after adjusting for potential confounders including age, sex, smoking, alcohol consumption, physical activity, income, body mass index, estimated glomerular filtration rate, and history of stroke (model 3; HR, 95% CI: 1.24, 1.21–1.27). Each MetS component was positively associated with PD risk (HR, 95% CI: 1.13, 1.10–1.16 for abdominal obesity; 1.13, 1.10–1.15 for hypertriglyceridemia; 1.23, 1.20–1.25 for low high-density lipoprotein cholesterol; 1.05, 1.03–1.08 for high blood pressure; 1.21, 1.18–1.23 for hyperglycemia). PD incidence positively correlated with the number of MetS components (log-rank p < 0.001), and we observed a gradual increase in the HR for incident PD with increasing number of components (p < 0.001). A significant interaction between age and MetS on the risk of incident PD was observed (p for interaction < 0.001), and people aged ≥65 years old with MetS showed the highest HR of incident PD of all subgroups compared to those <65 years old without MetS (reference subgroup). Limitations of this study include the possibilities of misdiagnosis of PD and reverse causality.ConclusionsOur population-based large-scale cohort study suggests that MetS and its components may be risk factors of PD development.

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.

Relation of Enteric α-Synuclein to Gastrointestinal Dysfunction in Patients With Parkinson's Disease and in Neurologically Intact Subjects.

Background/Aimsα-Synucleinopathy in the brain is the neuropathological hallmark of Parkinson’s disease (PD). However, the functional impact of α-synucleinopathy in the enteric nervous system remains unknown. We aim to evaluate the association between gastrointestinal (GI) dysfunction and α-synuclein (αSYN) pathology in the stomach and colon of PD patients and controls, as well as to investigate the association between the αSYN pathology in GI tract and future PD risk.MethodsA total of 35 PD patients and 52 neurologically intact subjects were enrolled in this study. Endoscopic biopsies were performed, and then immunohistochemical staining for αSYN was performed. All subjects completed the validated Rome III questionnaire for the assessment of GI symptoms. The association between GI symptoms and the αSYN pathology in GI mucosa was evaluated. Incident PD cases were assessed during a median follow-up of 46 months.ResultsThe proportion of self-reported constipation and functional constipation through the Rome III questionnaire was significantly higher in PD patients than in controls (P < 0.001 and P = 0.015). However, no significant association was found between the αSYN pathology in the stomach and colon mucosa and constipation, as well as other GI symptoms including dyspepsia symptoms and abdominal discomfort or pain, regardless of the presence or absence of clinical PD (P > 0.05). No incident PD cases were diagnosed during study period.ConclusionsOur present study suggests that the deposition of αSYN in the mucosal enteric nervous system may not be reflected by functional impairment of the affected segment of the gut.

Nationwide study of Parkinson's disease incidence between 2010 and 2015 among the French agricultural population

Introduction The role of farming and professional pesticide exposure is well established in Parkinson's disease (PD). PD is multifactorial disease, and there are other risk/protective factors that may have an influence on the incidence of the disease in the agricultural population. The impact of professional pesticide exposure on the spatial distribution of the disease is not well known. Our objectives were to estimate PD incidence among the French agricultural population and to compare it to PD incidence in the general population, and to examine its spatial distribution. Methods We used French national drug claims databases to identify PD cases each year between 2010 and 2015 using a validated algorithm. We defined the agricultural population based on affiliation to the “Mutualite sociale agricole” (MSA), the only health insurance for farmers and agricultural workers. We compared PD incidence in MSA farmers, MSA workers, and affiliates to the General scheme (GS, that represents about 91% of the French population) of the social security using Poisson regression adjusted for overdispersion, 5-year groups of age, sex, age × sex, and year, and estimated relative risks (RRs) and 95% confidence intervals (CIs). We also examined multiplicative interactions of agricultural status with age, sex, and year. We estimated PD incidence ratios standardized for age, sex, and year in each French “departement” among MSA farmers and MSA workers and estimated the intraclass correlation coefficient (ICC), a measure of the proportion of the variance in PD incidence that is due to between-departement variation. Results During the study period, between 2253 and 2628 MSA affiliates were annually identified as newly treated for PD; the total number of incident PD cases was of 14,464 (72% farmers, 28% workers). The crude annual incidence ranged from 0.715 to 0.791 per 1,000 person-years. PD incidence was 7% higher in 2010 (P = 0.001) than in the rest of the period but no linear trend was observed between 2011 and 2015 (P for trend = 0.560). The mean age was 75 years (SD = 12) and 7990 (55%) were males. PD incidence was 12% higher among MSA affiliates compared to GS affiliates (RR = 1.12; 95% CI: 1.09–1.15). Among MSA affiliates, farmers had a higher risk of PD than other workers (RR = 1.10; 95% CI: 1.05–1.15). The increased PD risk in farmers depended on age (P for interaction = 0.004), with a stronger association at older ages, but not on sex (P for interaction = 0.085) or calendar year (P for interaction = 0.443). Regarding the spatial distribution of PD incidence, we observed a more pronounced between-departement variation among MSA farmers (ICC = 87%) than among other MSA workers (ICC = 79%). Conclusion Higher PD incidence among French farmers compared to the general population and agricultural workers, as well as the marked spatial variation of PD incidence in this population are consistent with the role of occupational pesticide exposure in PD. These findings warrant the epidemiological surveillance of PD among French farmers.

Do We Need to Rethink the Epidemiology and Healthcare Utilization of Parkinson's Disease in Germany?

Epidemiological aspects of Parkinson's disease (PD), co-occurring diseases and medical healthcare utilization of PD patients are still largely elusive. Based on claims data of 3.7 million statutory insurance members in Germany in 2015 the prevalence and incidence of PD was determined. PD cases had at least one main hospital discharge diagnosis of PD, or one physician diagnosis confirmed by a subsequent or independent diagnosis or by PD medication in 2015. Prevalence of (co-)occurring diseases, mortality, and healthcare measures in PD cases and matched controls were compared. In 2015, 21,714 prevalent PD cases (standardized prevalence: 511.4/100,000 persons) and 3,541 incident PD cases (standardized incidence: 84.1/100,000 persons) were identified. Prevalence of several (co-)occurring diseases/complications, e.g., dementia (PD/controls: 39/13%), depression (45/22%), bladder dysfunction (46/22%), and diabetes (35/31%), as well as mortality (10.7/5.8%) differed between PD cases and controls. The annual healthcare utilization was increased in PD cases compared to controls, e.g., regarding mean ± SD physician contacts (15.2 ± 7.6/12.2 ± 7.3), hospitalizations (1.3 ± 1.8/0.7 ± 1.4), drug prescriptions (overall: 37.7 ± 24.2/21.7 ± 19.6; anti-PD medication: 7.4 ± 7.4/0.1 ± 0.7), assistive/therapeutic devices (47/30%), and therapeutic remedies (57/16%). The standardized prevalence and incidence of PD in Germany as well as mortality in PD may be substantially higher than reported previously. While frequently diagnosed with co-occurring diseases/complications, such as dementia, depression, bladder dysfunction and diabetes, the degree of healthcare utilization shows large variability between PD patients. These findings encourage a rethinking of the epidemiology and healthcare utilization in PD, at least in Germany. Longitudinal studies of insurance claims data should further investigate the individual and epidemiological progression and healthcare demands in PD.

Excessive daytime sleepiness, objective napping and 11-year risk of Parkinson's disease in older men.

It is unknown whether subjective daytime sleepiness or objective napping could precede the risk of Parkinson's disease (PD) in the long term. We studied 2920 men (mean age 76 years) without a history of PD and followed them for 11 years. Excessive daytime sleepiness (EDS) was defined as having an Epworth Sleepiness Scale score >10. Objective naps were defined as ≥5 consecutive minutes of inactivity as measured by actigraphy, and napping duration was the accumulated time of naps outside the main sleep period. We used logistic regression to compare PD risk across four groups: no EDS& napping <1 h/day (N = 1739, 59.5%; referent group), EDS& napping <1 h/day (N = 215, 7.4%), no EDS& napping ≥ 1 h/day (N = 819, 28.1%) and EDS& napping ≥ 1 h/day (N = 147, 5.0%). We identified 106 incident PD cases over 11 years. After multivariable adjustment, men with napping ≥ 1h/day alone were twice as likely [odds ratio (OR) = 1.96, 95% confidence interval (CI) 1.25-3.08], and men with both EDS and napping ≥ 1 h/day were almost three times as likely to develop PD (2.52, 1.21-5.27), compared with the referent group. Compared with those with naps for <30 min, men who napped for ≥1 h/day had more than double the risk of PD. No association was found for EDS alone and PD risk. Further adjustment for chronotype and circadian stability, or excluding PD cases identified within 2 years after napping measurements, showed similar results. Objective long napping rather than subjective EDS was prospectively associated with a higher risk of PD in older men. Objective measures of napping might be valuable as a preclinical marker for PD.