Incident Parkinson's Disease Patients Research Articles

Identifying Protective Drugs for Parkinson's Disease in Health-Care Databases Using Machine Learning.

Available treatments for Parkinson's disease (PD) are only partially or transiently effective. Identifying existing molecules that may present a therapeutic or preventive benefit for PD (drug repositioning) is thus of utmost interest. We aimed at detecting potentially protective associations between marketed drugs and PD through a large-scale automated screening strategy. We implemented a machine learning (ML) algorithm combining subsampling and lasso logistic regression in a case-control study nested in the French national health data system. Our study population comprised 40,760 incident PD patients identified by a validated algorithm during 2016 to 2018 and 176,395 controls of similar age, sex, and region of residence, all followed since 2006. Drug exposure was defined at the chemical subgroup level, then at the substance level of the Anatomical Therapeutic Chemical (ATC) classification considering the frequency of prescriptions over a 2-year period starting 10 years before the index date to limit reverse causation bias. Sensitivity analyses were conducted using a more specific definition of PD status. Six drug subgroups were detected by our algorithm among the 374 screened. Sulfonamide diuretics (ATC-C03CA), in particular furosemide (C03CA01), showed the most robust signal. Other signals included adrenergics in combination with anticholinergics (R03AL) and insulins and analogues (A10AD). We identified several signals that deserve to be confirmed in large studies with appropriate consideration of the potential for reverse causation. Our results illustrate the value of ML-based signal detection algorithms for identifying drugs inversely associated with PD risk in health-care databases. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

β-Adrenoceptor Drugs and Parkinson's Disease: A Nationwide Nested Case-Control Study.

Potential relationships between β-adrenergic drugs and α-synuclein synthesis in Parkinson's disease (PD) have been recently suggested. This study investigated the putative association between β-adrenoceptor drug exposure and PD occurrence. A nested case-control study was performed in the Echantillon Généraliste des Bénéficiaires (EGB) (a 1/97th random sample of affiliates to the French Insurance System). Incident PD patients diagnosed between 01/01/2008 and 31/12/2017 (index date) were matched 1:1 to controls by gender, birth year, and insurance scheme. Exposure to any β-agonist and to any β-antagonist was compared between cases and controls within 1-2years before the index date, and exposure to salbutamol and to propranolol was individualized. The association between PD and β-adrenoceptor drugs was investigated through conditional logistic regression models adjusted for potential confounding factors. Because of a statistical interaction between β-agonists and diabetes, results were stratified according to the presence of diabetes. Among the 2225 incident PD patients identified in the EGB (mean age 75.6 ± 10.2years, sex ratio 1.04), no significant association was found between PD and β-antagonists (adjusted odds ratio [aOR] 1.05 [95% confidence interval 0.91-1.20]), except for propranolol (aOR 2.11 [1.38-3.23]). For β-agonists, a protective association in non-diabetic patients (aOR 0.75 [0.60-0.93]) and an opposite and significant association in diabetic patients (aOR 1.61 [1.02-2.55]) were observed. Similar results were found with salbutamol. This study did not identify an increased risk of PD occurrence after β-antagonist exposure, except for propranolol (potential protopathic bias). The discordant results observed with β-agonists in patients with or without diabetes deserve further exploration of the influence of diabetic comorbidity on PD occurrence and evolution.

Parkinson disease and the risk of epileptic seizures.

To assess the association between incident Parkinson disease (PD) and subsequent incident epileptic seizures. We conducted a retrospective cohort study with a nested case-control analysis using data from the U.K. Clinical Practice Research Datalink. We identified patients aged ≥40 years with an incident diagnosis of PD between 1995 and 2016 and a matched comparison group of PD-free individuals. We calculated crude incidence rates (IRs) with 95% confidence intervals (CIs) of epileptic seizures in PD patients and the PD-free comparison group, and corresponding crude incidence rate ratios (IRRs). In the nested case-control analysis, we calculated adjusted odds ratios (adj. ORs) of incident PD among cases with incident epileptic seizures and seizure-free controls overall and stratified by various seizure-provoking comorbidities. Among 23,086 incident PD patients and 92,343 PD-free individuals, we identified 898 patients with incident epileptic seizures. The crude IR of epileptic seizures in PD patients was 266.7/100,000 person-years (95% CI = 235.6-297.7), and in PD-free individuals it was 112.4/100,000 person-years (95% CI = 103.5-121.3; IRR = 2.37, 95% CI = 2.06-2.73). The adj. OR of epileptic seizures was 1.68 (95% CI = 1.43-1.98) in PD patients compared with PD-free individuals. PD patients with comorbid brain disorders (adj. OR = 12.36, 95% CI = 8.74-17.48) or with > 1 seizure-provoking comorbidity (adj. OR = 13.24, 95% CI = 10.15-17.25) were at the highest risk of epileptic seizures compared with PD-free individuals with no seizure-provoking comorbidities. This study suggests that incident PD is associated with an increased risk of incident epileptic seizures. Ann Neurol 2018;83:363-374.

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.

Traffic-related air pollution increased the risk of Parkinson's disease in Taiwan: A nationwide study

BackgroundAmbient air pollution has been associated with many health conditions, but little is known about its effects on neurodegenerative diseases, such as Parkinson's disease (PD). In this study, we investigated the influence of ambient air pollution on PD in a nationwide population-based case–control study in Taiwan. MethodsWe identified 11,117 incident PD patients between 2007 and 2009 from the Taiwanese National Health Insurance Research Database and selected 44,468 age- and gender-matched population controls from the longitudinal health insurance database. The average ambient pollutant exposure concentrations from 1998 through the onset of PD were estimated using quantile-based Bayesian Maximum Entropy models. Basing from logistic regression models, we estimated the odds ratios (ORs) and 95% confidence intervals (CIs) of ambient pollutant exposures and PD risk. ResultsWe observed positive associations between NOx, CO exposures, and PD. In multi-pollutant models, for NOx and CO above the 75th percentile exposure compared with the lowest percentile, the ORs of PD were 1.37 (95% CI=1.23–1.52) and 1.17 (95% CI=1.07–1.27), respectively. ConclusionsThis study suggests that ambient air pollution exposure, especially from traffic-related pollutants such as NOx and CO, increases PD risk in the Taiwanese population.

LEVODOPA–INDUCED MOTOR COMPLICATIONS IN AN INCIDENT PARKINSON'S DISEASE COHORT

BackgroundLevodopa is the mainstay of treatment for Parkinson's disease (PD) but is associated with potentially-disabling drug-induced motor fluctuations and dyskinesias. Previous studies have suggested that both of these complications develop...

Five-year fracture risk estimation in patients with Parkinson's disease

BackgroundPrevious studies have shown that patients with Parkinson's disease (PD) are at increased risk of fractures. However, no specific prediction model for fracture estimation among PD patients is currently available. Therefore, the aim of this study was to develop a simple score for estimating the 5-year osteoporotic and hip fracture risks among patients with PD. MethodsThe UK Clinical Practice Research Datalink (1987–2011) was used to identify incident PD patients. Cox proportional-hazards models were used to calculate the 5-year risks of osteoporotic and hip fracture among PD patients. The regression model was fitted with various risk factors for fracture and the final Cox model was converted into integer risk scores. ResultsWe identified 4411 incident PD patients without a history of osteoporotic treatment. The 5-year risks of osteoporotic and hip fracture were plotted in relation to the risk score. Risk scores increased with age, female gender, history of renal disease and history of dementia. The C-statistic, which is a parameter to test the internal validity of the model, was reasonable for the prediction of osteoporotic fracture (0.69) and hip fracture (0.73). ConclusionIn this study, we developed a simple model to estimate 5-year fracture risk among incident PD patients. It may be useful in daily practice after external validation.

Risk of fracture in patients with Parkinson’s disease

The aim of the study was to determine fracture risk in incident Parkinson's disease (PD) patients. This study showed that fracture risk assessment may be indicated among patients with PD, in particular when they have recently used selective serotonin re-uptake inhibitors or high-dose antipsychotics, or have a history of fracture, falling, low body mass index (BMI) or renal disease. PD is a movement disorder associated with falling and detrimental effects on bone. Both are recognized risk factors for fracture. Therefore, the aim was to determine fracture risk in incident PD patients stratified by treatment, severity, duration of disease and related comorbidities. We conducted a retrospective cohort study using the UK General Practice Research Database (1987-2011). Each PD patient was matched by age, sex, calendar time and practice to a control patient without history of PD. We identified 4,687 incident PD patients. Compared to controls, a statistically significant increased risk was observed for any fracture (adjusted hazard ratio [AHR], 1.89; 95 % confidence interval [CI], 1.67-2.14), osteoporotic fracture (AHR, 1.99; 95 % CI, 1.72-2.30) and hip fracture (AHR 3.08; 95 % CI, 2.43-3.89). Fracture risk further increased with history of fracture, falling, low BMI, renal disease, antidepressant use and use of high-dose antipsychotics. This study showed that incident PD patients have a statistically significant increased risk of fracture. Therefore, fracture risk assessment may be indicated among PD patients, who, besides the general risk factors for fracture, like increasing age and female gender, have recently used selective serotonin re-uptake inhibitors or high-dose antipsychotics or have a history of fracture, falling, low BMI or renal disease.

Parkinson disease: Associated disorders in the Norwegian population based incident ParkWest study

Parkinson's disease (PD) may be associated with a number of different diseases due to common risk factors or overlapping symptomatology. We have asked for possible associated disorders in a Norwegian population of incident PD patients and controls, the Norwegian ParkWest study. The patients were diagnosed according to the Gelb criteria. 212 incident PD patients and 175 age and gender matched controls were included. PD patients and controls were asked for information on earlier medical history and family history.PD patients had a higher frequency of self-reported symptoms of depression (p = 0.003) and anxiety disorders (p = 0.004) before baseline. They tended to have a higher frequency of diabetes (p = 0.09) and had a higher frequency of prior stroke or TIA (p = 0.004).

Personality Characteristics and Motor Skills Attributed to Occupations in Parkinson Disease

It has previously been speculated that a distinct premorbid personality characterized by introversion, rigidity, and over cautiousness might be associated with Parkinson disease (PD). Only 1 previous study has assessed personality before PD onset, and other data collected retrospectively do not exclude reverse causation. We relied on the longest held job reported in an interview to infer personality traits and motor skills for 355 incident PD patients and 335 population controls enrolled in a PD study in California. Jobs were coded according to the 1980 US Census Occupational Code and assigned scores for various demands, skills, and aptitudes required by the job. None of the occupational temperament or interest factors required, expected, or exhibited by workers were related to statistically significantly higher odds of having PD per unit increase in scores, whereas there was some suggestion of differences when the extremes were examined. Analyses of physical aptitude factors showed that PD cases were less likely to have worked in jobs that involved certain motor skills. This study uses a novel approach to assess personality traits using occupational characteristics. Most job attributes thought to reflect conservativeness; risk taking, stress resistance, and flexibility were not associated with PD in a linear manner. Thus, these occupation-derived traits do not seem to support the existence of a distinct parkinsonian personality. However, the negative associations with jobs requiring certain motor skills are intriguing, and may suggest very early premotor features or a lack of continuous motor training as a risk factor for PD.

The role of APOE alleles in incident Parkinson’s disease. The Norwegian ParkWest Study

Apolipoprotein E (APOE) gene alleles have been associated with various neurodegenerative disorders. However, there have been conflicting reports on associations between APOE alleles and Parkinson's disease (PD) and age at onset in PD. There exist no data on APOE alleles in an unselected cohort of patients with incident PD. To determine the role of APOE alleles in PD and age of onset in PD at time of diagnosis, 203 patients with incident PD and 187 healthy control subjects from Western and Southern Norway were investigated according to their APOE allele status. No association was observed between any APOE alleles and susceptibility to PD or age at onset in PD. In our cohort of unselected, incident PD patients APOE alleles do not seem to play a role for development of PD. Prospective, long-term follow-up may still reveal associations between APOE alleles and clinical and neuropsychological progression in PD.

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.