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?2-adrenoreceptor medications and risk of Parkinson disease.

ABSTRACT: OBJECTIVE:A recent study observed a 2-fold greater risk of Parkinson disease (PD) in relation to the ?2-adrenoreceptor antagonist propranolol and a markedly lower risk of PD for the ?2-adrenoreceptor agonist salbutamol. We examined whether confounding by clinical indication for these medications, that is, tremor and smoking-related pulmonary conditions, explained these associations. METHODS: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 ? antagonists (propranolol, carvedilol, metoprolol), the ?2 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. RESULTS: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. ? 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. INTERPRETATION:?2-adrenoreceptor agonists and antagonists do not appear to alter PD risk. Ann Neurol 2018;84:691-701.

SUBMITTER: Searles Nielsen S

PROVIDER: S-EPMC6881195 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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β2-adrenoreceptor medications and risk of Parkinson disease.

Searles Nielsen Susan S Gross Anat A Camacho-Soto Alejandra A Willis Allison W AW Racette Brad A BA

Annals of neurology 20181030 5

<h4>Objective</h4>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.<h4>Methods</h4>In a large, population-based case-control study of United States Medicare beneficiaries in ...[more]

PMID: 30225948

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Project description:BackgroundPsychoses such as hallucinations are a frequent non-motor problem in patients with Parkinson disease (PD) and serious psychosis requires anti-psychotic medications that worsen Parkinsonism. Although psychosis could be associated with patient-related or biological factors such as cognition, age, and severity of PD, it can also be associated with medications.Therefore we aimed to investigate patient-related and medication-related risks of psychosis requiring anti-psychotic medications (serious psychosis).MethodsA retrospective cohort of 331 PD patients was followed for 2 years. Patient-related factors associated with risk of psychosis were identified by a survival time analysis. In patients who developed psychosis, medications during the hazard period (1-14 days before psychosis) were contrasted with those during the control periods (1 and 3 months before psychosis) using a case-crossover analysis to identify medication-related risks of psychosis.ResultsSerious psychosis was detected in 52 patients and the incidence was estimated to be 116 (95% confidence interval [CI], 85-148) per 1,000 person-years. Analyses of baseline characteristics revealed the risk to be higher in patients with a modified Hoehn-Yahr stage of ?4 (hazard ratio [HR], 2.22; 95% CI, 1.11-4.40), those with a longer duration of PD (HR, 1.25; 95% CI, 1.00-1.55, per 5 years) and those with Mini-Mental State Examination scores of ?24 (HR, 2.66; 95% CI, 1.37-5.16). The case-crossover analysis revealed that anti-cholinergics use (HR, 19.7; 95% CI, 2.39-162) elevated the risk, while donepezil use reduced it (HR, 0.48; 95% CI, 0.27-0.85).ConclusionsRisk of psychosis was elevated by increasing severity of PD, cognitive dysfunction and duration of the disease. It was elevated by use of anti-cholinergic drugs and reduced by use of donepezil. The medication-related risk was higher in patients aged???70 years. In contrast, there was no significant medication-related risk in younger patients, suggesting different pathomechanisms between young and old patients.

Project description:ImportanceLoneliness is associated with morbidity and mortality, including higher risk of neurodegenerative diseases. To our knowledge, no study has examined whether the association between loneliness and detrimental outcomes extends to Parkinson disease (PD).ObjectiveTo assess whether loneliness is associated with risk of incident PD and whether the association is independent of other risk factors or modified by age, sex, and genetic vulnerability.Design, setting, and participantsThis prospective cohort study included a population-based sample of UK Biobank participants aged 38 to 73 years with loneliness data and without a diagnosis of PD at baseline who were first assessed from March 13, 2006, to October 1, 2010, and followed up to October 9, 2021.ExposureFeeling lonely and covariates that are known risk factors for or prodromal features of PD.Main outcome and measureIncident PD was ascertained through UK National Health Service health records.ResultsOf 491 603 participants (mean [SD] age, 56.54 [8.09] years; 54.4% female), 2822 developed PD during the 15-year follow-up. Individuals who reported being lonely had a higher risk of PD (hazard ratio [HR], 1.37; 95% CI, 1.25-1.51), an association that remained after accounting for demographic factors, socioeconomic status, social isolation, PD polygenetic risk score, smoking, physical activity, body mass index, diabetes, hypertension, stroke, myocardial infarction, depression, and ever seeing a psychiatrist (fully adjusted model: HR 1.25; 95% CI, 1.12-1.39). The association between loneliness and incident PD was not moderated by sex (HR for interaction, 0.98; 95% CI, 95% CI, 0.81-1.18), age (HR for interaction, 0.99; 95% CI, 0.98-1.01), or polygenic risk score (HR for interaction, 0.93; 95% CI, 0.85-1.02). Contrary to expectations for a prodromal syndrome, when stratified by time, loneliness was not associated with risk for incident PD during the first 5 years (HR, 1.15; 95% CI, 0.91-1.45) but was associated with PD risk during the subsequent 10 years (HR, 1.32; 95% CI, 1.19-1.46).Conclusions and relevanceThis large cohort study found that loneliness was associated with risk of incident PD across demographic groups and independent of depression and other prominent risk factors and genetic risk. The findings add to the evidence that loneliness is a substantial psychosocial determinant of health.

Project description:Few epidemiologic studies have evaluated the effects of air pollution on the risk of Parkinson disease (PD).We investigated the associations of long-term residential concentrations of ambient particulate matter (PM) < 10 ?m in diameter (PM10) and < 2.5 ?m in diameter (PM2.5) and nitrogen dioxide (NO2) in relation to PD risk.Our nested case-control analysis included 1,556 self-reported physician-diagnosed PD cases identified between 1995 and 2006 and 3,313 controls frequency-matched on age, sex, and race. We geocoded home addresses reported in 1995-1996 and estimated the average ambient concentrations of PM10, PM2.5, and NO2 using a national fine-scale geostatistical model incorporating roadway information and other geographic covariates. Air pollutant exposures were analyzed as both quintiles and continuous variables, adjusting for matching variables and potential confounders.We observed no statistically significant overall association between PM or NO2 exposures and PD risk. However, in preplanned subgroup analyses, a higher risk of PD was associated with higher exposure to PM10 (ORQ5 vs. Q1 = 1.65; 95% CI: 1.11, 2.45; p-trend = 0.02) among women, and with higher exposure to PM2.5 (ORQ5 vs. Q1 = 1.29; 95% CI: 0.94, 1.76; p-trend = 0.04) among never smokers. In post hoc analyses among female never smokers, both PM2.5 (ORQ5 vs. Q1 = 1.79; 95% CI: 1.01, 3.17; p-trend = 0.05) and PM10 (ORQ5 vs. Q1 = 2.34; 95% CI: 1.29, 4.26; p-trend = 0.01) showed positive associations with PD risk. Analyses based on continuous exposure variables generally showed similar but nonsignificant associations.Overall, we found limited evidence for an association between exposures to ambient PM10, PM2.5, or NO2 and PD risk. The suggestive evidence that exposures to PM2.5 and PM10 may increase PD risk among female never smokers warrants further investigation. Citation: Liu R, Young MT, Chen JC, Kaufman JD, Chen H. 2016. Ambient air pollution exposures and risk of Parkinson disease. Environ Health Perspect 124:1759-1765;?http://dx.doi.org/10.1289/EHP135.

Project description:ImportanceParkinson disease (PD) is an increasingly common neurodegenerative disorder in many aging societies. Although comorbidities with mental disorders are common in PD, whether PD is associated with an increased risk of suicide is unclear.ObjectiveTo use a large national representative PD cohort to compare the risk of suicide in patients with PD and control participants and identify potential risk factors.Design, setting, and participantsThis nationwide population-based cohort study used linked data from Taiwan's National Health Insurance data set and Taiwan Death Registry between January 2002 and December 2016. Patients with incident PD diagnosed between January 2005 and December 2014 were followed up until December 2016. Four control participants from the general population were randomly selected by risk set sampling and were matched on age, sex, and residence to each affected individual. Data analysis occurred from June 2019 to October 2020.ExposuresDiagnosis of PD retrieved from the National Health Insurance data set.Main outcomes and measuresSuicide was recorded in the Taiwan Death Registry. Cox proportional models and hazard ratios (HRs) were used to estimate the association between PD and the risk of suicide over the follow-up period.ResultsOver 11 years, 35 891 patients with PD were followed up (17 482 women [48.7%]; mean [SD] age, 72.5 [10.1] years) and matched to 143 557 control participants (69 928 women [48.7%]; mean [SD] age, 72.5 [10.1] years). A total of 151 patients with PD (cumulative incidence, 66.6 per 100 000 [95% confidence limits [CL], 78.1-91.7]) and 300 control participants (cumulative incidence, 32.3 per 100 000 [95% CL, 36.2-40.5]) died by suicide. The risk of suicide was higher (HR, 2.1 [95% CL, 1.7-2.5]) in patients with PD than control participants, after adjustment for markers of socioeconomic position, medical comorbidities, and dementia. After controlling for mental disorders, the association between PD and suicide risk remained (HR, 1.9 [95% CL, 1.6-2.3]). Compared with control participants who died by suicide, those who died by suicide in the PD group were slightly younger (mean [SD] age: patients with PD, 74.0 [10.4] years vs control participants, 76.0 [10.2] years; P = .05) and more likely to be urban dwelling (medium urbanization, 39 patients with PD [25.8%] vs 115 control participants [38.3%]; high urbanization, 84 patients with PD [55.6%] vs 136 control participants [45.3%]; P = .03), have mental disorders (depression, 15 of 151 patients with PD [9.9%] vs 15 of 300 control participants [5.0%]; other mental disorders, 12 patients with PD [8.0%] vs 11 control participants [3.7%]; P = .02), and adopt jumping as a method of suicide (21 patients with PD [13.9%] vs 16 control participants [5.3%]; P < .01).Conclusions and relevanceIn this population-based cohort study, Parkinson disease, a common neurodegenerative disorder common in elderly persons, was independently associated with an increased risk of suicide. Integrating mental health care into primary care and PD specialty care, along with socioenvironmental interventions, may help decrease the risk of suicide in patients with PD.

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?2-adrenoreceptor medications and risk of Parkinson disease.

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β2-adrenoreceptor medications and risk of Parkinson disease.

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