Use of antihypertensives and the risk of Parkinson disease.
ABSTRACT Recent studies related angiotensin converting enzyme (ACE) inhibitors and calcium channel blockers to possible neuroprotective effects. Little is known about neuroprotection of angiotensin II (AT II) antagonists or beta-blockers.
To explore the association between antihypertensive drug use and the risk of developing a first-time diagnosis of Parkinson disease (PD).
This was a case-control analysis within the UK-based General Practice Research Database. Cases were >or=40 years of age with an incident PD diagnosis between 1994 and 2005. We matched one control to each PD case on age, sex, general practice, index date, and duration of previous history in the database. We assessed antihypertensive drug use by timing and by exposure duration. We calculated ORs using conditional logistic regression, adjusted for body mass index, smoking, and various cardiovascular, metabolic, and psychiatric diseases and dementia.
We identified 3,637 cases with a first-time diagnosis of idiopathic PD and an equal number of matched controls. As compared to nonuse of antihypertensive drugs, the adjusted OR for current use of >or=30 prescriptions was 1.08 (95% CI 0.85 to 1.37) for ACE inhibitors, 0.91 (95% CI 0.41 to 2.00) for AT II antagonists, 1.16 (95% CI 0.95 to 1.41) for beta-blockers, and 0.77 (95% CI 0.63 to 0.95) for calcium channel blockers.
Current long-term use of calcium channel blockers was associated with a significantly reduced risk of a Parkinson disease diagnosis, while the risk was not materially altered for users of angiotensin converting enzyme inhibitors or beta-blockers and, with less statistical precision, for users of angiotensin II antagonists.
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ABSTRACT: Constipation is one of most frequent non-motor symptoms of Parkinson's disease (PD) and it may precede the clinical diagnosis of PD by years, with negative effects on quality of life. In contrast to motor features, levodopa is ineffective and possibly detrimental on constipation. Treatment of constipation in PD is non-specific and frequently unsuccessful. Stemming from a clinical observation of unexpected relief of bothersome constipation, abdominal bloating and pain after treatment with the beta-blocker carvedilol in one patient, we have evaluated the association between the use of beta-blockers and the presence of constipation in a large, unselected PD cohort. Retrospective review of the medical records of every patient with a diagnosis of PD seen in the Movement Disorders clinic at Cedars-Sinai Medical Center from October 2010 to April 2014. 341 medical records with a primary diagnosis of PD were reviewed, 336 of which contained information about constipation. Overall, 205/336 patients (61%) reported constipation. Among the 66 subjects treated with beta-blockers at the time of the encounter of record, only 28 (42.4%) reported constipation. By comparison, among the 270 subjects not treated with beta-blockers, 177 (65.5%) had constipation (χ(2) test p value = 0.001). Multivariate logistic analysis showed an odds ratio (OR) of 0.293 for beta-blockers (95% C.I. 0.161-0.535, p = 0.0001), 2.287 for levodopa (95% C.I. 1.271-4.117, p = 0.006) and 1.805 for dopamine agonists (95% C.I. 1.039-3.136, p = 0.036). Beta-blockers are associated with a lower risk of constipation, while dopaminergic treatments appear to increase risk of constipation. Copyright © 2014 Elsevier Ltd. All rights reserved.Parkinsonism & Related Disorders 11/2014; · 4.13 Impact Factor
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ABSTRACT: Substantia nigra dopamine neurons are involved in behavioral processes that include cognition, reward learning, and voluntary movement. Selective deterioration of these neurons is responsible for the motor deficits associated with Parkinson's disease (PD). Aging is the leading risk factor for PD, suggesting that adaptations occurring in dopamine neurons during normal aging may predispose individuals to the development of PD. Previous studies suggest that the unique set of ion conductances that drive spontaneous, rhythmic firing of action potentials could predispose substantia nigra dopamine neurons to selective neurodegeneration. Here we show, using patch-clamp electrophysiological recordings in brain slices, that substantia nigra dopamine neurons from mice 25-30 months of age (old) have comparable membrane capacitance and input resistance to neurons from mice 2-7 months of age (young). However, neurons from old mice exhibit slower firing rates, narrower spike widths, and more variable interspike intervals compared with neurons from young mice. Dopamine neurons from old mice also exhibit smaller L-type calcium channel currents, providing a plausible mechanism that likely contributes to the changes in impulse activity. Age-related decrements in the physiological function of dopamine neurons could contribute to the decrease in voluntary movement and other dopamine-mediated behaviors observed in aging populations. Furthermore, as pharmacological antagonism of L-type calcium channels has been proposed as a potential treatment for the early stages of PD, our results could point to a limited temporal window of opportunity for this therapeutic intervention.Journal of Neuroscience 07/2014; 34(28):9310-8. · 6.75 Impact Factor
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ABSTRACT: Introduction Constipation is a non-motor symptom of Parkinson's disease (PD). We investigated the association between the severity of constipation and subsequent risk of PD in a population-based sample. Methods 551,324 participants free of PD, dementia, and stroke were retrospectively ascertained between January 1, 2005 and December 31, 2005 using the Taiwan National Health Insurance Research Database. The association between constipation at the beginning of the study and the incidence of PD was examined using a Cox regression model. Information regarding comorbidities and concomitant medications use was adjusted in the proportional hazards models. Results After an average follow-up of 5.5 years, 2336 incident PD cases were diagnosed. The crude incidence rate of PD per 1,000,000 person-days was 1.57 for subjects without constipation and 4.04, 5.28, and 12.67 for mild, moderate, and severe constipation, respectively. After adjusting for age, sex, comorbidities, and concomitant medication use, patients with constipation were more likely to develop PD than subjects without constipation; the adjusted hazard ratio (aHR) was 3.28 (95% CI: 2.14–5.03), 3.83 (2.51–5.84), and 4.22 (2.95–6.05) for individual constipation severity categories. Constipation severity was also associated with an increased likelihood of PD in the time-varying analysis; the aHR was 2.84 (2.43–3.33), 5.22 (4.61–5.92), and 10.47 (9.46–11.58) for mild, moderate, and severe constipation, respectively (P < 0.0001). After excluding PD patients diagnosed within 3 years of constipation, the association remained significant. Conclusions Our study suggests that the severity of constipation is associated with a future diagnosis of PD in a dose-dependent manner.Parkinsonism & Related Disorders 09/2014; · 4.13 Impact Factor