Dataset Information

Methamphetamine/amphetamine abuse and risk of Parkinson's disease in Utah: a population-based assessment.

ABSTRACT: Despite widespread use of methamphetamine and other amphetamine-type stimulants (METH/AMPH), little is known about the long-term medical consequences of METH/AMPH abuse and dependence. Preclinical neurotoxicity findings raise public health concerns that these stimulants may damage dopamine neurons, resulting in dopamine-related disorders such as Parkinson's disease (PD).A retrospective design was used to examine statewide medical records (1996 through 2011) linked to the Utah Population Database. Individuals 30 years or older on December 31, 2011 were assigned to a METH/AMPH cohort (ICD-9-CM 304.4, 305.7, 969.7, E854.2; N=4935), a cocaine cohort (ICD-9-CM 304.2, 305.6, 968.5, E855.2; N=1867) or a population cohort unexposed to drugs or alcohol for control selection. A competing-risks, proportional hazards model was used to determine whether the METH/AMPH or cocaine cohorts were at increased risk of developing PD (ICD-9-CM 332.0) or PD/parkinsonism/essential tremor (PD/PT; ICD-9-CM 332.0, 332.1, 333.0, 333.1) compared to individually sex- and age-matched controls (5:1 control to case ratio; N=34,010).In METH/AMPH users, we observed an increased risk of PD and PD/PT (HRPD=2.8, 95%CI 1.6-4.8, P<10(-3); HRPD/PT=3.1, 95%CI 1.9-4.9, P<10(-4)) compared to population-based controls. Conversely, cocaine users exhibited no elevated risk of PD compared to controls.We observed a near three-fold increased risk of PD in METH/AMPH users vs. controls which confirms prior observations and supports that PD risk in users may be higher than previous estimates. A suggestion that female and male users may differ in PD susceptibility warrants further study.

SUBMITTER: Curtin K

PROVIDER: S-EPMC4295903 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

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Methamphetamine/amphetamine abuse and risk of Parkinson's disease in Utah: a population-based assessment.

Curtin Karen K Fleckenstein Annette E AE Robison Reid J RJ Crookston Michael J MJ Smith Ken R KR Hanson Glen R GR

Drug and alcohol dependence 20141116

<h4>Background</h4>Despite widespread use of methamphetamine and other amphetamine-type stimulants (METH/AMPH), little is known about the long-term medical consequences of METH/AMPH abuse and dependence. Preclinical neurotoxicity findings raise public health concerns that these stimulants may damage dopamine neurons, resulting in dopamine-related disorders such as Parkinson's disease (PD).<h4>Methods</h4>A retrospective design was used to examine statewide medical records (1996 through 2011) lin ...[more]

PMID: 25479916

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Project description:Sleep disturbances may signal presence of prodromal parkinsonism, including Parkinson's disease. Whether general sleep quality or duration in otherwise healthy subjects is related to the risk of parkinsonism remains unclear. We hypothesized that both worse self-reported sleep quality and duration, as well as a longitudinal deterioration in these measures, are associated with the risk of parkinsonism, including Parkinson's disease. In the prospective population-based Rotterdam Study, we assessed sleep quality and duration with the Pittsburgh Sleep Quality Index in 7726 subjects (mean age 65 years, 57% female) between 2002 and 2008, and again in 5450 subjects between 2009 and 2014. Participants were followed until 2015 for a diagnosis of parkinsonism and Parkinson's disease. Outcomes were assessed using multiple modalities: interviews, physical examination, and continuous monitoring of pharmacy records and medical records of general practitioners. We used Cox regression to associate sleep, and changes in sleep over time, with incident parkinsonism and Parkinson's disease, adjusting for age, sex, education and smoking status. Over 64 855 person-years in 13 years of follow-up (mean: 8.4 years), 75 participants developed parkinsonism, of whom 47 developed Parkinson's disease. We showed that within the first 2 years of follow-up, worse sleep quality {hazard ratio (HR) 2.38 per standard deviation increase [95% confidence interval (CI 0.91-6.23)]} and shorter sleep duration [HR 0.61 per standard deviation increase (95% CI 0.31-1.21)] related to a higher risk of parkinsonism. Associations of worse sleep quality [HR 3.86 (95% CI 1.19-12.47)] and shorter sleep duration [HR 0.48 (95% CI 0.23-0.99)] with Parkinson's disease were more pronounced, and statistically significant, compared to parkinsonism. This increased risk disappeared with longer follow-up duration. Worsening of sleep quality [HR 1.76 per standard deviation increase (95% CI 1.12-2.78)], as well as shortening of sleep duration [HR 1.72 per standard deviation decrease (95% CI 1.08-2.72)], were related to Parkinson's disease risk in the subsequent 6 years. Therefore, we argue that in the general population, deterioration of sleep quality and duration are markers of the prodromal phase of parkinsonism, including Parkinson's disease.

Project description:BACKGROUND:Although hair testing is well established for the assessment of past drug exposure, uncertainties persist about mechanisms of drug incorporation into hair and interpretation of results. The aim of this study was to administer methamphetamine (MAMP) under controlled conditions as a model drug to investigate drug incorporation into human hair. MATERIAL AND METHODS:Seven volunteers with a history of stimulant use received 4×10 mg (low) doses of sustained release S-(+)-MAMP HCl within 1 week, with weekly head hair samples collected by shaving. 3 weeks later, 4 of them received 4×20 mg (high) doses. After extensive isopropanol/phosphate buffer washing of the hair, MAMP and its metabolite amphetamine (AMP) concentrations were determined in all weekly hair samples by LC-MS-MS in selected reaction monitoring mode with the undeca- and deca-deuterated drugs, respectively, as internal standards (LLOQ, 0.005 ng mg(-1)). RESULTS:MAMP T(max) occurred from 1 to 2 weeks after both doses, with C(max) ranging from 0.6 to 3.5 ng mg(-1) after the low and 1.2 to 5.3 ng mg(-1) after the high MAMP doses. AMP C(max) in hair was 0.1-0.3 ng mg(-1) and 0.2-0.5 ng mg(-1), respectively, for low and high doses. Highly dose-related concentrations within subjects, but large variability between subjects were observed. MAMP concentrations were above the 0.2 ng mg(-1) cut-off for at least 2 weeks following administration of both low and high doses. The overall AMP/MAMP ratio ranged from 0.07 to 0.37 with a mean value of 0.15 ± 0.07, and a median of 0.13. The percentage of MAMP and AMP removed with the washing procedure decreased with time after administration. A strong correlation was found between area under the curve of MAMP (r(2)=0.90, p=0.00) and AMP (r(2)=0.94, p=0.00) concentrations calculated for the 3-week period following administration and the total melanin concentration in hair. Significant correlations were observed also between C(max) and melanin. CONCLUSIONS:This study demonstrated that despite large inter-individual differences, the incorporation of MAMP and AMP into hair is dose-related with much of the observed scatter of MAMP and AMP concentrations explained by melanin concentration in hair.

Dataset Information

Methamphetamine/amphetamine abuse and risk of Parkinson's disease in Utah: a population-based assessment.

Publications

Methamphetamine/amphetamine abuse and risk of Parkinson's disease in Utah: a population-based assessment.

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