Curtin Karen, Fleckenstein Annette E, Robison Reid J, Crookston Michael J, Smith Ken R, Hanson Glen R
Department of Internal Medicine, University of Utah, Salt Lake City, UT 84112, United States; Population Sciences, Huntsman Cancer Institute, Salt Lake City, UT 84112, United States.
Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT 84112, United States; School of Dentistry, University of Utah, Salt Lake City, UT 84112, United States.
Drug Alcohol Depend. 2015 Jan 1;146:30-8. doi: 10.1016/j.drugalcdep.2014.10.027. Epub 2014 Nov 16.
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.
尽管甲基苯丙胺和其他苯丙胺类兴奋剂(METH/AMPH)被广泛使用,但对于METH/AMPH滥用和依赖的长期医学后果却知之甚少。临床前神经毒性研究结果引发了公众对这些兴奋剂可能损害多巴胺神经元的担忧,进而导致诸如帕金森病(PD)等与多巴胺相关的疾病。
采用回顾性设计,对与犹他州人口数据库相关联的全州医疗记录(1996年至2011年)进行审查。将2011年12月31日年满30岁及以上的个体分为METH/AMPH队列(国际疾病分类第九版临床修订本[ICD-9-CM]编码:304.4、305.7、969.7、E854.2;N = 4935)、可卡因队列(ICD-9-CM编码:304.2、305.6、968.5、E855.2;N = 1867)或未接触过毒品或酒精的人群队列作为对照。使用竞争风险比例风险模型来确定METH/AMPH队列或可卡因队列与按性别和年龄匹配的个体对照(对照与病例比例为5:1;N = 34,010)相比,患帕金森病(ICD-9-CM编码:332.0)或帕金森病/帕金森综合征/特发性震颤(PD/PT;ICD-9-CM编码:332.0、332.1、333.0、333.)的风险是否增加。
与基于人群的对照相比,在METH/AMPH使用者中,我们观察到患帕金森病和PD/PT的风险增加(帕金森病风险比[HRPD]=2.8,95%置信区间[CI]为1.6 - 4.8,P<10⁻³;HRPD/PT = 3.1,95%CI为1.9 - 4.9,P<10⁻⁴)。相反,与对照相比,可卡因使用者患帕金森病的风险没有升高。
我们观察到METH/AMPH使用者患帕金森病的风险比对照增加了近三倍,这证实了先前的观察结果,并支持使用者患帕金森病的风险可能高于先前的估计。关于男性和女性使用者在帕金森病易感性方面可能存在差异的提示值得进一步研究。