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JAMA Neurology:帕金森病病患者早期体重减轻可能预示更严重的疾病形式

来源:wendong 2016-01-18 11:22

2016年1月18日讯 /生物谷BIOON/ --一项由麻省总医院(MGH)研究人员领导的新研究发现了早期帕金森病患者体重减轻和疾病更快发展之间相关性的证据。虽然体重减轻在帕金森患者中是很常见的,但研究结果可能表明:病程早期体重减轻预示更严重的疾病形式。这项研究2016年1月11日在线发表于《 JAMA Neurology 》期刊。

"我怀疑这种疾病可能存在几种亚型"该论文领导和通讯作者、哈佛医学院神经病学助理教授、MGH神经内科和神经疾病临床研究所Anne-Marie Wills博士说,"早期体重减轻的患者,似乎罹患的是更为严重、系统性的帕金森病,可能是因为神经内分泌系统或胃肠道神经系统受累,而体重增加的患者可能罹患的是更温和的疾病形式。"

虽然之前的研究已经发现,高体重指数(BMI)与亨廷顿病和肌萎缩性脊髓侧索硬化(ALS)中较好的生存状况有关,但还没有发表在帕金森病中探究体重与疾病发展和生存期关系的研究。Wills和来自其他8个美国研究中心的共同作者们调查了一项NIH-发起的临床试验的数据,这项试验于2007年到2013年进行,目的是研究使用肌酸来治疗早期帕金森病。该试验招募了超过1700位患者(诊断5年之内,开始多巴胺释放药物治疗90天到2年),在发现肌酸治疗没有益处后早期停止。

新研究所需的数据包括:年度身高、体重测量和参试者3到5年的帕金森病统一评定量表(UPDRS)结果(1673位参试者的数据可用)。1282位参试者(77%)的BMI在研究期间保持稳定,158位参试者(9%)体重减轻,233位参试者(14%)体重增加。与体重保持稳定的患者相比,研究期间体重减轻的患者,UPDRS得分在运动症状和总体方面都平均增加得更多--指示症状恶化。体重增加的参试者,UPDRS得分年度增幅最小。三组患者在生存期方面没有显着差异,但这也许反映了参试者都处于疾病早期阶段的事实。

作者们指出,目前还无法确定维持甚至增加体重是否有助于延缓病情发展,虽然这种假设得到Wills在2014年领导的ALS干预性研究的支持。"因为这是首次在帕金森病中观察到这种关联,我们现在还不能推荐对标准临床护理进行任何改变"她说,"但在我自己的实践中,我会试着防止患者的体重减轻,而且会建议护理者关注患者的体重变化,甚至是在疾病的早期阶段。"(生物谷Bioon.com)

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doi10.1001/jamaneurol.2015.4265

Association Between Change in Body Mass Index, Unified Parkinson's Disease Rating Scale Scores, and Survival Among Persons With Parkinson Disease

Importance  Greater body mass index (BMI, calculated as weight in kilograms divided by height in meters squared) is associated with improved survival among persons with Huntington disease or amyotrophic lateral sclerosis. Weight loss is common among persons with Parkinson disease (PD) and is associated with worse quality of life.

Objective  To explore the association between change in BMI, Unified Parkinson's Disease Rating Scale (UPDRS) motor and total scores, and survival among persons with PD and to test whether there is a positive association between BMI at randomization and survival.

Design, Setting, and Participants  Secondary analysis (from May 27, 2014, to October 13, 2015) of longitudinal data (3-6 years) from 1673 participants who started the National Institute of Neurological Disorders and Stroke Exploratory Trials in PD Long-term Study-1 (NET-PD LS-1). This was a double-blind randomized placebo-controlled clinical trial of creatine monohydrate (10 g/d) that was performed at 45 sites throughout the United States and Canada. Participants with early (within 5 years of diagnosis) and treated (receiving dopaminergic therapy) PD were enrolled from March 2007 to May 2010 and followed up until September 2013.

Main Outcomes and Measures  Change across time in motor UPDRS score, change across time in total UPDRS score, and time to death. Generalized linear mixed models were used to estimate the effect of BMI on the change in motor and total UPDRS scores after controlling for covariates. Survival was analyzed using Cox proportional hazards models of time to death. A participant's BMI was measured at randomization, and BMI trajectory groups were classified according to whether participants experienced weight loss ("decreasing BMI"), weight stability ("stable BMI"), or weight gain ("increasing BMI") during the study.

Results  Of the 1673 participants (mean [SD] age, 61.7 [9.6] years; 1074 [64.2%] were male), 158 (9.4%) experienced weight loss (decreasing BMI), whereas 233 (13.9%) experienced weight gain (increasing BMI). After adjusting for covariates, we found that the weight-loss group's mean (SE) motor UPDRS score increased by 1.48 (0.28) (P?<?.001) more points per visit than the weight-stable group's mean (SE) motor UPDRS score. The weight-gain group's mean (SE) motor UPDRS score decreased by ?0.51 (0.24) (P?=?.03) points per visit, relative to the weight-stable group. While there was an unadjusted difference in survival between the 3 BMI trajectory groups (log-rank P?<?.001), this was not significant after adjusting for covariates.

Conclusions and Relevance  Change in BMI was inversely associated with change in motor and total UPDRS scores in the NET-PD LS-1. Change in BMI was not associated with survival; however, these results were limited by the low number of deaths in the NET-PD LS-1.

Trial Registration  clinicaltrials.gov Identifier: NCT00449865

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