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Original Investigation |

Association Between Change in Body Mass Index, Unified Parkinson’s Disease Rating Scale Scores, and Survival Among Persons With Parkinson Disease Secondary Analysis of Longitudinal Data From NINDS Exploratory Trials in Parkinson Disease Long-term Study 1

Anne-Marie A. Wills, MD, MPH1; Adriana Pérez, PhD2; Jue Wang, MS3; Xiao Su, BSc3; John Morgan, MD4; Suja S. Rajan, PhD5; Maureen A. Leehey, MD6; Gregory M. Pontone, MD7; Kelvin L. Chou, MD8; Chizoba Umeh, MD9; Zoltan Mari, MD10; James Boyd, MD11 ; for the NINDS Exploratory Trials in Parkinson Disease (NET-PD) Investigators
[+] Author Affiliations
1Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston
2Department of Biostatistics, The University of Texas Health Science Center at Houston UTHealth, School of Public Health, Austin
3UTHealth, The University of Texas School of Public Health, Houston
4Department of Neurology, Medical College of Georgia, Georgia Regents University, Augusta
5Department of Management, Policy and Community Health, The University of Texas Health Science Center at Houston UTHealth, School of Public Health, Houston.
6Department of Neurology, University of Colorado Hospital and University of Colorado School of Medicine, Aurora
7Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, Maryland
8Departments of Neurology and Neurosurgery, University of Michigan, Ann Arbor
9Department of Neurology, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts
10Department of Neurology, Johns Hopkins University, Baltimore, Maryland
11Department of Neurological Sciences, University of Vermont College of Medicine, Burlington
JAMA Neurol. 2016;73(3):321-328. doi:10.1001/jamaneurol.2015.4265.
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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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Figure 1.
Change in Unified Parkinson’s Disease Rating Scale (UPDRS) by Body Mass Index (BMI) Trajectory Groups

A, After adjusting for covariates, we found that the change in the motor UPDRS score between decreasing BMI and stable BMI was P < .001 and that the change in the motor UPDRS score between stable BMI and increasing BMI was P = .03. B, After adjusting for covariates, we found that the change in the total UPDRS score between decreasing BMI and stable BMI was P < .001 and that the change in the total UPDRS score between stable BMI and increasing BMI was P = .02. Error bars indicate 95% CIs.

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Figure 2.
Kaplan-Meier Survival Curves by Body Mass Index (BMI) Trajectory Groups

Of 1673 participants, 76 (4.5%) died.

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