Anne-Marie A Wills1, Adriana Pérez2, Jue Wang3, Xiao Su3, John Morgan4, Suja S Rajan5, Maureen A Leehey6, Gregory M Pontone7, Kelvin L Chou8, Chizoba Umeh9, Zoltan Mari10, James Boyd11. 1. Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston. 2. Department of Biostatistics, The University of Texas Health Science Center at Houston UTHealth, School of Public Health, Austin. 3. UTHealth, The University of Texas School of Public Health, Houston. 4. Department of Neurology, Medical College of Georgia, Georgia Regents University, Augusta. 5. Department of Management, Policy and Community Health, The University of Texas Health Science Center at Houston UTHealth, School of Public Health, Houston. 6. Department of Neurology, University of Colorado Hospital and University of Colorado School of Medicine, Aurora. 7. Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, Maryland. 8. Departments of Neurology and Neurosurgery, University of Michigan, Ann Arbor. 9. Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. 10. Department of Neurology, Johns Hopkins University, Baltimore, Maryland. 11. Department of Neurological Sciences, University of Vermont College of Medicine, Burlington.
Abstract
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.
RCT Entities:
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.
Authors: J C Desport; P M Preux; C T Truong; L Courat; J M Vallat; P Couratier Journal: Amyotroph Lateral Scler Other Motor Neuron Disord Date: 2000-03
Authors: Marjolein A van der Marck; Heleen C Dicke; Ergun Y Uc; Zippora H A Kentin; George F Borm; Bastiaan R Bloem; Sebastiaan Overeem; Marten Munneke Journal: Parkinsonism Relat Disord Date: 2011-11-18 Impact factor: 4.891
Authors: R D Abbott; G W Ross; L R White; J S Nelson; K H Masaki; C M Tanner; J D Curb; P L Blanchette; J S Popper; H Petrovitch Journal: Neurology Date: 2002-10-08 Impact factor: 9.910
Authors: Alberto Ascherio; Peter A LeWitt; Kui Xu; Shirley Eberly; Arthur Watts; Wayne R Matson; Connie Marras; Karl Kieburtz; Alice Rudolph; Mikhail B Bogdanov; Steven R Schwid; Marsha Tennis; Caroline M Tanner; M Flint Beal; Anthony E Lang; David Oakes; Stanley Fahn; Ira Shoulson; Michael A Schwarzschild Journal: Arch Neurol Date: 2009-12
Authors: Umer Akbar; Ying He; Yunfeng Dai; Nawaz Hack; Irene Malaty; Nikolaus R McFarland; Christopher Hess; Peter Schmidt; Samuel Wu; Michael S Okun Journal: PLoS One Date: 2015-05-04 Impact factor: 3.240
Authors: Maureen Leehey; Sheng Luo; Saloni Sharma; Anne-Marie A Wills; Jacquelyn L Bainbridge; Pei Shieen Wong; David K Simon; Jay Schneider; Yunxi Zhang; Adriana Pérez; Rohit Dhall; Chadwick W Christine; Carlos Singer; Franca Cambi; James T Boyd Journal: Neurology Date: 2017-09-29 Impact factor: 9.910