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Body Mass Index Changes in Prodromal Huntington Disease

Body Mass Index Changes in Prodromal Huntington Disease. Nancy R. Downing, PhD, RN CANS September 13, 2012. Research Team. M. Kathleen Clark, PhD, RN 1 Spencer Lourens 1 Ashwini Rao, EdD, OTR 2 Karen Marder, MD 2 Jeffrey D. Long, PhD 1 James A. Mills, MS 1 Jane S. Paulsen, PhD 1

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Body Mass Index Changes in Prodromal Huntington Disease

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  1. Body Mass Index Changes in Prodromal Huntington Disease Nancy R. Downing, PhD, RN CANS September 13, 2012

  2. Research Team • M. Kathleen Clark, PhD, RN1 • Spencer Lourens1 • Ashwini Rao, EdD, OTR2 • Karen Marder, MD2 • Jeffrey D. Long, PhD1 • James A. Mills, MS1 • Jane S. Paulsen, PhD1 1University of Iowa 2Columbia University

  3. Huntington Disease • Progressive neurodegenerative disease • Single genetic mutation—autosomal dominant • Trio of symptom clusters • Motor • Cognitive • Psychiatric/behavioral • Middle age onset • Premature death • No cure

  4. Weight Loss and HD • Weight loss is associated with functional decline in HD • Occurs despite higher caloric intake • In the prodromal period, weight loss may be a harbinger of advancing disease

  5. Purpose • Examine baseline and longitudinal body BMI differences in a large sample of prodromal HD subjects compared with healthy controls • Examine ability of BMI to predict time to Huntington disease diagnosis

  6. Body Weight • A modulator of disease progression in prodromal HD that could be manipulated?

  7. Methods • Participants: Prodromal HD and gene mutation negative controls (N=1026) participants in PREDICT-HD study • Stratified: 3 disease-severity groups (Low, Medium, High) based on age at time of study entrance and length of gene mutation • Linear mixed effects regression: Compare BMI changes among groups over 5 years • Accelerated Failure Time modeling: Calculate odds ratio (OR) for BMI to predict time to diagnosis, controlling for age at baseline, years of education, gender, and motor rater experience

  8. Results: Participants

  9. Results

  10. Accelerated Failure Time Modeling Results • Odds Ratio for ability of BMI to predict HD diagnosis given a 2-unit decrease in BMI: • Males = 1.20 (CI 1.006 - 1.432) • Females = 0.98 (CI 0.906 - 1.063)

  11. Working Hypotheses for Current Research • Body composition changes occur prior to HD diagnosis • Weight loss in HD is primarily related to loss of muscle mass • Supported by decreased amount of BCAA in people with HD vs. healthy controls

  12. Significance • Body composition and BCAA changes may be useful biomarkers for clinical trials • May be possible to design interventions to prevent body composition changes and preserve function • Possible interventions include exercise and/or dietary interventions • Weight loss occurs in other neurodegenerative diseases such as Alzheimer and Parkinson • Mechanisms may have relevance to obesity

  13. Acknowledgements • During the time of this data analysis, Nancy Downing was supported by a NINR clinical genetics nursing research T32 grant to the University of Iowa College of Nursing • Jane S. Paulsen’s research is supported by the National Institutes for Health, National Institute of Neurological Disorders and Stroke (5R01NS040068-11) and CHDI Foundation, Inc.

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