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

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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 1 University of Iowa 2 Columbia University

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

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

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

Body Weight A modulator of disease progression in prodromal HD that could be manipulated? Weight loss occurs in HD Weight loss associated with ↓ function and ↓ QoL in HD Preserve body mass, preserve function?

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

Results: Participants MaleFemaleTotal Prodromal HD Healthy Controls Total

Sample N Age Mean(SD) Range BMI Mean(SD) Range Control male (±13.7) 27.4 (±4.4) Control female (±10.3)27.4 (±5.5) Low male (±6.6)29.2 (±6.6) Low female (±8.1)26.3 (±5.5) Med male (±9.8)26.9 (±3.8) Med female (±9.3)26.7 (±6.0) High male (±10.4)26.6 (±3.7) High female (±9.4)26.3 (±5.9)

MeasureInterceptsSlopes ControlLowMediumHighControlLowMediumHigh All * * Males ** ~-0.06* Females ~ Results

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 ) – Females = 0.98 (CI )

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

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

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 (5R01NS ) and CHDI Foundation, Inc.