Body Mass Index Changes in Prodromal Huntington Disease

Body Mass Index Changes in Prodromal Huntington Disease

Nancy R. Downing, PhD, RNCANS

September 13, 2012

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 Iowa2Columbia 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?

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

Male Female Total

Prodromal HD 293 504 797

Healthy Controls 84 145 229

Total 377 649 1026

SampleN Age Mean(SD)

RangeBMI Mean(SD)Range

Control male 84 43.8 (±13.7) 27.4 (±4.4)

Control female 145 43.4 (±10.3) 27.4 (±5.5)

Low male 68 35.6 (±6.6) 29.2 (±6.6)Low female 145 34.7 (±8.1) 26.3 (±5.5)Med male 100 41.3 (±9.8) 26.9 (±3.8)Med female 187 41.0 (±9.3) 26.7 (±6.0)

High male 131 45.2 (±10.4) 26.6 (±3.7)

High female 186 43.5 (±9.4) 26.3 (±5.9)

Measure Intercepts Slopes

Control Low Medium High Control Low Medium High

All 29.32 29.57 28.77 28.20* 0.09 0.16 0.05 -0.08*

Males 28.88 30.92** 28.46 27.91 0.14 0.17 -0.02~ -0.06*

Females 29.82 29.19 29.18 28.67~ 0.07 0.14 0.08 -0.08

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 1.006 - 1.432)– Females = 0.98 (CI 0.906 - 1.063)

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 (5R01NS040068-11) and CHDI Foundation, Inc.