Poster 12: A Metabolic Network Associated with the Progression of Preclinical Huntington's Disease: Application of the Ordinal Trends Analysis to a Longitudinal PET Study

C. Tang; A. Feigin; K.L. Poston; Y. Ma; M. Guttman; J.S. Paulsen; V. Dhawan; D. Eidelberg

doi:10.1016/j.nurt.2008.10.013

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Poster 12: A Metabolic Network Associated with the Progression of Preclinical Huntington's Disease: Application of the Ordinal Trends Analysis to a Longitudinal PET Study

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Poster 12: A Metabolic Network Associated with the Progression of Preclinical Huntington's Disease: Application of the Ordinal Trends Analysis to a Longitudinal PET Study

C. Tang, A. Feigin, K.L. Poston, Y. Ma, M. Guttman, J.S. Paulsen, V. Dhawan and D. Eidelberg

Neurotherapeutics, Vol.6(1), pp.207-208

2009

DOI: 10.1016/j.nurt.2008.10.013

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Abstract

To characterize longitudinal changes in metabolic network activity during phenoconversion in preclinical Huntington's disease (pHD) patients. Metabolic changes accompanying phenoconversion in HD are not well understood. The ordinal trends (OrT) model is a novel multivariate voxel-based approach developed to identify and quantify progression-related networks in individual subjects (Habeck et al., 2005). We used serial PET imaging to examine activity of an OrT network during the transition from preclinical to symptomatic HD. Twelve pHD gene carriers (CAG repeat length, 41.6 ± 1.7; age, 46.8 ± 11.0 years; estimated years-to-onset, 10.3 ± 8.6 years) underwent FDG PET at baseline, 18, and 44 months. Of these 12, four became symptomatic by 44 months. Four patients (2 phenoconverted and 2 non-phenoconverted) were additionally scanned at 68 months. Using OrT, we identified a highly significant spatial covariance pattern associated with progression in preclinical HD ( p < 0.0001). The pattern was characterized by declining metabolism in the caudate, putamen, thalamus, and prefrontal cortex across the first three time points. All but one mutation carrier exhibited monotonically increasing network activity over 44 months. The gene carriers who phenoconverted by 44 months had greater network activity ( p < 0.01) than those who did not phenoconvert during the same time period. This increasing trend continued in the phenoconverters and non-phenoconverters scanned again at 68 months. We found that OrT network activity increased in pHD subjects followed up to 68 months. This increasing trend was found in subjects who either did or did not phenoconvert during the follow-up period. However, the phenoconverters exhibited a higher level of network activity than the non-phenoconverters both before and after clinical onset. Thus, the OrT network is likely to be a useful biomarker of progression in preclinical HD, which may improve the prediction of symptom onset in mutation carriers.

Details

Title: Subtitle: Poster 12: A Metabolic Network Associated with the Progression of Preclinical Huntington's Disease: Application of the Ordinal Trends Analysis to a Longitudinal PET Study
Creators: C. Tang - Feinstein Institute for Medical Research
A. Feigin - Northwell Health
K.L. Poston - Feinstein Institute for Medical Research
Y. Ma - Feinstein Institute for Medical Research
M. Guttman - University of Toronto
J.S. Paulsen - University of Iowa
V. Dhawan - Feinstein Institute for Medical Research
D. Eidelberg - Feinstein Institute for Medical Research
Resource Type: Abstract
Publication Details: Neurotherapeutics, Vol.6(1), pp.207-208
Publisher: Elsevier Inc
DOI: 10.1016/j.nurt.2008.10.013
ISSN: 1933-7213
eISSN: 1878-7479
Language: English
Date published: 2009
Academic Unit: Psychiatry; Psychological and Brain Sciences
Record Identifier: 9984384316002771

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