Abstract Details

Title Test-Retest Reliability and Prospective Validation of an Abnormal Metabolic Network of Premanifest Huntington's Disease

Topic Movement Disorders

Presentation(s) S20 - (-)

Poster/Presentation
Number 001

Background We have previously identified a metabolic network specifically related to the progression of pHD mutation carriers in a 7-year longitudinal FDG PET study. This network was characterized by progressively declining metabolism in the striatum, thalamus, insular, prefrontal, cingulate and occipital cortical areas, associated with concurrent increases in the cerebellum, pons, and the orbitofrontal and temporal regions. In this study, we examine the test-retest reliability of the expression of this network, and also prospectively validate the rate of network progression in an independent longitudinal pHD cohort over 2 years.

Objective

Design/Methods For the test-retest study, nine pHD subjects (age:38.5±12.3 years; CAG repeat:41.4±1.4; predicted years-to-onset:13.8±5.9) were scanned twice with FDG-PET at four imaging sites over a three-week interval. For the validation study, 21 premanifest carriers (age:40.3±6.8 years; CAG repeat:42.9±2.3; predicted years-to-onset:11.7±6.5) were scanned twice with FDG-PET over 2.3±0.3 years. Network scores were prospectively quantified in individual scans of the pHD subjects.

Results Network scores in the nine premanifest carriers were highly reproducible (intraclass correlation coefficient=0.96, p<0.001) on repeat measurement at four imaging sites. In the longitudinal cohort of 21 pHD subjects, there was a significant linear relationship between increases in network activity and declining predicted years-to-onset. The rate of network progression in this prospective cohort was 0.19/year (p<0.0001), which was nearly identical to that previously determined in the original longitudinal pHD cohort (0.21/year, p<0.0001).

Conclusions The expression of the metabolic network related to premanifest HD is highly reliable with repeat imaging across different sites. Our findings further validate the rate of network progression in premanifest HD subjects. Thus, this network is likely to be useful as a quantitative imaging biomarker in disease-modifying trials for premenifest HD carriers.

Authors/Disclosures
Chris Tang, MD (The Feinstein Institute for Medical Research) PRESENTER	No disclosure on file
Andrew S. Feigin, MD (NYU Langone Health)	Dr. Feigin has received personal compensation for serving as an employee of Rho, Inc.. Dr. Feigin has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Kenai. Dr. Feigin has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for ADCS/ATRI. Dr. Feigin has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for PTC. Dr. Feigin has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB. Dr. Feigin has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lundbeck. The institution of Dr. Feigin has received research support from Huntngton Study Group. The institution of Dr. Feigin has received research support from Prilenia.
Yilong Ma, PhD (Feinstein Institute for Medical Research)	The institution of Dr. Ma has received research support from AskBio. The institution of Dr. Ma has received research support from Aspen Neuroscience . The institution of Dr. Ma has received research support from Blue Rock . The institution of Dr. Ma has received research support from Bayer.
	No disclosure on file
Jane S. Paulsen, PhD (University of Wisconsin, Madison)	Dr. Paulsen has received personal compensation in the range of $0-$499 for serving as a Consultant for CHDI. Dr. Paulsen has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Wave Life Sciences. Dr. Paulsen has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for HDSA. The institution of Dr. Paulsen has received research support from NIH/NIA. The institution of Dr. Paulsen has received research support from NIH/NINDS.
Klaus L. Leenders, MD (UMCG)	No disclosure on file
	No disclosure on file
Michael S. Okun, MD, FAAN (University of Florida)	Dr. Okun has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for NIH. Dr. Okun has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Parkinson's Foundation. Dr. Okun has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for JAMA Neurology. Dr. Okun has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for NEJM Journal Watch. The institution of Dr. Okun has received research support from NIH. The institution of Dr. Okun has received research support from Parkinson's Foundation. The institution of Dr. Okun has received research support from Tourette Association of America. The institution of Dr. Okun has received research support from Michael J Fox. Dr. Okun has received publishing royalties from a publication relating to health care.
	No disclosure on file
Mark Guttman, MD	No disclosure on file
Vijay Dhawan, PhD	No disclosure on file
David Eidelberg, MD, FAAN (Feinstein Institute for Medical Research)	Dr. Eidelberg has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for MeiraGTx. Dr. Eidelberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for TreeFrog Therapeutics. Dr. Eidelberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Blue Rock Therapeutics, Inc.. Dr. Eidelberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for SANA Biotechnology, Inc. Dr. Eidelberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bio Vie, Inc.. Dr. Eidelberg has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for KenaiTx, Inc.. Dr. Eidelberg has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Aspen Neuroscience. Dr. Eidelberg has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Oxford University Press. The institution of Dr. Eidelberg has received research support from The Michael J. Fox Foundation for Parkinson's Research. The institution of Dr. Eidelberg has received research support from Lupus Research Alliance. The institution of Dr. Eidelberg has received research support from National Institutes of Health. The institution of Dr. Eidelberg has received research support from Blue Rock Therapeutics. The institution of Dr. Eidelberg has received research support from National Institute of Neurological Disorders and Stroke. The institution of Dr. Eidelberg has received research support from The Michael J. Fox Foundation for Parkinson's Research. The institution of Dr. Eidelberg has received research support from National Institute of Allergy and Infectious Diseases. The institution of Dr. Eidelberg has received research support from Aspen Neurosciences, Inc. . The institution of Dr. Eidelberg has received research support from NIH. Dr. Eidelberg has received intellectual property interests from a discovery or technology relating to health care. Dr. Eidelberg has received intellectual property interests from a discovery or technology relating to health care.

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