Tracking Huntington's Disease Progression Using Motor, Functional, Cognitive, and Imaging Markers

Pubu M Abeyasinghe; Jeffrey D Long; Adeel Razi; Dorian Pustina; Jane S Paulsen; Sarah J Tabrizi; Govinda R Poudel; Nellie Georgiou-Karistianis

doi:10.1002/mds.28650

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Tracking Huntington's Disease Progression Using Motor, Functional, Cognitive, and Imaging Markers

Journal article

Peer reviewed

Tracking Huntington's Disease Progression Using Motor, Functional, Cognitive, and Imaging Markers

Pubu M Abeyasinghe, Jeffrey D Long, Adeel Razi, Dorian Pustina, Jane S Paulsen, Sarah J Tabrizi, Govinda R Poudel and Nellie Georgiou-Karistianis

Movement disorders, Vol.36(10), pp.2282-2292

10/2021

DOI: 10.1002/mds.28650

PMCID: PMC8590922

PMID: 34014005

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https://www.ncbi.nlm.nih.gov/pmc/articles/8590922View

Open Access

Abstract

Potential therapeutic targets and clinical trials for Huntington's disease have grown immensely in the last decade. However, to improve clinical trial outcomes, there is a need to better characterize profiles of signs and symptoms across different epochs of the disease to improve selection of participants. The objective of the present study was to best distinguish longitudinal trajectories across different Huntington's disease progression groups. Clinical and morphometric imaging data from 1082 participants across IMAGE-HD, TRACK-HD, and PREDICT-HD studies were combined, with longitudinal times ranging between 1 and 10 years. Participants were classified into 4 groups using CAG and age product. Using multivariate linear mixed modeling, 63 combinations of markers were tested for their sensitivity in differentiating CAG and age product groups. Next, multivariate linear mixed modeling was applied to define the best combination of markers to track progression across individual CAG and age product groups. Putamen and caudate volumes, individually and/or combined, were identified as the best variables to both differentiate CAG and age product groups and track progression within them. The model using only caudate volume best described advanced disease progression in the combined data set. Contrary to expectations, combining clinical markers and volumetric measures did not improve tracking longitudinal progression. Monitoring volumetric changes throughout a trial (alongside primary and secondary clinical end points) may provide a more comprehensive understanding of improvements in functional outcomes and help to improve the design of clinical trials. Alternatively, our results suggest that imaging deserves consideration as an end point in clinical trials because of the prospect of greater sensitivity. © 2021 International Parkinson and Movement Disorder Society.

Biomarkers

Cognition

Disease Progression

Humans

Huntington Disease - diagnostic imaging

Longitudinal Studies

Magnetic Resonance Imaging

Details

Title: Subtitle: Tracking Huntington's Disease Progression Using Motor, Functional, Cognitive, and Imaging Markers
Creators: Pubu M Abeyasinghe - Monash University
Jeffrey D Long - University of Iowa
Adeel Razi - Monash University
Dorian Pustina - CHDI Foundation
Jane S Paulsen - University of Wisconsin–Madison
Sarah J Tabrizi - UK Dementia Research Institute
Govinda R Poudel - Australian Catholic University
Nellie Georgiou-Karistianis - Monash University
Resource Type: Journal article
Publication Details: Movement disorders, Vol.36(10), pp.2282-2292
DOI: 10.1002/mds.28650
PMID: 34014005
PMCID: PMC8590922
NLM abbreviation: Mov Disord
ISSN: 0885-3185
eISSN: 1531-8257
Grant note: U01 NS105509 / NINDS NIH HHS R01 NS040068 / NINDS NIH HHS Wellcome Trust 200181/Z/15/Z / Wellcome Trust U01 NS103475 / NINDS NIH HHS
Language: English
Date published: 10/2021
Academic Unit: Psychiatry; Psychological and Brain Sciences; Biostatistics
Record Identifier: 9984280842802771

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