Disease Progression in Huntington Disease: An Analysis of Multiple Longitudinal Outcomes

Tanya P Garcia; Yuanjia Wang; Ira Shoulson; Jane S Paulsen; Karen Marder

doi:10.3233/JHD-180297

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Disease Progression in Huntington Disease: An Analysis of Multiple Longitudinal Outcomes

Journal article

Peer reviewed

Disease Progression in Huntington Disease: An Analysis of Multiple Longitudinal Outcomes

Tanya P Garcia, Yuanjia Wang, Ira Shoulson, Jane S Paulsen and Karen Marder

Journal of Huntington's disease, Vol.7(4), pp.337-344

01/01/2018

DOI: 10.3233/JHD-180297

PMCID: PMC9012322

PMID: 30400103

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Abstract

Critical to discovering targeted therapies for Huntington disease (HD) are validated methods that more precisely predict when clinical outcomes occur for different patient profiles. To more precisely predict the probability of when motor diagnosis (diagnostic confidence level 4) on the Unified Huntington's Disease Rating Scale (UHDRS), cognitive impairment (two or more neuropsychological scores on the UHDRS were 1.5 standard deviations below normative means) and Stage II Total Functional Capacity (TFC) first occur by accounting for dependencies between these outcomes. Adult premanifest participants with ≥36 CAG repeats were selected from multi-center, longitudinal, observational studies: Prospective Huntington At Risk Observational Study (PHAROS, n = 346), Neurobiological Predictors of Huntington Disease (PREDICT, n = 909); and Cooperative Huntington Observational Research Trial (COHORT, n = 430). Probabilities were estimated for each study, and pooled using the Joint Progression of Risk Assessment Tool (JPRAT) which accounts for dependencies between outcomes. All studies had similar probabilities of when motor diagnosis, cognitive impairment, and Stage II TFC first occurred. Probability estimates from JPRAT were 43% less variable than from models that ignored dependencies between outcomes. The probability of experiencing motor-diagnosis, cognitive impairment, and Stage II TFC within 5 years was 10%, 18%, and 7%, respectively for 45-year-olds with 42 CAG repeats, and was 4%, 10% and 5%, respectively, for 40 year olds with 42 CAG repeats. Improved predictions from JPRAT may benefit treatment studies of rare diseases and is an alternative to composite outcomes when the objective is interpreting individual outcomes within the same model.

Adult

Cohort Studies

Disease Progression

Female

Humans

Huntington Disease - genetics

Huntington Disease - physiopathology

Longitudinal Studies

Male

Middle Aged

Outcome Assessment, Health Care

Prospective Studies

Trinucleotide Repeat Expansion

Details

Title: Subtitle: Disease Progression in Huntington Disease: An Analysis of Multiple Longitudinal Outcomes
Creators: Tanya P Garcia - Department of Statistics, Texas A&M University, College Station, TX, USA
Yuanjia Wang - Columbia University
Ira Shoulson - Georgetown University
Jane S Paulsen - University of Iowa
Karen Marder - Columbia University Irving Medical Center
Resource Type: Journal article
Publication Details: Journal of Huntington's disease, Vol.7(4), pp.337-344
DOI: 10.3233/JHD-180297
PMID: 30400103
PMCID: PMC9012322
NLM abbreviation: J Huntingtons Dis
ISSN: 1879-6397
eISSN: 1879-6400
Grant note: R01 NS040068 / NINDS NIH HHS R01 NS073671 / NINDS NIH HHS K01 NS099343 / NINDS NIH HHS R01 HG002449 / NHGRI NIH HHS
Language: English
Date published: 01/01/2018
Academic Unit: Psychiatry; Psychological and Brain Sciences
Record Identifier: 9984383306702771

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