Evidence map›Paper›PMID 25453459›Full record

Observational studyThe Lancet. Neurology2014

Prediction of manifest Huntington's disease with clinical and imaging measures: a prospective observational study.

Jane S Paulsen, Jeffrey D Long, Christopher A Ross, Deborah L Harrington, Cheryl J Erwin, Janet K Williams, Holly James Westervelt, Hans J Johnson, Elizabeth H Aylward, Ying Zhang and 3 more

Open access · greenAbstract readMulticenter StudyObservational Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in The Lancet. Neurology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 131 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
131citing papers in PubMed, 3 pooled it
10.3field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

131 citing papers in PubMed, 3 syntheses or guidelines pooled it, 223 citations in OpenAlex.

  1. Pooled it
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  4. Trial
  5. Sample enrichment for clinical trials to show delay of onset in huntington disease.Movement disorders : official journal of the Movement Disorder Society · 2019
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71 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 7 institutions in 2 countries.

Jane S PaulsenDepartment of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, IA, USA; Department of Neurology, Carver College of Medicine, University of Iowa, Iowa City, IA, USA; Department of Psychology, University of Iowa, Iowa City, IA, USA. Electronic address: predict-publications@uiowa.edu.
Jeffrey D LongDepartment of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, IA, USA; Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, IA, USA.
Christopher A RossDivision of Neurobiology, Departments of Psychiatry, Neurology, Neuroscience and Pharmacology, Johns Hopkins University, Baltimore, MD, USA.
Deborah L HarringtonDepartment of Radiology, School of Medicine, University of California, San Diego, CA, USA; Veterans Affairs San Diego Healthcare System, San Diego, CA, USA.
Cheryl J ErwinCenter of Excellence for Ethics, Humanities & Spirituality, Texas Tech University Health Sciences Center, School of Medicine, Lubbock, TX, USA.
Janet K WilliamsCollege of Nursing, University of Iowa, Iowa City, IA, USA.
Holly James WesterveltDepartment of Psychiatry and Human Behavior, Division of Biology and Medicine, Alpert Medical School, Brown University, Providence, RI, USA; Department of Psychiatry, Rhode Island Hospital, Providence, RI, USA.
Hans J JohnsonDepartment of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, IA, USA; Departments of Electrical and Computer Engineering and Biomedical Engineering, College of Engineering, University of Iowa, Iowa City, IA, USA.
Elizabeth H AylwardCenter for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA, USA.
Ying ZhangDepartment of Biostatistics, Fairbanks School of Public Health, and Indiana University School of Medicine, Indiana University, Indianapolis, IN, USA.
H Jeremy BockholtAdvanced Biomedical Informatics Group, Iowa City, IA, USA.
Roger A BarkerDepartment of Clinical Neurosciences, John van Geest Centre for Brain Repair, University of Cambridge, Cambridge, UK.
PREDICT-HD Investigators and Coordinators of the Huntington Study Group
University of Iowa · USIndiana University School of MedicineJohns Hopkins University · USRhode Island Hospital · USTexas Tech University · USUniversity of Cambridge · GBVA San Diego Healthcare System · US

Funding

NEUROBIOLOGICAL PREDICTORS OF HUNTINGTON'S DISEASER01NS040068 · NINDS · UNIVERSITY OF IOWA · PI PAULSEN, JANE S · 2001 to 2013
$48.5M
Clinical and Translational Science AwardUL1TR000040 · NCATS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI GINSBERG, HENRY N · 2012 to 2015
$26.2M
University of Iowa Clinical and Translational Science ProgramUL1TR000442 · NCATS · UNIVERSITY OF IOWA · PI ROSENTHAL, GARY E · 2012 to 2013
$10.0M
Cognitive and functional brain changes in preclinical Huntington's disease (HD)R01NS054893 · NINDS · UNIVERSITY OF IOWA · PI PAULSEN, JANE S · 2007 to 2011
$2.0M
Functional Connectivity in Premanifest Huntington's DiseaseU01NS082083 · NINDS · CLEVELAND CLINIC LERNER COM-CWRU · PI RAO, STEPHEN MARK · 2012 to 2014
$1.2M
Basal Ganglia Shape Analysis and Circuitry in Huntington's DiseaseU01NS082085 · NINDS · JOHNS HOPKINS UNIVERSITY · PI MILLER, MICHAEL I, ROSS, CHRISTOPHER A · 2012 to 2013
$1.1M
BRAINS Morphology and Image AnalysisR01NS050568 · NINDS · UNIVERSITY OF IOWA · PI MAGNOTTA, VINCENT A · 2007 to 2009
$1.0M
Enterprise Storage In A Collaborative Neuroimaging EnvironmentS10RR023392 · NCRR · UNIVERSITY OF IOWA · PI JOHNSON, HANS JOSEPH · 2007 to 2007
$405k
NCATS NIH HHS 2UL1TR000442-06NCATS NIH HHS UL1 TR000040NCATS NIH HHS UL1 TR000442NCRR NIH HHS 1S10RR023392NCRR NIH HHS S10 RR023392NINDS NIH HHS 1U01NS082083NINDS NIH HHS 1U01NS082085NINDS NIH HHS 5R01NS040068NINDS NIH HHS 5R01NS050568NINDS NIH HHS 5R01NS054893NINDS NIH HHS R01 NS040068NINDS NIH HHS R01 NS050568NINDS NIH HHS R01 NS054893NINDS NIH HHS U01 NS082083NINDS NIH HHS U01 NS082085
6 · The paper itself

Abstract

backgroundAlthough the association between cytosine-adenine-guanine (CAG) repeat length and age at onset of Huntington's disease is well known, improved prediction of onset would be advantageous for clinical trial design and prognostic counselling. We compared various measures for tracking progression and predicting conversion to manifest Huntington's disease.

methodsIn this prospective observational study, we assessed the ability of 40 measures in five domains (motor, cognitive, psychiatric, functional, and imaging) to predict time to motor diagnosis of Huntington's disease, accounting for CAG repeat length, age, and the interaction of CAG repeat length and age. Eligible participants were individuals from the PREDICT-HD study (from 33 centres in six countries [USA, Canada, Germany, Australia, Spain, UK]) with the gene mutation for Huntington's disease but without a motor diagnosis (a rating below 4 on the diagnostic confidence level from the 15-item motor assessment of the Unified Huntington's Disease Rating Scale). Participants were followed up between September, 2002, and July, 2014. We used joint modelling of longitudinal and survival data to examine the extent to which baseline and change of measures analysed separately was predictive of CAG-adjusted age at motor diagnosis.

findings1078 individuals with a CAG expansion were included in this analysis. Participants were followed up for a mean of 5·1 years (SD 3·3, range 0·0-12·0). 225 (21%) of these participants received a motor diagnosis of Huntington's disease during the study. 37 of 40 cross-sectional and longitudinal clinical and imaging measures were significant predictors of motor diagnosis beyond CAG repeat length and age. The strongest predictors were in the motor, imaging, and cognitive domains: an increase of one SD in total motor score (motor domain) increased the risk of a motor diagnosis by 3·07 times (95% CI 2·26-4·16), a reduction of one SD in putamen volume (imaging domain) increased risk by 3·32 times (2·37-4·65), and a reduction of one SD in Stroop word score (cognitive domain) increased risk by 2·32 times (1·88-2·87).

interpretationPrediction of diagnosis of Huntington's disease can be improved beyond that obtained by CAG repeat length and age alone. Such knowledge about potential predictors of manifest Huntington's disease should inform discussions about guidelines for diagnosis, prognosis, and counselling, and might be useful in guiding the selection of participants and outcome measures for clinical trials.

fundingUS National Institutes of Health, US National Institute of Neurological Disorders and Stroke, and CHDI Foundation.

Indexed as

AdultAgedAged, 80 and overDiagnostic ImagingFemaleFollow-Up StudiesHumansHuntington DiseaseLongitudinal StudiesMaleMiddle AgedPredictive Value of TestsProspective Studies

Identifiers

PMID25453459
PMCPMC4373455
OpenAlexW2098935457

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.