Evidence map›Paper›PMID 33766994›Full record

Trial reportNeurology2021

Timing and Impact of Psychiatric, Cognitive, and Motor Abnormalities in Huntington Disease.

Branduff McAllister, James F Gusella, G Bernhard Landwehrmeyer, Jong-Min Lee, Marcy E MacDonald, Michael Orth, Anne E Rosser, Nigel M Williams, Peter Holmans, Lesley Jones and 2 more

Registry-linked trialOpen access · hybridAbstract readClinical TrialMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Neurology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01590589 (REGISTRY - an Observational Study of the European Huntington's Disease Network), which is not on this map. Cited by 61 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed, 1 pooled it
7.5field-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.

NCT01590589 completednot on this map

REGISTRY - an Observational Study of the European Huntington's Disease Network (EHDN)

TypeobservationalSponsorEuropean Huntington's Disease NetworkRan2004 to 2017Enrolled10,000ConditionsHuntington Disease, Huntington's Disease
3 · Its place in the literature

Who cites it

61 citing papers in PubMed, 1 synthesis or guideline pooled it, 111 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Psychosis in Huntington disease: a short update.Journal of neural transmission (Vienna, Austria : 1996) · 2026
    Review
  4. Article
  5. A case report of Huntington's disease presenting with psychiatric symptoms as initial manifestation combined with memory decline and motor dysfunction.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026
    Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Goal-directedness deficit in Huntington's disease.Cognitive, affective & behavioral neuroscience · 2025
    Article
  17. Article
  18. Article
  19. Understanding the genetics and neurology: an overview of adult neurogenetics.Asian biomedicine : research, reviews and news · 2025
    Review
  20. Article

1 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 2 institutions in 3 countries.

Branduff McAllisterFrom the Division of Psychological Medicine and Clinical Neurosciences (B.M., N.M.W., P.H., L.J., T.H.M.), Brain Repair Group (A.E.R.), Schools of Medicine and Biosciences, and Neuroscience and Mental Health Research Institute (A.E.R.), Cardiff University, UK; Molecular Neurogenetic Unit (J.F.G., J.-M.L., M.E.M.), Center for Genomic Medicine, Massachusetts General Hospital; Department of Genetics (J.F.G., J.-M.L., M.E.M.), Harvard Medical School, Boston, MA; Department of Neurology (G.B.L.), University of Ulm, Germany; and Swiss Huntington's Disease Centre (M.O.), Siloah, Bern, Switzerland.ORCID 0000-0001-6308-2136
James F GusellaFrom the Division of Psychological Medicine and Clinical Neurosciences (B.M., N.M.W., P.H., L.J., T.H.M.), Brain Repair Group (A.E.R.), Schools of Medicine and Biosciences, and Neuroscience and Mental Health Research Institute (A.E.R.), Cardiff University, UK; Molecular Neurogenetic Unit (J.F.G., J.-M.L., M.E.M.), Center for Genomic Medicine, Massachusetts General Hospital; Department of Genetics (J.F.G., J.-M.L., M.E.M.), Harvard Medical School, Boston, MA; Department of Neurology (G.B.L.), University of Ulm, Germany; and Swiss Huntington's Disease Centre (M.O.), Siloah, Bern, Switzerland.
G Bernhard LandwehrmeyerFrom the Division of Psychological Medicine and Clinical Neurosciences (B.M., N.M.W., P.H., L.J., T.H.M.), Brain Repair Group (A.E.R.), Schools of Medicine and Biosciences, and Neuroscience and Mental Health Research Institute (A.E.R.), Cardiff University, UK; Molecular Neurogenetic Unit (J.F.G., J.-M.L., M.E.M.), Center for Genomic Medicine, Massachusetts General Hospital; Department of Genetics (J.F.G., J.-M.L., M.E.M.), Harvard Medical School, Boston, MA; Department of Neurology (G.B.L.), University of Ulm, Germany; and Swiss Huntington's Disease Centre (M.O.), Siloah, Bern, Switzerland.
Jong-Min LeeFrom the Division of Psychological Medicine and Clinical Neurosciences (B.M., N.M.W., P.H., L.J., T.H.M.), Brain Repair Group (A.E.R.), Schools of Medicine and Biosciences, and Neuroscience and Mental Health Research Institute (A.E.R.), Cardiff University, UK; Molecular Neurogenetic Unit (J.F.G., J.-M.L., M.E.M.), Center for Genomic Medicine, Massachusetts General Hospital; Department of Genetics (J.F.G., J.-M.L., M.E.M.), Harvard Medical School, Boston, MA; Department of Neurology (G.B.L.), University of Ulm, Germany; and Swiss Huntington's Disease Centre (M.O.), Siloah, Bern, Switzerland.
Marcy E MacDonaldFrom the Division of Psychological Medicine and Clinical Neurosciences (B.M., N.M.W., P.H., L.J., T.H.M.), Brain Repair Group (A.E.R.), Schools of Medicine and Biosciences, and Neuroscience and Mental Health Research Institute (A.E.R.), Cardiff University, UK; Molecular Neurogenetic Unit (J.F.G., J.-M.L., M.E.M.), Center for Genomic Medicine, Massachusetts General Hospital; Department of Genetics (J.F.G., J.-M.L., M.E.M.), Harvard Medical School, Boston, MA; Department of Neurology (G.B.L.), University of Ulm, Germany; and Swiss Huntington's Disease Centre (M.O.), Siloah, Bern, Switzerland.
Michael OrthFrom the Division of Psychological Medicine and Clinical Neurosciences (B.M., N.M.W., P.H., L.J., T.H.M.), Brain Repair Group (A.E.R.), Schools of Medicine and Biosciences, and Neuroscience and Mental Health Research Institute (A.E.R.), Cardiff University, UK; Molecular Neurogenetic Unit (J.F.G., J.-M.L., M.E.M.), Center for Genomic Medicine, Massachusetts General Hospital; Department of Genetics (J.F.G., J.-M.L., M.E.M.), Harvard Medical School, Boston, MA; Department of Neurology (G.B.L.), University of Ulm, Germany; and Swiss Huntington's Disease Centre (M.O.), Siloah, Bern, Switzerland.
Anne E RosserFrom the Division of Psychological Medicine and Clinical Neurosciences (B.M., N.M.W., P.H., L.J., T.H.M.), Brain Repair Group (A.E.R.), Schools of Medicine and Biosciences, and Neuroscience and Mental Health Research Institute (A.E.R.), Cardiff University, UK; Molecular Neurogenetic Unit (J.F.G., J.-M.L., M.E.M.), Center for Genomic Medicine, Massachusetts General Hospital; Department of Genetics (J.F.G., J.-M.L., M.E.M.), Harvard Medical School, Boston, MA; Department of Neurology (G.B.L.), University of Ulm, Germany; and Swiss Huntington's Disease Centre (M.O.), Siloah, Bern, Switzerland.
Nigel M WilliamsFrom the Division of Psychological Medicine and Clinical Neurosciences (B.M., N.M.W., P.H., L.J., T.H.M.), Brain Repair Group (A.E.R.), Schools of Medicine and Biosciences, and Neuroscience and Mental Health Research Institute (A.E.R.), Cardiff University, UK; Molecular Neurogenetic Unit (J.F.G., J.-M.L., M.E.M.), Center for Genomic Medicine, Massachusetts General Hospital; Department of Genetics (J.F.G., J.-M.L., M.E.M.), Harvard Medical School, Boston, MA; Department of Neurology (G.B.L.), University of Ulm, Germany; and Swiss Huntington's Disease Centre (M.O.), Siloah, Bern, Switzerland.
Peter HolmansFrom the Division of Psychological Medicine and Clinical Neurosciences (B.M., N.M.W., P.H., L.J., T.H.M.), Brain Repair Group (A.E.R.), Schools of Medicine and Biosciences, and Neuroscience and Mental Health Research Institute (A.E.R.), Cardiff University, UK; Molecular Neurogenetic Unit (J.F.G., J.-M.L., M.E.M.), Center for Genomic Medicine, Massachusetts General Hospital; Department of Genetics (J.F.G., J.-M.L., M.E.M.), Harvard Medical School, Boston, MA; Department of Neurology (G.B.L.), University of Ulm, Germany; and Swiss Huntington's Disease Centre (M.O.), Siloah, Bern, Switzerland.ORCID 0000-0003-0870-9412
Lesley JonesFrom the Division of Psychological Medicine and Clinical Neurosciences (B.M., N.M.W., P.H., L.J., T.H.M.), Brain Repair Group (A.E.R.), Schools of Medicine and Biosciences, and Neuroscience and Mental Health Research Institute (A.E.R.), Cardiff University, UK; Molecular Neurogenetic Unit (J.F.G., J.-M.L., M.E.M.), Center for Genomic Medicine, Massachusetts General Hospital; Department of Genetics (J.F.G., J.-M.L., M.E.M.), Harvard Medical School, Boston, MA; Department of Neurology (G.B.L.), University of Ulm, Germany; and Swiss Huntington's Disease Centre (M.O.), Siloah, Bern, Switzerland.
Thomas H MasseyFrom the Division of Psychological Medicine and Clinical Neurosciences (B.M., N.M.W., P.H., L.J., T.H.M.), Brain Repair Group (A.E.R.), Schools of Medicine and Biosciences, and Neuroscience and Mental Health Research Institute (A.E.R.), Cardiff University, UK; Molecular Neurogenetic Unit (J.F.G., J.-M.L., M.E.M.), Center for Genomic Medicine, Massachusetts General Hospital; Department of Genetics (J.F.G., J.-M.L., M.E.M.), Harvard Medical School, Boston, MA; Department of Neurology (G.B.L.), University of Ulm, Germany; and Swiss Huntington's Disease Centre (M.O.), Siloah, Bern, Switzerland. masseyt1@cardiff.ac.uk.ORCID 0000-0002-9804-2131
REGISTRY Investigators of the European Huntington's Disease Network
Harvard University · USNeurosciences Institute · US

Funding

Disease-Modifying Genes in Huntington's DiseaseR01NS091161 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI JAMES F GUSELLA · 2015 to 2026
$7.2M
Genetic foundation for complete mutant allele-specific CRISPR in neurodegenerative diseasesR01NS105709 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI LEE, JONG-MIN · 2018 to 2022
$2.4M
Medical Research Council MR/L010305/1Medical Research Council MR/P001629/1Medical Research Council MR/T033428/1NINDS NIH HHS R01 NS091161NINDS NIH HHS R01 NS105709Wellcome Trust
6 · The paper itself

Abstract

objectiveTo assess the prevalence, timing, and functional impact of psychiatric, cognitive, and motor abnormalities in Huntington disease (HD) gene carriers, we analyzed retrospective clinical data from individuals with manifest HD.

methodsClinical features of patients with HD were analyzed for 6,316 individuals in an observational study of the European Huntington's Disease Network (REGISTRY) from 161 sites across 17 countries. Data came from clinical history and the patient-completed Clinical Characteristics Questionnaire that assessed 8 symptoms: motor, cognitive, apathy, depression, perseverative/obsessive behavior, irritability, violent/aggressive behavior, and psychosis. Multiple logistic regression was used to analyze relationships between symptoms and functional outcomes.

resultsThe initial manifestation of HD is increasingly likely to be motor and less likely to be psychiatric as age at presentation increases and is independent of pathogenic CAG repeat length. The Clinical Characteristics Questionnaire captures data on nonmotor symptom prevalence that correlate specifically with validated clinical measures. Psychiatric and cognitive symptoms are common in HD gene carriers, with earlier onsets associated with longer CAG repeats. Of patients with HD, 42.4% reported at least 1 psychiatric or cognitive symptom before motor symptoms, with depression most common. Each nonmotor symptom was associated with significantly reduced total functional capacity scores.

conclusionsPsychiatric and cognitive symptoms are common and functionally debilitating in HD gene carriers. They require recognition and targeting with clinical outcome measures and treatments. However, because it is impossible to distinguish confidently between nonmotor symptoms arising from HD and primary psychiatric disorders, particularly in younger premanifest patients, nonmotor symptoms should not be used to make a clinical diagnosis of HD. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier: NCT01590589.

Indexed as

InternationalityNeuropsychological TestsAdultAgedCognition DisordersFemaleHumansHuntington DiseaseMaleMental DisordersMiddle AgedMotor Skills DisordersRetrospective StudiesTime Factors

Identifiers

PMID33766994
PMCPMC8166441
OpenAlexW3136008922

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Registered trials

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.