Evidence map›Paper›PMID 32470422›Full record

ArticleThe Lancet. Neurology2020

Biological and clinical characteristics of gene carriers far from predicted onset in the Huntington's disease Young Adult Study (HD-YAS): a cross-sectional analysis.

Rachael I Scahill, Paul Zeun, Katherine Osborne-Crowley, Eileanoir B Johnson, Sarah Gregory, Christopher Parker, Jessica Lowe, Akshay Nair, Claire O'Callaghan, Christelle Langley and 18 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Lancet. Neurology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
115citing papers in PubMed, 3 pooled it
13.0field-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

115 citing papers in PubMed, 3 syntheses or guidelines pooled it, 181 citations in OpenAlex.

  1. Pooled it
  2. Systematic Review with Meta-Analysis of Biofluid Markers for Huntington's Disease.Movement disorders : official journal of the Movement Disorder Society · 2025
    Pooled it
  3. Systemic Symptoms in Huntington's Disease: A Comprehensive Review.Movement disorders clinical practice · 2024
    Pooled it
  4. Trial
  5. Trial
  6. Trial
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. SPARCC: Semi-Parametric Robust Estimation in a Right-Censored Covariate Model.Journal of the American Statistical Association · 2026
    Article
  17. Review
  18. Article
  19. Review
  20. Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

28 authors at 9 institutions in 4 countries.

Rachael I ScahillHuntington's Disease Centre, Department of Neurodegenerative disease, UCL Queen Square Institute of Neurology, University College London, London, UK.
Paul ZeunHuntington's Disease Centre, Department of Neurodegenerative disease, UCL Queen Square Institute of Neurology, University College London, London, UK.
Katherine Osborne-CrowleyHuntington's Disease Centre, Department of Neurodegenerative disease, UCL Queen Square Institute of Neurology, University College London, London, UK; Division of Equity, Diversity and Inclusion, University of New South Wales, Sydney, NSW, Australia.
Eileanoir B JohnsonHuntington's Disease Centre, Department of Neurodegenerative disease, UCL Queen Square Institute of Neurology, University College London, London, UK.
Sarah GregoryHuntington's Disease Centre, Department of Neurodegenerative disease, UCL Queen Square Institute of Neurology, University College London, London, UK.
Christopher ParkerDepartment of Computer Science and Centre for Medical Image Computing, University College London, London, UK.
Jessica LoweHuntington's Disease Centre, Department of Neurodegenerative disease, UCL Queen Square Institute of Neurology, University College London, London, UK.
Akshay NairHuntington's Disease Centre, Department of Neurodegenerative disease, UCL Queen Square Institute of Neurology, University College London, London, UK; Max Planck University College London Centre for Computational Psychiatry and Ageing Research, UCL Queen Square Institute of Neurology, London, UK.
Claire O'CallaghanDepartment of Psychiatry and Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK; Brain and Mind Centre, University of Sydney, Sydney, NSW, Australia.
Christelle LangleyDepartment of Psychiatry and Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK.
Marina PapoutsiHuntington's Disease Centre, Department of Neurodegenerative disease, UCL Queen Square Institute of Neurology, University College London, London, UK.
Peter McColganHuntington's Disease Centre, Department of Neurodegenerative disease, UCL Queen Square Institute of Neurology, University College London, London, UK.
Carlos Estevez-FragaHuntington's Disease Centre, Department of Neurodegenerative disease, UCL Queen Square Institute of Neurology, University College London, London, UK.
Kate FayerHuntington's Disease Centre, Department of Neurodegenerative disease, UCL Queen Square Institute of Neurology, University College London, London, UK.
Henny WellingtonDepartment of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, UK; Dementia Research Institute at University College London, London, UK.
Filipe B RodriguesHuntington's Disease Centre, Department of Neurodegenerative disease, UCL Queen Square Institute of Neurology, University College London, London, UK.
Lauren M ByrneHuntington's Disease Centre, Department of Neurodegenerative disease, UCL Queen Square Institute of Neurology, University College London, London, UK.
Amanda HeselgraveDepartment of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, UK; Dementia Research Institute at University College London, London, UK.
Harpreet HyareDepartment of Brain Repair and Rehabilitation, University College London Institute of Neurology, London, UK.
Cristina SampaioCHDI Foundation, Princeton, NJ, USA; Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Lisbon, Portugal.
Henrik ZetterbergDepartment of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, UK; Dementia Research Institute at University College London, London, UK; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden.
Hui ZhangDepartment of Computer Science and Centre for Medical Image Computing, University College London, London, UK.
Edward J WildHuntington's Disease Centre, Department of Neurodegenerative disease, UCL Queen Square Institute of Neurology, University College London, London, UK.
Geraint ReesUniversity College London Institute of Cognitive Neuroscience, University College London, London, UK.
Trevor W RobbinsDepartment of Psychology and Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK.
Barbara J SahakianDepartment of Psychiatry and Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK.
Douglas LangbehnDepartment of Psychiatry, University of Iowa, Iowa City, IA, USA.
Sarah J TabriziHuntington's Disease Centre, Department of Neurodegenerative disease, UCL Queen Square Institute of Neurology, University College London, London, UK; Dementia Research Institute at University College London, London, UK. Electronic address: s.tabrizi@ucl.ac.uk.
University College London · GBHuntington's Disease Association · GBNational Hospital for Neurology and Neurosurgery · GBUniversity of Cambridge · GBUK Dementia Research Institute · GBCHDI Foundation · USUniversity of Gothenburg · SEUniversity of Iowa · USUniversity of Sydney · AU

Funding

Department of HealthMedical Research Council MR/M008592/1Wellcome TrustWellcome Trust 200181/Z/15/Z
6 · The paper itself

Abstract

backgroundDisease-modifying treatments are in development for Huntington's disease; crucial to their success is to identify a timepoint in a patient's life when there is a measurable biomarker of early neurodegeneration while clinical function is still intact. We aimed to identify this timepoint in a novel cohort of young adult premanifest Huntington's disease gene carriers (preHD) far from predicted clinical symptom onset.

methodsWe did the Huntington's disease Young Adult Study (HD-YAS) in the UK. We recruited young adults with preHD and controls matched for age, education, and sex to ensure each group had at least 60 participants with imaging data, accounting for scan fails. Controls either had a family history of Huntington's disease but a negative genetic test, or no known family history of Huntington's disease. All participants underwent detailed neuropsychiatric and cognitive assessments, including tests from the Cambridge Neuropsychological Test Automated Battery and a battery assessing emotion, motivation, impulsivity and social cognition (EMOTICOM). Imaging (done for all participants without contraindications) included volumetric MRI, diffusion imaging, and multiparametric mapping. Biofluid markers of neuronal health were examined using blood and CSF collection. We did a cross-sectional analysis using general least-squares linear models to assess group differences and associations with age and CAG length, relating to predicted years to clinical onset. Results were corrected for multiple comparisons using the false discovery rate (FDR), with FDR <0·05 deemed a significant result.

findingsData were obtained between Aug 2, 2017, and April 25, 2019. We recruited 64 young adults with preHD and 67 controls. Mean ages of participants were 29·0 years (SD 5·6) and 29·1 years (5·7) in the preHD and control groups, respectively. We noted no significant evidence of cognitive or psychiatric impairment in preHD participants 23·6 years (SD 5·8) from predicted onset (FDR 0·22-0·87 for cognitive measures, 0·31-0·91 for neuropsychiatric measures). The preHD cohort had slightly smaller putamen volumes (FDR=0·03), but this did not appear to be closely related to predicted years to onset (FDR=0·54). There were no group differences in other brain imaging measures (FDR >0·16). CSF neurofilament light protein (NfL), plasma NfL, and CSF YKL-40 were elevated in this far-from-onset preHD cohort compared with controls (FDR<0·0001, =0·01, and =0·03, respectively). CSF NfL elevations were more likely in individuals closer to expected clinical onset (FDR <0·0001).

interpretationWe report normal brain function yet a rise in sensitive measures of neurodegeneration in a preHD cohort approximately 24 years from predicted clinical onset. CSF NfL appears to be a more sensitive measure than plasma NfL to monitor disease progression. This preHD cohort is one of the earliest yet studied, and our findings could be used to inform decisions about when to initiate a potential future intervention to delay or prevent further neurodegeneration while function is intact.

fundingWellcome Trust, CHDI Foundation.

Indexed as

AdultBiomarkersBrainChitinase-3-Like Protein 1Cross-Sectional StudiesDisease ProgressionFemaleHeterozygoteHumansHuntington DiseaseMagnetic Resonance ImagingMaleNeurofilament ProteinsNeuroimagingNeuropsychological TestsPutamenBiomarkersCHI3L1 protein, humanChitinase-3-Like Protein 1neurofilament protein LNeurofilament Proteins

Identifiers

PMID32470422
PMCPMC7254065
OpenAlexW3029880661

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.