Evidence map›Paper›PMID 34660889›Full record

ArticleNeurology. Genetics2021

Revealing the Timeline of Structural MRI Changes in Premanifest to Manifest Huntington Disease.

Peter A Wijeratne, Sara Garbarino, Sarah Gregory, Eileanoir B Johnson, Rachael I Scahill, Jane S Paulsen, Sarah J Tabrizi, Marco Lorenzi, Daniel C Alexander

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

Article in Neurology. Genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
2.6field-weighted citation impact, top 10% 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

14 citing papers in PubMed, 30 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 1 institution in 2 countries.

Peter A WijeratneCentre for Medical Image Computing (P.A.W., D.C.A.), Department of Computer Science, University College London, Gower Street; Huntington's Disease Research Centre (P.A.W., S. Gregory, E.B.J., R.I.S., S.J.T.), Department of Neurodegenerative Disease, University College London, Queen Square Institute of Neurology, London, United Kingdom; Dipartimento di Matematica (S. Garbarino), UNIGE, DIMA, Genova, Italy; Departments of Neurology and Psychiatry (J.S.P.), Carver College of Medicine, University of Iowa; and Université Côte d'Azur (M.L.), Inria, Epione Research Project, Valbonne, France.ORCID 0000-0002-4885-6241
Sara GarbarinoCentre for Medical Image Computing (P.A.W., D.C.A.), Department of Computer Science, University College London, Gower Street; Huntington's Disease Research Centre (P.A.W., S. Gregory, E.B.J., R.I.S., S.J.T.), Department of Neurodegenerative Disease, University College London, Queen Square Institute of Neurology, London, United Kingdom; Dipartimento di Matematica (S. Garbarino), UNIGE, DIMA, Genova, Italy; Departments of Neurology and Psychiatry (J.S.P.), Carver College of Medicine, University of Iowa; and Université Côte d'Azur (M.L.), Inria, Epione Research Project, Valbonne, France.ORCID 0000-0002-3583-3630
Sarah GregoryCentre for Medical Image Computing (P.A.W., D.C.A.), Department of Computer Science, University College London, Gower Street; Huntington's Disease Research Centre (P.A.W., S. Gregory, E.B.J., R.I.S., S.J.T.), Department of Neurodegenerative Disease, University College London, Queen Square Institute of Neurology, London, United Kingdom; Dipartimento di Matematica (S. Garbarino), UNIGE, DIMA, Genova, Italy; Departments of Neurology and Psychiatry (J.S.P.), Carver College of Medicine, University of Iowa; and Université Côte d'Azur (M.L.), Inria, Epione Research Project, Valbonne, France.ORCID 0000-0001-9864-8240
Eileanoir B JohnsonCentre for Medical Image Computing (P.A.W., D.C.A.), Department of Computer Science, University College London, Gower Street; Huntington's Disease Research Centre (P.A.W., S. Gregory, E.B.J., R.I.S., S.J.T.), Department of Neurodegenerative Disease, University College London, Queen Square Institute of Neurology, London, United Kingdom; Dipartimento di Matematica (S. Garbarino), UNIGE, DIMA, Genova, Italy; Departments of Neurology and Psychiatry (J.S.P.), Carver College of Medicine, University of Iowa; and Université Côte d'Azur (M.L.), Inria, Epione Research Project, Valbonne, France.ORCID 0000-0002-5271-0747
Rachael I ScahillCentre for Medical Image Computing (P.A.W., D.C.A.), Department of Computer Science, University College London, Gower Street; Huntington's Disease Research Centre (P.A.W., S. Gregory, E.B.J., R.I.S., S.J.T.), Department of Neurodegenerative Disease, University College London, Queen Square Institute of Neurology, London, United Kingdom; Dipartimento di Matematica (S. Garbarino), UNIGE, DIMA, Genova, Italy; Departments of Neurology and Psychiatry (J.S.P.), Carver College of Medicine, University of Iowa; and Université Côte d'Azur (M.L.), Inria, Epione Research Project, Valbonne, France.ORCID 0000-0002-1832-106X
Jane S PaulsenCentre for Medical Image Computing (P.A.W., D.C.A.), Department of Computer Science, University College London, Gower Street; Huntington's Disease Research Centre (P.A.W., S. Gregory, E.B.J., R.I.S., S.J.T.), Department of Neurodegenerative Disease, University College London, Queen Square Institute of Neurology, London, United Kingdom; Dipartimento di Matematica (S. Garbarino), UNIGE, DIMA, Genova, Italy; Departments of Neurology and Psychiatry (J.S.P.), Carver College of Medicine, University of Iowa; and Université Côte d'Azur (M.L.), Inria, Epione Research Project, Valbonne, France.ORCID 0000-0002-6536-9138
Sarah J TabriziCentre for Medical Image Computing (P.A.W., D.C.A.), Department of Computer Science, University College London, Gower Street; Huntington's Disease Research Centre (P.A.W., S. Gregory, E.B.J., R.I.S., S.J.T.), Department of Neurodegenerative Disease, University College London, Queen Square Institute of Neurology, London, United Kingdom; Dipartimento di Matematica (S. Garbarino), UNIGE, DIMA, Genova, Italy; Departments of Neurology and Psychiatry (J.S.P.), Carver College of Medicine, University of Iowa; and Université Côte d'Azur (M.L.), Inria, Epione Research Project, Valbonne, France.ORCID 0000-0003-2716-2045
Marco LorenziCentre for Medical Image Computing (P.A.W., D.C.A.), Department of Computer Science, University College London, Gower Street; Huntington's Disease Research Centre (P.A.W., S. Gregory, E.B.J., R.I.S., S.J.T.), Department of Neurodegenerative Disease, University College London, Queen Square Institute of Neurology, London, United Kingdom; Dipartimento di Matematica (S. Garbarino), UNIGE, DIMA, Genova, Italy; Departments of Neurology and Psychiatry (J.S.P.), Carver College of Medicine, University of Iowa; and Université Côte d'Azur (M.L.), Inria, Epione Research Project, Valbonne, France.ORCID 0000-0003-0521-2881
Daniel C AlexanderCentre for Medical Image Computing (P.A.W., D.C.A.), Department of Computer Science, University College London, Gower Street; Huntington's Disease Research Centre (P.A.W., S. Gregory, E.B.J., R.I.S., S.J.T.), Department of Neurodegenerative Disease, University College London, Queen Square Institute of Neurology, London, United Kingdom; Dipartimento di Matematica (S. Garbarino), UNIGE, DIMA, Genova, Italy; Departments of Neurology and Psychiatry (J.S.P.), Carver College of Medicine, University of Iowa; and Université Côte d'Azur (M.L.), Inria, Epione Research Project, Valbonne, France.ORCID 0000-0003-2439-350X
University of Iowa · US

Funding

Preparing for preventive clinical trials in Huntington's diseaseU01NS105509 · NINDS · UNIVERSITY OF WISCONSIN-MADISON · PI PAULSEN, JANE S · 2020 to 2025
$2.5M
Statistical disease modeling and clinimetrics to prepare for preventive trials in huntington diseaseU01NS103475 · NINDS · UNIVERSITY OF WISCONSIN-MADISON · PI PAULSEN, JANE S · 2020 to 2022
$1.7M
Medical Research Council MR/T027770/1NINDS NIH HHS U01 NS103475NINDS NIH HHS U01 NS105509
6 · The paper itself

Abstract

BACKGROUND AND

objectivesLongitudinal measurements of brain atrophy using structural MRI (sMRI) can provide powerful markers for tracking disease progression in neurodegenerative diseases. In this study, we use a disease progression model to learn individual-level disease times and hence reveal a new timeline of sMRI changes in Huntington disease (HD).

methodsWe use data from the 2 largest cohort imaging studies in HD-284 participants from TRACK-HD (100 control, 104 premanifest, and 80 manifest) and 159 participants from PREDICT-HD (36 control and 128 premanifest)-to train and test the model. We longitudinally register T1-weighted sMRI scans from 3 consecutive time points to reduce intraindividual variability and calculate regional brain volumes using an automated segmentation tool with rigorous manual quality control.

resultsOur model reveals, for the first time, the relative magnitude and timescale of subcortical and cortical atrophy changes in HD. We find that the largest (∼20% average change in magnitude) and earliest (∼2 years before average abnormality) changes occur in the subcortex (pallidum, putamen, and caudate), followed by a cascade of changes across other subcortical and cortical regions over a period of ∼11 years. We also show that sMRI, when combined with our disease progression model, provides improved prediction of onset over the current best method (root mean square error = 4.5 years and maximum error = 7.9 years vs root mean square error = 6.6 years and maximum error = 18.2 years). DISCUSSION: Our findings support the use of disease progression modeling to reveal new information from sMRI, which can potentially inform imaging marker selection for clinical trials.

Identifiers

PMID34660889
PMCPMC8515202
OpenAlexW3206815807

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Registered trials

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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.