Evidence map›Paper›PMID 36975168›Full record

ArticleBrain : a journal of neurology2023

Progression of atypical parkinsonian syndromes: PROSPECT-M-UK study implications for clinical trials.

Duncan Street, Edwin Jabbari, Alyssa Costantini, P Simon Jones, Negin Holland, Timothy Rittman, Marte T Jensen, Viorica Chelban, Yen Y Goh, Tong Guo and 23 more

Abstract readMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Brain : a journal of neurology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

32 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
  3. Article
  4. Article
  5. A Brainstem Radiomics Framework to Distinguish Progressive Supranuclear Palsy from Parkinson's Disease.Movement disorders : official journal of the Movement Disorder Society · 2026
    Article
  6. Article
  7. Review
  8. Article
  9. Review
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Brain Atrophy Does Not Predict Clinical Progression in Progressive Supranuclear Palsy.Movement disorders : official journal of the Movement Disorder Society · 2025
    Article
  16. Article
  17. Article
  18. Article
  19. Review
  20. Differences in neuropsychological performance across clinical variants of progressive supranuclear palsy.Journal of the International Neuropsychological Society : JINS · 2025
    Article
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

33 authors.

Duncan StreetUniversity of Cambridge Department of Clinical Neurosciences and Cambridge University Hospitals NHS Trust, Cambridge, CB2 OQQ, UK.ORCID 0000-0003-2168-2242
Edwin JabbariDepartment of Clinical and Movement Neurosciences, University College London, Queen Square Institute of Neurology, London, WC1N 3BG, UK.ORCID 0000-0001-6844-882X
Alyssa CostantiniDepartment of Clinical and Movement Neurosciences, University College London, Queen Square Institute of Neurology, London, WC1N 3BG, UK.
P Simon JonesUniversity of Cambridge Department of Clinical Neurosciences and Cambridge University Hospitals NHS Trust, Cambridge, CB2 OQQ, UK.
Negin HollandUniversity of Cambridge Department of Clinical Neurosciences and Cambridge University Hospitals NHS Trust, Cambridge, CB2 OQQ, UK.
Timothy RittmanUniversity of Cambridge Department of Clinical Neurosciences and Cambridge University Hospitals NHS Trust, Cambridge, CB2 OQQ, UK.ORCID 0000-0003-1063-6937
Marte T JensenDepartment of Clinical and Movement Neurosciences, University College London, Queen Square Institute of Neurology, London, WC1N 3BG, UK.
Viorica ChelbanDepartment of Neuromuscular Diseases, University College London, Queen Square Institute of Neurology, London, WC1N 3BG, UK.ORCID 0000-0002-7797-0756
Yen Y GohDepartment of Neuromuscular Diseases, University College London, Queen Square Institute of Neurology, London, WC1N 3BG, UK.
Tong GuoDepartment of Clinical and Movement Neurosciences, University College London, Queen Square Institute of Neurology, London, WC1N 3BG, UK.
Amanda J HeslegraveDepartment of Neurodegenerative Disease, University College London, Queen Square Institute of Neurology, London, WC1N 3BG, UK.
Federico RoncaroliGeoffrey Jefferson Brain Research Centre, Division of Neuroscience, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, M6 8HD, UK.
Johannes C KleinWellcome Centre for Integrative Neuroimaging, Oxford Centre for Functional MRI of the Brain, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, OX3 9DU, UK.
Olaf AnsorgeNuffield Department of Clinical Neurosciences, University of Oxford, Oxford, OX3 9DU, UK.
Kieren S J AllinsonUniversity of Cambridge Department of Clinical Neurosciences and Cambridge University Hospitals NHS Trust, Cambridge, CB2 OQQ, UK.
Zane JaunmuktaneDepartment of Clinical and Movement Neurosciences, University College London, Queen Square Institute of Neurology, London, WC1N 3BG, UK.
Tamas ReveszQueen Square Brain Bank for Neurological Disorders, University College London, Queen Square Institute of Neurology, London, WC1N 3BG, UK.
Thomas T WarnerQueen Square Brain Bank for Neurological Disorders, University College London, Queen Square Institute of Neurology, London, WC1N 3BG, UK.ORCID 0000-0001-6195-6995
Andrew J LeesQueen Square Brain Bank for Neurological Disorders, University College London, Queen Square Institute of Neurology, London, WC1N 3BG, UK.ORCID 0000-0002-2476-4385
Henrik ZetterbergDepartment of Neurodegenerative Disease, University College London, Queen Square Institute of Neurology, London, WC1N 3BG, UK.
Lucy L RussellDepartment of Neurodegenerative Disease, University College London, Queen Square Institute of Neurology, London, WC1N 3BG, UK.
Martina BocchettaCentre for Cognitive and Clinical Neuroscience, Division of Psychology, Department of Life Sciences, College of Health, Medicine and Life Sciences, Brunel University London, London, UB8 3PH, UK.ORCID 0000-0003-1814-5024
Jonathan D RohrerDepartment of Neurodegenerative Disease, University College London, Queen Square Institute of Neurology, London, WC1N 3BG, UK.
David J BurnFaculty of Medical Sciences, Newcastle University, Newcastle, NE2 4HH, UK.
Nicola PaveseClinical Ageing Research Unit, Newcastle University, Newcastle, NE4 5PL, UK.
Alexander GerhardDivision of Neuroscience, Wolfson Molecular Imaging Centre, University of Manchester, Manchester, N20 3LJ, UK.ORCID 0000-0002-8071-6062
Christopher KobyleckiDivision of Neuroscience, Wolfson Molecular Imaging Centre, University of Manchester, Manchester, N20 3LJ, UK.
P Nigel LeighDepartment of Neuroscience, Brighton and Sussex Medical School, Brighton, BN1 9PX, UK.
Alistair ChurchDepartment of Neurology, Royal Gwent Hospital, Newport, NP20 2UB, UK.
Michele T M HuNuffield Department of Clinical Neurosciences, University of Oxford, Oxford, OX3 9DU, UK.
Henry HouldenDepartment of Clinical and Movement Neurosciences, University College London, Queen Square Institute of Neurology, London, WC1N 3BG, UK.ORCID 0000-0002-2866-7777
Huw MorrisDepartment of Clinical and Movement Neurosciences, University College London, Queen Square Institute of Neurology, London, WC1N 3BG, UK.ORCID 0000-0002-5473-3774
James B RoweUniversity of Cambridge Department of Clinical Neurosciences and Cambridge University Hospitals NHS Trust, Cambridge, CB2 OQQ, UK.

Funding

Medical Research Council MR/M008525/1Medical Research Council MR/T046015/1Medical Research Council MR/Y008219/1Wellcome Trust 103838Wellcome Trust 220258
6 · The paper itself

Abstract

The advent of clinical trials of disease-modifying agents for neurodegenerative disease highlights the need for evidence-based end point selection. Here we report the longitudinal PROSPECT-M-UK study of progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), multiple system atrophy (MSA) and related disorders, to compare candidate clinical trial end points. In this multicentre UK study, participants were assessed with serial questionnaires, motor examination, neuropsychiatric and MRI assessments at baseline, 6 and 12 months. Participants were classified by diagnosis at baseline and study end, into Richardson syndrome, PSP-subcortical (PSP-parkinsonism and progressive gait freezing subtypes), PSP-cortical (PSP-frontal, PSP-speech and language and PSP-CBS subtypes), MSA-parkinsonism, MSA-cerebellar, CBS with and without evidence of Alzheimer's disease pathology and indeterminate syndromes. We calculated annual rate of change, with linear mixed modelling and sample sizes for clinical trials of disease-modifying agents, according to group and assessment type. Two hundred forty-three people were recruited [117 PSP, 68 CBS, 42 MSA and 16 indeterminate; 138 (56.8%) male; age at recruitment 68.7 ± 8.61 years]. One hundred and fifty-nine completed the 6-month assessment (82 PSP, 27 CBS, 40 MSA and 10 indeterminate) and 153 completed the 12-month assessment (80 PSP, 29 CBS, 35 MSA and nine indeterminate). Questionnaire, motor examination, neuropsychiatric and neuroimaging measures declined in all groups, with differences in longitudinal change between groups. Neuroimaging metrics would enable lower sample sizes to achieve equivalent power for clinical trials than cognitive and functional measures, often achieving N < 100 required for 1-year two-arm trials (with 80% power to detect 50% slowing). However, optimal outcome measures were disease-specific. In conclusion, phenotypic variance within PSP, CBS and MSA is a major challenge to clinical trial design. Our findings provide an evidence base for selection of clinical trial end points, from potential functional, cognitive, clinical or neuroimaging measures of disease progression.

Indexed as

Multiple System AtrophyParkinsonian DisordersSupranuclear Palsy, ProgressiveAgedFemaleHumansMagnetic Resonance ImagingMaleMiddle AgedUnited Kingdomclinical trialscorticobasal syndromemultiple system atrophyprogressive supranuclear palsysample size

Identifiers

PMID36975168
PMCPMC10393398

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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.