Evidence map›Paper›PMID 36384636›Full record

ArticleGenome medicine2022

Universal clinical Parkinson's disease axes identify a major influence of neuroinflammation.

Cynthia Sandor, Stephanie Millin, Andrew Dahl, Ann-Kathrin Schalkamp, Michael Lawton, Leon Hubbard, Nabila Rahman, Nigel Williams, Yoav Ben-Shlomo, Donald G Grosset and 3 more

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

Article in Genome medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.9field-weighted citation impact, top 13% 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

6 citing papers in PubMed, 17 citations in OpenAlex.

  1. Peripheral inflammation predicts motor, cognitive, and disease progression in Parkinson's disease: A 4-year longitudinal study from the PPMI cohorts.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026
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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

13 authors at 7 institutions in 2 countries.

Cynthia Sandor *UK Dementia Research Institute, Cardiff University, Cardiff, CF24 4HQ, UK. sandorc@cardiff.ac.uk.ORCID 0000-0002-8905-1052
Stephanie Millin *Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, OX1 3PT, UK.
Andrew DahlWellcome Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK.
Ann-Kathrin SchalkampUK Dementia Research Institute, Cardiff University, Cardiff, CF24 4HQ, UK.
Michael LawtonSchool of Social and Community Medicine, University of Bristol, Bristol, BS8 1TH, UK.
Leon HubbardMRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, CF24 4HQ, UK.
Nabila RahmanUK Dementia Research Institute, Cardiff University, Cardiff, CF24 4HQ, UK.
Nigel WilliamsMRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, CF24 4HQ, UK.
Yoav Ben-ShlomoSchool of Social and Community Medicine, University of Bristol, Bristol, BS8 1TH, UK.
Donald G GrossetDepartment of Neurology, Institute of Neurological Sciences, Queen Elizabeth University Hospital, G51 4LB, Glasgow, UK.
Michele T HuDepartment of Physiology, Anatomy and Genetics, Le Gros Clark Building, Oxford Parkinson's Disease Centre, University of Oxford, Oxford, OX1 3PT, UK.
Jonathan MarchiniWellcome Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK.
Caleb WebberUK Dementia Research Institute, Cardiff University, Cardiff, CF24 4HQ, UK. webberc4@cardiff.ac.uk.
UK Dementia Research Institute · GBCardiff University · GBCentre for Human Genetics · GBUniversity of Bristol · GBUniversity of Oxford · GBNuffield Orthopaedic Centre · GBQueen Elizabeth University Hospital · GB

Funding

Department of HealthHCRW_ HS-20-11Medical Research Council G0900747Medical Research Council G0900747 91070Medical Research Council MR/L010305/1Parkinson's UK J-0901Wellcome TrustWellcome Trust 090532/Z/09/Z
6 · The paper itself

Abstract

backgroundThere is large individual variation in both clinical presentation and progression between Parkinson's disease patients. Generation of deeply and longitudinally phenotyped patient cohorts has enormous potential to identify disease subtypes for prognosis and therapeutic targeting.

methodsReplicating across three large Parkinson's cohorts (Oxford Discovery cohort (n = 842)/Tracking UK Parkinson's study (n = 1807) and Parkinson's Progression Markers Initiative (n = 472)) with clinical observational measures collected longitudinally over 5-10 years, we developed a Bayesian multiple phenotypes mixed model incorporating genetic relationships between individuals able to explain many diverse clinical measurements as a smaller number of continuous underlying factors ("phenotypic axes").

resultsWhen applied to disease severity at diagnosis, the most influential of three phenotypic axes "Axis 1" was characterised by severe non-tremor motor phenotype, anxiety and depression at diagnosis, accompanied by faster progression in cognitive function measures. Axis 1 was associated with increased genetic risk of Alzheimer's disease and reduced CSF Aβ1-42 levels. As observed previously for Alzheimer's disease genetic risk, and in contrast to Parkinson's disease genetic risk, the loci influencing Axis 1 were associated with microglia-expressed genes implicating neuroinflammation. When applied to measures of disease progression for each individual, integration of Alzheimer's disease genetic loci haplotypes improved the accuracy of progression modelling, while integrating Parkinson's disease genetics did not.

conclusionsWe identify universal axes of Parkinson's disease phenotypic variation which reveal that Parkinson's patients with high concomitant genetic risk for Alzheimer's disease are more likely to present with severe motor and non-motor features at baseline and progress more rapidly to early dementia.

Indexed as

Alzheimer DiseaseParkinson DiseaseBayes TheoremCohort StudiesHumansNeuroinflammatory DiseasesDeeply phenotyped cohortsNeuro-inflammationParkinson’s disease

Identifiers

PMID36384636
PMCPMC9670420
OpenAlexW4309323259

What OpenQuestion holds

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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.