Evidence map›Paper›PMID 33395965›Full record

ArticleNeuroImage. Clinical2020

Dementia risk in Parkinson's disease is associated with interhemispheric connectivity loss and determined by regional gene expression.

Angeliki Zarkali, Peter McColgan, Mina Ryten, Regina H Reynolds, Louise-Ann Leyland, Andrew J Lees, Geraint Rees, Rimona S Weil

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in NeuroImage. Clinical, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
–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

9 citing papers in PubMed.

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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

8 authors.

Angeliki ZarkaliDementia Research Centre, University College London, 8-11 Queen Square, London WC1N 3AR, UK. Electronic address: a.zarkali@ucl.ac.uk.
Peter McColganHuntington's Disease Centre, University College London, Russell Square House, London WC1B 5EH, UK.
Mina RytenNIHR Great Ormond Street Hospital Biomedical Research Centre, University College London, London, UK; Great Ormond Street Institute of Child Health, Genetics and Genomic Medicine, University College London, London, UK; Department of Neurodegenerative Disease, UCL Institute of Neurology, 10-12 Russell Square House, London WC1B 5EH, UK.
Regina H ReynoldsNIHR Great Ormond Street Hospital Biomedical Research Centre, University College London, London, UK; Great Ormond Street Institute of Child Health, Genetics and Genomic Medicine, University College London, London, UK; Department of Neurodegenerative Disease, UCL Institute of Neurology, 10-12 Russell Square House, London WC1B 5EH, UK.
Louise-Ann LeylandDementia Research Centre, University College London, 8-11 Queen Square, London WC1N 3AR, UK.
Andrew J LeesReta Lila Weston Institute of Neurological Studies, 1 Wakefield Street, London WC1N 1PJ, UK.
Geraint ReesInstitute of Cognitive Neuroscience, University College London, 17-19 Queen Square, London WC1N 3AR, UK; Wellcome Centre for Human Neuroimaging, University College London, 12 Queen Square, London WC1N 3AR, UK.
Rimona S WeilDementia Research Centre, University College London, 8-11 Queen Square, London WC1N 3AR, UK; Wellcome Centre for Human Neuroimaging, University College London, 12 Queen Square, London WC1N 3AR, UK; Movement Disorders Consortium, University College London, London WC1N 3BG, UK.

Funding

Department of HealthMedical Research Council MR/N008324/1Wellcome Trust 201567/Z/16/ZWellcome Trust 205167/Z/16/Z
6 · The paper itself

Abstract

Parkinson's dementia is a common and devastating part of Parkinson's disease. Whilst timing and severity vary, dementia in Parkinson's is often preceded by visual dysfunction. White matter changes, representing axonal loss, occur early in the disease process. Clarifying which white matter connections are affected in Parkinson's with visual dysfunction and why specific connections are vulnerable will provide important mechanistic insights. Here, we use diffusion tractography in 100 Parkinson's patients (33 low visual performers) and 34 controls to identify patterns of connectivity loss in Parkinson's with visual dysfunction. We examine the relationship between regional transcription and connectivity loss, using the Allen Institute for Brain Science transcriptome atlas. We show that interhemispheric connections are preferentially affected in Parkinson's low visual performers. Interhemispheric connection loss was associated with downweighted genes related to the smoothened signalling pathway (enriched in glutamatergic neurons) and upweighted metabolic genes. Risk genes for Parkinson's but not Alzheimer's or Dementia with Lewy bodies were over-represented in upweighted genes associated with interhemispheric connection loss. Our findings suggest selective vulnerability in Parkinson's patients at highest risk of dementia (those with visual dysfunction), where differences in gene expression and metabolic dysfunction, affecting longer connections with higher metabolic burden, drive connectivity loss.

Indexed as

DementiaParkinson DiseaseWhite MatterBrainGene ExpressionHumansConnectomicsDiffusion weighted imagingParkinson’s diseaseParkinson’s disease dementiaRegional gene expressionWhite matter

Identifiers

PMID33395965
PMCPMC7581968

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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.