Evidence map›Paper›PMID 29456161›Full record

ArticleThe Lancet. Neurology2018

The effect of LRRK2 mutations on the cholinergic system in manifest and premanifest stages of Parkinson's disease: a cross-sectional PET study.

Shu-Ying Liu, Daryl J Wile, Jessie Fanglu Fu, Jason Valerio, Elham Shahinfard, Siobhan McCormick, Rostom Mabrouk, Nasim Vafai, Jess McKenzie, Nicole Neilson and 14 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Lancet. Neurology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed, 1 pooled it
5.6field-weighted citation impact, top 4% 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

46 citing papers in PubMed, 1 synthesis or guideline pooled it, 81 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. Review
  6. Article
  7. Article
  8. Heartbeat signature for predicting motor and non-motor involvement among nonparkinsonian LRRK2 G2019S mutation carriers.Clinical autonomic research : official journal of the Clinical Autonomic Research Society · 2025
    Article
  9. Article
  10. Article
  11. Article
  12. Parkinson's Disease: Biomarkers for Diagnosis and Disease Progression.International journal of molecular sciences · 2024
    Review
  13. Review
  14. Article
  15. Article
  16. Review
  17. Article
  18. Review
  19. Altered Cholinergic Innervation in De Novo Parkinson's Disease with and Without Cognitive Impairment.Movement disorders : official journal of the Movement Disorder Society · 2022
    Article
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

24 authors at 8 institutions in 4 countries.

Shu-Ying LiuDjavad Mowafaghian Centre for Brain Health, Pacific Parkinson's Research Centre, University of British Columbia and Vancouver Coastal Health, Vancouver, BC, Canada; Department of Neurobiology, Neurology, and Geriatrics, Xuanwu Hospital Capital Medical University, Beijing, China.
Daryl J WileUniversity of British Columbia-Okanagan Southern Medical Program, Kelowna, BC, Canada.
Jessie Fanglu FuDepartment of Physics and Astronomy, University of British Columbia, Vancouver, BC, Canada.
Jason ValerioDjavad Mowafaghian Centre for Brain Health, Pacific Parkinson's Research Centre, University of British Columbia and Vancouver Coastal Health, Vancouver, BC, Canada.
Elham ShahinfardDjavad Mowafaghian Centre for Brain Health, Pacific Parkinson's Research Centre, University of British Columbia and Vancouver Coastal Health, Vancouver, BC, Canada.
Siobhan McCormickDjavad Mowafaghian Centre for Brain Health, Pacific Parkinson's Research Centre, University of British Columbia and Vancouver Coastal Health, Vancouver, BC, Canada.
Rostom MabroukDepartment of Physics and Astronomy, University of British Columbia, Vancouver, BC, Canada.
Nasim VafaiDjavad Mowafaghian Centre for Brain Health, Pacific Parkinson's Research Centre, University of British Columbia and Vancouver Coastal Health, Vancouver, BC, Canada.
Jess McKenzieDjavad Mowafaghian Centre for Brain Health, Pacific Parkinson's Research Centre, University of British Columbia and Vancouver Coastal Health, Vancouver, BC, Canada.
Nicole NeilsonDjavad Mowafaghian Centre for Brain Health, Pacific Parkinson's Research Centre, University of British Columbia and Vancouver Coastal Health, Vancouver, BC, Canada.
Alexandra Perez-SorianoDjavad Mowafaghian Centre for Brain Health, Pacific Parkinson's Research Centre, University of British Columbia and Vancouver Coastal Health, Vancouver, BC, Canada.
Julieta E ArenaDjavad Mowafaghian Centre for Brain Health, Pacific Parkinson's Research Centre, University of British Columbia and Vancouver Coastal Health, Vancouver, BC, Canada.
Mariya CherkasovaDjavad Mowafaghian Centre for Brain Health, Pacific Parkinson's Research Centre, University of British Columbia and Vancouver Coastal Health, Vancouver, BC, Canada.
Piu ChanDepartment of Neurobiology, Neurology, and Geriatrics, Xuanwu Hospital Capital Medical University, Beijing, China.
Jing ZhangDepartment of Pathology, University of Washington, Seattle, WA, USA.
Cyrus P ZabetianVeterans Affairs Puget Sound Health Care System and Department of Neurology, University of Washington, Seattle, WA, USA.
Jan O AaslyNorwegian University of Science and Technology, Trondheim, Norway.
Zbigniew K WszolekMayo Clinic, Jacksonville, FL, USA.
Martin J McKeownDjavad Mowafaghian Centre for Brain Health, Pacific Parkinson's Research Centre, University of British Columbia and Vancouver Coastal Health, Vancouver, BC, Canada.
Michael J AdamDepartment of Chemistry, University of British Columbia, Vancouver, BC, Canada.
Thomas J RuthTRIUMF (Tri-University Meson Facility), Vancouver, BC, Canada.
Michael SchulzerDjavad Mowafaghian Centre for Brain Health, Pacific Parkinson's Research Centre, University of British Columbia and Vancouver Coastal Health, Vancouver, BC, Canada.
Vesna SossiDepartment of Physics and Astronomy, University of British Columbia, Vancouver, BC, Canada.
A Jon StoesslDjavad Mowafaghian Centre for Brain Health, Pacific Parkinson's Research Centre, University of British Columbia and Vancouver Coastal Health, Vancouver, BC, Canada. Electronic address: jstoessl@mail.ubc.ca.
Vancouver Coastal Health · CAUniversity of British Columbia · CAUniversity of Washington · USCapital Medical University · CNNorwegian University of Science and Technology · NOOkanagan University College · CATRIUMF · CAWinnMed · US

Funding

Udall Center Director's meeting poster awardP50NS062684 · NINDS · UNIVERSITY OF WASHINGTON · PI MONTINE, THOMAS J · 2009 to 2020
$18.3M
Neuropathology CoreP50NS072187 · NINDS · MAYO CLINIC JACKSONVILLE · PI DICKSON, DENNIS WILLIAM · 2010 to 2017
$8.7M
Biomarkers for Preclinical Parkinson's diseaseR01NS057567 · NINDS · UNIVERSITY OF WASHINGTON · PI ZHANG, JING · 2008 to 2012
$3.1M
Using Multiplex Families to map Genes that Modify Susceptibility and Age at OnsetR01NS065070 · NINDS · UNIVERSITY OF WASHINGTON · PI ZABETIAN, CYRUS P · 2009 to 2012
$2.0M
NINDS NIH HHS P50 NS062684NINDS NIH HHS P50 NS072187NINDS NIH HHS R01 NS057567NINDS NIH HHS R01 NS065070
6 · The paper itself

Abstract

backgroundMarkers of neuroinflammation are increased in some patients with LRRK2 Parkinson's disease compared with individuals with idiopathic Parkinson's disease, suggesting possible differences in disease pathogenesis. Previous PET studies have suggested amplified dopamine turnover and preserved serotonergic innervation in LRRK2 mutation carriers. We postulated that patients with LRRK2 mutations might show abnormalities of central cholinergic activity, even before the diagnosis of Parkinson's disease.

methodsBetween June, 2009, and December, 2015, we recruited participants from four movement disorder clinics in Canada, Norway, and the USA. Patients with Parkinson's disease were diagnosed by movement disorder neurologists on the basis of the UK Parkinson's Disease Society Brain Bank criteria. LRRK2 carrier status was confirmed by bidirectional Sanger sequencing. We used the PET tracer N-

findingsWe recruited 14 patients with LRRK2 Parkinson's disease, 16 LRRK2 mutation carriers without Parkinson's disease, eight patients with idiopathic Parkinson's disease, and 11 healthy controls. We noted significant between-group differences in rates of acetylcholinesterase hydrolysis in cortical regions (average cortex p=0·009, default mode network-related regions p=0·006, limbic network-related regions p=0·020) and the thalamus (p=0·008). LRRK2 mutation carriers without Parkinson's disease had increased acetylcholinesterase hydrolysis rates compared with healthy controls in the cortex (average cortex, p=0·046). Patients with LRRK2 Parkinson's disease had significantly higher acetylcholinesterase activity in some cortical regions (average cortex p=0·043, default mode network-related regions p=0·021) and the thalamus (thalamus p=0·004) compared with individuals with idiopathic disease. Acetylcholinesterase hydrolysis rates in healthy controls were correlated inversely with age.

interpretationLRRK2 mutations are associated with significantly increased cholinergic activity in the brain in mutation carriers without Parkinson's disease compared with healthy controls and in LRRK2 mutation carriers with Parkinson's disease compared with individuals with idiopathic disease. Changes in cholinergic activity might represent early and sustained attempts to compensate for LRRK2-related dysfunction, or alteration of acetylcholinesterase in non-neuronal cells.

fundingMichael J Fox Foundation, National Institutes of Health, and Pacific Alzheimer Research Foundation.

Indexed as

AcetylcholinesteraseAdultAgedBrainCholinergic NeuronsCross-Sectional StudiesFemaleHumansLeucine-Rich Repeat Serine-Threonine Protein Kinase-2MaleMiddle AgedMutationParkinson DiseasePositron-Emission TomographyProdromal SymptomsAcetylcholinesteraseLeucine-Rich Repeat Serine-Threonine Protein Kinase-2LRRK2 protein, human

Identifiers

PMID29456161
PMCPMC5942215
OpenAlexW2786632296

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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.