ReviewJournal of Parkinson's disease2019
Brain-First versus Gut-First Parkinson's Disease: A Hypothesis.
Review in Journal of Parkinson's disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 265 papers, 1 of them a synthesis that pooled 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.
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.
Ketogenic Diet Interventions in Parkinson's Disease: Safeguarding the Gut Microbiome
A Comprehensive, Multimodal Characterization of Prodromal PD in Subjects With RBD
Who cites it
265 citing papers in PubMed, 1 synthesis or guideline pooled it.
- "Brain-First" vs. "Body-First" PD: Definitions and Implications in Everyday Clinical Practice: A Systematic Review.Medicina (Kaunas, Lithuania) · 2026Pooled it
- Feasibility, safety and efficacy of multi-dose vagus nerve stimulation in Parkinson's disease: a double-blind, randomised sham-controlled proof-of-concept study.Journal of neurology · 2025Trial
- An acoustic-only multivariable diagnostic model for Parkinson's disease using bowel sound acoustic signatures.Journal of Parkinson's disease · 2026Article
- Repurposing Anticancer Drugs in Parkinson's Treatment: Molecular Pathways Driving Neuroprotection and Therapeutic Advancement.Molecular neurobiology · 2026Review
- Brain-first and body-first subtypes of Lewy body disease.Nature reviews. Neurology · 2026Review
- An exploratoryEuropean journal of nuclear medicine and molecular imaging · 2026Article
- Stress and Parkinson's disease: from dysfunctional detection to impaired handling: a narrative review.Journal of neural transmission (Vienna, Austria : 1996) · 2026Review
- Article
- Review
- Pesticide exposure and multidomain symptom burden in Parkinson's disease: a longitudinal triangulation study.NPJ Parkinson's disease · 2026Article
- Review
- Decoding Prodromal Lewy Body Disease: Clinical Differences Between Isolated REM Sleep Behavior Disorder and Hyposmia With Dopamine Transporter Deficit.European journal of neurology · 2026Article
- Review
- Global network and local vulnerabilities underlie brain atrophy across Parkinson's disease stages.Brain : a journal of neurology · 2026Article
- Brain-first versus body-first Parkinson's disease: Differential findings on pupillary, brainstem and vagus sonography.Journal of neurology · 2026Article
- Cardiac sympathetic degeneration informs the duration of the prodromal stage of body-first Lewy body disease.NPJ Parkinson's disease · 2026Article
- Preparing for Parkinson's disease prevention trials: Current progress and future directions.Journal of Parkinson's disease · 2026Review
- The axonal transport velocity of prions is independent of prion formation.PLoS pathogens · 2026Article
- 6-Shogaol Complements Levodopa Therapy by Modulating Brain-Gut Metabolomes in a Parkinson's Disease Model.Biomolecules & therapeutics · 2026Article
- Role of α-Synuclein in the Prefrontal Cortex: From Physiological Synaptic Modulation to Synaptic Failure in Parkinson's Disease.Biomedicines · 2026Review
205 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Parkinson's disease (PD) is a highly heterogeneous disorder, which probably consists of multiple subtypes. Aggregation of misfolded alpha-synuclein and propagation of these proteinacious aggregates through interconnected neural networks is believed to be a crucial pathogenetic factor. It has been hypothesized that the initial pathological alpha-synuclein aggregates originate in the enteric or peripheral nervous system (PNS) and invade the central nervous system (CNS) via retrograde vagal transport. However, evidence from neuropathological studies suggests that not all PD patients can be reconciled with this hypothesis. Importantly, a small fraction of patients do not show pathology in the dorsal motor nucleus of the vagus. Here, it is hypothesized that PD can be divided into a PNS-first and a CNS-first subtype. The former is tightly associated with REM sleep behavior disorder (RBD) during the prodromal phase and is characterized by marked autonomic damage before involvement of the dopaminergic system. In contrast, the CNS-first phenotype is most often RBD-negative during the prodromal phase and characterized by nigrostriatal dopaminergic dysfunction prior to involvement of the autonomic PNS. The existence of these subtypes is supported by in vivo imaging studies of RBD-positive and RBD-negative patient groups and by histological evidence- reviewed herein. The present proposal provides a fresh hypothesis-generating framework for future studies into the etiopathogenesis of PD and seems capable of explaining a number of discrepant findings in the neuropathological literature.
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Registered trials
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.