ArticleNPJ Parkinson's disease2023
Two distinct trajectories of clinical and neurodegeneration events in Parkinson's disease.
Article in NPJ Parkinson's disease, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 40 papers, 2 of them syntheses that pooled it.
What it found
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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.
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Who cites it
40 citing papers in PubMed, 2 syntheses or guidelines pooled it, 55 citations in OpenAlex.
- Challenges and Opportunities in Exploring Non-Motor Symptoms in 6-Hydroxydopamine Models of Parkinson's Disease: A Systematic Review.Journal of neurochemistry · 2025Pooled it
- Houston, We Have AI Problem! Quality Issues with Neuroimaging-Based Artificial Intelligence in Parkinson's Disease: A Systematic Review.Movement disorders : official journal of the Movement Disorder Society · 2024Pooled it
- Brain-first and body-first subtypes of Lewy body disease.Nature reviews. Neurology · 2026Review
- Spatiotemporal Progression Patterns of Striatal Dopamine Depletion and Cerebral Hypoperfusion in Parkinson's Disease.Movement disorders : official journal of the Movement Disorder Society · 2026Article
- Data-driven trajectories of atrophy explain clinical heterogeneity across Lewy body diseases.medRxiv : the preprint server for health sciences · 2026Article
- Differentiating tremor-dominant parkinson's disease from essential tremor using neuromelanin- sensitive imaging and T1w/T2w ratio.NPJ Parkinson's disease · 2026Article
- M[Formula: see text]DGAT: Multi-view multi-scale dynamic graph attention network(GAT) based prediction of Parkinson's disease(PD) progression using whole-blood RNA sequencing data.Scientific reports · 2026Article
- Characteristics and mechanisms of cognitive impairment in Parkinson disease.Nature reviews. Neurology · 2026Review
- Parkinson's disease beyond motor symptoms: a review of the validity and limitations of current classification of non-motor symptoms.Frontiers in psychiatry · 2026Review
- Differential Proteomic Landscape of Plasma Neuron-Derived Extracellular Vesicles in Parkinson's Disease with and without RBD: A Pilot Investigation.International journal of nanomedicine · 2026Article
- Visuospatial dysfunction indicates an increased risk of rapid dementia conversion in Parkinson's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Olfactory impairment and probable REM sleep behavior disorder in Parkinson's disease: clinical relevance to the single- and dual-hit hypotheses.Frontiers in aging neuroscience · 2026Article
- Progression of fragile X-associated tremor/ataxia syndrome revealed by subtype and stage inference.Brain communications · 2026Article
- Novel applications of machine learning and computational neuroscience models to neuroimaging in Parkinson's disease and related disorders.Frontiers in aging neuroscience · 2026Review
- MRI Epicenters Differentiate Spatiotemporal Patterns of Neurodegeneration in Parkinson's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- MRI structural and functional axial asymmetry in the brain-first versus body-first subtypes of Parkinson's disease.NPJ Parkinson's disease · 2025Article
- Neuropathology of Lewy body dementia: Lewy-related pathology, α-synuclein oligomers, and comorbid pathologies.Molecular neurodegeneration · 2025Review
- DualGCN-GE: integration of spatiotemporal representations from whole-blood expression data with dual-view graph convolution network to identify Parkinson's disease subtypes.BMC bioinformatics · 2025Article
- Clinical correlates of data-driven subtypes of deep gray matter atrophy and dopamine availability in early Parkinson's disease.NPJ Parkinson's disease · 2025Article
- Integrating plasma circulating protein-centered multi-omics to identify potential therapeutic targets for Parkinsonian cognitive disorders.Journal of translational medicine · 2025Article
Corrections and comments
- Erratum issued
Authors and funding
21 authors at 2 institutions in 2 countries.
Funding
Abstract
Increasing evidence suggests that Parkinson's disease (PD) exhibits disparate spatial and temporal patterns of progression. Here we used a machine-learning technique-Subtype and Stage Inference (SuStaIn) - to uncover PD subtypes with distinct trajectories of clinical and neurodegeneration events. We enrolled 228 PD patients and 119 healthy controls with comprehensive assessments of olfactory, autonomic, cognitive, sleep, and emotional function. The integrity of substantia nigra (SN), locus coeruleus (LC), amygdala, hippocampus, entorhinal cortex, and basal forebrain were assessed using diffusion and neuromelanin-sensitive MRI. SuStaIn model with above clinical and neuroimaging variables as input was conducted to identify PD subtypes. An independent dataset consisting of 153 PD patients and 67 healthy controls was utilized to validate our findings. We identified two distinct PD subtypes: subtype 1 with rapid eye movement sleep behavior disorder (RBD), autonomic dysfunction, and degeneration of the SN and LC as early manifestations, and cognitive impairment and limbic degeneration as advanced manifestations, while subtype 2 with hyposmia, cognitive impairment, and limbic degeneration as early manifestations, followed later by RBD and degeneration of the LC in advanced disease. Similar subtypes were shown in the validation dataset. Moreover, we found that subtype 1 had weaker levodopa response, more GBA mutations, and poorer prognosis than subtype 2. These findings provide new insights into the underlying disease biology and might be useful for personalized treatment for patients based on their subtype.
Identifiers
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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.