{
  "abstract": "Background Digital health technologies offer high-frequency, objective measures for Parkinson’s disease (PD) yet individual stratification is lacking. This study aimed to identify and predict fast versus slow PD motor progressors by integrating longitudinal clinical evaluation with smartphone motor testing.Methods In this 96-week subgroup analysis of participants in the Exenatide-PD3 trial, motor progression was measured using Movement Disorder Society-Unified Parkinson’s Disease Rating Scale Part III OFF scores and smartphone testing (baseline, weeks 24, 48, 72, 96). Fast versus slow progressors were identified using data-driven subtyping; linear mixed-effects models assessed longitudinal OFF scores. Baseline clinical and digital features (in-clinic and at-home) were used to predict 96-week motor progression. Model performance was quantified by the area under the receiver operating curve (AUC).Results Data-driven clustering identified 26.5% (26/98) as fast progressors, with higher baseline OFF scores (+18.16, 95% CI 13.70 to 22.62; adjusted p<0.001) and greater 96-week progression (+8.17, 95% CI 2.75 to 13.60; adjusted p=0.019), undetected by prespecified approaches. Baseline prediction models combining smartphone features, alone or with clinical scores, consistently outperformed the clinical model alone (best AUC=0.78 vs 0.53). Translational value of smartphone assessments was strengthened by high user acceptability (>96% support future in-clinic use) and predictive value in a deployment scenario (AUC 0.80, 95% CI 0.79 to 0.82).Conclusion Data-driven clustering identified one in four early-to-mid stage PD patients as fast motor progressors. Integrating smartphone-derived features with clinical scores improved baseline motor prediction. High user acceptability supports this approach for individual-level PD stratification, addressing heterogeneity in motor progression that may obscure treatment trial effects.",
  "authors": [
    {
      "affiliations": [
        "Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK",
        "Oxford Parkinson’s Disease Centre, Oxford, UK"
      ],
      "name": "Timothee Aubourg"
    },
    {
      "affiliations": [
        "Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK",
        "Oxford Parkinson’s Disease Centre, Oxford, UK"
      ],
      "name": "Katarina M Gunter"
    },
    {
      "affiliations": [
        "Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK",
        "Department of Clinical Neurology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK"
      ],
      "name": "Christine Lo"
    },
    {
      "affiliations": [
        "Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK",
        "Oxford Parkinson’s Disease Centre, Oxford, UK"
      ],
      "name": "Jessica Welch"
    },
    {
      "affiliations": [
        "Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK",
        "Oxford Parkinson’s Disease Centre, Oxford, UK"
      ],
      "name": "Karolien Groenewald"
    },
    {
      "affiliations": [
        "Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK",
        "Oxford Parkinson’s Disease Centre, Oxford, UK"
      ],
      "name": "Johannes C Klein"
    },
    {
      "affiliations": [
        "Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK",
        "Oxford Parkinson’s Disease Centre, Oxford, UK"
      ],
      "name": "Jamil Razzaque"
    },
    {
      "affiliations": [
        "Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK",
        "Oxford Parkinson’s Disease Centre, Oxford, UK"
      ],
      "name": "Ludo Van Hillegondsberg"
    },
    {
      "affiliations": [
        "Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK",
        "Oxford Parkinson’s Disease Centre, Oxford, UK"
      ],
      "name": "Pietro Luca Ratti"
    },
    {
      "affiliations": [
        "Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK",
        "Oxford Parkinson’s Disease Centre, Oxford, UK"
      ],
      "name": "Adriana Nastasa"
    },
    {
      "affiliations": [
        "Comprehensive Clinical Trials Unit, University College London, London, UK"
      ],
      "name": "Grace Auld"
    },
    {
      "affiliations": [
        "Comprehensive Clinical Trials Unit, University College London, London, UK"
      ],
      "name": "Rachel Mccomish"
    },
    {
      "affiliations": [
        "Comprehensive Clinical Trials Unit, University College London, London, UK"
      ],
      "name": "Alexa King"
    },
    {
      "affiliations": [
        "Comprehensive Clinical Trials Unit, University College London, London, UK"
      ],
      "name": "Kashfia Chowdhury"
    },
    {
      "affiliations": [
        "Department of Clinical and Movement Neurosciences, University College London Queen Square Institute of Neurology, London, UK"
      ],
      "name": "Nirosen Vijiaratnam"
    },
    {
      "affiliations": [
        "Department of Clinical and Movement Neurosciences, University College London Queen Square Institute of Neurology, London, UK"
      ],
      "name": "Christine Girges"
    },
    {
      "affiliations": [
        "University Hospitals Plymouth, Plymouth, UK"
      ],
      "name": "Abigail Patrick"
    },
    {
      "affiliations": [
        "University Hospitals Plymouth, Plymouth, UK"
      ],
      "name": "Jemma Inches"
    },
    {
      "affiliations": [
        "University Hospitals Plymouth, Plymouth, UK",
        "Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK"
      ],
      "name": "Camille B Carroll"
    },
    {
      "affiliations": [
        "Department of Clinical and Movement Neurosciences, University College London Queen Square Institute of Neurology, London, UK"
      ],
      "name": "Thomas Foltynie"
    },
    {
      "affiliations": [
        "Said Business School, University of Oxford, Oxford, UK",
        "Somerville College, University of Oxford, Oxford, UK"
      ],
      "name": "Siddharth Arora"
    },
    {
      "affiliations": [
        "Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK",
        "Oxford Parkinson’s Disease Centre, Oxford, UK"
      ],
      "name": "Michele T. Hu"
    }
  ],
  "title": "Identifying and predicting fast versus slow Parkinson’s disease motor progressors using clinical and digital data",
  "uid": "010a2b7f-6aa6-5300-a9b3-522caa8524ff"
}