Integrated Digital and Neurogenic Exosome Biomarkers for Early Diagnosis of Parkinson's Disease: Development and Application

Based on the high-quality Parkinson's disease cohort population and biological sample database in the early stage of the team, multi-dimensional intelligent wearable device technology and machine learning were used to screen and classify digital biomarkers in the prodromal PD cohort, early PD cohort and healthy population cohort. Using peptide nanoprobes, metabolomics and Simoa technology to find the pathological molecular biomarkers of high-purity blood neurogenic exosomes in the prodromal stage of PD cohort, early PD cohort and healthy population cohort, and conduct classification and combination study. The association analysis was used to explore the specific internal relationship between digital biomarkers and neurogenic exosome molecular biomarkers, to explore the potential relationship between the two types of biomarkers, and to further apply machine learning methods to establish a fusion model for early diagnosis of PD including markers related to digital phenotype and pathological molecular mechanism, and to verify it clinically. The research results of this project are expected to bring new strategies for the early diagnosis of PD biomarkers, provide theoretical support for clinical transformation, and have important clinical significance for achieving the goal of early diagnosis and early treatment.

Study Overview

• Status: Recruiting
• Conditions: PARKINSON DISEASE (Disorder)

• Study Type: Observational
• Enrollment (Estimated): 700

Contacts and Locations

• Study Contact: Name: qinyong ye; Phone Number: 13365910205; Email: unionqyye@163.com

Study Locations

• China
  • Fujian
    • Fuzhou, Fujian, China, 350000
      • Recruiting
      • Department of Neurology, Fujian Institute of Geriatrics, Fujian Medical University Union Hospital
      • Contact: Department of Neurology, Fujian Institute of Geriatrics, Fujia Department of Neurology, Fujian Institute of Geriatrics, Fujia; Phone Number: +86 591 8621 8329

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

This study comprises a combined retrospective and prospective cohort of patients with idiopathic Parkinson's disease (PD), selected from the PD registry database maintained by our team at Fujian Medical University Union Hospital. The study population includes individuals who meet all of the following criteria: (1) diagnosed with idiopathic PD based on the Movement Disorder Society (MDS) clinical diagnostic criteria; (2) Hoehn-Yahr (H-Y) stage ≤ 2.0 during off-medication periods; and (3) Mini-Mental State Examination (MMSE) score > 24 points. Eligible participants will be identified from the existing database for retrospective data collection, while prospective follow-up data will be collected for the same cohort to enable comprehensive longitudinal analyses.

Description

Inclusion Criteria:

• 1. Healthy Control Group

  1. No severe mental illness;
  2. Mini-Mental State Examination (MMSE) score >24 points; 2. Prodromal PD Group
  1. Meets the diagnostic criteria for rapid eye movement sleep behavior disorder;
  2. Has no severe mental disorders;
  3. Mini-Mental State Examination (MMSE) score is greater than 24 points. 3. Early PD Group

  (1) Diagnosed with idiopathic Parkinson's disease based on the MDS clinical diagnostic criteria ; (3) Hoehn-Yahr (H-Y) stage <=2.0 during off-medication periods; (4) Mini-Mental State Examination (MMSE) score >24 points;

Exclusion Criteria:

1. Presence of mental, cognitive, or psychological disorders, unable to sign informed consent;
2. Presence of other diseases affecting walking distance, such as lower limb joint lesions, spinal lesions, neurological disorders, or severe cardiopulmonary diseases;
3. Presence of intracranial structural changes, cerebrovascular disease, or other neurological disorders;
4. Presence of tumors, severe liver or kidney dysfunction (indicators exceeding three times the normal value), or other conditions that significantly impact health;
5. Claustrophobia or presence of implants affecting MRI scanning.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Health control
PD prodromal group
Early PD group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mini-mental State Examination	Mini-Mental State Examination (MMSE) is a 30-item cognitive screening tool assessing orientation, memory, attention, calculation, and language, with total scores ranging from 0 to 30. Higher scores indicate better cognitive function. Scores ≥27 generally indicate normal cognition, while lower scores suggest varying degrees of impairment, with cutoffs adjusted for education and age.	baseline
Montreal Cognitive Assessment	Montreal Cognitive Assessment (MoCA) is a 10-15 minute screening tool covering 8 cognitive domains through 12 tasks, with total scores ranging from 0 to 30. Higher scores indicate better cognitive function. Scores ≥26 are generally considered normal, with a 1-point adjustment for education ≤12 years; scores <26 suggest possible cognitive impairment.	baseline
The 39-Item Parkinson's Disease Questionnaire	Non-Motor Symptoms Scale (NMSS) assesses frequency and severity of non-motor symptoms across all stages of Parkinson's disease, covering autonomic, affective, cognitive, sleep, and other domains. Total scores range from 0 to 360. Higher scores indicate worse outcome (greater symptom burden).	baseline
Hamilton Depression Rating Scale	Hamilton Depression Rating Scale (HAM-D) is a clinician-rated instrument assessing depression severity across multiple dimensions including mood, somatic symptoms, anxiety, and sleep disturbance. The 17-item version (HAM-D17) yields total scores ranging from 0 to 52. Higher scores indicate worse outcome (greater depressive symptom severity), with scores ≥23 indicating very severe depression.	baseline
hoehn-yahr stage	Hoehn and Yahr Scale (HY) is a clinician-rated instrument assessing clinical severity and disease staging in Parkinson's disease. Staging ranges from 0 (no symptoms) to 5 (severe disability requiring full dependence). Higher stages indicate worse outcome (more advanced disease with greater functional impairment), primarily based on postural instability and disability.	baseline
Movement Disorder Society-Sponsored Revision Of The Unified Parkinson's Disease Rating Scale	Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) is a comprehensive instrument assessing Parkinson's disease across four parts: non-motor symptoms, activities of daily living, motor symptoms, and complications. Total scores range from 0 to 260 (Part I: 0-52, Part II: 0-52, Part III: 0-132, Part IV: 0-24). Higher scores indicate worse outcome (greater impairment).	baseline
Wearable devices measure gait parameters	Wearable Device System (GYENNO MATRIX) is a 10-sensor system sampling at 100 Hz to capture 3D angular velocity, acceleration, and geomagnetic field data. It extracts gait parameters (step length, stride, gait cycle) and detects postural transitions (standing, sitting, turning).	baseline
Sniffin' Sticks 12	Sniffin' Sticks 12 (SS-12) is a brief olfactory screening test assessing odor identification ability using 12 pen-like odor pens. Total scores range from 0 to 12, based on the number of correctly identified odors. Higher scores indicate better outcome (superior olfactory function). It is widely used for early Parkinson's disease screening and cognitive disorder assessment.	baseline
REM sleep behavior disorderscreening questionnaire	REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ) is a 10-item self-rated scale screening for REM sleep behavior disorder, covering dream content, dream-enactment behaviors, injuries, and neurological conditions. Total scores range from 0 to 13. Higher scores indicate worse outcome (greater likelihood of abnormality), with scores ≥5 considered abnormal.	baseline
Parkinson's disease sleep scale	Parkinson's Disease Sleep Scale (PDSS) is a 15-item scale assessing sleep disturbances in Parkinson's disease, covering nighttime quality, sleep onset, maintenance, limb discomfort, dreaming, hallucinations, nocturia, and daytime sleepiness. Total scores range from 0 to 150 (0-10 per item). Higher scores indicate better outcome (fewer or less severe sleep problems).	baseline

Collaborators and Investigators

• Sponsor: Fujian Medical University Union Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2024
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: December 22, 2025
• First Submitted That Met QC Criteria: June 25, 2026
• First Posted (Actual): July 1, 2026

Study Record Updates

• Last Update Posted (Actual): July 1, 2026
• Last Update Submitted That Met QC Criteria: June 25, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Synucleinopathies; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; Movement Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Parkinson Disease
• Other Study ID Numbers: 2026KY647

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No