A Multimodal Prospective Cohort Study of Parkinsonism

This is a single-center, prospective, observational cohort study designed to investigate the progression and differential diagnosis of Parkinsonism using a multimodal approach. The study plans to enroll 400 patients with Parkinsonism, 120 patients with rapid eye movement sleep behavior disorder, and 120 healthy controls, with follow-up for 5 years.

Assessments will include neuroimaging, clinical rating scales, biological samples, blood flow evaluation, neurophysiological testing, tremor analysis, and voice and video assessments. The study aims to characterize disease progression, explore factors associated with progression from rapid eye movement sleep behavior disorder to Parkinsonism, and improve the ability to distinguish among different Parkinsonian disorders.

Study Overview

• Status: Recruiting
• Conditions: Parkinsonism; REM Sleep Behavior Disorder

• Study Type: Observational
• Enrollment (Estimated): 640

Contacts and Locations

• Study Contact: Name: Jun Liu, Professor; Phone Number: +86-021-64370045; Email: lj11128@rjh.com.cn

Study Locations

• China
  • Shanghai, China, 200025
    • Recruiting
    • Department of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Participants will include patients with Parkinsonism, patients with rapid eye movement sleep behavior disorder, and healthy controls. Patients will be mainly recruited from the inpatient wards of the Department of Neurology at Ruijin Hospital after diagnostic and eligibility screening. Healthy controls will be recruited mainly from patients' family members or the community.

Description

Inclusion Criteria:

For participants with rapid eye movement sleep behavior disorder:

• Meets the diagnostic criteria for rapid eye movement sleep behavior disorder established by the American Academy of Sleep Medicine
• Chinese citizen
• Age >30 years and <80 years
• Able to understand the study, show good compliance, and provide written informed consent personally or through a legal representative

For participants with Parkinsonism:

• Meets the diagnostic criteria for Parkinsonism established by the International Parkinson and Movement Disorder Society
• Chinese citizen
• Age >30 years and <80 years
• Able to understand the study, show good compliance, and provide written informed consent personally or through a legal representative

For healthy controls:

• No neurodegenerative disease, no history of head trauma or head surgery, no history of stroke, epilepsy, tumor, or psychiatric disease
• No metal implants or cardiac pacemaker
• No severe chronic disease or severe hepatic or renal insufficiency
• Chinese citizen
• Age >30 years and <80 years
• Education level of primary school or above
• Able to understand the study, show good compliance, and provide written informed consent personally or through a legal representative

Exclusion Criteria:

• Significant cognitive impairment (MMSE ≤23)
• Unable to sign the informed consent form or unable to complete study procedures for other reasons
• Any other condition that, in the opinion of the investigator, makes the participant unsuitable for this study

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Parkinsonism; Participants with Parkinsonism who meet the study eligibility criteria. This cohort includes patients diagnosed according to the International Parkinson and Movement Disorder Society criteria. Participants will undergo multimodal assessments, including neuroimaging, clinical rating scales, biospecimen collection, blood flow evaluation, neurophysiological testing, tremor analysis, and voice and video assessments during follow-up.
REM Sleep Behavior Disorder; Participants with rapid eye movement sleep behavior disorder who meet the study eligibility criteria. Participants will undergo multimodal assessments, including neuroimaging, clinical rating scales, biospecimen collection, blood flow evaluation, neurophysiological testing, tremor analysis, and voice and video assessments during follow-up to evaluate progression toward Parkinsonism.
Healthy Controls; Healthy control participants who meet the study eligibility criteria and have no major neurological disorders. Participants will undergo the same multimodal assessments as the disease cohorts for comparison, including neuroimaging, clinical rating scales, biospecimen collection, blood flow evaluation, neurophysiological testing, tremor analysis, and voice and video assessments.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Substantia nigra quantitative susceptibility mapping value	Quantitative susceptibility mapping (QSM) value measured in the substantia nigra by neuroimaging to assess disease-related imaging changes.	Baseline and annually for up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
UMSARS total score	Unified Multiple System Atrophy Rating Scale total score to assess motor and disease-related clinical severity. Higher scores indicate worse impairment.	Baseline and annually for up to 5 years
MDS-UPDRS total score	Movement Disorder Society-Unified Parkinson's Disease Rating Scale total score to assess Parkinsonian symptom severity. Higher scores indicate worse impairment.	Baseline and annually for up to 5 years
PSPRS total score	Progressive Supranuclear Palsy Rating Scale total score to assess disease severity in participants with PSP features. Higher scores indicate worse impairment.	Baseline and annually for up to 5 years
Tinetti gait and balance test score	Tinetti gait and balance test score to assess gait and balance performance. Lower scores indicate worse gait and balance function.	Baseline and annually for up to 5 years
Berg Balance Scale score	Berg Balance Scale score to assess balance function. Lower scores indicate worse balance.	Baseline and annually for up to 5 years
Hoehn and Yahr stage	Hoehn and Yahr stage to assess Parkinsonian disease stage. Higher stages indicate more advanced disease.	Baseline and annually for up to 5 years
NMSQ total score	Non-Motor Symptoms Questionnaire total score to assess non-motor symptom burden. Higher scores indicate greater non-motor symptom burden.	Baseline and annually for up to 5 years
SCOPA-AUT total score	Scales for Outcomes in Parkinson's Disease-Autonomic total score to assess autonomic dysfunction. Higher scores indicate worse autonomic symptoms.	Baseline and annually for up to 5 years
SS-16 olfactory score	Sniffin' Sticks 16-item olfactory identification score to assess olfactory function. Higher scores indicate better olfactory performance.	Baseline and annually for up to 5 years
Wexner constipation score	Wexner constipation score to assess constipation severity. Higher scores indicate worse constipation symptoms.	Baseline and annually for up to 5 years
PDQ-39 total score	Parkinson's Disease Questionnaire-39 total score to assess health-related quality of life. Higher scores indicate worse quality of life.	Baseline and annually for up to 5 years
EAT score	Eating Assessment Tool score to assess swallowing difficulty. Higher scores indicate worse swallowing symptoms.	Baseline and annually for up to 5 years
RBDSQ total score	Rapid Eye Movement Sleep Behavior Disorder Screening Questionnaire total score to assess REM sleep behavior disorder symptoms. Higher scores indicate worse symptom burden.	Baseline and annually for up to 5 years
PSQI total score	Pittsburgh Sleep Quality Index total score to assess sleep quality. Higher scores indicate worse sleep quality.	Baseline and annually for up to 5 years
HAMD-17 total score	17-item Hamilton Depression Rating Scale total score to assess depressive symptoms. Higher scores indicate worse depressive symptom severity.	Baseline and annually for up to 5 years
HAMA total score	Hamilton Anxiety Rating Scale total score to assess anxiety symptoms. Higher scores indicate worse anxiety symptom severity.	Baseline and annually for up to 5 years
MoCA score	Montreal Cognitive Assessment score to assess global cognitive function. Higher scores indicate better cognitive performance.	Baseline and annually for up to 5 years
MMSE score	Mini-Mental State Examination score to assess global cognitive function. Higher scores indicate better cognitive performance.	Baseline and annually for up to 5 years
FAB score	Frontal Assessment Battery score to assess frontal executive function. Higher scores indicate better executive performance.	Baseline and annually for up to 5 years
Oxyhemoglobin level during postural and motor testing	Oxyhemoglobin level measured by near-infrared spectroscopy during postural and motor testing as a quantitative indicator of brain functional response.	Baseline and annually for up to 5 years
Deoxyhemoglobin level during postural and motor testing	Deoxyhemoglobin level measured by near-infrared spectroscopy during postural and motor testing as a quantitative indicator of brain functional response.	Baseline and annually for up to 5 years
Total hemoglobin level during postural and motor testing	Total hemoglobin level measured by near-infrared spectroscopy during postural and motor testing as a quantitative indicator of brain functional response.	Baseline and annually for up to 5 years
24-hour mean systolic blood pressure	Mean systolic blood pressure measured by 24-hour ambulatory blood pressure monitoring. Units: mmHg.	Baseline and annually for up to 5 years
24-hour mean diastolic blood pressure	Mean diastolic blood pressure measured by 24-hour ambulatory blood pressure monitoring. Units: mmHg.	Baseline and annually for up to 5 years
24-hour mean heart rate	Mean heart rate measured by 24-hour ambulatory blood pressure monitoring. Units: beats per minute.	Baseline and annually for up to 5 years
Tremor frequency	Tremor frequency measured by tremor analysis as a quantitative indicator of tremor characteristics.	Baseline and annually for up to 5 years
Tremor amplitude	Tremor amplitude measured by tremor analysis as a quantitative indicator of tremor severity.	Baseline and annually for up to 5 years
Timed Up and Go test duration derived from wearable assessment	Timed Up and Go (TUG) test duration derived from wearable device-based assessment to evaluate mobility and functional movement performance.	Baseline and annually for up to 5 years
Machine vision-derived UPDRS Part III score	Unified Parkinson's Disease Rating Scale Part III motor score estimated using machine vision-based video assessment to quantify motor impairment.	Baseline and annually for up to 5 years
Structural MRI	Prespecified structural MRI-derived quantitative measure, such as regional brain volume or cortical thickness, assessed to characterize disease-related neuroanatomical changes.	Baseline and annually for up to 5 years
Resting-state functional MRI	Prespecified resting-state functional MRI quantitative measure, such as functional connectivity within a predefined brain network, assessed to characterize disease-related functional brain changes.	Baseline and annually for up to 5 years
Diffusion tensor imaging	Prespecified diffusion tensor imaging quantitative parameter, such as fractional anisotropy or mean diffusivity in a predefined tract or region of interest, assessed to characterize microstructural changes.	Baseline and annually for up to 5 years
Quantitative susceptibility mapping	Quantitative susceptibility mapping value measured in a prespecified brain region to assess iron-related imaging changes.	Baseline and annually for up to 5 years
Neuromelanin-sensitive MRI	Neuromelanin-sensitive magnetic resonance imaging signal intensity measured in a prespecified brain region to assess disease-related imaging changes.	Baseline and annually for up to 5 years
Tau PET/MR	Standardized uptake value ratio measured by tau PET/MR in a prespecified brain region using a prespecified tau tracer to assess tau-related signal.	Baseline and annually for up to 5 years
DAT PET/MR	Standardized uptake value ratio measured by dopamine transporter PET/MR in a prespecified brain region to assess dopaminergic terminal integrity.	Baseline and annually for up to 5 years
FDG PET/MR	Standardized uptake value ratio measured by FDG PET/MR in a prespecified brain region to assess regional glucose metabolism.	Baseline and annually for up to 5 years
Mean cerebral blood flow velocity during postural testing	Mean cerebral blood flow velocity measured during postural testing using continuous cerebral blood flow monitoring and transcranial Doppler ultrasonography to assess hemodynamic changes associated with postural challenge.	Baseline and annually for up to 5 years
Heart rate during postural testing with continuous hemodynamic monitoring	Heart rate measured during postural testing using continuous hemodynamic monitoring performed together with transcranial Doppler ultrasonography to assess autonomic and hemodynamic responses to postural challenge.	Baseline and annually for up to 5 years
Quantitative speech parameter from standardized speech assessment	Quantitative speech parameter measured during standardized speech assessment performed in a sound-controlled room to evaluate speech-related changes associated with Parkinsonism.	Baseline and annually for up to 5 years
Quantitative high-density electroencephalography parameter	Quantitative parameter derived from 64-channel high-density electroencephalography to assess neurophysiological changes associated with disease progression.	Baseline and annually for up to 5 years
Quantitative polysomnography parameter	Quantitative parameter derived from respiratory sleep monitoring to assess sleep-related physiological abnormalities during follow-up.	Baseline and annually for up to 5 years
Quantitative paired transcranial stimulation parameter	Quantitative parameter derived from paired transcranial stimulation to assess cortical excitability and related neurophysiological changes.	Baseline and annually for up to 5 years
Quantitative blood biomarker level	Quantitative level of a prespecified blood biomarker measured in biospecimens collected during follow-up to assess biological changes associated with disease progression.	Baseline and annually for up to 5 years

Collaborators and Investigators

• Sponsor: Ruijin Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2024
• Primary Completion (Estimated): May 1, 2029
• Study Completion (Estimated): May 1, 2029

Study Registration Dates

• First Submitted: April 7, 2026
• First Submitted That Met QC Criteria: April 20, 2026
• First Posted (Actual): April 28, 2026

Study Record Updates

• Last Update Posted (Actual): April 28, 2026
• Last Update Submitted That Met QC Criteria: April 20, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Sleep Wake Disorders; Movement Disorders; Basal Ganglia Diseases; Parasomnias; REM Sleep Parasomnias; Parkinsonian Disorders; REM Sleep Behavior Disorder
• Other Study ID Numbers: Multimodal Parkinsonism Cohort

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