Study of Axial and Cognitive Symptoms and Biomarkers of Neurodegeneration in Brain-first and Body-first PD

NCT07187843 | Recruiting

• 1 other identifier: 350/2024/OSS/AUSLRE
• Study Type: observational
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

This observational study aims to systematically characterize a cohort of patients with early-stage Parkinson's disease (PD) attending the Movement Disorders Center of AUSL-IRCCS Reggio Emilia, Italy. PD is the second most common neurodegenerative disorder, affecting about 1% of individuals over 60 years of age. The project will explore clinical and biological differences between the recently proposed "Brain-First" and "Body-First" phenotypes of PD. Patients will undergo detailed clinical evaluation, neuroimaging, and biomarker assessments (including neurodegeneration and neuroinflammation markers). Particular attention will be given to the progression of axial and cognitive symptoms, which represent major contributors to disability. Findings from this study are expected to improve early patient stratification, clarify disease mechanisms, and support the development of precision medicine strategies and future disease-modifying therapies.

Conditions

Parkinson Disease; Parkinsonian Disorders; Brain Disease; Basal Ganglia Diseases; Synucleinopathies

Keywords

Neurodegenerative Diseases; Nervous System Diseases; Movement Disorders; biomarker; neuroinflammation; brain-first; body-first; axial symptoms

Outcome Measures

Primary Outcomes (4)

• Assessment of the progression of axial symptoms

  Differences in quantitative parameters of gait (phase duration, root mean square of the acceleration of the trunk in x, y, z axes) assessed through the instrumented Timed Up and Go test (phases considered: overall iTUG, sit-to-stand, sitting, first turn, second turn, walking forward, return gait) between the brain-first and body-first groups at diagnosis and at subsequent annual follow-up visits (5-year follow-up) in OFF-medication and ON-Medication (both in single and dual task) conditions.

  baseline, 12, 24, 36,48, 60 months

• Risk of falling in the two subgroups, brain-first and body-first

  Assessment of possible differences in scores obtained on the Walking Handicap Scale (WHS) at baseline and at subsequent annual follow-up visits (5-year follow-up). The Walking Handicap Scale (WHS) measures walking ability and community mobility across six levels, from limited physiological walking to unrestricted social ambulation. Possible scores range from 1 (most limited walking ability) to 6 (fully independent walking in social environments); higher scores indicate better walking function.

  baseline, 12, 24, 36,48, 60 months

• Risk of falling in the two subgroups, brain-first and body-first

  Assessment of possible differences in scores obtained on the Hendrich II Fall Risk Model (HIIFRM) at baseline and at subsequent annual follow-up visits (5-year follow-up). The Hendrich II Fall Risk Model (HIIFRM) assesses fall risk using clinical variables including confusion/disorientation/impulsivity, symptomatic depression, altered elimination, dizziness, gender, use of antiepileptics or benzodiazepines, and performance on the "Get-Up-and-Go" test. Possible total scores range from 0 (lowest fall risk) upwards (commonly up to about 16 depending on version); higher scores indicate greater fall risk.

  baseline, 12, 24, 36,48, 60 months

• Assessment of the progression of axial symptoms

  Differences in quantitative parameters of balance (center of pressure mean position referred to the mid-point of the heels, area of the 95% confidence ellipse, sway mean velocities and root mean square displacements in the antero-posterior and medio-lateral directions) assessed through a static posturography test (with eyes open) between the brain-first and body-first groups at diagnosis and at subsequent annual follow-up visits (5-year follow-up) in OFF-medication and ON-Medication (both in single and dual task) conditions.

  baseline, 12, 24, 36,48, 60 months

Secondary Outcomes (4)

• Assessment of disease progression

  baseline, 12, 24, 36,48, 60 months

• Assessment of the progression of neurodegeneration and inflammatory biomarkers (neurofilaments, interferon-γ, cell-mediated anti-α-synuclein responses).

  baseline, 12, 24, 36,48, 60 months

• Brain MRI: analysis of differences in qualitative and quantitative parameters extrapolated at diagnosis.

  24 months

• Baseline Assessment of Nigrostriatal and Myocardial Denervation.

  24 months

Study Arms (2)

Early Parkinson's Disease (Brain-First phenotype)

Patients with early-stage Parkinson's disease without REM sleep behavior disorder (RBD), consistent with a Brain-First phenotype. These patients typically show early central dopaminergic deficits followed by peripheral involvement.

Other: Clinical assessments; Other: Phenotypic classification

Early Parkinson's Disease (Body-First phenotype)

Patients with early-stage Parkinson's disease with REM sleep behavior disorder (RBD) before or at motor onset, consistent with a Body-First phenotype. These patients are expected to show early peripheral involvement (e.g., cardiac MIBG denervation) preceding central dopaminergic loss.

Other: Clinical assessments; Other: Phenotypic classification

Interventions

Clinical assessments OTHER

standardized neurological examination, motor and non-motor symptom scales, cognitive testing, and autonomic symptom questionnaires.

Early Parkinson's Disease (Body-First phenotype); Early Parkinson's Disease (Brain-First phenotype)

Phenotypic classification OTHER

patients will be stratified into Brain-First and Body-First phenotypes based on the presence of RBD and instrumental findings.

Early Parkinson's Disease (Body-First phenotype); Early Parkinson's Disease (Brain-First phenotype)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study population will consist of patients with early-stage Parkinson's disease (PD) attending the Movement Disorders Center of AUSL-IRCCS Reggio Emilia. Eligible participants will be adults diagnosed with PD according to international clinical criteria, in the initial stages of the disease, and not yet affected by major motor or cognitive disability. Patients will be characterized from both a clinical and instrumental perspective, including motor and non-motor symptoms, genetic background, and biomarkers of neurodegeneration and neuroinflammation.

You may qualify if:

• Patients diagnosed with PD according to the MDS Clinical Diagnostic Criteria for Parkinson's Disease divided into brain-first and body-first phenotypes, based on the presence or absence of a REM sleep behavior disorder diagnosed using ambulatory polysomnography methods according to the criteria of the International Classification of Sleep Disorders (ICSD-3) criteria and on data from SPECT with DATSCAN and myocardial innervation scintigraphy \[123I-MIBG\].
• Free and informed consent expressed by the participant.
• At least 18 years of age.

You may not qualify if:

• Inability to express free and informed consent.
• Patient with a doubtful diagnosis.
• Participant under 18 years of age.

Sponsors & Collaborators

• Azienda USL Reggio Emilia - IRCCS: lead

Study Sites (1)

Azienda USL IRCCS di Reggio Emilia

Reggio Emilia, Italy

RECRUITING

Related Publications (6)

• Piancino MG, Farina D, Talpone F, Merlo A, Bracco P. Muscular activation during reverse and non-reverse chewing cycles in unilateral posterior crossbite. Eur J Oral Sci. 2009 Apr;117(2):122-8. doi: 10.1111/j.1600-0722.2008.00601.x.

  PMID: 19320720 BACKGROUND

• Cavallieri F, Gessani A, Merlo A, Campanini I, Budriesi C, Fioravanti V, Di Rauso G, Feletti A, Damiano B, Scaltriti S, Guagnano N, Bardi E, Corni MG, Antonelli F, Cavalleri F, Molinari MA, Contardi S, Menozzi E, Puzzolante A, Vannozzi G, Bergamini E, Pavesi G, Fraix V, Meoni S, Fraternali A, Versari A, Lusuardi M, Biagini G, Pinto S, Moro E, Valzania F. Interplay between speech and gait variables in Parkinson's disease patients treated with subthalamic nucleus deep brain stimulation: A long-term instrumental assessment. Eur J Neurol. 2023 Jul;30(7):1963-1972. doi: 10.1111/ene.15803. Epub 2023 Apr 10.

  PMID: 36971736 BACKGROUND

• Merlo A, Zemp D, Zanda E, Rocchi S, Meroni F, Tettamanti M, Recchia A, Lucca U, Quadri P. Postural stability and history of falls in cognitively able older adults: the Canton Ticino study. Gait Posture. 2012 Sep;36(4):662-6. doi: 10.1016/j.gaitpost.2012.06.016. Epub 2012 Jul 24.

  PMID: 22832469 BACKGROUND

• Horsager J, Knudsen K, Sommerauer M. Clinical and imaging evidence of brain-first and body-first Parkinson's disease. Neurobiol Dis. 2022 Mar;164:105626. doi: 10.1016/j.nbd.2022.105626. Epub 2022 Jan 11.

  PMID: 35031485 BACKGROUND

• Horsager J, Andersen KB, Knudsen K, Skjaerbaek C, Fedorova TD, Okkels N, Schaeffer E, Bonkat SK, Geday J, Otto M, Sommerauer M, Danielsen EH, Bech E, Kraft J, Munk OL, Hansen SD, Pavese N, Goder R, Brooks DJ, Berg D, Borghammer P. Brain-first versus body-first Parkinson's disease: a multimodal imaging case-control study. Brain. 2020 Oct 1;143(10):3077-3088. doi: 10.1093/brain/awaa238.

  PMID: 32830221 BACKGROUND

• Bohnen NI, Postuma RB. Body-first versus brain-first biological subtyping of Parkinson's disease. Brain. 2020 Oct 1;143(10):2871-2873. doi: 10.1093/brain/awaa293.

  PMID: 33103732 BACKGROUND

MeSH Terms

Conditions

Parkinson Disease; Parkinsonian Disorders; Brain Diseases; Basal Ganglia Diseases; Synucleinopathies; Neurodegenerative Diseases; Nervous System Diseases; Movement Disorders; Neuroinflammatory Diseases

Condition Hierarchy (Ancestors)

Central Nervous System Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Francesco Cavallieri, MD

CONTACT

francesco.cavallieri@ausl.re.it

Stefania Croci, BSc

CONTACT

stefania.Croci@ausl.re.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 3, 2025
• First Posted: September 23, 2025
• Study Start: September 4, 2024
• Primary Completion: October 30, 2025
• Study Completion (Estimated): May 1, 2031
• Last Updated: April 23, 2026

Record last verified: 2025-08

Locations

IT (1)