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.
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.
Inability to express free and informed consent.
Patient with a doubtful diagnosis.
Participant under 18 years of age.
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.
Cohort
Prospective
Clinical assessments
Other interventionstandardized neurological examination, motor and non-motor symptom scales, cognitive testing, and autonomic symptom questionnaires.
Phenotypic classification
Other interventionpatients will be stratified into Brain-First and Body-First phenotypes based on the presence of RBD and instrumental findings.
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.
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.
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.
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.
Assessment of disease progression
Assessment of the differences in the MDS-UPDRS total scores (part I, II, III, IV) and subscores (tremor, bradykinesia, rigidity, postural instability and gait difficulty, gait, dyskinesia and fluctuations subscores) in the study population at baseline and at subsequent annual follow-up visits (5-year follow-up).
Assessment of the progression of neurodegeneration and inflammatory biomarkers (neurofilaments, interferon-γ, cell-mediated anti-α-synuclein responses).
Assessment of the differences in neurodegeneration and inflammatory biomarkers (neurofilaments, interferon-γ, cell-mediated anti-α-synuclein responses) in a subset of 50 patients in the study population. Analysis of differences in neurofilament levels and cell-mediated responses at baseline and at subsequent annual follow-up visits (5-year follow-up).
Brain MRI: analysis of differences in qualitative and quantitative parameters extrapolated at diagnosis.
Assessment of quantitative differences in the degree of cortical and subcortical atrophy (volumetric automated segmentation of cerebral regions with the Quibim Precision software® quantified as % of intracranial volume) in the study population assessed through volumetric 1.5 Tesla brain MRI at baseline.
Baseline Assessment of Nigrostriatal and Myocardial Denervation.
Semiquantitative assessment (heart to mediastinum ratio \[H/M\]) of differences in myocardial denervation in the study population through cardiac 123I-MIBG scintigraphy (early and delayed imaging)
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