Objective: To demonstrate the neurodegeneration status implied by mild parkinsonian signs (MPS) in patients with isolated REM sleep behavior disorder (iRBD) by analyzing longitudinal clinical and multimodal imaging markers.

Background: iRBD is regarded as the most robust clinical prodromal marker of Lewy bodies diseases (LBDs). During the prodromal phase of LBDs, subtle motor abnormalities, referred to as MPS, frequently emerge. However, the clinical significance of MPS in the prodromal stage of LBDs, particularly in relation to neurodegeneration status demonstrated by longitudinal changes in clinical and multimodal imaging markers remains unclear.

Method: In this prospective cohort study, 135 patients with polysomnography-confirmed iRBD were followed for a mean of 3.2 years (maximum f/u, 11.0 years), of whom 30 were eventually diagnosed with Parkinson’s disease (PD) and 14 with dementia with Lewy bodies. Patients underwent baseline and biennial assessments including the Movement Disorder Society–Unified PD Rating Scale for motor function, neuropsychological evaluations for cognitive function, volumetric MRI for basal forebrain (BF) volumes, and ¹⁸F-FDG PET for quantification of PD-specific brain metabolic patterns.

Results: When analyses were aligned to MPS onset, motor impairment across all motor domains, executive and visuospatial dysfunction, PD-related metabolic pattern scores, and posterior BF atrophy showed significant progression over time, with an exponential function providing a better fit than a linear function. PD-related metabolic pattern scores increased earliest, beginning before the onset of MPS and rising more steeply thereafter, approaching the PD reference range approximately 6 years after MPS onset. Motor impairment increased sharply from the time of MPS onset, followed by posterior BF atrophy and subsequent decline in executive and visuospatial functions.

Conclusion: Our findings indicate that MPS in iRBD reflect a more advanced stage of prodromal LBDs, characterized by a sequential pattern of neurodegeneration beginning with brain metabolic changes, followed by motor deterioration, cholinergic BF atrophy, and subsequent cognitive decline. MPS may therefore a useful milestone for identifying patients at a stage suitable for early therapeutic intervention trials in prodromal LBDs.

« Back to 2026 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/sequential-neurodegenerative-trajectories-across-the-onset-of-mild-parkinsonian-signs-in-isolated-rem-sleep-behavior-disorder-a-longitudinal-multimodal-imaging-study/