Progressive Prefrontal Cortex Dysfunction in Parkinson's Disease With Probable REM Sleep Behavior Disorder: A 3-Year...

Area of Science:

• Neuroscience
• Neurology
• Sleep Medicine

Background:

• Parkinson's disease (PD) is a neurodegenerative disorder with diverse clinical presentations.
• Rapid eye movement sleep behavior disorder (RBD) is a non-motor symptom that can precede or co-occur with PD.
• Prefrontal cortex (PFC) dysfunction is implicated in PD, but its specific role in PD with RBD (PD-pRBD) is less understood.

Purpose of the Study:

• To investigate prefrontal cortex activity differences in early PD patients with and without probable RBD (PD-pRBD).
• To examine the progression of these neural alterations over time.
• To explore the association between PFC connectivity deficits and neuropsychological performance in PD-pRBD.

Main Methods:

• Utilized structural and functional MRI (fMRI) data from 96 early PD patients in the Parkinson's Progression Markers Initiative (PPMI) database.
• Conducted seed-to-voxel functional connectivity analysis focusing on the left dorsolateral prefrontal cortex (DLPFC).
• Compared PD-pRBD+ and PD-pRBD- groups at baseline and 3-year follow-up, correlating findings with neuropsychological assessments.

Main Results:

• PD-pRBD+ patients initially showed reduced left DLPFC connectivity with the medial frontopolar cortex compared to PD-pRBD- patients.
• At 3-year follow-up, PD-pRBD+ patients exhibited further disrupted DLPFC connectivity in the lateral frontopolar cortex.
• Left DLPFC-frontopolar cortex connectivity positively correlated with executive function in PD-pRBD+ patients.

Conclusions:

• Progressive prefrontal cortex dysfunction is associated with RBD in early Parkinson's disease.
• These PFC alterations may serve as subtype-specific biomarkers for neurodegenerative progression in PD.
• Findings contribute to understanding the neuropathological basis of clinical heterogeneity in Parkinson's disease.