Cholinergic basal forebrain degeneration in isolated REM sleep behaviour disorder

Area of Science:

• Neuroscience
• Neurology
• Radiology

Background:

• Cholinergic basal forebrain degeneration is linked to cognitive and motor symptoms in Lewy body disorders.
• The specific role of cholinergic deficits in the prodromal phase of these disorders remains unclear.
• Understanding early neurodegenerative changes is crucial for timely diagnosis and intervention.

Purpose of the Study:

• To investigate the location and extent of basal forebrain degeneration in prodromal Lewy body disorders.
• To correlate basal forebrain alterations with other brain changes and monoaminergic deficits.
• To determine the contribution of basal forebrain atrophy to clinical symptoms in early-stage disease.

Main Methods:

• Volumetric MRI and PET scans were used to assess basal forebrain nuclei (Ch1-3, Ch4) in patients with isolated REM sleep behaviour disorder (iRBD), de novo Parkinson's disease with RBD (dnPDRBD), and healthy controls.
• Voxel-based and surface-based morphometric analyses identified brain regions associated with basal forebrain atrophy.
• Longitudinal motor and cognitive assessments were performed on iRBD subgroups.

Main Results:

• Patients with iRBD showed significant reductions in Ch4 nucleus volume, not Ch1-3.
• Ch4 volume reduction correlated with limbic and neocortical regions.
• Both Ch1-3 and Ch4 volume reductions were associated with axial motor symptoms; Ch1-3 reduction predicted dementia incidence, while Ch4 reduction predicted bradykinesia progression.

Conclusions:

• Basal forebrain degeneration, particularly in Ch4, occurs early in prodromal Lewy body disorders.
• Cholinergic deficits are linked to specific clinical manifestations and disease progression trajectories.
• Findings highlight the importance of cholinergic pathways in the early stages of Lewy body disorders, differentiating progression towards Parkinson's disease or dementia with Lewy bodies.