Cholinergic changes in Lewy body disease: implications for presentation, progression and subtypes.

Area of Science:

• Neuroscience
• Neurology
• Pathology

Background:

• Cholinergic system dysfunction is a hallmark of Lewy body diseases (LBD), including Parkinson's disease (PD), dementia with Lewy bodies (DLB), and REM sleep behavior disorder (RBD).
• Previous research focused on central nervous system (CNS) cholinergic alterations in LBD.
• Emerging evidence indicates peripheral cholinergic denervation in LBD.

Purpose of the Study:

• To comprehensively review cholinergic changes in LBD, integrating central and peripheral findings.
• To explore the continuum of cholinergic alterations across different LBD subtypes and disease stages.
• To investigate the impact of Alzheimer's co-pathology on cholinergic degeneration in LBD.

Main Methods:

• Systematic review of existing literature on cholinergic alterations in LBD.
• Analysis of brain regions and peripheral organs affected by cholinergic denervation.
• Comparison of cholinergic changes in LBD with and without dementia, and in comorbid Alzheimer's disease.

Main Results:

• Cholinergic impairment is comparable or greater in DLB brain regions versus non-demented LBD.
• Posterior basal forebrain cholinergic regions are affected early; anterior regions later.
• Peripheral cholinergic denervation in abdominal organs is observed in isolated RBD, suggesting early prodromal involvement.

Conclusions:

• Cholinergic degeneration in LBD follows a specific topographical pattern, potentially indicating disease progression.
• Alzheimer's co-pathology significantly influences cholinergic degeneration patterns in LBD.
• Peripheral cholinergic changes in RBD highlight its role in early LBD pathogenesis and offer therapeutic targets.