In this review, researchers synthesize post-mortem, imaging, and electrophysiologic evidence implicating central cholinergic dysfunction in Parkinson’s disease (PD) visual hallucinations. Visual hallucinations in PD are common and not fully explained by dopaminergic therapy. Converging post-mortem, imaging, and electrophysiology show central cholinergic degeneration—especially in the nucleus basalis of Meynert and pedunculopontine nucleus—as a key driver. Reduced cortical/thalamic cholinergic markers, posterior structural changes, and default-mode overcoupling with visual networks point to weakened bottom-up input and overweighted top-down predictions. This hypocholinergic state disrupts arousal, attention, and sensory gating, offering a unifying account across leading models.
Clinically, cholinesterase inhibitors can lessen hallucinations in some patients, with benefit likely tied to baseline receptor integrity and network health—supporting biomarker-guided use. Emerging strategies include M1/M4 muscarinic positive allosteric modulators, exploratory α7 nicotinic approaches, and early evidence for nucleus basalis deep-brain stimulation in refractory cases. Overall, restoring cholinergic signaling and stabilizing thalamocortical/attentional dynamics may rebalance perception, warranting personalized, mechanism-informed trials.
Reference: Ignatavicius A, Matar E, Lewis SJG. Visual hallucinations in Parkinson’s disease: spotlight on central cholinergic dysfunction. Brain. 2025;148(2):376-393. doi: 10.1093/brain/awae289.
