Researchers of this autopsy study examined whether pathology in the nucleus basalis of Meynert (nbM) relates to visual hallucinations (VH) in Parkinson’s disease (PD). Brains from 28 patients with PD were analyzed with immunohistochemistry (choline acetyltransferase [ChAT] for cholinergic neurons; phosphorylated α-synuclein, tau, and TDP-43 for proteinopathies). Compared with those without VH, patients with VH showed a selective loss of cholinergic neurons in the intermediate nbM (137 vs 191 ChAT+ neurons, p=0.04) and a higher ratio of α-synuclein–positive to ChAT+ cells (p=0.03), despite similar absolute α-synuclein counts. Tau and TDP-43 burdens did not differ. Sensitivity analyses partially matching for age and disease duration preserved the pattern, supporting a link between intermediate nbM degeneration and VH.
Findings implicate strategic basal forebrain cholinergic loss—particularly in the nbM sector projecting widely to cortex—as a key substrate for VH in PD, aligning with models that emphasize attentional and perceptual network dysregulation. Clinically, they strengthen the rationale for cholinergic-based therapies (eg, cholinesterase inhibitors) to target visual symptoms and motivate development of imaging biomarkers of nbM integrity. Limitations include the small, retrospective autopsy cohort and incomplete medication data. Future longitudinal, multimodal studies are needed to map nbM pathology to VH onset, severity, and treatment response.
Reference: Hatsuta H, Mizutani M, Yagita K, Sano T, Takao M. Visual hallucinations in Parkinson’s disease: The critical role of intermediate nucleus basalis of Meynert. Parkinsonism Relat Disord. 2025;137:107935. doi: 10.1016/j.parkreldis.2025.107935.
Link: https://www.sciencedirect.com/science/article/pii/S1353802025006765
