Assessment of the visual thalamic circuitry in hallucinations in dementia with Lewy bodies

Abstract

Background Visual hallucinations occur in 70-90% of patients with dementia with Lewy bodies (DLB) and are related to decreased quality of life for patients. However, the underlying neuropathological changes that promote the manifestation of visual hallucinations in DLB are not known. Several hypotheses of visual hallucinations in DLB have either directly implicated the lateral geniculate nucleus (LGN), pulvinar and superior colliculus or suggested impairments in their putative functions. Methods Post-mortem LGN, pulvinar and superior colliculus tissue was obtained from DLB cases with a clinical history of visual hallucinations and compared to cognitively normal control and Alzheimer’s disease (AD) cases without visual hallucinations. Neuropathological lesions were quantified in individual cases using densitometry and neuronal and glial cell populations were quantified with stereology. RNA sequencing and subsequent bioinformatics analysis of biological pathway alterations was performed by a collaborator on pulvinar tissue from DLB and non-hallucinating control cases. The bioinformatics data was used to identify protein targets based on pathway alterations, which were then investigated using western blot analysis. Results Lewy body pathology and neuronal loss was specifically found in the pulvinar and superior colliculus of DLB cases, particularly in regions implicated in visual attention and target selection. In contrast, AD cases had more widespread degenerative changes. Molecular analysis of the pulvinar demonstrated reduced expression of several synaptic markers, concomitant with elevated expression of several astrocytic markers in DLB. Conclusion ii The relative specificity of changes in visual thalamic regions may contribute to the occurrence of visual hallucinations in DLB. Synaptic degeneration in the pulvinar likely further impedes visual attentional function in DLB. The present results may indicate DLB patients have impairments in directing visual attention to external stimuli, thus facilitating visual hallucinations by an over-reliance upon expectations and experience rather than stimulus-driven perception.