Visual hallucinations in Alzheimer's disease do not seem to be associated with chronic hypoperfusion of to visual processing areas V2 and V3 but may be associated with reduced cholinergic input to these areas

Abstract

Background Up to 20% of patients with AD experience hallucinations. The pathological substrate is not known. Visual hallucinations (VH) are more common in dementia with Lewy bodies (DLB). In autopsy studies, up to 60% of patients with AD have concomitant Lewy body pathology. Decreased perfusion of the occipital lobe has been implicated in DLB patients with VH, and post-mortem studies point to both decreased cholinergic activity and reduced oxygenation of the occipital cortex in DLB. Methods We used biochemical methods to assess microvessel density (level of von Willebrand factor, a marker of endothelial cell content), ante-mortem oxygenation (vascular endothelial growth factor, a marker of tissue hypoxia; myelin-associated glycoprotein to proteolipid protein-1 ratio, a measure of tissue oxygenation relative to metabolic demand), cholinergic innervation (acetylcholinesterase and choline acetyltransferase), butyrylcholinesterase and insoluble α-synuclein content in the BA18 and BA19 occipital cortex obtained post-mortem from 23 AD patients who had experienced visual hallucinations, 19 AD patients without hallucinations, 19 DLB patients, and 36 controls. The cohorts were matched for age, gender and post-mortem interval. Results There was no evidence of reduced microvessel density, hypoperfusion or reduction in ChAT activity in AD with visual hallucinations. Acetylcholinesterase activity was reduced in both BA18 and BA19, in all 3 dementia groups, and the concentration was also reduced in BA19 in the DLB and AD without visual hallucinations groups. Insoluble α-synuclein was raised in the DLB group in both areas but not in AD either with or without visual hallucinations. Conclusions Our results suggest that visual hallucinations in AD are associated with cholinergic denervation rather than chronic hypoperfusion or α-synuclein accumulation in visual processing areas of the occipital cortex.

Psychosis in Alzheimer disease — mechanisms, genetics and therapeutic opportunities

“…Among individuals with AD, reduced acetylcholinesterase activity was found in those with hallucinations. These findings suggest that cholinergic denervation is an additional mechanism that contributes to psychosis in AD 114 .…”

Prevalence of Hallucinations in the General Croatian Population

“…The highest rate of prevalence have the intrusive thoughts (63%) while the least spread were acoustic hallucinations (25%) and visual hallucinations (29%) [ 23 ]. Several studies have found that visual hallucinations are more likely in those with Alzheimer’s disease and Lewy body pathology [ 24 ]. People who live alone are focused on their daily lives, from organizing their private lives to leaving and returning from work and maintaining a home in all aspects.…”

Relevance of 5-HT2A Receptor Modulation of Pyramidal Cell Excitability for Dementia-Related Psychosis: Implications for Pharmacotherapy

“…It contains structures crucial for the production of ACh, and thus damage to the basal forebrain could cause a loss of ACh. Loss of cholinergic signaling in the visual cortex is correlated with VHs in AD [ 122 ]. Loss of cholinergic innervation of the visual cortex also occurs in DLB and may even exceed losses seen in AD [ 123 ].…”