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.
Keywords: Acetylcholine; Alzheimer’s disease; Dementia; Myelin-associated glycoprotein; PLP1; Post-mortem tissue; Vascular endothelial growth factor; Visual hallucinations; von Willebrand factor.