Abstract
BackgroundUp 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.MethodsWe 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.ResultsThere 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.ConclusionsOur 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.
Highlights
Alzheimer’s disease (AD) is the most common form of late-life dementia
We previously demonstrated that the ratio of the hypoxia-sensitive myelin-associated glycoprotein (MAG) to the hypoxia-resistant proteolipid oprotein-1 (PLP) is a robust measure of antemortem perfusion in relation to metabolic demand [26, 27]
We previously showed that Vascular endothelial growth factor (VEGF) and capillary density are reduced in the primary visual cortex in dementia with Lewy bodies (DLB) [18]
Summary
Alzheimer’s disease (AD) is the most common form of late-life dementia. Its incidence is set to nearly triple by 2050, due to the ageing of the population [1]. Visual hallucinations can be very distressing for both patients and their relatives. They occur in most forms of dementia but are common in dementia with Lewy bodies (DLB) [4]. Up to 60% of Sinclair et al Alzheimer's Research & Therapy (2019) 11:80 patients with AD had at least some concomitant Lewy body pathology [4]. Several studies have found that visual hallucinations are more likely in those with AD and Lewy body pathology [6,7,8,9]. Visual hallucinations (VH) are more common in dementia with Lewy bodies (DLB). 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
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