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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

Research output: Contribution to journalArticle

Original languageEnglish
Article number 80 (2019)
Number of pages15
JournalAlzheimer's Research and Therapy
Issue number1
DateAccepted/In press - 8 Jul 2019
DatePublished (current) - 12 Sep 2019


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.

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: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 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.
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 in AD either with or without visual hallucinations.
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 occipital cortex.

    Research areas

  • visual hallucinations, post-mortem tissue, Acetylcholine, von Willebrand Factor, PLP1, dementia, Alzheimer’s disease, glycoprotein myelin associated, vascular endothelial growth factor

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