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Delusions associated with elevated muscarinic binding in dementia with Lewy bodies

Lookup NU author(s): Dr Clive Ballard, Dr Margaret Piggott, Emeritus Professor Robert Perry, Professor Ian McKeith, Dr Evelyn Jaros, Emeritus Professor Elaine Perry


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The relation between disturbances of cholinergic neurotransmission and delusions (DELs) has not been investigated in degenerative dementias such as dementia with Lewy bodies (DLB). A cohort of dementia patients were assessed with standardized clinical evaluations (including the Columbia University Scale for Psychopathology in Alzheimer's Disease), which were repeated annually until death. DLB was confirmed neuropathologically in 21 patients. Neurochemical evaluation included M1 receptor autoradiography (pirenzepine binding), biochemical measurement of choline acetyltransferase (ChAT), and acetylcholinesterase (AChE) histochemistry in brain regions hypothesized to be involved in the genesis of psychosis. Compared with II age-matched controls, ChAT and pirenzepine levels were most extensively reduced in the temporal and parietal neocortex of DLB patients. In Brodmann area 36, DELs were significantly associated with elevated pirenzepine binding (131.0 vs 93.5, t = 2.7), whereas visual hallucinations were associated with significant reductions in ChAT (1.7 vs 2.5, t = 2.5). There were no significant associations with other areas or with cholinesterase. Although DELs and visual hallucinations were both linked with disturbances in cholinergic neurotransmission, the nature of the associations was different. Upregulation of the postsynaptic muscarinic receptor may be central in the genesis of DELs, with important treatment implications.

Publication metadata

Author(s): Ballard C, Piggott M, Johnson M, Cairns N, Perry R, McKeith I, Jaros E, O'Brien J, Holmes C, Perry E

Publication type: Article

Publication status: Published

Journal: Annals of Neurology

Year: 2000

Volume: 48

Issue: 6

Pages: 868-876

ISSN (print): 0364-5134

ISSN (electronic): 1531-8249

Publisher: Wiley-Blackwell Publishing