30 - Altered consciousness and transmitter signalling in Lewy body dementia

Summary

Summary

Neurochemical pathology associated with alterations in consciousness in Lewy body dementia (LBD) is discussed in relation to cholinergic and monoaminergic systems projecting to the cortex. Extensive loss of cholinergic activity from neocortical areas in hallucinating <B>LBD cases is consistent with the ability of anticholinergic drugs (antimuscarinics such as scopolamine) to induce similar types of hallucinations in normal individuals. Evidence is reviewed which suggests the M4 muscarinic subtype, which is particularly high in primate visual cortex and is activated by the atypical neuroleptic clozapine, may be involved in atropine psychosis. The possible role of non-cortical areas such as the brainstem reticular activating system in abnormal conscious activity in LBD is also considered, as is the involvement of the cholinergic system in schizophrenic psychosis. Amongst a range of potential approaches to cholinergic therapy in LBD, it is argued that stimulation of the nicotinic cholinergic receptor may be particularly useful since this may benefit both cognitive and motor dysfunction and also provide some degree of neuroprotection.

Introduction

‘Consciousness: the having of perceptions, thoughts, and feelings awareness. The term is impossible to define except in terms that are unintelligible, without a grasp of what consciousness means. Consciousness is a fascinating but elusive phenomenon: it is impossible to specify what it is, what it does or why it evolved. Nothing worth reading has been written about it’ (Sutherland, 1989).

The bridge between mind and brain in dementing disorders such as Alzheimer's disease (AD), has generally been supported by objective measures of memory loss and related cognitive impairment, or psychotic features such as depression and aggression which also have overt behavioural counterparts.