The Cholinergic Neurotransmitter System in Human Memory and Dementia: A Review

Abstract

The present paper reviews three types of evidence implicating the role of acetylcholine in human memory and dementia: (1) neuropathological evidence that the cholinergic transmitter system is depleted in Alzheimer-type dementia; (2) psychopharmacological studies that have employed “cholinergic blockade” as a model of cholinergic depletion; and (3) clinical studies of cholinergic “replacement” therapy in Alzheimer-type dementia. The evidence that the cholinergic system is depleted in Alzheimer-type dementia has been complemented by the finding that cholinergic blockade in healthy subjects causes a substantial learning (or “acquisition”) deficit in episodic memory. The overall results of studies of replacement therapy have generally been disappointing, but a few have reported benefits in recall and recognition tests. The role of the cholinergic system in many aspects of memory remains to be elucidated; but it seems unlikely that cholinergic depletion accounts for all aspects of the memory disorder in Alzheimer-type dementia, and possibly the depletions of other neurotransmitters also contribute to the memory impairment.

Mode shifting between storage and recall based on novelty detection in oscillating hippocampal circuits

“…Many behavioral experiments suggest that ACh is necessary for episodic learning, while it is less important in retrieval (Ghoneim and Mewaldt, 1975;Peterson, 1977;Mewaldt and Ghoneim, 1979;Kopelman, 1986;Whishaw, 1989;Aigner et al, 1991). Most convincingly, a recent study showed that activation of the forebrain cholinergic pathways occurs during the acquisition of a rewarded operant response, while recall of the same behavior was not associated with the same activation of the cholinergic system (Orsetti et al, 1996).…”

Free recall and recognition in a network model of the hippocampus: simulating effects of scopolamine on human memory function

“…Addition of neocortical networks will allow the model to address many of the effects of scopolamine which have been described as 'attentional' [21], based on data from continuous performance type tasks. For example, scopolamine impairs the ability to detect small changes in the intensity of a light [119], to detect changes in the movement of a clock hand [120] or to detect specific sequences of digits [152].…”

“…Since the turn of the century, anaesthesiologists have been aware that administration of the muscarinic antagonist scopolamine (to decrease respiratory tract secretions in preparation for surgery) often strongly impairs memory [21]. Experimental work has demonstrated a striking impairment of the free recall of lists of words learned under the influence of scopolamine [22 -28].…”

The cholinergic pharmacology of tetrahydroaminoacridine in vivo and in vitro

“…Therefore many attempts have been made to reverse the cognitive deficits by increasing cholinergic activity (reviewed by Brinkman & Gershon, 1983;Kopelman, 1986). In general these attempts have met with little success.…”