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

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.