Cholinergic modulation, visual function and Alzheimer's dementia

Electrophysiological evidence at a cellular level and in vivo macroelectrode recordings converge in indicating a degree of specificity of acetylcholine action in vision. Acetylcholine (ACh) function is also thought to play a significant role in memory, learning and other cognitive processes. In this respect, ACh action is suggested to serve in both sensory and cognitive processes. The pharmacological blocking of brain muscarinic transmission has been proposed as a model of geriatric memory impairment and Alzheimer's dementia. Visual electrophysiological testing is deemed of diagnostic specificity for this disease. ACh brain neurotransmission, however, mostly contributes to the modulation of nonspecific aspects of cognition, such as arousal or attention. Alzheimer's dementia results from complex neuron alterations [which also affect muscarinic receptors among other (sub)cellular structures] rather than simply reflecting ACh impoverishment. A substantial loss of retinal ganglion cells is documented in patients with Alzheimer's disease and is consistent with electrophysiological observations. However, it is unclear to what extent the dysfunction of the visual system observable in Alzheimer's dementia is qualitatively different from that occurring spontaneously during aging. The dissimilarities between the effect of acute muscarinic blocking (e.g. by scopolamine) and dementia outnumber the similarities. Accordingly, the conventional ACh agonist-antagonist model of dementia now appears questionable, and replacement treatment with compounds enhancing ACh function proved disappointing. It is suggested that (nonspecific) ACh action becomes function-specific, as determined by the architecture of local brain circuits in which it is involved.