Cholinergic modulation, visual function and Alzheimer's dementia

Abstract

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.

Donepezil effects on sources of cortical rhythms in mild Alzheimer's disease: Responders vs. Non-Responders

“…This idea is based on the assumption that long-term treatment of donepezil modulates cholinergic systems in AD Responders to the therapy. To this regard, the present results suggest that cholinergic tone may be crucial to sustain normal alpha rhythms in posterior cortex including occipital and temporal areas, in line with projections to these regions from basal forebrain cholinergic neurons of nucleus basalis (Nobili and Sannita, 1997;Oda and Nakanishi, 2000). Future investigations could evaluate the effects of preventive cholinergic therapy in elderly subjects with very mild cognitive impairment in order to probe clinical utility of this therapy at preclinical AD stages and to further enlighten the effects of cholinergic tone on the generation of cortical EEG rhythms in humans.…”

Nicotinic Acetylcholine Receptor Distribution in Alzheimer's Disease, Dementia with Lewy Bodies, Parkinson's Disease, and Vascular Dementia: In Vitro Binding Study Using 5-[125I]-A-85380

“…In the occipital cortex, 5-[ 125 I]-A-85380 binding appears to be concentrated in the visual cortex (Ba17) and the secondary visual area (Ba18), with highest levels in lower cortical layers, consistent with the specific action of acetylcholine in vision (Nobili and Sannita, 1997). Acetylcholine is thought to serve both sensory and cognitive processes involved in vision, and 5-[ 125 I]-A-85380 binding in the LG nucleus may reflect the 'gating' of sensory information to the visual cortex.…”

Ocular Biomarkers for Early Detection of Alzheimer's Disease

“…Reported visual deficits in AD have generally been attributed to neuronal damage in the visual pathways of the brain [64][65] as well as deficiency of the neurotransmitter acetylcholine in AD, which is important in visual processing [66][67][68]. Indeed there is evidence that during the pathogenesis of AD, plaques and tangles occur in visual processing brain regions prior to their occurrence in the hippocampus [65].…”