Cholinergic Deficiency Hypothesis in Delirium: A Synthesis of Current Evidence
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Open Access
- 1 July 2008
- journal article
- review article
- Published by Oxford University Press (OUP) in The Journals of Gerontology: Series A
- Vol. 63 (7), 764-772
- https://doi.org/10.1093/gerona/63.7.764
Abstract
Deficits in cholinergic function have been postulated to cause delirium and cognitive decline. This review examines current understanding of the cholinergic deficiency hypothesis in delirium by synthesizing evidence on potential pathophysiological pathways. Acetylcholine synthesis involves various precursors, enzymes, and receptors, and dysfunction in these components can lead to delirium. Insults to the brain, like ischemia and immunological stressors, can precipitously alter acetylcholine levels. Imbalances between cholinergic and other neurotransmitter pathways may result in delirium. Furthermore, genetic, enzymatic, and immunological overlaps exist between delirium and dementia related to the cholinergic pathway. Important areas for future research include identifying biomarkers, determining genetic contributions, and evaluating response to cholinergic drugs in delirium. Understanding how the cholinergic pathway relates to delirium may yield innovative approaches in the diagnosis, prevention, and treatment of this common, costly, and morbid condition.Keywords
This publication has 73 references indexed in Scilit:
- Apolipoprotein E4 polymorphism as a genetic predisposition to delirium in critically ill patients*Critical Care Medicine, 2007
- Review Article: The Role of Neuroimaging in Elucidating Delirium PathophysiologyThe Journals of Gerontology: Series A, 2006
- Review Article: Serum Biomarkers for DeliriumThe Journals of Gerontology: Series A, 2006
- Peripheral cholinergic disturbances in Alzheimer's diseaseChemico-Biological Interactions, 2005
- DeliriumJournal of Neurology, Neurosurgery & Psychiatry, 2004
- The nature of interactions involving prefrontal and striatal dopamine systemsJournal of Psychopharmacology, 1997
- Traumatic brain injury reduces hippocampal high-affinity [3H]choline uptake but not extracellular choline levels in ratsNeuroscience Letters, 1994
- The immune-neuro-link and the macrophage: Postcardiotomy delirium, HIV-associated dementia and psychiatryProgress in Neurobiology, 1994
- Cholinergic mechanisms in physical dependence on barbiturates, ethanol and benzodiazepinesJournal of Neural Transmission, 1992
- The Cholinergic Hypothesis of Geriatric Memory DysfunctionScience, 1982