Article
Cholinergic deficiency hypothesis in delirium: a synthesis of current evidence.
Warren Alpert Medical School of Brown University, Providence, RI, USA.
The Journals of Gerontology Series A Biological Sciences and Medical Sciences (impact factor:
4.6).
08/2008;
63(7):764-72.
pp.764-72
Source: PubMed
-
Article: Association of interleukin-1 gene polymorphisms with Alzheimer's disease.
[show abstract] [hide abstract]
ABSTRACT: Interleukin-1 (IL-1) is markedly overexpressed in Alzheimer's disease. We found the IL-1A 2,2 genotype in 12.9% of 232 neuropathologically confirmed Alzheimer's disease patients and 6.6% of 167 controls from four centers in the United Kingdom and United States (odds ratio, 3.0; controlled for age and for ApoE [apolipoprotein E] genotype). Homozygosity for both allele 2 of IL-1A and allele 2 of IL-1B conferred even greater risk (odds ratio, 10.8). IL-1 genotypes may confer risk for Alzheimer's disease through IL-1 overexpression and IL-1-driven neurodegenerative cascades.Annals of Neurology 04/2000; 47(3):365-8. · 11.09 Impact Factor -
Article: Muscarinic acetylcholine receptor subtypes in cerebral cortex and hippocampus.
[show abstract] [hide abstract]
ABSTRACT: The M1, M2 and M4 subtypes of mAChRs are the predominant receptors in the CNS. These receptors activate a multitude of signaling pathways important for modulating neuronal excitability, synaptic plasticity and feedback regulation of ACh release. In addition, novel functions mediated by mAChRs are currently being discovered. These studies are greatly facilitated by the recent development of subtype selective toxins and mice lacking individual mAChR genes. Studies in cell culture and the rodent brain demonstrate that mAChR internalization and intracellular trafficking is an important component of mAChR regulation. Characterizing mAChR intracellular trafficking could help facilitate the development of selective mAChR ligands. For example, a selective M1 agonist would cause a shift in the distribution of M1 from the cell surface to an intracellular distribution, while M2 and M4 would remain on the cell surface. Characterizing mAChR intracellular trafficking is also important for understanding the cellular mechanisms that regulate mAChR cell surface expression and signaling. Furthermore, intracellular trafficking has recently been demonstrated to play a role in the development of tolerance to drugs (Whistler et al., 1999; He et al., 2002). Because individual mAChR subtypes are novel targets for treatments of diseases such as Alzheimer's disease and schizophrenia, understanding the mechanisms that regulate mAChR signaling and intracellular trafficking following acute and chronic stimulation might lead to the development of rational strategies.Progress in brain research 02/2004; 145:59-66. · 3.04 Impact Factor -
Article: Donepezil in the prevention and treatment of post-surgical delirium.
[show abstract] [hide abstract]
ABSTRACT: Delirium is a frequent complication of major surgery in older persons. The authors evaluated the possible benefit of donepezil versus placebo in the prevention and treatment of postoperative delirium in an older population without dementia undergoing elective total joint-replacement surgery. A sample of 80 patients participated in this randomized, double-blind, placebo-controlled trial of donepezil. Each participant was evaluated before surgery and then received donepezil or placebo for 14 days before surgery and 14 days afterward. Postoperative delirium was assessed with the Delirium Symptom Interview, Confusion Assessment Method, daily medical record, nurse-observation reviews, and DSM-IV diagnostic criteria for delirium. Subsyndromal delirium was also assessed for each participant. Delirium, diagnosed by DSM-IV criteria, was found on at least 1 postoperative day in 18.8% of subjects, but there were no significant differences between the donepezil and placebo groups. When delirium was present, it lasted only 1 day, and there was no difference between the groups. Subsyndromal delirium was found on at least 1 postoperative day for 68.8% of subjects, and, when this occurred, lasted 2 days or less, on average. There was no difference between the groups in the occurrence or duration of subsyndromal delirium. There was no difference between the groups in disposition to home or to another facility. This pilot study was unable to demonstrate a benefit for donepezil in preventing or treating delirium in a relatively young and cognitively-intact group of elderly patients undergoing elective orthopedic surgery. Furthermore, postoperative delirium was not a major problem in this population.American Journal of Geriatric Psychiatry 01/2006; 13(12):1100-6. · 3.64 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed.
The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual
current impact factor.
Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence
agreement may be applicable.
Keywords
biomarkers
cause delirium
cholinergic deficiency hypothesis
cholinergic drugs
cholinergic function
cholinergic pathway
cholinergic pathway relates
cognitive decline
common
delirium
dementia
future research
genetic contributions
immunological overlaps
immunological stressors
morbid condition
neurotransmitter pathways
potential pathophysiological pathways
review examines current understanding
various precursors
