Journal of Alzheimer's disease : JAD
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Review Meta Analysis
The impact of general and regional anesthesia on the incidence of post-operative cognitive dysfunction and post-operative delirium: a systematic review with meta-analysis.
Post-operative cognitive complications such as delirium have been consistently associated with poor short and long term outcomes, and the role of anesthesia, particularly the role of general versus regional anesthesia, remains unclear. The objective of this systematic review with meta-analysis was to compare the influence of general, regional, or a combination of anesthesia on the development of Post-Operative Cognitive Dysfunction (POCD) and Post-Operative Delirium (POD). Standard bibliographic databases were searched and complimented by hand searching of original and review article references. ⋯ In conclusion, it appears that general anesthesia, compared to others, may increase the risk of developing POCD; however this has not been shown for POD. Possible reasons for this finding have been explored. This data would advocate for the use of regional anesthesia wherever possible especially in people otherwise vulnerable to developing cognitive symptoms.
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Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the accumulation and aggregation of amyloid-β peptide and loss of forebrain cholinergic neurons, resulting in progressive loss of memory and irreversible impairment of higher cognitive functions. Several studies have accounted for the close relationship between AD and the central cholinergic system, suggesting that a dysfunction of acetylcholine containing neurons in the brain contributes significantly to the cognitive deficit of individuals with AD. ⋯ The implications for anesthesia are also discussed. This knowledge could be valuable to improve anesthesia performance and patient safety.
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Randomized Controlled Trial
Effect of donepezil on cognition in severe Alzheimer's disease: a pooled data analysis.
To better characterize response to donepezil in patients with severe AD, Severe Impairment Battery (SIB) data were pooled from four donepezil clinical trials (N=904). Changes in SIB total and domain scores from baseline to week 24 were compared between placebo and donepezil treatment groups (observed case analysis). Analyses were stratified by baseline severity (Mini-Mental State Examination [MMSE] scores 1-5, 6-9, 10-12 and 13-17) to allow investigation of responses at different stages of cognitive impairment. ⋯ Change in total SIB score correlated significantly with change in measures of activities of daily living and global status. These results indicate that donepezil provides cognitive benefits in patients with severe AD, including those most markedly impaired. The treatment effect size and correlation between improvements in SIB scores and functional and global outcome measures suggest the drug-placebo differences are clinically meaningful.
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Review
Protective role of methylene blue in Alzheimer's disease via mitochondria and cytochrome c oxidase.
The key cytopathologies in the brains of Alzheimer's disease (AD) patients include mitochondrial dysfunction and energy hypometabolism, which are likely caused by the accumulation of toxic species of amyloid-beta (Abeta) peptides. This review discusses two potential approaches to delay the onset of AD. The first approach is use of diaminophenothiazines (e.g., methylene blue; MB) to prevent mitochondrial dysfunction and to attenuate energy hypometabolism. ⋯ Osmolytes may inhibit the formation of Abeta species in vivo, thus preventing the formation of soluble oligomers. Osmolytes are efficient antioxidants that may also increase neural resistance to Abeta. The potential significance of combining MB and osmolytes to treat AD are discussed.
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Amyloid-β (Aβ) peptide-induced impairment of hippocampal synaptic plasticity is considered an underlying mechanism for memory loss in the early stages of Alzheimer's disease and its animal models. We previously reported inhibition of long-term potentiation (LTP) and miniature excitatory postsynaptic currents by oligomeric Aβ(1-42) at hippocampal synapses. While multiple cellular mechanisms could be involved in Aβ-induced synaptic dysfunction, blockade of activity-dependent autophosphorylation of Ca2+ and calmodulin-dependent protein kinase II (CaMKII) appeared to be a major component of Aβ action in our studies. ⋯ Aβ-induced LTP impairment, however, was prevented when slices were co-treated with neurotrophin 4 (NT4). Western blotting and immunohistochemical analyses confirmed that treatment with NT4 or brain-derived neurotrophic factor, another trkB-acting neurotrophin, could oppose Aβ action, enhancing autophosphorylation of CaMKII, and AMPA receptor phosphorylation at a CaMKII-dependent site. These findings support the view that CaMKII is a key synaptic target of Aβ toxicity as well as a potential therapeutic site of neurotrophins for Alzheimer's disease.