Acetylcholinesterase Inhibitor in Combination With Cognitive Training in Older Adults
To determine if donepezil, an acetylcholinesterase (AChE) inhibitor, improved the assimilation of cognitive training by older adults with memory complaints, we gave 168 nondemented, community-dwelling volunteers with memory complaints either 5 mg of donepezil (Aricept) or placebo daily for 6 weeks in a randomized, double-blind, placebo-controlled trial. The dosage rose to 10 mg daily for another 6 weeks before a 2-week course of cognitive training and was maintained for the remainder of a year. Cognitive training improved performance; donepezil was well tolerated. However, there were no significant benefits of donepezil compared with placebo. An additional dose-ranging study with a starting dose of 5 mg a day suggests that the high dose was not the reason. Physiological tolerance may occur with chronic donepezil treatment and may increase AChE levels; this may be why short-term studies have shown the benefit of AChE inhibitor use in nondemented participants whereas chronic use has failed to enhance cognition.
Available from: Vinay V Parikh
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ABSTRACT: Traditional descriptions of the cortical cholinergic input system focused on the diffuse organization of cholinergic projections and the hypothesis that slowly changing levels of extracellular acetylcholine (ACh) mediate different arousal states. The ability of ACh to reach the extrasynaptic space (volume neurotransmission), as opposed to remaining confined to the synaptic cleft (wired neurotransmission), has been considered an integral component of this conceptualization. Recent studies demonstrated that phasic release of ACh, at the scale of seconds, mediates precisely defined cognitive operations. This characteristic of cholinergic neurotransmission is proposed to be of primary importance for understanding cholinergic function and developing treatments for cognitive disorders that result from abnormal cholinergic neurotransmission.
Nature Reviews Neuroscience 06/2009; 10(5):383-90. DOI:10.1038/nrn2635 · 31.43 Impact Factor
Available from: Nicola J Gates
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ABSTRACT: Converging lines of research indicate that complex mental activity is associated with reduced dementia risk. Thus, intense interest exists in whether different forms of cognitive exercise can help protect against cognitive decline and dementia. However, there is considerable confusion in terminology that is hindering progress in the field. We therefore introduce a concrete definition of cognitive training (CT) and make this the focus of our article. Clinical research that has evaluated CT in normal aging, mild cognitive impairment, and dementia is then critically reviewed. Despite many methodological shortcomings, the overall findings indicate that multidomain CT has the potential to improve cognitive function in healthy older adults and slow decline in affected individuals. Finally, practical issues, including the strengths and weaknesses of commercial products, are explored, and recommendations for further research and clinical implementation are made.
Current Psychiatry Reports 02/2010; 12(1):20-7. DOI:10.1007/s11920-009-0085-y · 3.24 Impact Factor
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ABSTRACT: Many biological, behavioral, social, and environmental factors may contribute to the delay or prevention of cognitive decline.
To summarize evidence about putative risk and protective factors for cognitive decline in older adults and the effects of interventions for preserving cognition.
English-language publications in MEDLINE, HuGEpedia, AlzGene, and the Cochrane Database of Systematic Reviews from 1984 through 27 October 2009.
Observational studies with 300 or more participants and randomized, controlled trials (RCTs) with 50 or more adult participants who were 50 years or older, drawn from general populations, and followed for at least 1 year were included. Relevant, good-quality systematic reviews were also eligible.
Information on study design, outcomes, and quality were extracted by one researcher and verified by another. An overall rating of the quality of evidence was assigned by using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) criteria.
127 observational studies, 22 RCTs, and 16 systematic reviews were reviewed in the areas of nutritional factors; medical factors and medications; social, economic, or behavioral factors; toxic environmental exposures; and genetics. Few of the factors had sufficient evidence to support an association with cognitive decline. On the basis of observational studies, evidence that supported the benefits of selected nutritional factors or cognitive, physical, or other leisure activities was limited. Current tobacco use, the apolipoprotein E epsilon4 genotype, and certain medical conditions were associated with increased risk. One RCT found a small, sustained benefit from cognitive training (high quality of evidence) and a small RCT reported that physical exercise helps to maintain cognitive function.
The categorization and definition of exposures were heterogeneous. Few studies were designed a priori to assess associations between specific exposures and cognitive decline. The review included only English-language studies, prioritized categorical outcomes, and excluded small studies.
Few potentially beneficial factors were identified from the evidence on risk or protective factors associated with cognitive decline, but the overall quality of the evidence was low.
Agency for Healthcare Research and Quality and the National Institute on Aging, through the Office of Medical Applications of Research, National Institutes of Health.
Annals of internal medicine 08/2010; 153(3):182-93. DOI:10.1059/0003-4819-153-3-201008030-00258 · 17.81 Impact Factor
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