Effects of Donepezil on Verbal Memory After Semantic Processing in Healthy Older Adults

Department of Neurology, University of Florida, Jacksonville, FL 32610-0236, USA.
Cognitive and behavioral neurology: official journal of the Society for Behavioral and Cognitive Neurology (Impact Factor: 0.95). 07/2008; 21(2):57-64. DOI: 10.1097/WNN.0b013e3181799df1
Source: PubMed


To learn if acetylcholinesterase inhibitors alter verbal recall by improving semantic encoding in a double-blind randomized placebo-controlled trial.
Cholinergic supplementation has been shown to improve delayed recall in adults with Alzheimer disease. With functional magnetic resonance imaging, elderly adults, when compared with younger participants, have reduced cortical activation with semantic processing. There have been no studies investigating the effects of cholinergic supplementation on semantic encoding in healthy elderly adults.
Twenty elderly participants (mean age 71.5, SD+/-5.2) were recruited. All underwent memory testing before and after receiving donepezil (5 mg, n=11 or 10 mg, n=1) or placebo (n=8) for 6 weeks. Memory was tested using a Levels of Processing task, where a series of words are presented serially. Subjects were either asked to count consonants in a word (superficially process) or decide if the word was "pleasant" or "unpleasant" (semantically process).
After 6 weeks of donepezil or placebo treatment, immediate and delayed recall of superficially and semantically processed words was compared with baseline performance. Immediate and delayed recall of superficially processed words did not show significant changes in either treatment group. With semantic processing, both immediate and delayed recall performance improved in the donepezil group.
Our results suggest that when using semantic encoding, older normal subjects may be aided by anticholinesterase treatment. However, this treatment does not improve recall of superficially encoded words.

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    • "A level of processing approach was used in order to assess whether cortisol had differential effects according to the strength of the cognitive challenge resulting in different strength of the memory trace. This information is of crucial relevance, as several psychopharmacological studies have demonstrated that the effects of pharmacological administration on recognition memory largely depend upon depth of encoding (Bentley, Driver, & Dolan, 2009; FitzGerald et al., 2008; Honey et al., 2005). Consequently, any comprehensive account of druginduced effects on memory should consider that the effects may vary according to the specific cognitive strategies used to lay down the memory trace. "
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    ABSTRACT: We aimed at investigating rapid effects of plasma cortisol elevations on the episodic memory phase of encoding or retrieval, and on the strength of the memory trace. Participants were asked either to select a word containing the letter "e" (shallow encoding task) or to judge if a word referred to a living entity (deep encoding task). We intravenously administered a bolus of 20 mg of cortisol either 5 minutes before encoding or 5 minutes before retrieval, in a between-subjects design. The study included only male participants tested in the late afternoon, and neutral words as stimuli. When cortisol administration occurred prior to retrieval, a main effect of group emerged. Recognition accuracy was higher for individuals who received cortisol compared to placebo. The higher discrimination accuracy for the cortisol group was significant for words encoded during deep but not shallow task. Cortisol administration before encoding did not affect subsequent retrieval performance (either for deep or shallow stimuli) despite a facilitatory trend. Because genomic mechanisms take some time to develop, such a mechanism cannot apply to our findings where the memory task was performed shortly after the enhancement of glucocorticoid levels. Therefore, glucocorticoids, through non-genomic fast effects, determine an enhancement in episodic memory if administered immediately prior to retrieval. This effect is more evident if the memory trace is laid down through deep encoding operations involving the recruitment of specific neural networks.
    Full-text · Article · Jun 2014 · Neurobiology of Learning and Memory
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    • "A few studies have investigated behavioral and brain activation patterns associated with LOP effects following administration of drugs acting on cholinergic pathways, namely the acetylcholinesterase inhibitors Donepezil and physostigmine (30, 41), and nicotine (42). In all these studies, memory accuracy increased following drug administration. "
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    ABSTRACT: When we form new memories, their mnestic fate largely depends upon the cognitive operations set in train during encoding. A typical observation in experimental as well as everyday life settings is that if we learn an item using semantic or "deep" operations, such as attending to its meaning, memory will be better than if we learn the same item using more "shallow" operations, such as attending to its structural features. In the psychological literature, this phenomenon has been conceptualized within the "levels of processing" framework and has been consistently replicated since its original proposal by Craik and Lockhart in 1972. However, the exact mechanisms underlying the memory advantage for deeply encoded items are not yet entirely understood. A cognitive neuroscience perspective can add to this field by clarifying the nature of the processes involved in effective deep and shallow encoding and how they are instantiated in the brain, but so far there has been little work to systematically integrate findings from the literature. This work aims to fill this gap by reviewing, first, some of the key neuroimaging findings on the neural correlates of deep and shallow episodic encoding and second, emerging evidence from studies using neuromodulatory approaches such as psychopharmacology and non-invasive brain stimulation. Taken together, these studies help further our understanding of levels of processing. In addition, by showing that deep encoding can be modulated by acting upon specific brain regions or systems, the reviewed studies pave the way for selective enhancements of episodic encoding processes.
    Full-text · Article · May 2014 · Frontiers in Psychiatry
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    • "In one study it was found that donepezil improved the retention of training on complex aviation tasks (Yesavage et al., 2002). In an another case, verbal memory for semantically processed words was improved (Fitzgerald et al., 2008a). Donepezil might also improve episodic memory (Gron et al., 2005), but interestingly, two studies reported transient negative effects on episodic memory (Beglinger et al., 2004, 2005). "
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    ABSTRACT: The term "cognitive enhancement" usually characterizes interventions in humans that aim to improve mental functioning beyond what is necessary to sustain or restore good health. While the current bioethical debate mainly concentrates on pharmaceuticals, according to the given characterization, cognitive enhancement also by non-pharmacological means has to be regarded as enhancement proper. Here we summarize empirical data on approaches using nutrition, physical exercise, sleep, meditation, mnemonic strategies, computer training, and brain stimulation for enhancing cognitive capabilities. Several of these non-pharmacological enhancement strategies seem to be more efficacious compared to currently available pharmaceuticals usually coined as cognitive enhancers. While many ethical arguments of the cognitive enhancement debate apply to both pharmacological and non-pharmacological enhancers, some of them appear in new light when considered on the background of non-pharmacological enhancement. This article is part of a Special Issue entitled 'Cognitive Enhancers'.
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