Effects of donepezil on memory and cognition in multiple sclerosis

Department of Neurology, State University of New York, Stony Brook, HSC T12-020, 11794-8121, USA.
Journal of the Neurological Sciences (Impact Factor: 2.47). 07/2006; 245(1-2):127-36. DOI: 10.1016/j.jns.2005.08.021
Source: PubMed


Acetylcholinesterase inhibitors are used to treat dementia associated with Alzheimer's disease, but their cognitive benefits may extend to additional disorders such as multiple sclerosis (MS). A single-center double-blind placebo-controlled randomized clinical trial evaluated the effectiveness of donepezil in a sample of 69 MS persons selected for initial memory difficulties. Subjects received neuropsychological assessment at baseline and after 24 weeks of treatment. The primary outcome was change in total recall on the Selective Reminding Test, a measure of verbal learning and memory. Secondary outcomes included other neuropsychological tests from the Brief Repeatable Battery, patient-reported change in memory, and physician-reported impression of cognitive change. Donepezil improved memory performance on the SRT compared to placebo. This benefit remained significant after controlling for various covariates including Expanded Disability Status Scale (EDSS), MS subtype, interferon beta use, treatment group beliefs, gender, baseline selected reminding test (SRT) score, and reading ability. Subjects on donepezil were more likely to report memory improvement (65.7%) than those on placebo (32.4%). The clinician also reported cognitive improvement in more donepezil (54.3%) than placebo (29.4%) subjects. No serious adverse events related to study medication occurred. However, more donepezil (34.3%) than placebo (8.8%) subjects reported unusual/abnormal dreams. Donepezil improved learning and memory in MS patients with initial cognitive difficulties in a single-center clinical trial. Replication of results in a larger multi-center investigation is warranted in order to more definitively assess the efficacy of this intervention.

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    • "Even so, some authors have tried acetylcholinesterase inhibitors, as donepezil, rivastigmine, and galantamine, as well as memantine, an antagonist of NMDA receptors (Doraiswamy and Rao, 2004). Donepezil (10 mg/day) showed an improvement in learning and memory in a randomized placebo-controlled trial enrolling 69 MS patients (Krupp et al., 2004), further showing clinical benefit to patients and physicians (Christodoulou et al., 2006); however negative results were recently reported by other groups which found that donepezil 10 mg daily for 24 weeks is not superior to placebo in improving MS-related cognitive dysfunction, in randomized control trials (Krupp et al., 2011; O’Carroll et al., 2012). Rivastigmine has also been tested in MS patients with neurocognitive dysfunction, where no benefit in a general score memory in comparison to placebo (Shaygannejad et al., 2008) or a trend to an improvement in cognitive processing speed by enhancing compensatory brain activation (Huolman et al., 2011) have been found so far; positive effects were detected in imaging studies, since MS patients treated with rivastigmine displayed increased brain activity during cognitive tasks in fMRI studies (Parry et al., 2003). "
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    ABSTRACT: In Multiple Sclerosis (MS) prevalence studies of community and clinical samples, indicate that 45-60% of patients are cognitively impaired. These cognitive dysfunctions have been traditionally described as heterogeneous, but more recent studies suggest that there is a specific pattern of MS-related cognitive dysfunctions. With the advent of disease-modifying medications for MS and emphasis on early intervention and treatment, detection of cognitive impairment at its earliest stage becomes particularly important. In this review the authors address: the cognitive domains most commonly impaired in MS (memory, attention, executive functions, speed of information processing, and visual-spatial abilities); the pathophysiological mechanism implied in MS cognitive dysfunction and correlated brain MRI features; the importance of neuropsychological assessment of MS patients in different stages of the disease and the influence of its course on cognitive performance; the most used tests and batteries for neuropsychological assessment; therapeutic strategies to improve cognitive abilities.
    Frontiers in Neurology 05/2012; 3:74. DOI:10.3389/fneur.2012.00074
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    • "Above the molecular and genetic level, research may also look at the role of particular neurotransmitters and firing of specific subsets of neurons, which we will refer to as the neural activity level. As with research at a molecular and genetic level, the focus of research here is on dysfunction rather than function and reading ability is often considered as part of general cognitive function during the testing of medications for specific disorders, such as bipolar disorder (Pavuluri and others 2006), ADHD (Bonafina and others 2000), and multiple sclerosis (Christodoulou and others 2006), or following substance abuse (Davis and others 1993; Delaney-Black and others 1998). Moreover, this research does not involve actual neuronal recordings or measurements of neurotransmitter release, which is, of course, unsurprising given the invasive nature of such experiments. "
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    ABSTRACT: As a relatively young science, neuroscience is still finding its feet in potential collaborations with other disciplines. One such discipline is education, with the field of neuroeducation being on the horizon since the 1960s. However, although its achievements are now growing, the partnership has not been as successful as first hopes suggested it should be. Here the authors discuss the theoretical barriers and potential solutions to this, which have been suggested previously, with particular focus on levels of research in neuroscience and their applicability to education. Moreover, they propose that these theoretical barriers are driven and maintained by practical barriers surrounding common language and research literacy. They propose that by overcoming these practical barriers through appropriate training and shared experience, neuroeducation can reach its full potential.
    The Neuroscientist 08/2010; 16(4):349-56. DOI:10.1177/1073858410370900 · 6.84 Impact Factor
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    • "Extensive data support the use of acetylcholinesterase inhibitors (AChEIs), including donepezil, to treat mild to moderate AD (Burns et al., 1999; Tariot et al., 2000; Doraiswamy et al., 2002). Some treatment studies with AChEIs targeting non-demented patient populations with CI have shown cognitive benefits though the effect size is consistently small (Christodoulou et al., 2006; Demaerschalk and Wingerchuk, 2007) and the benefit may not last beyond a few months (Salloway et al., 2004; Petersen et al., 2005). "
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    ABSTRACT: To assess combined antidepressant and cognitive enhancer treatment in elderly patients presenting with depression plus cognitive impairment. Twenty-three elderly (>50 years old) depressed, cognitively impaired (DEP-CI) patients participated in a pilot study. We evaluated whether, after 8 weeks of open antidepressant treatment, donepezil HCl (Aricept) would afford added cognitive benefit compared to placebo in a randomized 12-week trial. A subsample continued in an 8-month extension phase of open treatment with donepezil. Neuropsychological testing (NPT) was performed and antidepressant response monitored at baseline and the 8, 20, and 52-week time points. At 8-weeks, the antidepressant response rate was 61% (14/23). Improvement in SRT immediate recall (SRT-IR; e.g. episodic verbal memory) was observed in responders compared to non-responders. During the 12-week, placebo-controlled, donepezil add-on trial, patients on donepezil showed further improvement in SRT-IR versus patients on placebo. In the open extension phase, patients who continued open donepezil treatment (n = 6) maintained improvement in memory and tended to show an advantage over patients who never received donepezil and were evaluated at the 52-week time point (n = 6). There were no observed significant donepezil effects on non-memory cognitive domains. These preliminary findings suggest that addition of a cholinesterase inhibitor (AChEI) following antidepressant medication treatment in elderly Dep-CI patients may improve cognition, and support the need for a confirmatory, larger randomized placebo-controlled trial.
    International Journal of Geriatric Psychiatry 07/2008; 23(7):670-6. DOI:10.1002/gps.1958 · 2.87 Impact Factor
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