Effects of donepezil on memory and cognition in multiple sclerosis.
ABSTRACT 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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ABSTRACT: Approximately 50% of persons with multiple sclerosis experience cognitive impairment, which adversely affects daily functioning. Although patients report that fatigue contributes to cognitive difficulties, previous empirical studies do not show a clear association. This study assessed coping style as a moderator of the relationship between fatigue and cognition in a 3-year longitudinal sample. Scores on the Fatigue Impact Scale and the Coping Orientation to Problems Experienced (COPE) at baseline were modeled to predict later performance on a composite of cognitive tests to investigate the hypothesis that coping would have a significant moderating effect on fatigue in predicting cognitive performance. Findings partially supported hypotheses by showing that avoidant coping moderated the relationship between fatigue and cognitive performance. Patients who experienced relatively high fatigue performed better on cognitive tests if they used less avoidant coping. Those who reported lower fatigue had relatively good cognitive performance regardless of their coping style. This study provides evidence that coping style is associated with the ability to deal with stress, like fatigue, and their interaction can impact functional outcomes of disease. These results could benefit understanding of prognosis and improve treatment for patients with MS. (JINS, 2014, 20, 1-5.).Journal of the International Neuropsychological Society 07/2014; · 3.01 Impact Factor
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ABSTRACT: The range of symptoms which occur in multiple sclerosis (MS) can have disabling functional consequences for patients and lead to significant reductions in their quality of life. MS symptoms can also interact with each other, making their management challenging. Clinical trials aimed at identifying symptomatic therapies have generally been poorly designed and have tended to be underpowered. Therefore, the evidence base for the management of MS symptoms with pharmacologic therapies is not strong and tends to rely upon open-label studies, case reports, and clinical trials with small numbers of patients and poorly validated clinical outcome measures. Recently, there has been a growing interest in the management of MS symptoms with pharmacologic treatments, and better-designed, randomized, double-blind, controlled trials have been reported. This chapter will describe the evidence base predominantly behind the various pharmacologic approaches to the management of MS symptoms, which in most, if not all, cases, requires multidisciplinary input. Drugs routinely recommended for individual symptoms and new therapies, which are currently in the development pipeline, will be reviewed. More interventional therapies related to symptoms that are refractory to pharmacotherapy will also be discussed, where relevant.Handbook of Clinical Neurology 01/2014; 122:513-62.
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ABSTRACT: The purpose of the present study was to investigate if acute exposure to diphenyl ditelluride (PhTe)2 causes impairment of developmental behavioral performance in rat pups. Rat pups received a single subcutaneous injection of (PhTe)2 (0.1 mg kg-1, 3 mL kg-1) or vehicle (3 mL kg-1) at 14th postnatal day. After exposure to (PhTe)2, the general parameters of neurotoxicity, behavioral tasks, cerebral myelin content, histological analysis and acetilcholinesterase (AChE) activity were performed during seven days. The appearance of classic signs of toxicity, behavioral alterations and the reduction in myelin content were dependent on the time after (PhTe)2 exposure to pups. Neuronal damage, reduction of myelin content, and the increase in AChE activity occurred mainly at 4th and 5th day after (PhTe)2 exposure, indicating that the critical period of neurotoxicity is coincident with the major behavioral alterations. In conclusion, exposure to (PhTe)2 induced neurotoxicity and impairment of developmental behavioral in rat pups.Journal of the Brazilian Chemical Society 12/2009; 21(11):2130-2137. · 1.25 Impact Factor