Donepezil improved memory in multiple sclerosis in a randomized clinical trial

Department of Neurology, State University of New York at Stony Brook, HSC T12-020, Stony Brook, NY 11794-8121, USA.
Neurology (Impact Factor: 8.29). 12/2004; 63(9):1579-85. DOI: 10.1212/01.WNL.0000142989.09633.5A
Source: PubMed


To determine the effect of donepezil in treating memory and cognitive dysfunction in multiple sclerosis (MS).
This single-center double-blind placebo-controlled clinical trial evaluated 69 MS patients with cognitive impairment who were randomly assigned to receive a 24-week treatment course of either donepezil (10 mg daily) or placebo. Patients underwent neuropsychological assessment at baseline and after 24 weeks of treatment. The primary outcome was change in verbal learning and memory on the Selective Reminding Test (SRT). Secondary outcomes included other tests of cognitive function, patient-reported change in memory, and clinician-reported impression of cognitive change.
Donepezil-treated patients showed significant improvement in memory performance on the SRT compared to placebo (p = 0.043). The benefit of donepezil remained significant after controlling for various covariates including age, Expanded Disability Status Scale, baseline SRT score, reading ability, MS subtype, and sex. Donepezil-treated patients did not show significant improvements on other cognitive tests, but were more than twice as likely to report memory improvement than those in the placebo group (p = 0.006). The clinician also reported cognitive improvement in almost twice as many donepezil vs placebo patients (p = 0.036). No serious adverse events related to study medication occurred, although more donepezil (34.3%) than placebo (8.8%) subjects reported unusual/abnormal dreams (p = 0.010).
Donepezil improved memory in MS patients with initial cognitive impairment in a single center clinical trial. A larger multicenter investigation of donepezil in MS is warranted in order to more definitively assess the efficacy of this intervention.

Download full-text


Available from: Leigh E Charvet, Apr 27, 2015
17 Reads
  • Source
    • "Based on case reports of benefit of Cholinesterase inhibitors in MS patients [12] we offered a trial of Rivastigmine patch which was ineffective. Patient inquired about TMS as an enhancer of brain function. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Multiple Sclerosis (MS) is a chronic central nervous system (CNS) demyelinating disease. Gait abnormalities are common and disabling in patients with MS with limited treatment options available. Emerging evidence suggests a role of prefrontal attention networks in modulating gait. High-frequency repetitive transcranial magnetic stimulation (rTMS) is known to enhance cortical excitability in stimulated cortex and its correlates. We investigated the effect of high-frequency left prefrontal rTMS on gait parameters in a 51-year-old Caucasian male with chronic relapsing/remitting MS with residual disabling attention and gait symptoms. Patient received 6 Hz, rTMS at 90% motor threshold using figure of eight coil centered on F 3 location (using 10-20 electroencephalography (EEG) lead localization system). GAITRite gait analysis system was used to collect objective gait measures before and after one session and in another occasion three consecutive daily sessions of rTMS. Two-tailed within subject repeated measure t -test showed significant enhancement in ambulation time, gait velocity, and cadence after three consecutive daily sessions of rTMS. Modulating left prefrontal cortex excitability using rTMS resulted in significant change in gait parameters after three sessions. To our knowledge, this is the first report that demonstrates the effect of rTMS applied to the prefrontal cortex on gait in MS patients.
    07/2015; Volume 2015(2015):6. DOI:10.1155/2015/251829
  • Source
    • "Although there have been a number of MS studies examining potential improvement due to the effects of a pharmaceutical agent on individual tests of cognitive functioning over the course of a trial [20] [21] [22], little research has been published examining the effects of such an agent on general neuropsychological test performance in MS. An earlier investigation by Fischer et al. [23] examined the effects of intramuscular interferon beta-1a (Avonex®) in MS patients using a comprehensive neuropsychological test battery administered over a 2 year time span in a subset of English speaking subjects from the Phase 3 registrational clinical trial (MSCRG study). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Determine reliability and basic psychometric properties of a composite cognitive endpoint, MS-COG, for monitoring change in cognitive function in MS drug trials. 50% of MS patients have cognitive impairment that impacts ability to work and quality of life. We selected neuropsychological tests based on sensitivity to MS cognitive impairment, availability of alternate forms, cross-cultural utility, and feasibility for multicenter trials, and assessed the reliability and validity of a composite endpoint, MS-COG. Administered SRT, BVMT-R, PASAT, and SDMT to 60 MS patients at 4 US centers twice over 45days, along with symptom inventories by patients and informants. The MS-COG had test-retest reliability of 0.91. Processing Speed and Memory indices had reliabilities of 0.89 and 0.86, with modest practice effects. Reliability was high for the RR MS and SP MS subgroups as well, with correlations of .90 and .93, respectively for MS-COG. Overall, 42% of subjects obtained MS-COG scores in the impaired range, with SP MS subjects performing 0.8 SD below RR MS subjects. Impairment correlated well (r=0.37 to 0.40) with informant reports but was inconsistent with patient report, with the least reliable assessments by those with greater symptom severity. The MS-COG is a reliable, repeatable measure of MS cognitive functioning that is sensitive to cognitive impairment in SP MS and RR MS patients and feasible for multicenter clinical trials. Further development is warranted.
    Journal of the neurological sciences 03/2014; 340(1-2). DOI:10.1016/j.jns.2014.03.009 · 2.47 Impact Factor
    • "The explanation could be that the three symptoms are often co-occurring and possibly synergistic in persons with MS and are etiologically linked through cytokine induced manifestations of sickness behavior with diffuse axonal damage across different regions of the central nervous system.[313536] Researchers have identified fatigue, depression, and pain as a symptom cluster, which is associated with reduced physical activity and QoL in persons with MS.[3738] Another study reported decreased QoL in all domains with physical functioning being the most affected in patients with MS.[19] "
    [Show abstract] [Hide abstract]
    ABSTRACT: This prospective study was carried out to observe the prevalence of fatigue in patients with multiple sclerosis (MS) and its effect on quality-of-life (QoL). Prospective observational study in a University Tertiary Research Hospital in India. A total of 31 patients (25 females) with definite MS according to McDonald's criteria presented in out-patient/admitted in the Department of Neurology (between February 2010 and December 2011) were included in the study. Disease severity was evaluated using the Kurtzke's expanded disability status scale (EDSS). Fatigue was assessed using Krupp's fatigue severity scale (FSS). QoL was assessed by the World Health Organization QoL-BREF questionnaire. The mean age of patients was 30.1 ± 9.1 years. The mean age at first symptom was 25.23 ± 6.4 years. The mean number of relapses was 4.7 ± 3.6 in the patients. The mean duration of illness was 4.9 ± 4.4 years. The mean EDSS score was 3.5 ± 2.2. Mean fatigue score was 38.7 ± 18.5 (cut-off value 36 in FSS). The prevalence of fatigue in patients with MS was 58.1% (18/31). MS patients with fatigue were significantly more impaired (P < 0.05) on all QoL domains (i.e., physical, psychosocial, social, and environment) than MS patients without fatigue. Prevalence of fatigue was found to be high in the MS patients in the study. All four domains of QoL were significantly more impaired in the group with fatigue than in those without fatigue.
    07/2013; 4(3):278-82. DOI:10.4103/0976-3147.118774
Show more