Memantine for cognitive impairment in multiple sclerosis: a randomized placebo-controlled trial

2010 ◽  
Vol 16 (6) ◽  
pp. 715-723 ◽  
Author(s):  
JF Lovera ◽  
E. Frohman ◽  
TR Brown ◽  
D. Bandari ◽  
L. Nguyen ◽  
...  

Background: Memantine, an NMDA antagonist, is effective for moderate to severe Alzheimer’s disease. Objective: Determine whether memantine improves cognitive performance (CP) among subjects with multiple sclerosis (MS) and cognitive impairment (CI). Methods: This double-blind, randomized, placebo-controlled trial (Clinicaltrials.gov NCT00300716) compared memantine 10 mg twice a day (4 week titration followed by 12 weeks on the highest tolerated dose) with placebo. The primary outcome was the change from baseline to exit on the Paced Auditory Serial Addition Test (PASAT) and the California Verbal Learning Test-II (CVLT-II) Long Delay Free Recall (LDFR). Secondary outcomes included additional neuropsychological tests; self-report measures of quality of life, fatigue, and depression; and family/caregiver reports of subjects’ CI and neuropsychiatric symptoms. Results: The differences between the groups on the change on the PASAT (placebo—memantine = 0.0 correct responses, 95% CI 3.4, 3.4; p = 0.9) and on CVLT-II LDFR (placebo—memantine =—0.6 words, 95% CI —2.1, 0.8; p = 0.4) as well as on the other cognitive tests were not significant. Subjects on memantine had no serious adverse events (AEs) but had more fatigue and neurological AEs as well as, per family members’ reports, less cognitive improvement and greater neuropsychiatric symptoms than subjects on placebo. Conclusion: Memantine 10 mg twice a day does not improve CP in subjects with MS, ages 18—65, without major depression, who have subjective cognitive complaints and perform worse than one SD below the mean on the PASAT or on the California Verbal Learning Test-II (total recall or delayed free recall).

2016 ◽  
Vol 74 (12) ◽  
pp. 974-981 ◽  
Author(s):  
Marco A. G. de Caneda ◽  
Maria Cecília A. de Vecino

ABSTRACT Multiple sclerosis (MS) may present with a cognitive impairment as disabling as the physical disabilities. Therefore, routine cognitive evaluation is pivotal. Valid and reliable neuropsychological tests are essential in follow-up and to define future therapeutic interventions. Objectives To investigate the correlation between the disabilities of MS patients and their cognitive impairment assessed by the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS). Methods Forty patients with definitive diagnoses of MS were selected. The correlation coefficient (r) between the Expanded Disability Status Scale (EDSS) and the neuropsychological tests of BICAMS were calculated. Results The correlation was clinically substantial and significant with r = 0.55 (p < 0.01) in the Symbol Digit Modalities Test (SDMT), 0.54 (p < 0.01) in the Brief Visuospacial Memory Test (BVMT) and 0.40 (p < 0.05) in the California Verbal Learning Test (CVLT). Conclusion BICAMS has easy and satisfactory application and evaluation for routine visits and presents a significant correlation with the EDSS. Its use may be indicated for screening and monitoring of cognitive impairment in patients with MS.


2016 ◽  
Vol 41 (5-6) ◽  
pp. 303-313
Author(s):  
Sofia Madureira ◽  
Ana Verdelho ◽  
Carla Moleiro ◽  
Catarina Santos ◽  
Philip Scheltens ◽  
...  

Aims: To describe the contribution of white matter lesions to the long-term neuropsychological profiles of different groups of clinical diagnoses, and to identify neuropsychological predictors of cognitive impairment in a 10-year follow-up. Methods: The Lisbon subcohort of the Leukoaraiosis and Disability (LADIS) study was re-evaluated performing a clinical, functional and cognitive evaluation [including Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale - Cognition (ADAS-Cog) and ADAS-Cog with the extension for vascular impairment (VADAS-Cog), the 9-word version of the California Verbal Learning Test (CVLT-9), the Trail-Making test and the Stroop test] as well as an MRI scan. Using clinical diagnostic criteria, participants were identified as having no cognitive impairment (NI), cognitive impairment but no dementia (CIND) or dementia (DEM), and the effect of time on clinical diagnosis and neuropsychological profiles was analyzed. Results: From the initial group of 66 participants, 37 out of 41 survivors (90%) were re-evaluated (mean age 81.40 years, 57% women). Fifteen patients (41%) had DEM, 12 (32%) CIND and 10 (27%) NI. Over time, the three groups presented distinct profiles in the MMSE [F2, 62 = 15.85, p = 0.000], ADAS [F2, 62 = 15.85, p = 0.000] and VADAS [F2, 48 = 5.87, p = 0.008]. Logistic regression analysis identified higher scores on MMSE (β = 1.14, p = 0.03, OR = 3.13, 95% CI 1.09-8.97) as predictors of NI after 10 years of follow-up. Conclusion: Higher scores on baseline MMSE were the only neuropsychological predictors of NI after 10 years.


2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 438-438
Author(s):  
Yuri Agrawal ◽  
Jennifer Schrack ◽  
Alden Gross ◽  
Nicole Armstrong ◽  
Eleanor Simonsick ◽  
...  

Abstract Sensory function has been linked to cognitive impairment and dementia, but the link between multiple sensory impairments and early cognitive impairment (ECI) is unclear. Sensory function (vision, hearing, vestibular, proprioception, and olfaction) was measured in 390 BLSA participants (age=75±8 years; 57% women; 69% white) from 2012 to 2018 over a mean 3.6 years. ECI was defined based on 1 standard deviation below age-and race-specific means in Card Rotations or California Verbal Learning Test immediate recall. Cox proportional hazard models examined the risk of ECI for each sensory impairment and across categories of impairments. Vision impairment (vs. no vision impairment) was associated with a 70% greater risk of ECI (HR=1.70, p=0.05). Participants with 1 or ≥2 sensory impairments had triple the risk of ECI (HR=3.74 and 3.44, p=0.008 and 0.02, respectively) compared to those without impairment. Future studies are needed to examine whether treatment for sensory impairments can modify these risks.


2019 ◽  
Vol 26 (14) ◽  
pp. 1919-1928 ◽  
Author(s):  
Sharon Jean Baetge ◽  
Melanie Filser ◽  
Alina Renner ◽  
Sebastian Ullrich ◽  
Christoph Lassek ◽  
...  

Background: The international standard to screen for cognitive impairment in multiple sclerosis (MS) is BICAMS (Brief International Cognitive Assessment for MS). However, with an application time of approximately 20 minutes, the battery might be too time consuming from a pragmatic perspective of a routine examination. Objectives: To examine the relative sensitivity and specificity of a BICAMS short version and its validity compared to the total battery. Methods: The German BICAMS version was applied comprising the Symbol Digit Modalities Test (SDMT), the Brief Visuospatial Memory Test–Revised (BVMT-R) and the Rey Auditory Verbal Learning Test (RAVLT; German VLMT). Single tests and two-test combinations were compared regarding conformity with the total battery. Results: Examining 1320 MS patients, the two-test combination of SDMT-BVMT-R was the most sensitive (92.7%) to impairment and showed the strongest agreement with the total battery (κ = 0.95). Performing binary logistic regression analyses, this combination was also validated by its association with employment status. Conclusion: Application of the total BICAMS battery should be the goal to strive for. However, in time-restricted clinical settings, the combined application of SDMT and BVMT-R is a recommendable alternative with an application time of 10 minutes, while single tests alone are not sufficiently sensitive.


2014 ◽  
Vol 15 (1) ◽  
pp. 18-27 ◽  
Author(s):  
Arie J. Wester ◽  
Renée L. Roelofs ◽  
Jos I.M. Egger ◽  
Roy P.C. Kessels

Objectives: Neuropsychological assessment of memory disorders is an important prerequisite in the treatment of patients with alcohol-related cognitive disorders. Although many memory tests are available in clinical practice, a question remains regarding which test is most appropriate for this purpose. Our study's goal was to evaluate the discriminative power of indices of a standard memory test (the California Verbal Learning Test; CVLT) versus the subtests of an ecologically valid everyday memory test (the Rivermead Behavioural Memory Test; RBMT) in patients with alcohol-use disorder.Method: The patients included 136 with Korsakoff's syndrome (KS), 73 alcoholics with cognitive impairment (CI) not fulfilling the criteria for KS, and 24 cognitively unimpaired alcoholics (ALC).Results: KS patients performed significantly lower on all RBMT and CVLT variables than CI patients. ALC patients performed significantly better than CI patients on only one RBMT subtest, and had a significantly lower rate of forgetting and higher scores on free recall on CVLT. A combination of RBMT subtests and CVLT indices was able to discriminate KS patients from CI and ALC patients. The RBMT subtests could not significantly distinguish ALC from CI patients. Both rate of forgetting and a comparison between free and cued recall testing on the CVLT showed the largest between-group differences.Conclusion: Although the RBMT provides information about everyday memory performance, the CVLT indices are better able to distinguish between uncomplicated alcoholics and those with cognitive impairment or KS.


2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 438-438
Author(s):  
Yang An ◽  
Frank Lin ◽  
Luigi Ferrucci ◽  
Jennifer Schrack ◽  
Yuri Agrawal ◽  
...  

Abstract The long prodromal period for dementia pathology demands valid and reliable approaches to detect cases before clinically recognizable symptoms emerge, by which time it may be too late to effectively intervene. We derived and compared several algorithms for early cognitive impairment (ECI) using longitudinal data on 1704 BLSA participants. Algorithms were based on cognitive impairment in various combinations of memory and non-memory tests, and the CDR. The best-performing algorithm was defined based on 1SD below age-and race-specific means in Card Rotations or California Verbal Learning Test immediate recall, two tests that in prior work show the earliest declines prior to dementia onset. While this ECI algorithm showed low concordance with concurrent adjudicated MCI/dementia (AUC: 0.63, sensitivity: 0.54, specificity: 0.73), it was among the best predictors of progression to MCI/dementia (HR: 3.65, 95% CI: 1.69,7.87). This algorithm may be useful in epidemiologic work to evaluate risk factors for early cognitive impairment.


2020 ◽  
pp. 135245852093738
Author(s):  
Lisa F Barcellos ◽  
Mary Horton ◽  
Xiaorong Shao ◽  
Kalliope H Bellesis ◽  
Terrence Chinn ◽  
...  

Objectives: Determine the validity and reliability of a remote, technician-guided cognitive assessment for multiple sclerosis (MS), incorporating the Symbol Digit Modalities Test (SDMT) and the California Verbal Learning Test, Second Edition (CVLT-II). Methods: In 100 patients, we compared conventional in-person testing to remote, web-assisted assessments, and in 36 patients, we assessed test–retest reliability using two equivalent, alternative forms. Results: In-person and remote-administered SDMT ( r = 0.85) and CVLT-II ( r = 0.71) results were very similar. Reliability was adequate and alternative forms of SDMT ( r = 0.92) and CVLT-II ( r = 0.81) produced similar results. Conclusions: Findings indicate remote assessment can provide valid, reliable measures of cognitive function in MS.


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