Polymorphisms of the cannabinoid 1 receptor gene and cognitive impairment in multiple sclerosis

2007 ◽  
Vol 14 (2) ◽  
pp. 177-182 ◽  
Author(s):  
JA Woolmore ◽  
MJ Stone ◽  
SL Holley ◽  
PM Jenkinson ◽  
A. Ike ◽  
...  

Cognitive impairment occurs in 45—65% of multiple sclerosis (MS) patients. The cannabinoid system may potentially be neuroprotective in MS. We examined the relationship between polymorphisms of the CNR1 gene and neuropsychological outcome in MS using a test and confirmatory sample of patients. One hundred and ninety-four MS patients were assessed over five key areas of neuropsychological function, which are most commonly impaired in MS. The first 97 patients formed the test sample. A further confirmatory sample of 97 patients was used to test association found in the test sample. The schedule included: Wisconsin card sorting test 64 version, Rey auditory verbal learning task immediate and delayed scores, controlled oral word association task, judgement of line orientation and symbol digit modalities task. Three single nucleotide polymorphisms (SNPs) were typed within the CNR1 gene. For the overall neuropsychological assessment score we used a multiple linear regression model with selected covariates to show that subjects with the AA genotype of the SNP RS1049353 were more impaired (mean -2.47, SD 5.75, P = 0.008, Bonferroni corrected P = 0.024) than the other subjects (mean 0.24, SD 4.24). This was not confirmed when the association was retested in the confirmatory sample. No associations were identified between these CNR1 variants and cognitive impairment in MS. Multiple Sclerosis 2008; 14: 177—182. http://msj.sagepub.com

2019 ◽  
Vol 11 ◽  
pp. 117957351988404
Author(s):  
Stijn Denissen ◽  
Alexander De Cock ◽  
Tom Meurrens ◽  
Luc Vleugels ◽  
Ann Van Remoortel ◽  
...  

Background: Cognitive dysfunction is a frequent manifestation of multiple sclerosis (MS) but its effect on locomotor rehabilitation is unknown. Objective: To study the impact of cognitive impairment on locomotor rehabilitation outcome in people with MS. Methods: We performed a retrospective analysis involving ambulatory patients with MS who were admitted for intensive, inpatient, multidisciplinary rehabilitation at the National Multiple Sclerosis Center of Melsbroek between the years 2012 and 2017. The Brief Repeatable Battery of Neuropsychological Tests (BRB-N) was used to determine the cognitive status of subjects as either impaired (COG–) or preserved (COG+). Locomotor outcome was compared between groups with the difference in 6-minute walk test (6MWT) measured at admission and discharge (Δ6MWT). In addition, individual test scores of the BRB-N for attention (Paced Auditory Serial Addition Test 2” and 3”), visuospatial learning/memory (7/24 Spatial Recall Test), verbal learning/memory (Selective Reminding Test) and verbal fluency (Controlled Oral Word Association Test) were correlated to the Δ6MWT. Results: A total of 318 complete and unique records were identified. Both groups showed a significant within-group Δ6MWT during hospitalization (COG+: 47.51 m; COG–: 40.97 m; P < .01). In contrast, Δ6MWT values were comparable between groups. The odds of achieving a minimal clinical important difference on the 6MWT did not differ significantly between both groups. Only attention/concentration was significantly correlated with Δ6MWT (r = 0.16, P = .013). Conclusion: Cognitive impairment based on BRB-N results appears not to impede locomotor rehabilitation in ambulatory patients with MS. Attentional deficits are correlated to the extent of locomotor rehabilitation, suggesting the presence of a subtle effect of cognition.


2016 ◽  
Vol 33 (S1) ◽  
pp. S405-S405
Author(s):  
E. Aydın ◽  
M. Güleç ◽  
E. Oral ◽  
A.G. Daloğlu

IntroductionIn major depressive disorder (MDD) neurocognitive functions are impaired. In addition to melatonergic properties of agomelatine, via 5-HT2C antagonism it increases extracellular noradrenaline and dopamine in frontal cortex and may improve the neurocognitive functions of patients with MDD.Aims and objectivesTo investigate the extent of neurocognitive improvement and efficacy of agomelatine and fluoxetine in patients with MDD.Material and methodAgomelatine 25 mg/day (n: 24) and fluoxetine 20 mg/day (n: 24) were administered to drug-naive unipolar, non-psychotic, non-suicidal MDD patients according to DSM-IV. Evaluations were performed just before the treatment and at the sixth week of treatment via administering Hamilton Depression Rating Scale, Rey Auditory Verbal Learning Test, Controlled Oral Word Association Test (COWAT), Digit Span Test (DST), Trail Making Test (TMT-A/B), Stroop Test and Wisconsin Card Sorting Test.ResultsBoth agomelatine and fluoxetine was found to be efficacious for the treatment of MDD (P < 0.05 for both). Further there was no difference between the antidepressant efficacy of two drugs. Both of the drugs improved measured neurocognitive functions (P < 0.05), except scores of DST (P > 0.05) and only fluoxetine improved significantly scores of COWAT (P < 0.05). Only in terms of TMT-B there was significant difference between groups and agomelatine was superior to fluoxetine (P < 0.05).ConclusionAgomelatine and fluoxetine were efficacious in treatment of MDD. Furthermore both of the drugs improved cognitive functions in patients with MDD. Superiority of agomelatine in improvement of executive functioning (TMT-B) is important and therefore it could be an appropriate choice for MDD patients who have pronounced executive disturbances.Disclosure of interestThe authors have not supplied their declaration of competing interest.


2020 ◽  
Vol 17 (11) ◽  
pp. 1143-1148
Author(s):  
Dong Jin Shin ◽  
Taehee Kim ◽  
Do-Un Jung ◽  
Jung-Joon Moon ◽  
Dong-Wook Jeon ◽  
...  

Objective Cognition of peritoneal dialysis patients is influenced by various factors including dialysis adequacy such as fractional urea clearance (Kt/V) and relative overhydration (RelOH). This study aimed to discover the potential contribution of dialysis adequacy to cognitive function in patients undergoing peritoneal dialysis.Methods Fifty-nine patients undergoing peritoneal dialysis were recruited. Demographic information, comorbidities, and clinical lab findings were retrospectively collected, and dialysis adequacy was determined by the Kt/V and RelOH calculation. Cognition and depression were measured with Digit Symbol Substitution Test, Hopkins Verbal Learning Test, Wechsler memory scale (spatial span), Wisconsin Card Sorting Test, and Beck’s depression inventory. Partial correlation test was used to explore the correlation of dialysis adequacy with cognitive function.Results RelOH showed significant correlation with some of the Wisconsin Card Sorting test results. The categories achieved showed negative correlation (r=-0.32, p=0.02) and trials to complete first category showed positive correlation (r=0.31, p=0.02) with RelOH. Other tasks showed no significant correlation with RelOH. Kt/V.Conclusion Our study demonstrates that peritoneal dialysis adequacy, measured by RelOH, seems to be significantly correlated with the occurrence of cognitive impairment. The outcome suggests that RelOH may have the potential to clarify the role of cognitive impairment in peritoneal dialysis patients.


2004 ◽  
Vol 10 (7) ◽  
pp. 948-956 ◽  
Author(s):  
DOUGLAS R. DENNEY ◽  
SHARON G. LYNCH ◽  
BRETT A. PARMENTER ◽  
NIKKI HORNE

Based on the assumption that cognitive impairment in MS is consistent with subcortical dementia, a battery of neuropsychological tests was assembled that included measures of executive function (Tower of London and Wisconsin Card Sorting Test), verbal learning and memory (a paired associates learning test), and speeded information processing (Stroop Color Word Interference Test). The battery was administered to patients with relapsing and primary progressive MS and to healthy controls. Differences between patients and controls occurred on several of the measures. However, when differences with respect to fatigue and depression were statistically controlled, the only differences that remained significant involved measures relating to the speed of information processing. Patients performed more slowly than controls, with the disparity being greater for relapsing patients than for those with primary progressive disease. The slowing was evident on measures of automatic as well as controlled processing and regardless of whether speed was an explicit feature of successful performance or recorded unobstrusively while the patient concentrated on planning a correct solution to a problem. Parallels were noted between cognitive slowing associated with MS and that of normal aging. (JINS, 2004, 10, 948–956.)


2001 ◽  
Vol 17 (2) ◽  
pp. 112-119 ◽  
Author(s):  
Karl H. Wiedl ◽  
Henning Schöttke ◽  
M. Dolores Calero Garcia

Summary: Dynamic assessment is a diagnostic approach in which specific interventions are integrated into assessment procedures to estimate cognitive modifiability. The study investigates the utility of this approach in persons with compelling rehabilitational needs. Samples of schizophrenic patients and of elderly with and without dementia were assessed with dynamic versions of the Wisconsin Card Sorting Test and the Auditory Verbal Learning Test. Both tests were administered by applying specific procedures of verbal mediation designed to increase performance. Results demonstrated superior predictive validity with regard to proficiency in a clinical training in schizophrenic subjects and better discrimination of nondemented and demented elderly with the help of dynamic measures compared to static test scores. Subsequent correlational analyses indicated that, for both tests, performance change following intervention is related to the processing of verbal context information. Results are discussed with respect to the concept of verbal working memory as one component of the patients' rehabilitation potential.


2021 ◽  
pp. 135245852110331
Author(s):  
Olga Marchesi ◽  
Raffaello Bonacchi ◽  
Paola Valsasina ◽  
Paolo Preziosa ◽  
Elisabetta Pagani ◽  
...  

Background: Executive dysfunctions, including difficulties in attention, working memory, planning, and inhibition affect 15%–28% of multiple sclerosis (MS) patients. Objectives: To investigate structural and functional magnetic resonance imaging (MRI) abnormalities underlying executive function (EF) in MS patients. Methods: A total 116 MS patients and 65 controls underwent resting-state (RS) and diffusion-weighted sequences and neuropsychological examination, including Wisconsin Card Sorting Test (WCST) to test EF. Brain RS cognitive networks and fractional anisotropy (FA) from a priori selected white matter tracts were derived. Associations of WCST scores with RS functional connectivity (FC) and FA abnormalities were investigated. Results: In MS patients, predictors of working memory/updating were: lower corpus callosum (CC) FA, lower left working-memory network (WMN), right WMN RS FC for worse performance; lower executive control network (ECN), higher default-mode network (DMN), and salience network (SN) RS FC for better performance ( R2 = 0.35). Predictors of attention were lower CC genu FA, lower left WMN, and DMN RS FC for worse performance; higher left WMN and ECN RS FC for better performance ( R2 = 0.24). Predictors of worse shifting/inhibition were lower CC genu and superior cerebellar peduncle (SCP) FA, lower left WMN RS FC for worse performance; and higher ECN RS FC for better performance ( R2 = 0.24). Conclusions: CC and SCP microstructural damage and RS FC abnormalities in cognitive networks underlie EF frailty in MS.


2019 ◽  
Vol 21 (2) ◽  
pp. 208-216
Author(s):  
Maged Abdel Naseer ◽  
Shereen Fathi ◽  
Dalia M. Labib ◽  
Dalia H. Khalil ◽  
Alshaimaa M. Aboulfotooh ◽  
...  

AbstractObjective:Cognitive impairment in multiple sclerosis (MS) has a complex relationship with disease progression and neurodegeneration. The aim of this study was to shed light on the importance of early detection of cognitive impairment in MS patients.Methods:The study comprised two groups of definite MS patients, relapsing remitting multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS), each with 25 patients. Physical disability was assessed using the Expanded Disability Status Scale (EDSS), while the risk of secondary progression was assessed using the Bayesian Risk Estimate for Multiple Sclerosis (BREMS). Cognitive functions were assessed using the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) and Controlled Oral Word Association Test (COWAT). Assessment of neurodegeneration was done using optical coherence tomography (OCT) via quantification of retinal nerve fiber layer (RNFL).Results:MS patients with higher RNFL thickness demonstrated a larger learning effect size than patients who had lower values in RNFL thickness regardless of MS type. RRMS patients showed significant improvement in delayed recall after giving cues than SPMS. The symbol digit modalities test was the only neuropsychological test that showed a significant negative correlation with EDSS (P = 0.009). There was a statistically significant negative correlation between BREMS scores and performance in all neuropsychological tests.Conclusion:Inclusion of neurocognitive evaluation in the periodic assessment of MS patients is mandatory to detect patients at increased risk of secondary progression. The thickness of RNFL is suggested as a method to estimate the expected benefit of cognitive rehabilitation, regardless of MS type.


2019 ◽  
Vol 2019 ◽  
pp. 1-7
Author(s):  
Riwanti Estiasari ◽  
Yuhyi Fajrina ◽  
Diatri Nari Lastri ◽  
Syarli Melani ◽  
Kartika Maharani ◽  
...  

Introduction. Multiple Sclerosis (MS) can affect cognitive function that might interfere with quality of life. Processing speed and memory are the most common area of cognitive impairment. Cognitive evaluation in daily practice is often difficult to be performed since it needs neuropsychological expert and is time-consuming. Brief International Cognitive Assessment for MS (BICAMS) is valid and practical for cognitive evaluation. This study aims to validate BICAMS in Indonesian MS patients and healthy controls (HC) and to analyse the effect of cognitive impairment on quality of life. Methods. BICAMS, which composes Symbol Digits Modalities Test (SDMT), California Verbal Learning Test-Second Edition (CVLT-II), and Brief Visuospatial Memory Test-Revised (BVMT-R), was translated and cross-culturally adapted to Indonesian from the original BICAMS and then administered to 40 Indonesian MS patients and 66 HC matched by sex, age, and education. Test-retest reliability was performed on 16-MS patients and 42 HC. Quality of life was measured using Multiple Sclerosis Quality of Life (MSQOL-54) instrument. Results. The SDMT, CVLT-II, and BVMT-R score in MS patients were significantly lower than those in HC (effect size, r: 0.61, 0.36, and 0.47, respectively). Test-retest reliability for all tests was satisfactory with correlation coefficient for SDMT, CVLT-II, and BVMT-R in MS subjects 0.86, 0.81, and 0.83, respectively. Using 5th percentile of HC score as cut-off, 15% MS subjects had impairment in one test, 27.5% in two tests, and 40% in three tests. BICAMS was moderately correlated with EDSS but was not correlated with disease duration and relapse rate. SDMT score correlated with physical function and physical and mental role limitation. Conclusion. BICAMS is valid and reliable for assessing cognitive function of Indonesia MS patients.


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).


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