The PASAT performance among patients with multiple sclerosis: analyses of responding patterns using different scoring methods

2006 ◽  
Vol 12 (5) ◽  
pp. 586-593 ◽  
Author(s):  
E Rosti ◽  
P Hämäläinen ◽  
K Koivisto ◽  
L Hokkanen
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Trials ◽  
Cognitive Impairment ◽  
Assessment Tool ◽  
Cognitively Impaired ◽  
Healthy Controls ◽  
Scoring Methods ◽  
Multiple Sclerosis Functional Composite ◽  
Relapsing Remitting ◽  
Serial Addition

The Paced Auditory Serial Addition Test (PASAT) is widely used in the evaluation of multiple sclerosis (MS) patients’ cognitive performance, and also used as the sole measure of cognition in a recently developed assessment tool for MS clinical trials, the Multiple Sclerosis Functional Composite (MSFC). We analysed if MS patients and healthy controls have different patterns of responding in the PASAT, and whether different scoring methods influence the PASAT’s sensitivity and specificity in detecting disease-associated cognitive impairment. Forty-five relapsing-remitting MS patients and 48 healthy controls were evaluated using the PASAT and a comprehensive neuropsychological examination. Cognitively deteriorated MS patients compensated for their difficulties in PASAT by omitting rather than guessing answers. They skipped items intermittently, which reduces the difficulty of the task. Furthermore, towards the end of the PASAT’s 60-item series MS patients’ performance had a trend to fade whereas controls’ performance was more even throughout the task. The dyad score or the percent dyad score did not essentially improve the sensitivity or the specificity, but the accuracy improved when the answers at the end of the PASAT series were specifically emphasized. Using the combined score, 73% of the patients were correctly classified as cognitively impaired or unimpaired.

scholarly journals Reduced dynamics of functional connectivity and cognitive impairment in multiple sclerosis

2019 ◽  
Vol 26 (4) ◽  
pp. 476-488 ◽  
Author(s):  
Alessandro d’Ambrosio ◽  
Paola Valsasina ◽  
Antonio Gallo ◽  
Nicola De Stefano ◽  
Deborah Pareto ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cognitive Impairment ◽  
Functional Connectivity ◽  
Network Connectivity ◽  
Brain Network ◽  
Cognitively Impaired ◽  
Healthy Controls ◽  
Correlation Matrices ◽  
Relapsing Remitting ◽  
Frequent Switching

Background: In multiple sclerosis (MS), abnormalities of brain network dynamics and their relevance for cognitive impairment have never been investigated. Objectives: The aim of this study was to assess the dynamic resting state (RS) functional connectivity (FC) on 62 relapsing-remitting MS patients and 65 sex-matched healthy controls enrolled at 7 European sites. Methods: MS patients underwent clinical and cognitive evaluation. Between-group network FC differences were evaluated using a dynamic approach (based on sliding-window correlation analysis) and grouping correlation matrices into recurrent FC states. Results: Dynamic FC analysis revealed, in healthy controls and MS patients, three recurrent FC states: two characterized by strong intra- and inter-network connectivity and one characterized by weak inter-network connectivity (State 3). A total of 23 MS patients were cognitively impaired (CI). Compared to cognitively preserved (CP), CI-MS patients had reduced RS-FC between subcortical and default-mode networks in the low-connectivity State 3 and lower dwell time (i.e. time spent in a given state) in the high-connectivity State 2. CI-MS patients also exhibited a lower number and a less frequent switching between meta-states, as well as a smaller distance traveled through connectivity states. Conclusion: Time-varying RS-FC was markedly less dynamic in CI- versus CP-MS patients, suggesting that slow inter-network connectivity contributes to cognitive dysfunction in MS.

scholarly journals Monitoring cognitive change in multiple sclerosis using a computerized cognitive battery

2018 ◽  
Vol 4 (4) ◽  
pp. 205521731881551 ◽  
Author(s):  
L De Meijer ◽  
D Merlo ◽  
O Skibina ◽  
EJ Grobbee ◽  
J Gale ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cognitive Change ◽  
Progressive Multiple Sclerosis ◽  
Healthy Controls ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Serial Addition ◽  
Multiple Sclerosis Patients ◽  
Relapsing Remitting Multiple Sclerosis ◽  
Cognitive Monitoring

Background Cognitive monitoring that can detect short-term change in multiple sclerosis is challenging. Computerized cognitive batteries such as the CogState Brief Battery can rapidly assess commonly affected cognitive domains. Objectives The purpose of this study was to establish the acceptability and sensitivity of the CogState Brief Battery in multiple sclerosis patients compared to controls. We compared the sensitivity of the CogState Brief Battery to that of the Paced Auditory Serial Addition Test over 12 months. Methods Demographics, Expanded Disability Status Scale scores, depression and anxiety scores were compared with CogState Brief Battery and Paced Auditory Serial Addition Test performances of 51 patients with relapsing–remitting multiple sclerosis, 19 with secondary progressive multiple sclerosis and 40 healthy controls. Longitudinal data in 37 relapsing–remitting multiple sclerosis patients were evaluated using linear mixed models. Results Both the CogState Brief Battery and the Paced Auditory Serial Addition Test discriminated between multiple sclerosis and healthy controls at baseline ( p<0.001). CogState Brief Battery tasks were more acceptable and caused less anxiety than the Paced Auditory Serial Addition Test ( p<0.001). In relapsing–remitting multiple sclerosis patients, reaction time slowed over 12 months ( p<0.001) for the CogState Brief Battery Detection (mean change –34.23 ms) and Identification (–25.31 ms) tasks. Paced Auditory Serial Addition Test scores did not change over this time. Conclusions The CogState Brief Battery is highly acceptable and better able to detect cognitive change than the Paced Auditory Serial Addition Test. The CogState Brief Battery could potentially be used as a practical cognitive monitoring tool in the multiple sclerosis clinic setting.

The Paced Auditory Serial Addition Test: to what extent is it performed as instructed, and is it associated with disease course?

2005 ◽  
Vol 11 (1) ◽  
pp. 85-89 ◽  
Author(s):  
H Coo ◽  
W M Hopman ◽  
C M Edgar ◽  
E V McBride ◽  
D G Brunet
Keyword(s):  
Multiple Sclerosis ◽  
Cognitive Function ◽  
Correct Response ◽  
Disease Course ◽  
Scoring Methods ◽  
Scoring Method ◽  
Multiple Sclerosis Functional Composite ◽  
Proxy Measure ◽  
The Mean ◽  
Serial Addition

One commonly used outcome measure in multiple sclerosis (MS) clinical trials is the Multiple Sclerosis Functional Composite, which includes the Paced Auditory Serial Addition Test (PASAT) as a measure of cognitive function. Concerns have been raised about the standard PASAT scoring method, whereby the number of correct responses is summed. This method does not take into account whether the test is performed as intended, which may affect interpretation of the results. Accordingly, another scoring method has been proposed, which examines the number of times a correct response is immediately preceded by another correct response (termed a dyad). We compared the two scoring methods for the PASAT, and found that the mean percentage of correct responses not accounted for by dyads ranged from 27.5% to 49.5%, indicating that much of the time the test is not performed as instructed. We also examined disease course and the PASAT score, as studies have produced conflicting results as to whether disease course is associated with cognitive impairment. Although disease course was significantly associated with the PASAT score, it accounted for little of the variation in scores, even when adjusting for other predictors. Finally, as 14.2% of participants refused to do the PASATor failed to complete it, we also examined whether the Perceived Deficits Questionnaire (PDQ), a self-reported measure of cognitive function, is a potential proxy measure for the PASAT. The correlation between the two tools was low (-0.14), suggesting that the PDQ is not a useful substitute for the PASAT.

Cognitive impairment and its relation with disease measures in mildly disabled patients with relapsing–remitting multiple sclerosis: baseline results from the Cognitive Impairment in Multiple Sclerosis (COGIMUS) study

2009 ◽  
Vol 15 (7) ◽  
pp. 779-788 ◽  
Author(s):  
F Patti ◽  
MP Amato ◽  
M Trojano ◽  
S Bastianello ◽  
MR Tola ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cognitive Impairment ◽  
Cognitively Impaired ◽  
Common Symptom ◽  
Lesion Volume ◽  
Cognitive Tests ◽  
Impaired Performance ◽  
Relapsing Remitting ◽  
Disabled Patients ◽  
Edss Score

Background Cognitive impairment is a common symptom of multiple sclerosis (MS), but the association between cognitive impairment and magnetic resonance imaging (MRI) disease measures in patients with relapsing–remitting (RR) MS is unclear. Objectives To study the prevalence of cognitive impairment and its relation with MRI disease measures in mildly disabled patients with RRMS. Methods Patients aged 18–50 years with RRMS (McDonald criteria) and an Expanded Disability Status Scale (EDSS) score ≤4.0, who were enrolled in the Cognitive Impairment in Multiple Sclerosis (COGIMUS) study, underwent baseline standardized MRI complete neurological examination and neuropsychological testing. Results A total of 550 patients were enrolled, 327 of whom underwent MRI assessments. Cognitive impairment (impaired performance in ≥3 cognitive tests) was present in approximately 20% of all patients and in the subgroup who underwent MRI. T2 hyperintense and T1 hypointense lesion volumes were significantly higher in patients with cognitive impairment (defined as impaired performance on at least three tests of the Rao’s battery) than those without. EDSS score was also significantly higher in cognitively impaired than in cognitively preserved patients. Disease duration, depression, and years in formal education did not differ significantly between cognitively impaired and cognitively preserved patients. T2 lesion volume, performance intelligence quotient, and age were significant predictors of cognitive impairment in this population. Weak correlations were found between performance on individual cognitive tests and specific MRI measures, with T1 and T2 lesion volumes correlating with performance on most cognitive tests. Conclusions Cognitive impairment occurs in approximately one-fifth of mildly disabled patients with MS and is associated with specific MRI disease measures. Assessment of cognitive function at diagnosis could facilitate the identification of patients who may benefit from therapeutic intervention with disease-modifying therapies to prevent further lesion development.

scholarly journals Regional reduction in cortical blood flow among cognitively impaired adults with relapsing-remitting multiple sclerosis patients

2016 ◽  
Vol 22 (11) ◽  
pp. 1421-1428 ◽  
Author(s):  
Seyed-Parsa Hojjat ◽  
Charles Grady Cantrell ◽  
Rita Vitorino ◽  
Anthony Feinstein ◽  
Zahra Shirzadi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Blood Flow ◽  
Cognitive Impairment ◽  
Temporal Cortex ◽  
Surrogate Marker ◽  
Healthy Controls ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Multiple Sclerosis Patients ◽  
Relapsing Remitting Multiple Sclerosis

Purpose: Detection of cortical abnormalities in relapsing-remitting multiple sclerosis (RRMS) remains elusive. Structural magnetic resonance imaging (MRI) measures of cortical integrity are limited, although functional techniques such as pseudo-continuous arterial spin labeling (pCASL) show promise as a surrogate marker of disease severity. We sought to determine the utility of pCASL to assess cortical cerebral blood flow (CBF) in RRMS patients with (RRMS-I) and without (RRMS-NI) cognitive impairment. Methods: A total of 19 age-matched healthy controls and 39 RRMS patients were prospectively recruited. Cognition was assessed using the Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS) battery. Cortical CBF was compared between groups using a mass univariate voxel-based morphometric analysis accounting for demographic and structural variable covariates. Results: Cognitive impairment was present in 51.3% of patients. Significant CBF reduction was present in the RRMS-I compared to other groups in left frontal and right superior frontal cortex. Compared to healthy controls, RRMS-I displayed reduced CBF in the frontal, limbic, parietal and temporal cortex, and putamen/thalamus. RRMS-I demonstrated reduced left superior frontal lobe cortical CBF compared to RRMS-NI. No significant cortical CBF differences were present between healthy controls and RRMS-NI. Conclusion: Significant cortical CBF reduction occurs in RRMS-I compared to healthy controls and RRMS-NI in anatomically significant regions after controlling for structural and demographic differences.

CRYAB modulates the activation of CD4+ T cells from relapsing–remitting multiple sclerosis patients

2013 ◽  
Vol 19 (14) ◽  
pp. 1867-1877 ◽  
Author(s):  
Que Lan Quach ◽  
Luanne M Metz ◽  
Jenna C Thomas ◽  
Jonathan B Rothbard ◽  
Lawrence Steinman ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Cytokine Production ◽  
Clinical Signs ◽  
Healthy Controls ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Multiple Sclerosis Patients ◽  
Relapsing Remitting Multiple Sclerosis

Background: Suppression of activation of pathogenic CD4+ T cells is a potential therapeutic intervention in multiple sclerosis (MS). We previously showed that a small heat shock protein, CRYAB, reduced T cell proliferation, pro-inflammatory cytokine production and clinical signs of experimental allergic encephalomyelitis, a model of MS. Objective: We assessed whether the ability of CRYAB to reduce the activation of T cells translated to the human disease. Methods: CD4+ T cells from healthy controls and volunteers with MS were activated in vitro in the presence or absence of a CRYAB peptide (residues 73–92). Parameters of activation (proliferation rate, cytokine secretion) and tolerance (anergy, activation-induced cell death, microRNAs) were evaluated. Results: The secretion of pro-inflammatory cytokines by CD4+ T cells was decreased in the presence of CRYAB in a subset of relapsing–remitting multiple sclerosis (RRMS) participants with mild disease severity while no changes were observed in healthy controls. Further, there was a correlation for higher levels of miR181a microRNA, a marker upregulated in tolerant CD8+ T cells, in CD4+ T cells of MS patients that displayed suppressed cytokine production (responders). Conclusion: CRYAB may be capable of suppressing the activation of CD4+ T cells from a subset of RRMS patients who appear to have less disability but similar age and disease duration.

scholarly journals Short Report: Prevalence of Cognitive Impairment in Newly Diagnosed Relapsing-Remitting Multiple Sclerosis

2018 ◽  
Vol 20 (4) ◽  
pp. 153-157 ◽  
Author(s):  
Giulia DiGiuseppe ◽  
Mervin Blair ◽  
Sarah A. Morrow
Keyword(s):  
Multiple Sclerosis ◽  
Cognitive Impairment ◽  
Processing Speed ◽  
Clinical Population ◽  
Clinical Event ◽  
Routine Practice ◽  
Short Report ◽  
Newly Diagnosed ◽  
Mood Symptoms ◽  
Relapsing Remitting

Abstract Background: Cognitive impairment is common in multiple sclerosis (MS) and can manifest early in the disease process, sometimes as early as the first demyelinating event. However, the frequency of cognitive impairment in a newly diagnosed MS population has not been evaluated comprehensively in a clinical population. We sought to examine the prevalence of cognitive impairment in relapsing-remitting MS (RRMS) within a year of diagnosis in a clinic where cognitive testing at diagnosis is part of routine practice. Methods: A retrospective medical record review of persons with RRMS assessed in a cognitive MS clinic identified 107 patients assessed by the Minimal Assessment of Cognitive Function in Multiple Sclerosis battery within 1 year of a confirmed RRMS diagnosis. Results: The cohort was predominantly female (n = 82 [76.6%]) and white (n = 93 [86.9%]). Only 36 patients (33.6%) were diagnosed as having RRMS based on a second clinical event. Processing speed was the most frequently impaired domain (n = 38 [35.5%]). Only 37 patients (34.6%) were within normal limits on all cognitive domains. Regarding mood symptoms, 25 patients (23.4%) were positive for depressive symptoms; 59 (55.1%), for anxiety. Severe fatigue was correlated with a lower score on the Symbol Digit Modalities Test (SDMT) (r = −0.380, P &lt; .001), and higher depressive scores were correlated with lower performance on the SDMT (r = −0.397, P &lt; .001) and the Paced Auditory Serial Addition Test (r = −0.254, P = .009). Conclusions: Cognitive impairment, specifically processing speed, and mood symptoms are frequently present in persons with newly diagnosed RRMS.

scholarly journals Validation of Discrete and Regression-Based Performance and Cognitive Fatigability Normative Data for the Paced Auditory Serial Addition Test in Multiple Sclerosis

2021 ◽  
Vol 15 ◽  
Author(s):  
Caitlin S. Walker ◽  
Jason A. Berard ◽  
Lisa A. S. Walker
Keyword(s):  
Multiple Sclerosis ◽  
Normative Data ◽  
Cognitive Effort ◽  
Similar Proportion ◽  
Healthy Controls ◽  
Performance Decrement ◽  
Impaired Performance ◽  
Objective Performance ◽  
Serial Addition ◽  
Over Time

Cognitive fatigability is an objective performance decrement that occurs over time during a task requiring sustained cognitive effort. Although cognitive fatigability is a common and debilitating symptom in multiple sclerosis (MS), there is currently no standard for its quantification. The objective of this study was to validate the Paced Auditory Serial Addition Test (PASAT) discrete and regression-based normative data for quantifying performance and cognitive fatigability in an Ontario-based sample of individuals with MS. Healthy controls and individuals with MS completed the 3″ and 2″ versions of the PASAT. PASAT performance was measured with total correct, dyad, and percent dyad scores. Cognitive fatigability scores were calculated by comparing performance on the first half (or third) of the task to the last half (or third). The results revealed that the 3″ PASAT was sufficient to detect impaired performance and cognitive fatigability in individuals with MS given the increased difficulty of the 2″ version. In addition, using halves or thirds for calculating cognitive fatigability scores were equally effective methods for detecting impairment. Finally, both the discrete and regression-based norms classified a similar proportion of individuals with MS as having impaired performance and cognitive fatigability. These newly validated discrete and regression-based PASAT norms provide a new tool for clinicians to document statistically significant cognitive fatigability in their patients.

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