Symbol Digit Modalities Test Research Articles

Konectom™ cognitive processing speed test enables reliable remote, unsupervised cognitive assessment in people with multiple sclerosis: Exploring the use of substitution time as a novel digital outcome measure

Background: The Konectom™ smartphone-based cognitive processing speed (CPS) test is designed to assess processing speed and account for impact of visuomotor function on performance. Objective: Evaluate reliability and validity of Konectom CPS Test, performed in clinic and remotely. Methods: Data were collected from people with multiple sclerosis (PwMS) aged 18–64 years and healthy control participants (HC) matched for age, sex, and education. Remote test–retest reliability (intraclass correlation coefficients, ICC); correlation with established clinical measures (Spearman correlation coefficients); group analyses between cognitively impaired/unimpaired PwMS; and influence of age, sex, education, and upper limb motor function on CPS Test measures were assessed. Results: Eighty PwMS and 66 HC participated. CPS Test measures from remote tests had good test–retest reliability (ICC of 0.67–0.87) and correlated with symbol digit modalities test (highest |ρ| = 0.80, p < 0.0001). Remote measures were stable (change from baseline < 5%) and correlated with MS disability (highest |ρ| = 0.39, p = 0.0004) measured by Expanded Disability Status Scale. CPS Test measures displayed sensitivity to cognitive impairment (highest d = 1.47). Demographics and motor function had the lowest impact on CPS Test substitution time, a measure accounting for visuomotor function. Conclusion: Konectom CPS Test measures provide valid, reliable remote measurements of cognitive processing speed in PwMS.

Evaluation of machine learning-based classification of clinical impairment and prediction of clinical worsening in multiple sclerosis

BackgroundRobust predictive models of clinical impairment and worsening in multiple sclerosis (MS) are needed to identify patients at risk and optimize treatment strategies.ObjectiveTo evaluate whether machine learning (ML) methods can classify clinical impairment and predict worsening in people with MS (pwMS) and, if so, which combination of clinical and magnetic resonance imaging (MRI) features and ML algorithm is optimal.MethodsWe used baseline clinical and structural MRI data from two MS cohorts (Berlin: n = 125, Amsterdam: n = 330) to evaluate the capability of five ML models in classifying clinical impairment at baseline and predicting future clinical worsening over a follow-up of 2 and 5 years. Clinical worsening was defined by increases in the Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk Test (T25FW), 9-Hole Peg Test (9HPT), or Symbol Digit Modalities Test (SDMT). Different combinations of clinical and volumetric MRI measures were systematically assessed in predicting clinical outcomes. ML models were evaluated using Monte Carlo cross-validation, area under the curve (AUC), and permutation testing to assess significance.ResultsThe ML models significantly determined clinical impairment at baseline for the Amsterdam cohort, but did not reach significance for predicting clinical worsening over a follow-up of 2 and 5 years. High disability (EDSS ≥ 4) was best determined by a support vector machine (SVM) classifier using clinical and global MRI volumes (AUC = 0.83 ± 0.07, p = 0.015). Impaired cognition (SDMT Z-score ≤ −1.5) was best determined by a SVM using regional MRI volumes (thalamus, ventricles, lesions, and hippocampus), reaching an AUC of 0.73 ± 0.04 (p = 0.008).ConclusionML models could aid in classifying pwMS with clinical impairment and identify relevant biomarkers, but prediction of clinical worsening is an unmet need.

Changes of brain parenchyma free water fraction reflect tissue damage and impaired processing speed in multiple sclerosis.

Free water fraction (FWF) represents the amount of water per unit volume of brain parenchyma, which is not bound to macromolecules. Its excess in multiple sclerosis (MS) is related to increased tissue loss. The use of mcDESPOT (multicomponent driven single pulse observation of T1 and T2), a 3D imaging method which exploits both the T1 and T2 contrasts, allows FWF to be derived in clinically feasible times. However, this method has not been used to quantify changes of FWF and their potential clinical impact in MS. The aim of this study is to investigate the changes in FWF in MS patients and their relationship with tissue damage and cognition, under the hypothesis that FWF is a proxy of clinically meaningful tissue loss. To this aim, we tested the relationship between FWF, MS lesion burden and information processing speed, evaluated via the Symbol Digit Modalities Test (SDMT). In addition to standard sequences, used for T1- and T2-weighted lesion delineation, the mcDESPOT sequence with 1.7 mm isotropic resolution and a diffusion weighted imaging protocol (b = 0, 1200 s/mm2, 40 diffusion directions) were employed at 3 T. The fractional anisotropy map derived from diffusion data was used to define a subject-specific white matter (WM) atlas. Brain parenchyma segmentation returned masks of gray matter (GM) and WM, and normal-appearing WM (NAWM), in addition to the T1 and T2 lesion masks (T1L and T2L, respectively). Ninety-nine relapsing-remitting MS patients (age = 43.3 ± 9.9 years, disease duration 12.3 ± 7.7 years) were studied, together with twenty-five healthy controls (HC, age = 38.8 ± 11.0 years). FWF was higher in GM and NAWM of MS patients, compared to GM and WM of HC (both p < .001). In MS patients, FWF was the highest in the T1L and GM, followed by T2L and NAWM, respectively. FWF increased significantly with T1L and T2L volume (ρ ranging from 0.40 to 0.58, p < .001). FWF in T2L was strongly related to both T1L volume and the volume ratio T1L/T2L (ρ = 0.73, p < .001). MS patients performed worse than HC in the processing speed test (mean ± SD: 54.1 ± 10.3 for MS, 63.8 ± 10.8 for HC). FWF in GM, T2L, perilesional tissue and NAWM increased with SDMT score reduction (ρ = -0.30, -0.29, -0.33 respectively and r = -.30 for T2L, all with p < .005). A regional analysis, conducted to determine which NAWM regions were of particular importance to explain the relationship between FWF and cognitive impairment, revealed that FWF spatial variance was negatively related to SDMT score in the corpus callosum and the superior longitudinal fasciculus, WM structures known to be associated with cognitive impairment, in addition to the left corticospinal tract, the sagittal stratum, the right anterior limb of internal capsule. In conclusion, we found excess free water in brain parenchyma of MS patients, an alteration that involved not only MS lesions, but also the GM and NAWM, impinging on brain function and negatively associated with cognitive processing speed. We suggest that the FWF metric, derived from noninvasive, rapid MRI acquisitions and bearing good biological interpretability, may prove valuable as an MRI biomarker of tissue damage and associated cognitive impairment in MS.

Normative data for executive function tests in an Ecuadorian Waranka minority population

Objective: To generate normative data (ND) for executive functions tests in the Waranka minority population of Ecuador. Method: Four-hundred participants aged 6–17 completed the Symbol-Digit Modalities Test (SDMT), Trail-Making Test (TMT), Modified-Wisconsin Card Sorting Test (M-WCST), and Test of Colors-Words (STROOP). Scores were normed using multiple linear regressions, including age, age2, natural logarithm of mean parent education (MPE), sex, bilingualism, and two-way interactions as predictors. Results: Age by MPE and Age2 by MPE interactions arose for SDMT, so that children with illiterate parents scored lower than those with literate parents. Girls scored higher in SDMT. All TMT and M-WCST scores were influenced by age2. Age by MPE interaction was found for TMT–A, so that children with higher MPE went faster; and age by bilingualism interaction for TMT–B, so that more bilingual children needed less time. Stroop-Word and Color were influenced by age2 by MPE interaction, so that children, while older, scored higher, especially those with higher MPE. Also, age2 by sex interaction arose, so that girls increased scores curvilinearly while boys linearly. Word-Color was influenced by age, while Stroop-interference by age2. Age by MPE interaction was found for MCST-Categories and Perseveration, so that perseverations decreased to then increased, especially in those with illiterate parents. M-WCST-Category scores increased to then decrease later on age in children with illiterate parents. Z-scores calculated through indigenous ND were significantly lower than generated through non-indigenous norms. Conclusions: ND for minority populations are critical since Waranka sample performed worse when using non-indigenous norms for z-score calculation.

COGNITIVE IMPAIRMENT IN DIFFERENT CLINICAL FORMS OF MULTIPLE SCLEROSIS

Purpose: The aim of the study is to investigate cognitive impairment (CI) in patients with different clinical forms of Multiple Sclerosis (MS) and to propose a suitable cognitive evaluation based on available tools for diagnosis and monitoring purposes. Materials and Methods: The following tests were used: Paced Auditory Serial Addition Test (PASAT), Symbol Digit Modalities Test (SDMT), Brief Visuospatial Memory Test-Revised (BVMT-R), Expanded Disability Status Scale (EDSS) and Magnetic Resonance Tomography 1.5Т (МRТ) in 60 consecutive patients; 22 were with first demyelination episode and 38 with MS. The control group of 40 healthy persons matched for sex, age and years of education. The follow-up period is three years. Results: The average screening values of PASAT, SDMT, BVSMT-R are considerably lower (р&lt;0.05) in MS patients compared to the controls and CIS patients. Point's number in the progressive forms in comparison with RRMS is reliably smaller. There was no significant difference in results between SPMS and PPMS patients at screening (р&gt;0.05). In the 3rd year, there is a significant cognitive progression in all studied groups and for all tests (р&lt;0.05). Conclusion: The use of a neuropsychological screening test is a valuable method for registering CI in patients with relapsing-remitting course, as well as in patients with a progressive course of the disease. We recommend the SDMT for screening annual follow-up because it is easy to apply, validate and reliably report the progression of CI. In patients with visual disturbances and with arm weakness, it is better to use PASAT, taking into account the level of education and depression.

Structural and functional comparisons in cognitive impairments in patients with multiple sclerosis

Background. Multiple sclerosis (MS) is an inflammatory demyelinating and neurodegenerative disease characterized by a variety of neurological symptoms. Cognitive impairment is an important clinical aspect of MS and require careful interviewing and neuropsychological testing to detect it. Contrast-enhanced magnetic resonance imaging (MRI) is the primary diagnostic method in MS, which helps confirm the presence and assess the extent of structural damage to the brain and spinal cord. The purpose of the study was to determine the frequency and severity of cognitive impairment in patients with relapsing-remitting multiple sclerosis, taking into account the localization of brain lesions according to MRI. Materials and methods. Seventy-two patients with a diagnosis of relapsing-remitting MS according to the McDonald criteria (2017) were examined. All of them underwent a thorough neurolo-gical, neuropsychological, and instrumental examination. The average duration of the disease was 8.2 ± 0.8 years. The average score on the Expanded Disability Status Scale was 3.38 ± 0.18 points. Symbol Digit Modalities Test (SDMT), Paced Auditory Serial Addition Test 3 (PASAT-3), and Montreal Cognitive Assessment (MoСA) were used to assess the neuropsychological status of patients. All participants underwent a 1.5T MRI of the brain with dotavist contrast enhancement. Results. A thorough survey of examined patients with MS revealed the presence of complaints of cognitive decline in 91.67 % of cases (66 patients). The average score on the SDMT was 32.6 ± 1.6 (controls 57.1 ± 0.9), on the PASAT-3 — 30.3 ± 1.8 (controls 56.8 ± 0.5), the evaluation score on the MoСA was 22.4 ± ± 0.5 points compared to the control group (28.4 ± 0.2 points). The conducted correlation analysis revealed statistically significant negative correlations in the corpus callosum (MoCA: r = –0.255; SDMT: r = –0.263; PASAT-3: r = –0.171; p &lt; 0.05) and in the brainstem (MoCA: r = –0.191; SDMT: r = –0.209; PASAT-3: r = –0.214; p &lt; 0.05). The results of the analysis of variance confirmed the correlations described above between the localization of brain lesions and the results of neuropsychological testing and revealed statistically significant differences in the scores on the MoCA and SDMT depending on the localization of lesions (MoCA: F(14, 57) = 5.052, p &lt; 0.001; SDMT: F(14, 57) = 2.609, p &lt; 0.05). Conclusions. Patients with relapsing-remitting multiple sclerosis quite often have cognitive impairment, which is confirmed by the results of neuropsychological testing. Correlation analysis revealed a significant negative relationship between the localization of foci in the corpus callosum and the brainstem and cognitive decline according to the results of tests (MoCA, SDMT, PASAT-3). The results of our study confirm the presence of structural and functional connections between the localization of focal brain lesions and the development of cognitive disorders, which has important diagnostic and prognostic value.

Effect of methylphenidate on oculomotor function in individuals with multiple sclerosis: a pilot randomized placebo-controlled trial

IntroductionIndividuals with multiple sclerosis (MS) frequently experience visual and oculomotor symptoms that may impact and confound neuropsychological assessments of information processing speed (IPS). In this study, we examined the effect of the psychostimulant methylphenidate on oculomotor function and the association between change in oculomotor speed and change in information processing speed.MethodsWe used a repeated measures crossover design in which a sample of 11 participants with MS were randomly assigned to one of two treatment arms: one that received methylphenidate for 4 weeks and another that received a placebo for 4 weeks. After a 7-day washout period, the treatments were crossed over. The King Devick test, the Symbol Digit Modalities Test, and the Paced Auditory Serial Addition Test were administered at baseline and after each of the two study arms.ResultsWe found a significant improvement in oculomotor speed in the methylphenidate condition as compared to placebo. This improvement was significantly correlated with improvement on a visuomotor assessment of IPS (Symbol Digit Modalities Test), but no such association was found for an auditory-verbal assessment of IPS (Paced Auditory Serial Addition Test).DiscussionThese findings suggest that individuals with MS experience improved oculomotor speed while taking methylphenidate, which may, in turn, improve performance on assessments of IPS with visuomotor demands.

The impact of incident stroke on cognitive trajectories in later life

BackgroundCognitive impairment is common after stroke, and a large proportion of stroke patients will develop dementia. However, there have been few large prospective studies which have assessed cognition both prior to and after stroke. This study aims to determine the extent to which incident stroke impacts different domains of cognitive function in a longitudinal cohort of older community-dwelling individuals.Methods19,114 older individuals without cardiovascular disease or major cognitive impairment were recruited and followed over a maximum 11 years. Stroke included ischaemic and haemorrhagic stroke and was adjudicated by experts. Cognitive function was assessed regularly using Modified Mini-Mental State Examination (3MS), Hopkins Verbal Learning Test–Revised (HVLT-R), Symbol Digit Modalities Test (SDMT), and Controlled Oral Word Association Test (COWAT). Linear mixed models were used to investigate the change in cognition at the time of stroke and decline in cognitive trajectories following incident stroke.ResultsDuring a median follow-up period of 8.4 [IQR: 7.2, 9.6] years, 815 (4.3%) participants experienced a stroke. Over this time, there was a general decline observed in 3MS, HVLT-R delayed recall, and SDMT scores across participants. However, for individuals who experienced a stroke, there was a significantly greater decline across all cognitive domains immediately after the event immediately after the event (3MS: -1.03 [95%CI: -1.45, -0.60]; HVLT-R: -0.47 [-0.70, -0.24]; SDMT: -2.82 [-3.57, -2.08]; COWAT: -0.67 [-1.04, -0.29]) and a steeper long-term decline for three of these domains (3MS -0.62 [-0.88, -0.35]; COWAT: -0.30 [-0.46, -0.14]); HVLT-R: -0.12 [95%CI, -0.70, -0.24]). However individuals with stroke experienced no longer-term decline in SDMT compared to the rest of the participants.ConclusionsThese findings highlight the need for comprehensive neuropsychology assessments for ongoing monitoring of cognition following incident stroke; and potential early intervention.

Cognitive rehabilitation effects on grey matter volume and Go-NoGo activity in progressive multiple sclerosis: results from the CogEx trial

BackgroundResearch on cognitive rehabilitation (CR) and aerobic exercise (EX) to improve cognition in progressive multiple sclerosis (PMS) remains limited. CogEx trial investigated the effectiveness of CR and EX in PMS:...

The influence of depression and anxiety on cognition in people with multiple sclerosis: a cross-sectional analysis.

There are conflicting findings about the relationships between depression, anxiety, and cognitive dysfunction in people with multiple sclerosis (MS), and a paucity of research has examined the cumulative influence on cognition of depression plus anxiety. This study aimed to determine whether elevated symptoms of depression and anxiety alone or in combination are associated with worse cognition in people with MS. In this cross-sectional analysis, people with MS consecutively seen at a tertiary neuropsychiatry clinic completed the Hospital Anxiety and Depression Scale for symptoms of depression (HADS-D) and anxiety (HADS-A), and the Minimal Assessment of Cognitive Function in MS for cognitive indices. Accounting for covariates, regression models predicted cognitive indices from scores for HADS-D, HADS-A, and the interaction. Of 831 people with MS, 72% were female, mean age was 43.2years, and median Expanded Disability Status Scale score was 2.0. Depressive symptoms were independently predictive of lower verbal fluency (Controlled Oral Word Association Test, p < 0.01), verbal learning (California Verbal Learning Test-II (CVLT-II) total learning, p = 0.02), verbal delayed recall (CVLT-II delayed recall, p < 0.01), and processing speed (Symbol Digit Modalities Test, p < 0.01; three-second Paced Auditory Serial Addition Test (PASAT), p = 0.05; two-second PASAT, p = 0.01). Anxiety in people with depression predicted decreased visuospatial function (Judgment of Line Orientation, p = 0.05), verbal learning (p < 0.01), verbal delayed recall (p < 0.01), visuospatial recall (Brief Visuospatial Memory Test-Revised, p = 0.02), and executive function (Delis-Kaplan Executive Function System, p < 0.01). Anxiety alone was not independently predictive of cognition. In conclusion, depression, especially with comorbid anxiety, is associated with cognitive dysfunction in people with MS.

Reliability and validity of a novel attention assessment scale (broken ring enVision search test) in the Chinese population.

The correct assessment of attentional function is the key to cognitive research. A new attention assessment scale, the Broken Ring enVision Search Test (BReViS), has not been validated in China. The purpose of this study was to assess the reliability and validity of the BReViS in the Chinese population. From July to October 2023, 100 healthy residents of Changzhou were selected and subjected to the BReViS, Digital Cancelation Test (D-CAT), Symbol Digit Modalities Test (SDMT), and Digit Span Test (DST). Thirty individuals were randomly chosen to undergo the BReViS twice for test-retest reliability assessment. Correlation analysis was conducted between age, education level, gender, and various BReViS sub-tests including Selective Attention (SA), Orientation of Attention (OA), Focal Attention (FA), and Total Errors (Err). Intergroup comparisons and multiple linear regression analyses were performed. Additionally, correlation analyses between the BReViS sub-tests and with other attention tests were also analyzed. The correlation coefficients of the BReViS sub-tests (except for FA) between the two tests were greater than 0.600 (p < 0.001), indicating good test-retest reliability. The Cronbach's alpha coefficient was 0.874, suggesting high internal consistency reliability. SA showed a significant negative correlation with the net score of D-CAT (r = -0.405, p < 0.001), and a significant positive correlation with the error rate of D-CAT (r = 0.401, p < 0.001), demonstrating good criterion-related validity. The correlation analysis among the results of each sub-test showed that the correlation coefficient between SA and Err was 0.532 (p < 0.001), and between OA and Err was-0.229 (p < 0.05), whereas there was no significant correlation between SA, OA, and FA, which indicated that the scale had good informational content validity and structural validity. Both SA and Err were significantly correlated with age and years of education, while gender was significantly correlated with OA and Err. Multiple linear regression suggested that Err was mainly affected by age and gender. There were significant differences in the above indexes among different age, education level and gender groups. Correlation analysis with other attention tests revealed that SA negatively correlated with DST forward and backward scores and SDMT scores. Err positively correlated with D-CAT net scores and negatively with D-CAT error rate, DST forward and backward scores, and SDMT scores. OA and FA showed no significant correlation with other attention tests. The BReViS test, demonstrating good reliability and validity, assessing not only selective attention but also gauging capacities in immediate memory, information processing speed, visual scanning, and hand-eye coordination. The results are susceptible to demographic variables such as age, gender, and education level.

Meaningful cognitive change for the Minimal Assessment of Cognitive Function in Multiple Sclerosis

Background: There is limited information on interpretation of cognitive changes over time in multiple sclerosis (MS). Objective: This study aimed to provide normative data for the assessment of statistically meaningful change in all tests of the Minimal Assessment of Cognitive Function in MS (MACFIMS). Methods: We applied the reliable change methodology to a healthy Italian cohort, assessed with two alternate versions of the MACFIMS 1 year apart. We calculated confidence intervals of retest score variance using the reliable change index (RCI). Moreover, multivariable linear regression models adjusted for age, sex, education, and baseline score were built to calculate the regression-based change index (RB-CI). Results: Overall, 200 healthy individuals were enrolled. Thresholds for interpreting change in each test were calculated. In the multivariable models, baseline score was associated with retest score in all tests (B from 0.439 to 0.760; p < 0.001). RB-CI can be calculated with data of the multivariable models. Conclusion: We provide normative data for reliable cognitive change evaluation for all the tests of the MACFIMS, which includes the Symbol Digit Modalities Test and Brief International Cognitive Assessment in MS, two widely used tools for screening and monitoring cognition in MS. Our findings can significantly improve the interpretation of cognitive changes in MS.

Using Objective and Subjective Measures of Cognition to Predict Instrumental Activities of Daily Living Abilities in Multiple Sclerosis.

Cognitive impairment, difficulty performing basic activities of daily living (ADLs) and instrumental ADLs (IADLs), depression, and fatigue are common among individuals with multiple sclerosis (MS). Some associations between these symptoms are known; however, many of their relationships remain unclear. This study investigated the contributions of subjective and objective cognition, depressive symptom severity, and fatigue on ADLs and IADLs. Participants (N = 217) were individuals with MS from a comprehensive MS center, participating in a larger study characterizing upper extremity function in MS. Outcome measures of ADL and IADL abilities were the Functional Status Index-Assistance (FSI-A) and Functional Status Index-Difficulty (FSI-D) and the Test D'évaluation Des Membres Supérieurs de Personnes Âgées (TEMPA). Predictors were objective cognition (Symbol Digit Modalities Test; SDMT), subjective cognition (Performance Scales©-Cognition; PS-C), depressive symptom severity (Center for Epidemiologic Studies Depression Scale; CES-D-10), and fatigue (Modified Fatigue Impact Scale; MFIS-5). Correlations were conducted, followed by hierarchal linear regressions. The SDMT and PS-C were entered into separate models. After controlling for demographics, the SDMT significantly predicted the TEMPA and FSI-A, while the PS-C predicted only the FSI-D. The CES-D-10 predicted the FSI-D even after accounting for PS-C and SDMT, while the MFIS-5 only predicted the FSI-D when the SDMT was included. Neither the CES-D-10 nor MFIS-5 significantly predicted the FSI-A or TEMPA. The way an individual with MS perceived their symptoms significantly contributed to their reported difficulty with functional tasks, while only their objective cognitive functioning predicted ADL and IADL performance and the level of assistance they would require.

Hand Grip Strength as a Predictive Tool for Upper Extremity Functionality, Balance, and Quality of Life in People With Multiple Sclerosis.

Upper extremity strength and function are rarely assessed in routine multiple sclerosis (MS) care. This study aimed to evaluate hand muscle strength and functionality in individuals with MS and investigate correlations with upper extremity function, cognitive status, health-related quality of life (HRQOL), and balance. A cross-sectional study was conducted with 45 consecutive individuals with MS between the ages of 18 and 65. Upper limb motor strength was evaluated using a hand grip strength dynamometer. Upper limb functional capacity was assessed using the Nine-Hole Peg Test (9HPT) and the Duruoz Hand Index (DHI). Balance, coordination, and falls were measured with the Berg Balance Scale (BBS), Falls Efficacy Scale (FES), and the 30-Second Chair Stand Test (30CST). Cognitive function was evaluated using the Montreal Cognitive Assessment instrument and the Symbol Digit Modalities Test. Level of HRQOL was assessed using the self-reported 54-item MS Quality of Life-54 questionnaire. Out of the 45 participants (80% women, mean age 36.6 ± 8.6 years), higher hand grip dynamometer measures were strongly correlated with better DHI, 9HPT, BBS, FES, and 30CST scores. In the regression analysis, a 1-unit increase in dynamometer measures led to a 0.383 increase in overall HRQOL score. This study demonstrates that increased hand grip strength (HGS) is associated with better hand functionality, balance, and HRQOL in individuals with MS. It provides evidence to support more systematic measurement of HGS in the care of people with MS.

Association of serum glial fibrillary acidic protein with progression independent of relapse activity in multiple sclerosis

ObjectiveInsidious disability worsening is a common feature in relapsing–remitting multiple sclerosis (RRMS). Many patients experience progression independent of relapse activity (PIRA) despite being treated with high efficacy disease-modifying therapies. We prospectively investigated associations of body-fluid and imaging biomarkers with PIRA.MethodsPatients with early RRMS (n = 104) were prospectively included and followed up for 60 months. All patients were newly diagnosed and previously untreated. PIRA was defined using a composite score including the expanded disability status scale, 9-hole peg test, timed 25 foot walk test, and the symbol digit modalities test. Eleven body fluid and imaging biomarkers were determined at baseline and levels of serum neurofilament light (sNfL) and glial fibrillary acidic protein (sGFAP) were also measured annually thereafter. Association of baseline biomarkers with PIRA was investigated in multivariable logistic regression models adjusting for clinical and demographic confounding factors. Longitudinal serum biomarker dynamics were investigated in mixed effects models.ResultsOnly sGFAP was significantly higher in PIRA at baseline (median [IQR] 73.9 [60.9–110.1] vs. 60.3 [45.2–79.9], p = 0.01). A cut-off of sGFAP > 65 pg/mL resulted in a sensitivity of 68% and specificity of 61%, to detect patients at higher risk of PIRA. In a multivariable logistic regression, sGFAP > 65 pg/mL was associated with higher odds of developing PIRA (odds ratio 4.3, 95% CI 1.44–12.86, p = 0.009). Repeated measures of sGFAP levels showed that patients with PIRA during follow-up had higher levels of sGFAP along the whole follow-up compared to stable patients (p < 0.001).ConclusionDetermination of sGFAP at baseline and follow-up may be useful in capturing disability accrual independent of relapse activity in early RRMS.

VasCog Screen test: sensitive in detecting cognitive impairment in patients who had a stroke or with heart failure.

Vascular diseases, such as stroke and heart failure (HF), are associated with cognitive decline. Vascular cognitive impairment (CI) is commonly found in patients who had a stroke and with HF, ranging from mild CI to dementia. Early detection of CI is crucial for effective management and rehabilitation. This study aimed to develop the VasCog Screen test, a screening tool to detect CI in patients who had a stroke and with HF. 427 patients who had a stroke and with HF were assessed using cognitive measures including Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) and a formal neuropsychological battery. The short-MoCA was derived and combined with Symbol Digit Modalities Test (SDMT) to create the VasCog Screen. The discriminatory ability of different tests for CI was compared, establishing optimal cut-off points. Variants of short-MoCA including the SDMT were also evaluated. Similar prevalence rates of CI were found in stroke and HF cohorts. The most prevalent neuropsychological impairment was visuomotor speed, followed by visual memory and visuoconstruction. More than half of the patients were found to have CI. The VasCog Screen outperformed MMSE, MoCA and short-MoCA in detecting CI. The addition of SDMT to variants of the short-MoCA increased diagnostic accuracy. The VasCog Screen test offers a cognitive screening tool, which is sensitive to cognitive deficits characteristically found in patients who had a stroke and with HF. It was found to have good sensitivity, specificity and classification accuracy. It is easy to administer in busy clinics, enabling early detection of CI and facilitating appropriate interventions.

Positive Effect of a Cooling Cap on Functional Performance in Thermosensitive People with Multiple Sclerosis: A Randomized Controlled Trial

Background. Up to 80% of people with MS experience worsening of their condition upon an increase in body temperature. Therefore, various options of cooling are being evaluated to help improve physical performance in people with MS. Most previous studies used active cooling methods. Our aim was to study the effect of simple device providing passive cooling. Methods. A randomized crossover study was conducted in 21 thermosensitive people with mild to moderate disability. Subjects were tested immediately before and after intervention (experimental or sham cooling). The assessment included timed 25-foot walk test, the 2- and 6-minute walk test, nine-hole peg test, and symbol digit modalities test. Results. A significant improvement was found in the experimental group in timed 25-foot walk test (p=0.011) and in nine-hole peg test for dominant hand (p=0.033). No significant improvement was found in the control group (sham cooling). Conclusions. Wearing cooling cap can improve short-term functional performance (walking and fine motor skills) in thermosensitive people with MS. This passive cooling method can be considered as a symptomatic treatment for some people with MS. This trial is registered with ISRCTN56350227.

Human restricted CHRFAM7A gene increases brain efficiency.

CHRFAM7A, a uniquely human fusion gene, has been associated with neuropsychiatric disorders including Alzheimer's disease, schizophrenia, anxiety, and attention deficit disorder. Understanding the physiological function of CHRFAM7A in the human brain is the first step to uncovering its role in disease. CHRFAM7A was identified as a potent modulator of intracellular calcium and an upstream regulator of Rac1 leading to actin cytoskeleton reorganization and a switch from filopodia to lamellipodia implicating a more efficient neuronal structure. We performed a neurocognitive-MRI correlation exploratory study on 46 normal human subjects to explore the effect of CHRFAM7A on human brain. Dual locus specific genotyping of CHRFAM7A was performed on genomic DNA to determine copy number (TaqMan assay) and orientation (capillary sequencing) of the CHRFAM7A alleles. As only the direct allele is expressed at the protein level and affects α7 nAChR function, direct allele carriers and non-carriers are compared for neuropsychological and MRI measures. Subjects underwent neuropsychological testing to measure motor (Timed 25-foot walk test, 9-hole peg test), cognitive processing speed (Symbol Digit Modalities Test), Learning and memory (California Verbal Learning Test immediate and delayed recall, Brief Visuospatial Memory Test-Revised immediate and delayed recall) and Beck Depression Inventory-Fast Screen, Fatigue Severity Scale. All subjects underwent MRI scanning on the same 3 T GE scanner using the same protocol. Global and tissue-specific volumes were determined using validated cross-sectional algorithms including FSL's Structural Image Evaluation, using Normalization, of Atrophy (SIENAX) and FSL's Integrated Registration and Segmentation Tool (FIRST) on lesion-inpainted images. The cognitive tests were age and years of education-adjusted using analysis of covariance (ANCOVA). Age-adjusted analysis of covariance (ANCOVA) was performed on the MRI data. CHRFAM7A direct allele carrier and non-carrier groups included 33 and 13 individuals, respectively. Demographic variables (age and years of education) were comparable. CHRFAM7A direct allele carriers demonstrated an upward shift in cognitive performance including cognitive processing speed, learning and memory, reaching statistical significance in visual immediate recall (FDR corrected p = 0.018). The shift in cognitive performance was associated with smaller whole brain volume (uncorrected p = 0.046) and lower connectivity by resting state functional MRI in the visual network (FDR corrected p = 0.027) accentuating the cognitive findings. These data suggest that direct allele carriers harbor a more efficient brain consistent with the cellular biology of actin cytoskeleton and synaptic gain of function. Further larger human studies of cognitive measures correlated with MRI and functional imaging are needed to decipher the impact of CHRFAM7A on brain function.

Information processing speed and disease severity predict real-world ambulation in persons with multiple sclerosis

BackgroundImpairments in real-world gait quality and quantity are multifaceted for individuals with multiple sclerosis (MS), encompassing mobility, cognition, and fear of falling. However, these factors are often examined independently, limiting insights into the combined contributions they make to real-world ambulation. Research questionHow do mobility, cognition, and fear of falling contribute to real-world gait quality and quantity in individuals with MS? MethodsTwenty individuals with MS underwent a series of cognitive assessments, including the Paced Auditory Serial Addition Test (PASAT), Symbol Digits Modalities Test (SDMT), Stroop Test, and the Selective Reminding Test (SRT). Participants also completed the Falls Efficacy Scale – International (FES-I) and walking impairment using the Patient Determined Disease Steps (PDDS). Following the in-lab session, participants wore an inertial sensor on their lower back and asked to go about their typical daily routines for three days. Metrics of gait speed, stride regularity, time spent walking, and total bouts were extracted from the real-world data. ResultsSignificant correlations were found between both real-world gait speed and stride regularity and the SDMT, FES-I, and PDDS. Backward linear regression analysis was conducted for gait speed and stride regularity, with PDDS and SDMT included in the final model for both metrics. These variables explained 63% of the variance in gait speed and 69% of the variance in stride regularity. Results were not significant for gait quantity after adjusting for age and sex. SignificanceThe study's results provide insight regarding the roles of cognition, walking impairment, and fear of falling on real-world ambulation. Deeper understanding of these contributions can inform the development of targeted interventions that aim to improve walking. Additionally, the absence of significant correlations between gait metrics, cognition, and fear of falling with gait quantity underscores the need for further research to identify factors that increased walking in this population.

Patterns of prospective memory errors differ in persons with multiple sclerosis

ABSTRACT Introduction Prospective memory (PM) deficits have been documented in multiple sclerosis (MS). This study aimed to explore the specific types of errors made by persons with MS (PwMS), including differences between PwMS and healthy controls (HC) and PwMS who do and do not have impairments in processing speed and/or verbal learning and memory. Method PwMS (n = 111) and HC (n = 75) completed the Memory for Intentions Test (MIST), an objective measure of PM that has five types of errors that can be coded (PM failure, task substitution, loss of content, loss of time, and random errors). The number and types of PM errors were calculated for the overall MIST and six subscales, which break down performance by types of delay (2-Minute and 15-Minute), cue (Time and Event), and response (Verbal and Action). Impairment was defined as performing < 1.5 SD on either the Symbol Digit Modalities Test (SDMT) or Rey Auditory Verbal Learning Test (RAVLT). Bivariate analyses were used to examine group differences, with post-hoc pairwise comparisons with Bonferroni corrections. Results Nearly 93% of PwMS made at least one PM error, compared to 76% of HC (V = .24, p = .001). The most commonly made PM error by PwMS was loss of content errors (45.0%). PwMS made significantly more task substitution errors (26.4% vs. 7.6%, p < .001) and fewer loss of time errors (9.5% vs. 21.2%, p < .001) than HC. Impaired PwMS made more errors than non-impaired PwMS, specifically PM failures on time-based tasks. Conclusions PM errors are common in PwMS, particularly when there are longer delays and time-based cues. Not only do PwMS make more errors than demographically similar HC, but they exhibit different cognitive process failures.