Symbol Digit Modalities Test Scores Research Articles

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.

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.

Functional gradients reveal cortical hierarchy changes in multiple sclerosis

Functional gradients reveal cortical hierarchy changes in multiple sclerosis

Interpretable and Intuitive Machine Learning Approaches for Predicting Disability Progression in Relapsing-Remitting Multiple Sclerosis Based on Clinical and Gray Matter Atrophy Indicators

Rationale and objectivesTo investigate whether clinical and grey matter (GM) atrophy indicators can predict disability in relapsing-remitting multiple sclerosis (RRMS) and to enhance the interpretability and intuitiveness of a predictive machine learning model. Materials and methodsOne hundred forty-five and 50 RRMS patients with structural MRI and at least 1-year follow-up Expanded Disability Status Scale (EDSS) results were retrospectively enrolled and placed in the discovery and external test cohorts, respectively. Six clinical and radiomics feature-based machine learning classifiers were trained and tested to predict disability progression in the discovery cohort and validated in the external test set. Partial dependence plot (PDP) analysis and a Shiny web application were conducted to enhance the interpretability and intuitiveness. ResultsIn the discovery cohort, 98 patients had disability stability, and 47 patients were classified as having disability progression. In the external test set, 35 patients were disability stable, and 15 patients had disability progression. Models trained with both clinical and radiomics features (area under the curve (AUC), 0.725-0.950) outperformed those trained with clinical (AUC, 0.600-0.740) or radiomics features only (AUC, 0.615-0.945). Among clinical + radiomics feature models, the logistic regression (LR) classifier-based model performed best, with an AUC of 0.950. Only the radiomics feature-only models were applied in the external test set due to the data collection problem and showed fair performance, with AUCs ranging from 0.617 to 0.753. PDP analysis showed that female patients and those with lower volume, surface area, and symbol digit modalities test (SDMT) scores; greater mean curvature and age; and no disease modifying therapy (DMT) had increased probabilities of disease progression. Finally, a Shiny web application (https://lauralin1104.shinyapps.io/LRshiny/) was developed to calculate the risk of disability progression. ConclusionsInterpretable and intuitive machine learning approaches based on clinical and GM atrophy indicators can help physicians predict disability progression in RRMS patients for clinical decision-making and patient management.

Is impairment of facial emotion recognition independent of cognitive dysfunction in multiple sclerosis?

BackgroundEmotions expressed on the face play a key role in social cognition and communication by providing inner emotional experiences. This study aimed to evaluate facial emotion identification and discrimination and empathy abilities in patients with MS and whether it is related to cognitive dysfunction.MethodsOne hundred twenty patients with relapsing–remitting MS and age- and sex-matched 120 healthy controls were enrolled in the study. All the subjects were evaluated with the Facial Emotion Identification Test (FEIT), Facial Emotion Discrimination Test (FEIDT), and Empathy Quotient (EQ). We used the Beck Depression Inventory (BDI) for depression and detailed cognitive tests, including the Montreal Cognitive Assessment (MoCA), the Symbol Digit Modalities Test (SDMT), and the Paced Auditory Serial Addition Test (PASAT). The quality of life was assessed with Multiple Sclerosis Quality of Life-54 (MSQL-54).ResultsPatients with MS were 37.6 ± 9.5 years old, had a mean disease duration of 8.8 ± 6.6 (8–28) years, and a mean EDSS score of 1.6 ± 1.3 (0–4.5). We found significant differences in the identification of facial emotions, discrimination of facial emotions, and empathy in MS patients compared to controls (p < 0.05). Especially the recognition of feelings of sadness, fear, and shame was significantly lower in MS patients. The multivariate logistic regression analysis showed low SDMT and FEIDT scores which showed an independent association with MS.ConclusionsOur findings indicate that facial emotion recognition and identification deficits are remarkable among patients with MS and emotion recognition is impaired together with and independently of cognitive dysfunction in MS patients.

Disrupted brain structural networks associated with depression and cognitive dysfunction in cerebral small vessel disease with microbleeds

Emerging evidence highlights cerebral microbleeds (CMBs) as hallmarks of cerebral small vessel disease (CSVD) underlying depression and cognitive dysfunction. This study aimed to reveal how depression and cognition-related white matter (WM) abnormalities are topologically presented, and the network-level structural disruptions associated with CMBs in CSVD. We used probabilistic diffusion tractography and graph theory to investigate brain WM network topology in CSVD patients with (n = 64, CSVD-c) and without (n = 138, CSVD-n) CMBs and 90 healthy controls. Then we evaluated the Pearson's correlations between disrupted network metrics and neuropsychological parameters. For global topology, the CSVD-c group exhibited significantly decreased global (Eglob) and local (Eloc) efficiency and increased shortest path length compared with the controls, while no significant difference was found between the CSVD-c and CSVD-n groups. For regional topology, although all groups showed highly similar hub distributions, compare with control group, the CSVD-c group exhibited significantly decreased nodal efficiency mainly in the bilateral supplementary motor area (SMA), median cingulate gyrus (DCG) and right orbital middle frontal gyrus, while the CSVD-n group showed significantly decreased nodal efficiency only in the right SMA. Notably, Eglob, Eloc and nodal efficiency of the right anterior cingulate gyrus, DCG, middle temporal gyrus and left insula showed significantly negative correlations with depression score, significantly positive correlations with Rey auditory verbal learning test and symbol digit modalities test scores in CSVD-n group, as well as significantly negative correlations with Stroop color-word test scores in CSVD-c group. The WM networks of CSVD patients are characterized by decreased global integration and local specialization, and decreased nodal efficiency highly related to depression and cognitive dysfunction in the attention, default mode network and sensorimotor regions. These findings provide new insight into the neurobiological mechanisms of CSVD and concomitant affective and cognitive disorders.

Night Screen Time is Associated with Cognitive Function in Healthy Young Adults: A Cross-Sectional Study.

In recent years, a significant shift toward remote work, virtual education, and social distancing measures was witnessed, thereby leading people to increasingly depend on digital devices for communication, work, and entertainment. This increased exposure to screens has raised concerns regarding its potential impact on cognitive function. This study investigated the relationship between screen time and cognitive function among healthy young adults. One hundred forty-five healthy individuals (mean age 21.55 ± 2.84 years) participated in this cross-sectional study. Sociodemographic information including age, sex, height, weight, and level of education were obtained. Participants reported screen time using a screen time questionnaire. Cognitive function tests including, Paced Auditory Serial Addition Task (PASAT), Montreal Cognitive Assessment (MoCA) and Symbol Digit Modalities Test (SDMT) were conducted. Multilinear regression analyses were used to examine the associations between age, sex, level of education, screen time, and cognitive function. One hundred thirty-nine participants (76 women) completed the study. Increased night screen time, bachelor's educational level, and women were associated with lower PASAT scores (R2=0.258; p≤0.047). Moreover, increased night screen time was associated with lower MoCA scores (R2=0.029; p=0.035). However, no associations were found between night screen time and SDMT scores. Participants who had higher night screen exposure had lower cognitive scores in the information speed processing, working memory, calculation, and attention domains. Considering these findings, this study emphasizes on the importance of setting a future recommended screen time guidelines for young adults as well as to promote healthy cognitive habits in order to preserve cognitive function and reduce the risk of developing neurodegenerative disease in the future. Future prospective cohort studies involving a more diverse age range is needed.

Clinical features of sleep apnea syndrome and cognitive impairment in multiple sclerosis

Background: Complications of obstructive sleep apnea (OSA) have been reported in patients with multiple sclerosis (MS). Patients with sleep apnea syndrome (SAS) due to OSA also show cognitive decline, with similar clinical characteristics to that manifested in MS. SAS due to OSA is a treatable condition, and the associated cognitive decline is expected to improve. This study investigates clinical features of SAS in people living with MS and contribute to improve cognitive dysfunction of MS.Methods: A case-control study was conducted. Cognitive functions were evaluated by the Symbol Digit Modalities Test (SDMT) and the Paced Auditory Serial Addition Test 2 (PASAT-2) and 3 (PASAT-3). The Respiratory Event Index (REI) was measured using Out of Center Sleep Testing (OCST). We defined subjects with REI ≥ 5 as OSA and divided participants into two groups with or without SAS due to OSA. Cognitive and respiratory characteristics were statistically compared between patients with MS and healthy controls.Results: We enrolled 67 people living with MS and 31 age- and sex-matched controls. OCST detected OSA in people living with MS and controls, and the prevalence rates were 28.4 % and 25.8 %, respectively. REI values (5.2 ± 7.9 vs 3.9 ± 5.2, p = 0.509) and number of participants with REI ≥ 5 (19 vs 8, p = 0.793) were similar between the MS and control group. The SDMT, PASAT-2, and PASAT-3 scores were significantly lower in the MS group than the control group (p < 0.001, p = 0.001, and p < 0.001, respectively). The interaction effect of MS and SAS on cognitive function was not significant in the SDMT (p = 0.078), but in the PASAT-2 (p = 0.043) and PASAT-3 (p = 0.020).Conclusion: This study revealed the prevalence rates of SAS in Japanese people living with MS and the usefulness of OCST for detection of SAS. This study also revealed that concomitant SAS can facilitate cognitive decline in people living with MS. These findings suggest that an appropriate intervention for OSA can be beneficial for people living with MS with cognitive decline.

Role of white matter in cognitive impairment among relapsing remitting multiple sclerosis patients.

Multiple Sclerosis (MS) associated cognitive impairment is believed to be mostly connected with damage to gray matter. The contribution of white matter is still poorly understood. We aim to examine the relationship between cognition and white matter tracts among relapsing remitting MS (RRMS) patients. Thirty RRMS patients were selected undergo the (3-seconds-interstimulus-interval paced auditory serial addition test) PASAT-3, the (symbol digit modalities test (SDMT) and full-brain MRI scans on a SIEMENS 3 Tesla Verio scanner. Diffusion Tensor Imaging (DTI) parameters, such as fractional anisotropy (FA) and mean diffusivity (MD) were examined in 37 white matter (WM) tracts. WM tracts were selected from the association pathways, projection pathways, commissural pathways by applying Human Connectome project (HCP)842 tractography atlas after DTI data reconstruction and registration to HCP1065 diffusion template in DSI Studio (version March 2021) In SPSS v26, Spearman's rank correlation analysis was used to examine the connection between DTI WM tracts and cognitive scores. The power of the study was increased by using false discovery rate (FDR) software. The mean scores on the PASAT-3 and SDMT were 31.5±12.8 and 46.9±16.7 respectively. Better cognitive performance was correlated to higher FA values, while lower cognitive function was correlated to higher MD values. There was a positive correlation between FA values in the right medial lemniscus and superior cerebellar peduncle and SDMT scores (p 0.05). Additionally, there was a trend for significance between the FA values in the left corticothalamic tract and SDMT scores. MD values in the superior cerebellar peduncle, left arcuate Fasciculus and left extreme capsule were negatively correlated with SDMT scores (p<0.05). PASAT-3 scores were negatively correlated with MD values in the right cerebellum, however, there was no significant correlation between PASAT-3 and FA values. White matter tracts, particularly the superior cerebellar peduncle, contribute to the cognitive impairment in RRMS. Larger sample sizes for longitudinal research are necessary.

Delayed oculomotor response associates with optic neuritis in youth with demyelinating disorders.

Impairment in visual and cognitive functions occur in youth with demyelinating disorders such as multiple sclerosis, neuromyelitis optica spectrum disorder, and myelin oligodendrocyte glycoprotein antibody-associated disease. Quantitative behavioral assessment using eye-tracking and pupillometry can provide functional metrics for important prognostic and clinically relevant information at the bedside. Children and adolescents diagnosed with demyelinating disorders and healthy, age-matched controls completed an interleaved pro- and anti-saccade task using video-based eye-tracking and underwent spectral-domain optical coherence tomography examination for evaluation of retinal nerve fiber layer and ganglion cell inner plexiform layer thickness. Low-contrast visual acuity and Symbol Digit Modalities Test were performed for visual and cognitive functional assessments. We assessed saccade and pupil parameters including saccade reaction time, direction error rate, pupil response latency, peak constriction time, and peak constriction and dilation velocities. Generalized Estimating Equations were used to examine the association of eye-tracking parameters with optic neuritis history, structural metrics, and visual and cognitive scores. The study included 36 demyelinating disorders patients, aged 8-18 yrs. (75% F; median=15.22 yrs., SD=2.8) and 34 age-matched controls (65% F; median=15.26 yrs., SD=2.3). Surprisingly, pro- and anti-saccade performance was comparable between patients and controls, whereas pupil control was altered in patients. Oculomotor latency measures were strongly associated with the number of optic neuritis episodes, including saccade reaction time, pupil response latency, and peak constriction time. Peak constriction time was associated with both retinal nerve fiber layer and ganglion cell inner plexiform layer thickness. Pupil response latency and peak constriction time were associated with visual acuity. Pupil velocity for both constriction and dilation was associated with Symbol Digit Modalities Test scores. The strong associations between oculomotor measures with history of optic neuritis, structural, visual, and cognitive assessments in these cohorts demonstrates that quantitative eye-tracking can be useful for probing demyelinating injury of the brain and optic nerve. Future studies should evaluate their utility in discriminating between demyelinating disorders and tracking disease progression.

Effects of transcranial alternating current stimulation on cognitive function in people with multiple sclerosis: A randomized controlled trial

BackgroundCognitive impairment is a core symptom that profoundly impacts the lives of people with multiple sclerosis (PwMS). Since the existing disease modifying therapies can only stabilize, but not actively treat, cognition in PwMS, there is an unmet need to expand approaches to treat these cognitive symptoms. Transcranial alternating current stimulation (tACS) permits frequency-specific entrainment of neural oscillations intrinsic to cognitive activity. However, the effects of the tACS on cognitive function in PwMS have not yet been assessed. We aimed to evaluate the potential efficacy of applying frontal theta-tACS to improve information processing speed in PwMS. Methods60 PwMS with cognitive complaints were enrolled in a double-blinded, randomized, controlled trial with three stimulation groups: 2 mA, 1 mA, or sham control. A single session of theta-tACS was applied while participants were engaged in a cognitive program which has shown to improve processing speed in PwMS. tACS effects were examined by the Symbol Digit Modalities Test (SDMT). Tolerability, side effects and acceptability were measured. Results1 mA groups had a significantly higher SDMT score after stimulation compared to their pre-stimulation score, 2 mA group showed a marginally significant improvement of their SDMT score, while the SDMT score in the sham group did not change. Overall, 49% of the stimulation group participants showed a clinically meaningful SDMT improvement (4+-point increase). ConclusiontACS is a well-tolerated, non-pharmacological intervention. Based on the positive effects observed in the current study of a single session of tACS applied during cognitive engagement, the effects of repeated tACS on cognitive function in PwMS merit further research. Trial RegistrationClinicalTrials.gov NCT04466228.

Differences in resting state functional connectivity relative to multiple sclerosis and impaired information processing speed.

Fifty-one percent of individuals with multiple sclerosis (MS) develop cognitive impairment (CI) in information processing speed (IPS). Although IPS scores are associated with health and well-being, neural changes that underlie IPS impairments in MS are not understood. Resting state fMRI can provide insight into brain function changes underlying impairment in persons with MS. We aimed to assess functional connectivity (FC) differences in (i) persons with MS compared to healthy controls (HC), (ii) persons with both MS and CI (MS-CI) compared to HC, (iii) persons with MS that are cognitively preserved (MS-CP) compared to HC, (iv) MS-CI compared to MS-CP, and (v) in relation to cognition within the MS group. We included 107 participants with MS (age 49.5 ± 12.9, 82% women), and 94 controls (age 37.9 ± 15.4, 66% women). Each participant was administered the Symbol Digit Modalities Test (SDMT) and underwent a resting state fMRI scan. The MS-CI group was created by applying a z-score cut-off of -1.5 to locally normalized SDMT scores. The MS-CP group was created by applying a z-score of ≥0. Control groups (HCMS-CI and HCMS-CP) were based on the nearest age-matched HC participants. A whole-brain ROI-to-ROI analysis was performed followed by specific contrasts and a regression analysis. Individuals with MS showed FC differences compared to HC that involved the cerebellum, visual and language-associated brain regions, and the thalamus, hippocampus, and basal ganglia. The MS-CI showed FC differences compared to HCMS-CI that involved the cerebellum, visual and language-associated areas, thalamus, and caudate. SDMT scores were correlated with FC between the cerebellum and lateral occipital cortex in MS. No differences were observed between the MS-CP and HCMS-CP or MS-CI and MS-CP groups. Our findings emphasize FC changes of cerebellar, visual, and language-associated areas in persons with MS. These differences were apparent for (i) all MS participants compared to HC, (ii) MS-CI subgroup and their matched controls, and (iii) the association between FC and SDMT scores within the MS group. Our findings strongly suggest that future work that examines the associations between FC and IPS impairments in MS should focus on the involvement of these regions.

A - 112 Subjective and Objective Cognition in Patients Driving with Multiple Sclerosis.

Multiple sclerosis (MS) is a disease of the central nervous system that results in focal lesions of demyelination, inflammation, and axonal damage to the brain and spinal cord. MS affects nearly one million people in the United States. Drivers with MS have been characterized by shorter disease durations, milder disabilities and greater awareness of their deficits compared to non-drivers. Cognitive function can impact MS patients' driving abilities, specifically their processing speed, attention and visuospatial deficiencies. This study evaluates whether subjective cognitive decline (SCD) can predict objective cognitive functioning to improve identification of patients at risk for impaired driving. All participants were patients at an MS Center, and had a diagnosis of MS based on the McDonald criteria. One hundred and eight MS patients were included in the study, and all participants completed the symbol digit modality test (SDMT). The majority of patients were female (75.9%), and only 19.4% of study participants reported having SCD that impact their driving ability. Participants with poorer processing speed had endorsed cognitive difficulties impacting their driving, U = 503.00, p = 0.001. Results suggest that slower SDMT scores may likely predict SCD. Patients with MS with poorer processing speed were also likely to report a SCD, and had a higher incidence rate of motor vehicle accidents. This relationship needs to be further assessed to aid in the safety of patients of MS and understanding if barriers such as lack of social support or work obligations that require them to continue driving.

A - 82 Perceived Social Support Is Associated with Cognition but Not Physical Functioning in Older Adults with and without Multiple Sclerosis.

To examine the association between perceived social support, cognition, and physical functioning in older adults with and without Multiple Sclerosis (MS). Participants were dementia-free older adults with MS (N = 89; M age = 64.75, SD + 4.25years; 66.3% female) and community-residing older adults (N = 102; M age = 68.74, SD + 7.12years; 62.7% female). The medical outcomes study modified social support survey (MSSS), oral symbol digit modalities test (SDMT) and timed-25-foot-walk-test (T25FW) served as outcome measures. Linear regressions stratified by group status assessed the associations between PSS, cognition, and physical functioning. Higher total MSSS scores were associated with higher SDMT scores in the MS group (β= 0.24, p = 0.02) and in the control group (β= 0.26, p = 0.005). Positive social interaction (β= 0.27, p = 0.011) was associated with SDMT performance in the MS group. Emotional/informational support (β= 0.27, p = 0.003) and positive social interaction (β= 0.25, p = 0.007) were associated with SDMT performance in the control group. Depression scores attenuated associations between perceived social support and SDMT performance in the MS group (p > 0.05) but not the control group. In contrast, higher MSSS scores were not associated with higher T25FW scores in either group. Among older adults with and without MS, perceived social support was associated with cognition but not physical functioning. Depressive symptoms attenuated associations between perceived social support and cognition in the MS group only.

Kinematics, Kinetics and Muscle Activity Analysis during Single-leg Drop-jump Landing Followed by an Unanticipated Task: Focusing on Differences in Neurocognitive Function.

Lower neurocognitive function is a risk factor for anterior cruciate ligament (ACL) injury. However, the mechanism by which lower neurocognitive function increases the risk of ACL injury remains unclear. To clarify the effect of differences in neurocognitive function on landing mechanics during a single-leg drop-jump landing motion followed by an unanticipated task. Cross-sectional study. Fifteen collegiate female athletes were recruited (20.1 ± 1.3 years, 166.6 ± 7.3 cm, 60.6 ± 6.9 kg) and were divided into two groups (the high-performance (HP) group and the lower-performance (LP) group) using the median Symbol Digit Modalities Test (SDMT) score. Three-dimensional motion analysis was employed for the analysis during the experimental task of a single-leg drop-jump followed by an unanticipated landing task from a 30-cm high box. Joint angular changes of the trunk, pelvis, hip, and knee were calculated within the interval from initial contact (IC) to 40ms. Knee and hip moments were calculated as the maximum values within the interval from IC to 40ms. Surface electromyography data from key muscles were analyzed 50ms before and after IC. Independent t-tests were used to compare the effects of different neurocognitive function on the measurement items. Statistical significance was set at p < 0.05. The SDMT score was significantly higher in HP group (HP: 77.9 ± 5.5; LP: 66.0 ± 3.4; p < 0.001). The LP group had a significantly greater trunk rotation angular change to the stance leg side (HP: 0.4 ± 0.8; LP: 1.2 ± 0.4; p = 0.020). There were no significant differences between the two groups in terms of joint moments, and muscle activities. Differences in neurocognitive function by SDMT were found to be related to differences in motor strategies of the trunk in the horizontal plane. Although trunk motion in the sagittal and frontal planes during single-leg drop-jump landing increases the ACL injury risk by affecting knee joint motion, the effect of trunk motion in the horizontal plane remains unclear. 3© The Authors.

5 -Alpha-dihydroxyprogesterone may contribute to perceptual processing and attention of the cases with relapsing remitting multiple sclerosis

ABSTRACT Neurosteroids (NSs) are endogenous steroid hormones, which are synthesised and metabolised within the central nervous system (CNS). NSs aid myelination and glial differentiation and modulate cognitive functions. Herein, we aim to investigate the relationship between NS levels, 5-alpha-dihydroxyprogesterone (5-α-DHP) and allopregnanolone (ALPG), and their relationship with cognitive changes in relapsing remitting MS patients. A total of 43 cases with well controlled, relapsing remitting MS composed the study group. The control group included 21 age and gender matched healthy controls (HC). MS patients were assessed by calculating Expanded Disability Status Scale (EDSS) scores, and the Brief Repeatable Battery of Neuropsychological Tests (BRBNT) was performed in both MS group and HC. Levels of 5-α-DHP and ALPG levels were also evaluated for each participant. The median level of 5-α-DHP was 48 [IQR: 39.2–144.2] pg/mcgL in the MS group and 68.4 [IQR: 57.1–365.9] pg/mcgL in HC (p = 0.02). The median ALPG level was found to be 56.5 [IQR: 37.7–75.4] pg/mcgL in the MS group and 43.9 [IQR: 29.4–70.2] pg/mcgL in HC (p = 0.1). In both groups 5-α-DHP levels were positively correlated with Symbol Digit Modalities Test (SDMT) scores (HC: p = 0.01, r = 0.3 and MS: p = 0.03, r = 0.3). In the MS group, higher EDSS scores were associated with lower scores on Spatial Recall Test (SPART)-Delayed (p = 0.009, r= −0.4) and SDMT (p = 0.01, r= −0.4). The disease duration was negatively correlated with the scores on SPART-Immediate, SPART-Delayed and SDMT (p = 0.02, r= −0.4; p = 0.005, r= −0.4 and p = 0.05, r= −0.3). 5-α-DHP may be lower even in well-controlled cases. 5-α-DHP may contribute to better perceptual processing and attention in cases with MS.

Trajectories of cognitive processing speed and physical disability over 11 years following initiation of a first multiple sclerosis disease-modulating therapy

BackgroundWe analysed the COMparison Between All immunoTherapies for Multiple Sclerosis (NCT03193866), a Swedish nationwide observational study in relapsing-remitting multiple sclerosis (RRMS), to identify trajectories of processing speed and physical disability...

Predicting employment deterioration with the Processing Speed Test (PST) and SDMT in multiple sclerosis

Background: Employment deterioration is common in people with multiple sclerosis (PwMS). Clinicians often learn of job loss after its occurrence, leaving no opportunity for preventive measures. Objectives: Identify which neuropsychological measures discriminate between healthy volunteers (HVs) and employed/disabled PwMS at baseline and predict work deterioration over 2 years. Methods: We examined 198 PwMS with computerized tests such as the Processing Speed Test (PST) and conventional tests such as the Symbol-Digit Modalities Test (SDMT), administered at baseline. Employment was assessed via Buffalo Vocational Monitoring Survey. Univariate and regression analyses identified significant predictors of PwMS categorized as work-stable versus work-deteriorated status. Results: PwMS were impaired on all baseline assessments relative to HVs (p’s < 0.001). Post hoc analyses showed that employed PwMS and HVs performed similarly and better than work-disabled PwMS. At the univariate level, both PST and SDMT discriminated between work-deteriorated and work-stable PwMS (p’s < 0.01). The logistic regression model accounting for all measures retained PST and the computerized Walking Speed Test. PwMS with increased negative work events had lower PST (p < 0.001), SDMT (p < 0.001), and BVMT-R (p < 0.01) scores than stable PwMS. The related regression model retained PST and BVMT-R (p < 0.001). Conclusion: Cognition, as measured by the PST and BVMT-R, are predictive of job deterioration in PwMS and may be a useful screening tool to identify those at high risk of unemployment.

The Association of the Glymphatic Function with Parkinson's Disease Symptoms: Neuroimaging Evidence from Longitudinal and Cross-Sectional Studies.

Emerging pathological evidence suggests that there is an association between glymphatic dysfunction and the progression of Parkinson's disease (PD). However, the clinical evidence of this association remains lacking. In this study, the index for diffusion tensor image analysis along the perivascular space (ALPS index) was calculated to evaluate glymphatic function. Overall, 289 patients with PD were enrolled in the cross-sectional study. The ALPS index was found to be negatively correlated with age, disease severity, and dyskinesia. In the longitudinal study, the information on a total of 95 PD patients with 5-year follow-up examinations was collected from the Parkinson's Progression Marker Initiative, 33 of which were classified into the low ALPS index group, and all others were classified into the mid-high ALPS index group based on the first tertile of the baseline ALPS index. The results of longitudinal regression indicated that there was a significant main group effect on autonomic dysfunction, as well as on activities of daily living. In addition, the low ALPS index group had faster deterioration in MDS-UPDRS part III and part II, Symbol Digit Modalities Test and Hopkins Verbal Learning Test. Path analysis showed that ALPS index acted as a significant mediator between tTau/ Aβ1-42 and cognitive change in the Symbol Digit Modalities Test score at year 4 and year 5. The ALPS index, an neuroimaging marker of glymphatic function, is correlated with PD disease severity, motor symptoms, and autonomic function, and is predictive of faster deterioration in motor symptoms and cognitive function. Additionally, glymphatic function may mediate the pathological role of toxic protein in cognitive decline. ANN NEUROL 2023;94:672-683.

Effectiveness of teriflunomide on No Evidence of Disease Activity and cognition in relapsing remitting multiple sclerosis: results of the NEDA3PLUS study.

Cognitive impairment (CI) is a prevalent and debilitating manifestation of multiple sclerosis (MS); however, it is not included in the widely used concept of No Evidence of Disease Activity (NEDA-3). We expanded the NEDA-3 concept to NEDA-3 + by encompassing CI assessed through the Symbol Digit Modality Test (SDMT) and evaluated the effect of teriflunomide on NEDA3 + in patients treated in a real-world setting. The value of NEDA-3 + in predicting disability progression was also assessed. This 96-weeks observational study enrolled patients already on treatment with teriflunomide for ≥ 24weeks. The predictiveness of NEDA-3 and NEDA-3 + at 48weeks on the change in motor disability at 96weeks was compared through a two-sided McNemar test. The full analysis set (n = 128; 38% treatment naïve) featured relatively low level of disability (baseline EDSS = 1.97 ± 1.33). NEDA-3 and NEDA-3 + statuses were achieved by 82.8% and 64.8% of patients, respectively at 48weeks vs. baseline, and by 57.0% and 49.2% of patients, respectively at 96weeks vs. baseline. All patients except one were free of disability progression at Week 96, and NEDA-3 and NEDA-3 + were equally predictive. Most patients were free of relapse (87.5%), disability progression (94.5%) and new MRI activity (67.2%) comparing 96weeks with baseline. SDMT scores were stable in patients with baseline score ˃35 and improved significantly in those with baseline score ≤ 35. Treatment persistence was high (81.0% at Week 96). Teriflunomide confirmed its real-world efficacy and was found to have a potentially beneficial effect on cognition.