Symbol Digit Modalities Test Research Articles

Optical coherence tomography versus other biomarkers: Associations with physical and cognitive disability in multiple sclerosis

Background: Optical coherence tomography (OCT) is a biomarker of neuroaxonal loss in multiple sclerosis (MS). Objective: The objective was to assess the relative role of OCT, next to magnetic resonance imaging (MRI) and serum markers of disability in MS. Methods: A total of 100 patients and 52 controls underwent OCT to determine peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell-inner plexiform layers (GCIPL). Serum neurofilament light chain (sNfL), total lesion volume (TLV), and brain parenchymal fraction (BPF) were also assessed. The associations of OCT with disability were examined in linear regression models with correction for age, vision, and education. Results: In patients, pRNFL was associated with the Symbol Digit Modalities Test (SDMT; p = 0.030). In the multivariate analysis including sNfL and MRI measures, pRNFL (β = 0.19, p = 0.044) and TLV (β = −0.24, p = 0.023) were the only markers associated with the SDMT. pRNFL (p < 0.001) and GCIPL (p < 0.001) showed associations with the Expanded Disability Status Scale (EDSS). In the multivariate analysis, GCIPL showed the strongest association with the EDSS (β = −0.32, p < 0.001) followed by sNfL (β = 0.18, p = 0.024). Conclusion: The associations of OCT measures with cognitive and physical disability were independent of serum and brain MRI markers of neuroaxonal loss. OCT can be an important tool for stratification in MS, while longitudinal studies using combinations of biomarkers are warranted.

One-year regional brain volume changes as potential predictors of cognitive function in multiple sclerosis: a pilot study

BackgroundThe most reliable magnetic resonance imaging (MRI) marker of cognitive dysfunction in multiple sclerosis (MS) is brain atrophy. However, 1-year volumetric changes prior to cognitive assessment were never studied as potential predictors of cognition, which we aim to assess with this pilot work.MethodsTwenty-two MS patients were submitted to a baseline measure of 83 regional brain volumes with MRI and re-evaluated 1 year later; they were also tested with the Brief International Cognitive Assessment for MS (BICAMS): sustained attention and processing speed were examined with the Symbol Digit Modalities Test (SDMT), verbal and visuo-spatial learning and memory with the learning trials from the California Verbal Learning Test-II (CVLT) and the Brief Visuo-spatial Memory Test-revised (BVMT), respectively. Controlling for age, sex, and years of education, a multivariate linear regression model was created for each cognitive score at 1-year follow-up in a backward elimination manner, considering cross-sectional regional volumes and 1-year volume changes as potential predictors.ResultsDecreases in the volumes of the left amygdala and the right lateral orbitofrontal cortex in the year prior to assessment were identified as possible predictors of worse performance in verbal memory (P = 0.009) and visuo-spatial memory (P = 0.001), respectively, independently of cross-sectional brain regional volumes at time of testing.ConclusionOur work reveals novel 1-year regional brain volume changes as potential predictors of cognitive deficits in MS. This suggests a possible role of these regions in such deficits and might contribute to uncover cognitively deteriorating patients, whose detection is still unsatisfying in clinical practice.

A Phase II Trial of Intraoperative Radiotherapy after Surgical Resection of Brain Metastases: Feasibility and Efficacy NCT04847284

Intraoperative radiation therapy (IORT) is an alternative to local radiation therapy for brain metastases, reducing total treatment time, and improving patient comfort, but the most effective dose is unknown. The objective of this study is to evaluate the efficacy and safety of IORT in patients with surgical excision of brain metastases at a dose of 20 Gy. This trial is a single-institution, open-label, prospective, non-randomized study for intraoperative radiotherapy immediately after resection of brain metastases. Registered in January 2021, currently ongoing, planned to enroll 25 patients with IK ≥70, brain damage newly diagnosed by MRI, without dural contact and at least 1 cm to the optic nerve, chiasm and brainstem. In the baseline visit, the General Cognitive State will be carried out: Minimum Mental State Exams. Specific cognitive study: 1- Processing speed (SYmbol digit modalities test), 2- Executive function (TMT, back and forward digit span test, phonological and semantic verbal fluency test, Stroop color-word test), 3- Verbal memory (FCSRT). Quality of life will be monitored by completing the EORTC QL-C30 and BN20 questionnaires. Intraoperative radiation therapy will be performed with a 50 kV low energy X-ray portable linear accelerator using spherical applicators ranging from 1.5 to 4 cm kV to deliver 20 Gy to the surface. During IORT a maximum dose (DMax) of 8 Gy will be allowed to the optic nerve/chiasm and brainstem structures. MRI will be performed 72 hours after IORT. Neurocognitive Test and MRI after 6 weeks and every 3 months. The primary endpoint will be local progression free survival (PFS). Secondary endpoints will be overall survival, time to save cancer therapy, cognitive performance and quality of life, as well as IORT-related neurotoxicity complications will be evaluated according to the scale of the CTACAE version 4. The analysis of the median local progression free survival, overall survival will be analyzed using the Kaplan-Meier curve (long range test). All results will be considered statistically significant with a p value < 0.05. The statistical analysis will be carried out with statistical software. The trial is open and ongoing to recruitment; we have included 7 patients. The 85.7% were male, mean age was 61.4 years range (43-74). The 57.1% were lung cancer metastases. For now, no tumor recurrence or neurocognitive complications have been observed and then once you have the results ready, we will publish them. The limited current literature on the use of IORT in brain metastases appears to show efficacy and safety, but the most effective dose is unknown as well as whether it is as effective as other radiotherapy alternatives. Our study is ongoing and needs to be completed and evaluated with more follow-up in order to reach definitive conclusions.

A five-year observational prospective mono-center study of the efficacy of alemtuzumab in a real-world cohort of patients with multiple sclerosis.

Alemtuzumab (ALZ) is a pulsed immune reconstitution therapy for multiple sclerosis (MS). To assess basic characteristics, therapeutic effects, and prognostic biomarkers on clinical and imaging parameters of disease activity for relapsing-remitting MS (RRMS) patients selected for ALZ, in a real-world long-term setting. Fifty-one RRMS patients [female = 31; mean age 36 (standard deviation 7.1) years; median expanded disability status scale (EDSS) 2 (interquartile range (IQR) 1.5)] initiating ALZ treatment, were consecutively included. Patients were assessed at baseline and thereafter annually for 5 years with clinical measures, symbol digit modality test (SDMT), and magnetic resonance imaging (MRI). Concentrations of glial fibrillary acidic protein (GFAP), reflecting astrogliosis, and neurofilament light (NfL), reflecting axonal damage, were measured in cerebrospinal fluid (CSF) and serum samples collected at baseline and after 2 years in CSF, and annually in serum. Control subjects were symptomatic controls (SCs, n = 27), who were examined at baseline and after 5 years without evidence of neurological disease. While the mean annualized relapse rate was significantly reduced from baseline at each year of follow-up, disability was essentially maintained at a median EDSS of 1.5 and IQR between 1.13 and 2.25. New MRI activity was recorded in 26 patients (53%) over 5 years. The proportion of patients who achieved no evidence of disease activity (NEDA-3), 6-months confirmed disability worsening (CDW), and 6-months confirmed disability improvement (CDI) at 5 years were 33, 31, and 31%, respectively. The SDMT score was reduced for patients (p < 0.001), but unchanged for SCs. ALZ treatment did not change GFAP levels, whereas there was a significant decrease for RRMS patients in median CSF and serum NfL levels at follow-up [CSF month 24: 456 pg./mL (IQR 285.4) (p = 0.05); serum month 24: 6.7 pg/mL (IQR 4.7) (p < 0.01); serum month 60: 7.2 pg/mL (IQR 4.7) (p < 0.01)], compared to baseline [CSF: 1014 pg/mL (IQR 2832.5); serum 8.6 pg/mL (IQR 17.4)]. In this real-world mono-center population, we observed a progression-free survival of 69%, cumulative NEDA-3 of 33%, and reduced NfL levels, over a five-year follow-up. This confirms ALZ as an effective pulsed immune reconstitution therapy that significantly reduces neuro axonal loss, and therefore has the potential to reduce long-term neurological disability. ALZ did not appear to affect astrogliosis.

Cognitive rehabilitation and aerobic exercise for cognitive impairment in people with progressive multiple sclerosis (CogEx): a randomised, blinded, sham-controlled trial

Cognitive dysfunction in people with relapsing-remitting multiple sclerosis can improve with cognitive rehabilitation or exercise. Similar effects have not been clearly shown in people with progressive multiple sclerosis. We aimed to investigate the individual and synergistic effects of cognitive rehabilitation and exercise in patients with progressive multiple sclerosis. CogEx was a randomised, sham-controlled trial completed in 11 hospital clinics, universities, and rehabilitation centres in Belgium, Canada, Denmark, Italy, UK, and USA. Patients with progressive multiple sclerosis were eligible for inclusion if they were aged 25-65 years and had an Expanded Disability Status Scale (EDSS) score of less than 7. All had impaired processing speed defined as a performance of 1·282 SD or greater below normative data on the Symbol Digit modalities Tests (SDMT). Participants were randomly assigned (1:1:1:1), using an interactive web-response system accessed online from each centre, to cognitive rehabilitation plus exercise, cognitive rehabilitation plus sham exercise, exercise plus sham cognitive rehabilitation, or sham exercise plus sham cognitive rehabilitation. The study statistician created the randomisation sequence that was stratified by centre. Participants, outcome assessors, and investigators were blinded to group allocation. The study statistician was masked to treatment during analysis only. Interventions were conducted two times per week for 12 weeks: cognitive rehabilitation used an individualised, computer-based, incremental approach to improve processing speed; sham cognitive rehabilitation consisted of internet training provided individually; the exercise intervention involved individualised aerobic training using a recumbent arm-leg stepper; and the sham exercise involved stretching and balance tasks without inducing cardiovascular strain. The primary outcome measure was processing speed measured by SDMT at 12 weeks; least squares mean differences were compared between groups using linear mixed model in all participants who had a 12-week assessment. The trial is registered with ClinicalTrials.gov, NCT03679468, and is completed. Between Dec 14, 2018, and April 2, 2022, 311 people with progressive multiple sclerosis were enrolled and 284 (91%) completed the 12-week assessment (117/311 [38%] male and 194/311 [62%] female). The least squares mean group differences in SDMT at 12 weeks did not differ between groups (p=0·85). Compared with the sham cognitive rehabilitation and sham exercise group (n=67), differences were -1·30 (95% CI -3·75 to 1·16) for the cognitive rehabilitation plus exercise group (n=70); -2·78 (-5·23 to -0·33) for the sham cognitive rehabilitation plus exercise group (n=71); and -0·71 (-3·11 to 1·70) for the cognitive rehabilitation plus sham exercise group (n=76). 11 adverse events possibly related to the interventions occurred, six in the exercise plus sham cognitive rehabilitation group (pain, dizziness, and falls), two in the cognitive rehabilitation plus sham exercise group (headache and pain), two in the cognitive rehabilitation and exercise group (increased fatigue and pain), and one in the dual sham group (fall). Combined cognitive rehabilitation plus exercise does not seem to improve processing speed in people with progressive multiple sclerosis. However, our sham interventions were not inactive. Studies comparing interventions with a non-intervention group are needed to investigate whether clinically meaningful improvements in processing speed might be attainable in people with progressive multiple sclerosis. MS Canada.

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.

Associations Between Cognitive Impairment and Neuroimaging in Patients with Multiple Sclerosis.

Multiple sclerosis (MS) is a debilitating inflammatory and neurodegenerative disease which commonly involves cognitive dysfunction. Magnetic resonance imaging (MRI) studies have shown that patients with MS (pwMS) have diffuse patterns of brain atrophy, however, the relationship between the presentation of cognitive dysfunction and brain tissue loss remains understudied. Given the integral function of thalamus as a central nervous system relay center and its involvement in various brain circuits, thalamic atrophy may play a key role in the development and progression of cognitive dysfunction. The purpose of this study is to examine the relationship between cognitive impairment in pwMS and thalamic atrophy. A total of 121 pwMS who had neuropsychological testing and quantitative MRI within 1 year of each were retrospectively identified. Grouped LASSO linear regression with 10-fold cross validation was used to estimate each neuropsychological test score with thalamic volume as the focal predictor and all other demographic and MRI metrics as covariates. Rates of impairment ranged from 19% to 44%. Results showed notable associations between thalamic volume and Symbol Digit Modalities Test (β= 0.11), Brief Visuospatial Memory Test, delayed (β = 0.12), California Verbal Learning Test, delayed and total (β = 0.24 and β = 0.15 respectively), and Trail Making Test Part A (β = -0.01), after adjusting for covariates. These findings demonstrate an independent association between thalamic volumes and processing speed and memory performance, after accounting for demographic, clinical, and other MRI variables, among pwMS.

Oculomotor analysis to assess brain health: preliminary findings from a longitudinal study of multiple sclerosis using novel tablet-based eye-tracking software.

A growing body of evidence supports the link between eye movement anomalies and brain health. Indeed, the oculomotor system is composed of a diverse network of cortical and subcortical structures and circuits that are susceptible to a variety of degenerative processes. Here we show preliminary findings from the baseline measurements of an ongoing longitudinal cohort study in MS participants, designed to determine if disease and cognitive status can be estimated and tracked with high accuracy based on eye movement parameters alone. Using a novel gaze-tracking technology that can reliably and accurately track eye movements with good precision without the need for infrared cameras, using only an iPad Pro embedded camera, we show in this cross-sectional study that several eye movement parameters significantly correlated with clinical outcome measures of interest. Eye movement parameters were extracted from fixation, pro-saccade, anti-saccade, and smooth pursuit visual tasks, whereas the clinical outcome measures were the scores of several disease assessment tools and standard cognitive tests such as the Expanded Disability Status Scale (EDSS), Brief International Cognitive Assessment for MS (BICAMS), the Multiple Sclerosis Functional Composite (MSFC) and the Symbol Digit Modalities Test (SDMT). Furthermore, partial least squares regression analyses show that a small set of oculomotor parameters can explain up to 84% of the variance of the clinical outcome measures. Taken together, these findings not only replicate previously known associations between eye movement parameters and clinical scores, this time using a novel mobile-based technology, but also the notion that interrogating the oculomotor system with a novel eye-tracking technology can inform us of disease severity, as well as the cognitive status of MS participants.

The NHANES Biological Age Index demonstrates accelerated aging in MS patients.

Chronological age is associated with disability accumulation in multiple sclerosis (MS). Biological age may give more precise estimates of aging pathways associations with MS severity. Both normal aging and accelerated aging from MS may negatively impact disease course. Multi-marker indices of aging, such as the NHANES biological age index (BAI), may be more robust than single biomarkers in capturing biological age and are strongly associated with mortality risk and aging-related diseases. We sought to investigate whether the NHANES BAI, utilizing readily available measures in the clinic, captures accelerating aging and correlates with disability in MS participants. We conducted a prospective, cross-sectional case-control pilot study. Consecutive patients who met the 2017 McDonald's Criteria for MS were recruited from May 2020 to May 2022 along with age-similar healthy controls. BAI components included blood pressure, FEV1, serum creatinine, C-reactive protein, blood-urea nitrogen, albumin, alkaline phosphatase, cholesterol, CMV IgG, and hemoglobin A1c. The index was calculated using the Klemara and Doubal method. Spearman correlation and multivariable linear regression models were used to assess the association between BAI and MS clinical outcomes. A total of 51 MS (68.6% female) and 38 control (68.4% female) participants were recruited. BAI correlated with chronological age (CA) in MS (r2=0.90,p<0.0001) and control participants (r2 =0.87,p<0.0001). The mean BAI was 1.4 years older than CA in MS participants (range +15 to -10.5 years) and 2.2 years younger in control participants (range +11.2 to -14.1 years). In unadjusted Spearman analyses, BAI correlated with the timed 25-foot walk (T25FW, rhos=0.31, p=0.045) and symbol digit modalities test (SDMT rhos=0.35, p=0.018). In a multivariable regression model, a 5-year older BAI was associated with a 1.2-point lower score on SDMT (95%CI -2.2 to -0.25, p=0.014). MS participants were biologically older than their own chronological age and age-similar controls. In this modest-sized pilot sample, there was strongest correlation for MS outcome measures between BAI and the SDMT. These results support further study of the BAI as a marker of biological age variability in MS.

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

IntroductionImpairment 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. MethodsChildren 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. ResultsThe 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. ConclusionThe 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.

Physical activity and cognitive function in middle-aged adults: a cross-sectional analysis of the PATH through life study.

Investigate the independent associations of objectively measured or self-reported physical activity at different intensities with cognitive performance in middle-aged adults. Cross-sectional. 156 middle-aged adults (age: 40.6 ± 1.5, 58.3% female) participated in the physical activity sub-study of the Personality and Total Health through life (PATH) project. Physical activity was measured objectively with the SenseWear™ armband (SWA), worn for seven consecutive days, and measured via self-report with a Physical Activity Recall survey (PAR). Cognitive performance was assessed with the Symbol Digit Modalities Test, the Digit Span Backwards, and an Immediate and Delayed Recall task. Associations between physical activity intensity and cognitive function were investigated in general linear models, controlling for age, sex, and education. Neither objectively measured nor self-reported physical activity were associated with cognitive function at light-, moderate-, vigorous-, or combined moderate-to-vigorous intensity in this cohort of well educated, healthy middle-aged adults. Sensitivity analyses with additional moderators (e.g., body mass index, hypertension, alcohol intake) and the use of composite cognitive measures did not alter the results. In this cohort of middle-aged adults, objectively measured and self-reported physical activity do not appear to be associated with cognitive function. Longitudinal follow-ups utilising objective physical activity measures may be important in determining the impact of mid-life behaviours on the trajectory of cognitive changes into older age.

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...

Brain MRI disease burden and sex differences in cognitive performance of patients with multiple sclerosis.

Although there is evidence that shows worse cognitive functioning in male patients with multiple sclerosis (MS), the role of brain pathology in this context is under-investigated. To investigate sex differences in cognitive performance of MS patients, in the context of brain pathology and disease burden. Brain MRI, neurological examination, neuropsychological assessment (Brief International Cognitive Assessment in MS-BICAMS, and Paced Auditory Verbal Learning Test-PASAT), and patient-reported outcome questionnaires were performed/administered in 1052 MS patients. Females had higher raw scores in the Symbol Digit Modalities Test (SDMT) (57.0 vs. 54.0; p < 0.001) and Categorical Verbal Learning Test (CVLT) (63.0 vs. 57.0; p < 0.001), but paradoxically, females evaluated their cognitive performance by MS Neuropsychological Questionnaire as being worse (16.6 vs 14.5, p = 0.004). Females had a trend for a weaker negative correlation between T2 lesion volume and SDMT ([Formula: see text] = -0.37 in females vs. -0.46 in men; interaction p = 0.038). On the other hand, women had a trend for a stronger correlation between Brain Parenchymal Fraction (BPF) and a visual memory test (Spearman's [Formula: see text] = 0.31 vs. 0.21; interaction p = 0.016). All these trends were not significant after correction for false discovery rate. Although, females consider their cognition as worse, males had at a group level slightly worse verbal memory and information processing speed. However, the sex differences in cognitive performance were smaller than the variability of scores within the same sex group. Brain MRI measures did not explain the sex differences in cognitive performance among MS patients.

Effects of Hypothermia vs Normothermia on Societal Participation and Cognitive Function at 6 Months in Survivors After Out-of-Hospital Cardiac Arrest

The Targeted Hypothermia vs Targeted Normothermia After Out-of-Hospital Cardiac Arrest (TTM2) trial reported no difference in mortality or poor functional outcome at 6 months after out-of-hospital cardiac arrest (OHCA). This predefined exploratory analysis provides more detailed estimation of brain dysfunction for the comparison of the 2 intervention regimens. To investigate the effects of targeted hypothermia vs targeted normothermia on functional outcome with focus on societal participation and cognitive function in survivors 6 months after OHCA. This study is a predefined analysis of an international multicenter, randomized clinical trial that took place from November 2017 to January 2020 and included participants at 61 hospitals in 14 countries. A structured follow-up for survivors performed at 6 months was by masked outcome assessors. The last follow-up took place in October 2020. Participants included 1861 adult (older than 18 years) patients with OHCA who were comatose at hospital admission. At 6 months, 939 of 1861 were alive and invited to a follow-up, of which 103 of 939 declined or were missing. Randomization 1:1 to temperature control with targeted hypothermia at 33 °C or targeted normothermia and early treatment of fever (37.8 °C or higher). Functional outcome focusing on societal participation assessed by the Glasgow Outcome Scale Extended ([GOSE] 1 to 8) and cognitive function assessed by the Montreal Cognitive Assessment ([MoCA] 0 to 30) and the Symbol Digit Modalities Test ([SDMT] z scores). Higher scores represent better outcomes. At 6 months, 836 of 939 survivors with a mean age of 60 (SD, 13) (range, 18 to 88) years (700 of 836 male [84%]) participated in the follow-up. There were no differences between the 2 intervention groups in functional outcome focusing on societal participation (GOSE score, odds ratio, 0.91; 95% CI, 0.71-1.17; P = .46) or in cognitive function by MoCA (mean difference, 0.36; 95% CI,-0.33 to 1.05; P = .37) and SDMT (mean difference, 0.06; 95% CI,-0.16 to 0.27; P = .62). Limitations in societal participation (GOSE score less than 7) were common regardless of intervention (hypothermia, 178 of 415 [43%]; normothermia, 168 of 419 [40%]). Cognitive impairment was identified in 353 of 599 survivors (59%). In this predefined analysis of comatose patients after OHCA, hypothermia did not lead to better functional outcome assessed with a focus on societal participation and cognitive function than management with normothermia. At 6 months, many survivors had not regained their pre-arrest activities and roles, and mild cognitive dysfunction was common. ClinicalTrials.gov Identifier: NCT02908308.

Effect of Tai-chi on balance, mood, cognition, and quality of life in women with multiple sclerosis: A one-year prospective study

IntroductionOne of the most debilitating problems encountered by people with multiple sclerosis (MS) is the loss of balance and coordination. Our study aimed to comprehensively evaluate the effectiveness of one year of Tai-chi exercise in patients with MS using both subjective and objective methods, including posturography. MethodsThis was a single-group longitudinal one-year study performed from the 1st of January 2019 to the 1st of January 2020. The primary outcomes of interest were the Mini-Balance Evaluation Systems Test (Mini-BESTest) and static posturography measures as objective methods to detect subtle changes associated with postural control/balance impairment. Secondary outcomes were measures of depression, anxiety, cognitive performance, and quality of life. All objective and subjective parameters were assessed four times: at baseline, and after three, six and 12 months of regular Tai-chi training. The difference was calculated as a subtraction of baseline values from every timepoint value for each measurement. If the normality test was passed, parametric one-sample t-test was used, if failed, Wilcoxon signed ranks test was used to test the difference between the baseline and each timepoint. Alpha was set to 0.017 using Bonferroni correction for multiple comparisons. ResultsOut of 25 patients with MS enrolled, 15 women with MS (mean age 44.27 years) were included for statistical analyses after completing the 12-month program. After 12 months, significant improvements were found in all objective balance and gait tests: Mini-BESTest (p<0.001), static posturography measures (total area of the centre of foot pressure – TA; p = 0.015), 25 Feet Walk Test (25FWT; p = 0.001), anxiety (Beck Anxiety Inventory – BAI; p = 0.005) and cognition tests (Paced Auditory Serial Addition Test – PASAT; p = 0.003). Measures of depression (Beck Depression Inventory – BDI; p = 0.071), cognition (Symbol Digit Modalities Test – SDMT; p = 0.079), and health-related quality of life (European Quality of Life 5-Dimensions Questionnaire – EQ-5D-5L; p = 0.095) showed a trend of improvement but were not significant, which could be the result of a small sample and increased bias due the type II error. ConclusionAccording to these preliminary results, this study indicates the possible beneficial effects of long-term Tai-chi training on patients with MS. Although these findings need to be confirmed by further studies with a larger sample of participants of both genders and require more rigorous randomized controlled trials (RCT) design, our findings support the recommendation of regular and long-term Tai-chi exercise in patients with MS. ClinicalTrials.gov Identifier (retrospectively registered): NCT05474209

SPCR-05 ENVIRONMENTAL ENRICHMENT AMONG BRAINTUMOR SURVIVORS

Abstract Individuals from underserved communities who received photon radiation are at a disproportionately increased risk of accelerated aging and symptom burden that significantly impacts independence and overall functioning. There is limited knowledge of environmental factors that mitigate these long-term sequelae. The aim of the study is to explore if higher levels of environmental enrichment (EE) are neuroprotective against accelerated brain aging experienced by brain tumor (BT) survivors who received radiation. METHODS: The study employed a retrospective cohort design among persons with low-grade glioma treated with radiation approximately 5 years from the original diagnosis (N=39). EE consists of social network/engagement, physical activity, and employment status/financial stability measured by the Berkman-Syme Social Network Index, International Physical Activity Questionnaire, Vocational Index Scale, and Socioeconomic Questionnaires, respectively. EE at enrollment is classified into high, moderate, or low levels. Montreal Cognitive Assessment and Symbol Digit Modality Test at enrollment measure cognitive function. Karnofsky Performance Status Scale and the MD Anderson Symptom Inventory – BT module at enrollment are used to measure functional status. Cortical volume is measured using temporal brain MRI images from the time of diagnosis, 3 and 5 years after diagnosis. Images are processed using FreeSurfer segmentation software. Linear mixed models will estimate mean cerebral atrophy and explore the association to cognitive and functional data across time adjusted for covariates. RESULTS: Research analysis in progress. Thirty-nine participants have been enrolled in the study. The median age is 44, 22 are male, and 27 are female. There are 18 Individuals diagnosed with Astrocytoma and 19 with Oligodendroglioma. Thirty-three percent of individuals have low EE, 43.5% have moderate EE, and 23% have high EE. CONCLUSION: BT survivors are at an increased risk of accelerated aging and progressive neurological decline. EE may serve as a positive stimulation that improves neuroplasticity and reduces accelerated aging after brain radiation.

Adaptation and validation of the Greek version of the Speech Pathology-Specific Questionnaire for Persons with Multiple Sclerosis (SMS)

Purpose The aim of the present study was to adapt and validate the Speech Pathology-Specific Questionnaire for Persons with Multiple Sclerosis (SMS) into the Greek language. Method The study sample consisted of 124 people with multiple sclerosis (PwMS) and 50 healthy controls (HCs). All PwMS underwent cognitive assessment using the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS). Both PwMS and HCs completed the SMS, the Eating Assessment tool (EAT-10), the Voice Handicap Index (VHI), and the Stroke and Aphasia Quality of Life Scale-39 (SAQOL-39). Result Significant difference was found between PwMS and HCs for the EAT-10, SAQOL-39, the total SMS, and the SMS subscales. Discriminant validity analyses revealed a statistically significant difference between PwMS and HCs for the total and subscales SMS. Convergent validity analyses between the total SMS and the SMS subscales, and scores on the BICAMS, EAT-10, SAQOL-39, and VHI in PwMS were significantly correlated, with exception of the SMS Speech/Voice with the Symbol Digit Modalities Test (SDMT) and the Greek Verbal Learning Test-II (GVLT-II). Scores on the EAT-10, SAQOL-39, and VHI in PwMS were also correlated with the total SMS and the SMS subscales in PwMS, HCs, and the total sample. Construct validity analyses revealed that the total SMS and the SMS subscales were significantly correlated with the Expanded Disability Status Scale (EDSS) and years of education, while no associations were found with regards to age, MS subtype (relapsing-remitting MS [RRMS] vs progressive MS [PMS]), disease duration, or sex. The internal consistency of all items was excellent in PwMS and the total sample (Cronbach’s alpha was >0.7 after deletion of one item), with the exception of two items, which still fell within the acceptable range (>0.6) for PwMS and the total sample. Conclusion The Greek version of the SMS is a reliable and valid patient-reported outcome measure to assess speech-language and swallowing pathology related symptoms in PwMS, and can be used for research and clinical purposes.

Age and asymmetry of corticospinal excitability, but not cardiorespiratory fitness, predict cognitive impairments in multiple sclerosis

BackgroundCognitive impairment is a disabling and underestimated consequence of multiple sclerosis (MS), with multiple determinants that are poorly understood. ObjectivesWe explored predictors of MS-related processing speed impairment (PSI) and age-related mild cognitive impairment (MCI) and hypothesized that cardiorespiratory fitness and corticospinal excitability would predict these impairments. MethodsWe screened 73 adults with MS (53 females; median [range]: Age 48 [21–70] years, EDSS 2.0 [0.0–6.5]) for PSI and MCI using the Symbol Digit Modalities Test and Montréal Cognitive Assessment, respectively. We identified six persons with PSI (No PSI, n = 67) and 13 with MCI (No MCI, n = 60). We obtained clinical data from medical records and self-reports; used transcranial magnetic stimulation to test corticospinal excitability; and assessed cardiorespiratory fitness using a graded maximal exercise test. We used receiver operator characteristic (ROC) curves to discern predictors of PSI and MCI. ResultsInterhemispheric asymmetry of corticospinal excitability was specific for PSI, while age was both sensitive and specific for MCI. MS-related PSI was also associated with statin prescriptions, while age-related MCI was related to progressive MS and GABA agonist prescriptions. Cardiorespiratory fitness was associated with neither PSI nor MCI. DiscussionCorticospinal excitability is a potential marker of neurodegeneration in MS-related PSI, independent of age-related effects on global cognitive function. Age is a key predictor of mild global cognitive impairment. Cardiorespiratory fitness did not predict cognitive impairments in this clinic-based sample of persons with MS.

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.

Inhibitory dysfunction may cause prospective memory impairment in temporal lobe epilepsy (TLE) patients: an event-related potential study.

Prospective memory (PM) is the ability to remember future intentions, and PM function is closely related to independence in daily life, particularly in patients with temporal lobe epilepsy (TLE). As PM involves various cognitive components of attention, working memory, inhibition and other executive functions, this study investigated how TLE may affect PM components and the underlying neural mechanisms. Sixty-four subjects were recruited, including 20 refractory TLE patients, 18 well-controlled TLE patients and 26 age-matched healthy controls. A set of neuropsychological tests was administered to assess specific brain functions. An event-related potential (ERP) task was used to further explore how PM and its components would be differentially affected in the two TLE types. Our findings revealed that: (1) refractory TLE patients scored lower than the healthy controls in the digit span, Verbal Fluency Test and Symbol Digit Modalities Test; (2) refractory TLE patients exhibited impaired PM performance and reduced prospective positivity amplitudes over the frontal, central and parietal regions in ERP experiments when compared to the healthy controls; and (3) decreased P3 amplitudes in the nogo trials were observed over the frontal-central sites in refractory but not in well-controlled TLE patients. To our knowledge, this is the first ERP study on PM that has specifically identified PM impairment in refractory but not in well-controlled TLE patients. Our finding of double dissociation in PM components suggests that inhibition dysfunction may be the main reason for PM deficit in refractory TLE patients. The present results have clinical implications for neuropsychological rehabilitation in TLE patients.