•Attention was examined in relation to global EEG alpha power and frontal theta/beta ratio (T/B) in multiple sclerosis (MS).•Attention was related to alpha power and T/B ratio. T/B activity showed ...potential clinical sensitivity.•The examined EEG markers may represent feasible parameters for clinical monitoring in MS.
Neurophysiologic monitoring parameters related to cognition in Multiple Sclerosis (MS) are sparse. Previous work reported an association between magnetoencephalographic (MEG) alpha-1 activity and information processing speed. While this remains to be replicated by more available electroencephalographic (EEG) methods, also other established EEG markers, e.g. the slow-wave/fast-wave ratio (theta/beta ratio), remain to be explored in this context.
Performance on standard tests addressing information processing speed and attention (Symbol-Digit Modalities Test, SDMT; Test of Attention Performance, TAP) was examined in relation to resting-state EEG alpha-1 and alpha-2 activity and the theta/beta ratio in 25MS patients.
Increased global alpha-1 and alpha-2 activity and an increased frontal theta/beta ratio (pronounced slow-wave relative to fast-wave activity) were associated with lower SDMT processing speed. In an exploratory analysis, clinically impaired attention was associated with a significantly increased frontal theta/beta ratio whereas alpha power did not show sensitivity to clinical impairment.
EEG global alpha power and the frontal theta/beta ratio were both associated with attention. The theta/beta ratio involved potential clinical sensitivity.
Resting-state EEG recordings can be obtained during the routine clinical process. The examined resting-state measures may represent feasible monitoring parameters in MS. This notion should be explored in future intervention studies.
Abstract
Background
The progression of Huntington’s disease (HD) for gene-expanded carriers is well-studied. Natural aging effects, however, are not often considered in the evaluation of HD ...progression.
Objective
To examine the effects of natural aging for healthy controls and to develop normative curves by age, sex, and education from the distribution of observed scores for the Symbol Digit Modalities Test, Stroop Word Reading Test, Stroop Color Naming Test, Stroop Interference Test, Total Motor Score, and Total Functional Capacity (TFC) from the Unified Huntington’s Disease Rating Scale (UHDRS) along with a composite score.
Methods
After combining longitudinal REGISTRY and Enroll-HD data, we used quantile regression and natural cubic splines for age to fit models for healthy controls (N = 3,394; N observations = 8,619). Normative curves were estimated for the 0.05, 0.25, 0.50, 0.75, and 0.95 quantiles. Two types of reference curves were considered: unconditional curves were dependent on age alone, whereas conditional curves were dependent on age and other covariates, namely sex and education.
Results
Conditioning on education was necessary for the Symbol Digit, Stroop Word, Stroop Color, Stroop Interference, and composite UHDRS. Unconditional curves were sufficient for the Total Motor Score. TFC was unique in that the curve was constant over age with its intercept at the maximum score (TFC = 13). For all measures, sex effects were minimal, so conditioning on sex was unwarranted.
Conclusions
Extreme quantile estimates for each measure can be considered as boundaries for natural aging and scores falling beyond these thresholds are likely the result of disease progression. Normative curves and tables are developed and can serve as references for clinical characterization in HD.
Evolving evidence suggests that measurement of cerebrospinal fluid (CSF) kappa free light chain (KFLC) synthesis has high diagnostic sensitivity and specificity for multiple sclerosis (MS), but its ...prognostic ability is less investigated. The usefulness of KFLC in predicting cognitive impairment (CI) is still unknown.
In a monocentric longitudinal retrospecitve cohort study, KFLC-index (CSF KFLC/serum KFLC/CSF albumin/serum albumin) measured by latex-enhanced immunonephelometry was prospectively determined as part of the diagnostic workup in patients with early relapsing-remitting MS (RRMS, n=77). The ability of KFLC-index to predict information processing speed (IPS) worsening as assessed with the symbol digit modalities test (SDMT) was investigated in univariable and multivariable models.
In patients with KFLC-index>100 (n=31), 11 subjects (35.5%) showed reduced SDMT scores by ≥8 points at follow-up (mean follow-up time 7.3 ± 2.6 years), compared with their baseline scores (p=0.01). Baseline KFLC-index>100 was strongly associated with a higher hazard of SDMT score reduction at follow-up (adjusted hazard ratio 10.5, 95% confidence interval 2.2-50.8, p=0.003; median time to SDMT reduction 7 years).
Intrathecal KFLC synthesis has become an attractive diagnostic tool for MS. We show for the first time that in a real-world setting of early RRMS, KFLC-index predicted cognitive decline. Whether this predictive ability of KFLC-index also concerns other cognitive domains than IPS, warrants further investigations.
To study the cognitive function status, serum phosphorylated tau181 (P-tau181) protein level, and total tau (T-tau) protein level in patients with preeclampsia (PE), pregnant healthy controls (PHCs), ...and non-pregnant healthy controls (NPHCs), and to research their feasibility as serum biomarkers for evaluating cognitive functional impairment in PE patients.
Sixty-eight patients with PE, 48 NPHCs, and 30 PHCs were included. Cognitive functional status was assessed using standardized Symbol Digit Modalities Test (SDMT) and Montreal Cognitive Assessment (MoCA) scales. Enzyme-linked immunosorbent assay (ELISA) was used to detect the level of serum P-tau181 and T-tau protein. The concentration of serum P-tau181 and T-tau protein were compared by one-way analysis of variance in the three groups of subjects. The correlation between P-tau181, T-tau, and SDMT was explore by multiple linear regression analysis. The areas under the receiver operating characteristic (ROC) curves of serum P-tau181 and SDMT were calculated to predict the cognitive level of subjects.
PE patients significantly had lower scores on SDMT (47.97 ± 7.54) and MoCA (28.00 ± 2.00) than normotensive PHCs (30.00 ± 1.25, 54.73 ± 8.55, respectively). The significant difference was found in serum P-tau181 protein levels among the three groups
= 19.101,
< 0.001. Serum P-tau181 was thicker in PE patients than PHCs or NPHCs (both
< 0.05). According to the ROC curve, T-tau had no statistical significance in predicting the ability of cognizance, while P-tau181 and SDMT had. The DeLong test showed that P-tau181 was better than T-tau in predicting the ability of cognizance (
< 0.05).
The patients with PE have occurred the decline of cognitive function during pregnancy. The high level of serum P-tau181 can be used as a clinical laboratory indication for non-invasive assessment of cognitive functional impairment in PE patients.
Limitation of daily activities and impairment of working memory have received less attention in the clinical diagnosis and prognostic assessment of obstructive sleep apnea (OSA). In this study, the ...Activities and Participation component of the International Classification of Functioning, Disability and Health (ICF) Sleep Disorders Brief Core Set was evaluated for its performance in predicting impaired work ability in OSA patients.
A total of 221 subjects were recruited into this cross-sectional study. ICF Sleep Disorders Brief Core Set, polysomnography, and neuropsychological tests were applied for data acquisition. Data analysis was performed by regression analysis and receiver operating characteristic (ROC) construction.
The scores for the component Activities and Participation were significantly different between the no OSA/OSA group, and were elevated as the severity of OSA increased. Scores were positively correlated with apnea-hypopnea index (AHI), trail making test (TMT), and negatively correlated with symbol digit modalities test (SDMT) correct. The component Activities and Participation performed better with the threshold of 4 in the prediction of impaired attention and work ability in severe OSA AHI ≥30 events/h, bottom 10% of TMT part B (TMTb) scores as the diagnostic criteria, with area under the curve, sensitivity and specificity as 0.909, 71.43% and 96.72%, respectively.
The Activities and Participation component of the ICF Sleep Disorders Brief Core Set could have the potential to predict the impairment of attention and work ability in OSA patients. It provides a new perspective for the identification of OSA patients' disturbances in daily activities and improving the overall assessment level.
Cognitive impairment affects about 50% of multiple sclerosis (MS) patients, but the mechanisms underlying this remain unclear. The default mode network (DMN) has been linked with cognition, but in MS ...its role is still poorly understood. Moreover, within an extended DMN network including the cerebellum (CBL-DMN), the contribution of cortico-cerebellar connectivity to MS cognitive performance remains unexplored. The present study investigated associations of DMN and CBL-DMN structural connectivity with cognitive processing speed in MS, in both cognitively impaired (CIMS) and cognitively preserved (CPMS) MS patients. 68 MS patients and 22 healthy controls (HCs) completed a symbol digit modalities test (SDMT) and had 3T brain magnetic resonance imaging (MRI) scans that included a diffusion weighted imaging protocol. DMN and CBL-DMN tracts were reconstructed with probabilistic tractography. These networks (DMN and CBL-DMN) and the cortico-cerebellar tracts alone were modeled using a graph theoretical approach with fractional anisotropy (FA) as the weighting factor. Brain parenchymal fraction (BPF) was also calculated. In CIMS SDMT scores strongly correlated with the FA-weighted global efficiency (GE) of the network GE(CBL-DMN): ρ = 0.87,
= 0.76,
< 0.001; GE(DMN): ρ = 0.82,
= 0.67,
< 0.001; GE(CBL): ρ = 0.80,
= 0.64,
< 0.001. In CPMS the correlation between these measures was significantly lower GE(CBL-DMN): ρ = 0.51,
= 0.26,
< 0.001; GE(DMN): ρ = 0.48,
= 0.23,
= 0.001; GE(CBL): ρ = 0.52,
= 0.27,
< 0.001 and SDMT scores correlated most with BPF (ρ = 0.57,
= 0.33,
< 0.001). In a multivariable regression model where SDMT was the independent variable, FA-weighted GE was the only significant explanatory variable in CIMS, while in CPMS BPF and expanded disability status scale were significant. No significant correlation was found in HC between SDMT scores, MRI or network measures. DMN structural GE is related to cognitive performance in MS, and results of CBL-DMN suggest that the cerebellum structural connectivity to the DMN plays an important role in information processing speed decline.
Multiple sclerosis (MS) is defined as an inflammatory, progressive, and autoimmune disease in the central nervous system, recognized by its subsequent demyelination and neurodegeneration. Cognitive ...disorders are among the most severe problems in patients with MS, affecting their personal and professional life. This study is aimed to evaluate memory and visual learning, visual processing speed, and spatial perception in MS patients based on age, gender, and level of education. This cross-sectional study was carried out on 42 MS patients (based on McDonald’s criteria). The level of disability in patients was assessed using EDSS, and cognitive performance was evaluated by the use of judgment of line orientation (JLO), symbol digit modalities test (SDMT), and revised brief visuospatial memory test (BVMT-R). In this study, patients were within the age range of 20-51 years, 73.8% of which were female, and 61.9% had academic degrees. According to the classes of independent variables (gender, education level), no significant difference was observed in the mean scores of dependent variables (JLO, SDMT, and BVMR-T scores) (P>0.05). In addition, age as a confounding variable had no impact (P>0.05). In addition, gender and level of education had no significant interaction (P>0.05). According to the results of the study, age, gender, and education level had no significant effect on memory and visual learning, visual processing speed, and spatial perception.
Cognitive deficits including impaired information processing speed as assessed by the Symbol Digit Modalities Test (SDMT) are common in multiple sclerosis (MS). Oscillatory markers of processing ...speed may be extracted from magnetoencephalographic (MEG) and electroencephalographic (EEG) resting-state recordings. In this context, an increased proportion of frontal slow-wave (theta, 4-8 Hz) to fast-wave (beta, 13-30 Hz) EEG activity was indicative of impaired SDMT performance. Such an increased theta/beta ratio may reflect oscillatory slowing associated with deficits in attention control. Therapeutic approaches that consider atypical oscillatory activity in MS remain sparse.
In a cross-sectional design, we examined the relation between SDMT performance, the EEG theta/beta ratio and its components. We also explored longitudinally, whether EEG neurofeedback could be used to induce a putatively adaptive alteration in these EEG parameters, toward a pattern indicative of improved processing speed.
N = 58 MS patients (RRMS/SPMS/PPMS N: 18/35/3, 2 cases excluded) participated in a neuropsychological examination and a resting-state EEG recording. Subsequently, N = 10 patients received neurofeedback training for two weeks in a hospitalized setting. The purpose was to reduce the frontal theta/beta ratio through operant conditioning.
In the cross-sectional examination, patients with slow SDMT speed displayed an increased theta/beta ratio, relative to those with normal speed. This involved increased frontal theta power, whereas beta power was equal across groups. The theta/beta ratio remained stable during neurofeedback across sessions of the two-week training period. In an exploratory secondary analysis, within sessions a reduction in the theta/beta ratio during active training blocks relative pre/post session resting-states was observed, driven by reduced theta power.
These findings provide support for utilizing frontal EEG theta activity as an inverse marker of processing speed in MS. Across sessions, there was no support for successful operant conditioning of the theta/beta ratio during the two-week training period. The observed state-specific shift within sessions, involving a transient reduction in theta activity, nevertheless may provide a rationale for a further investigation of neurofeedback as a treatment approach in MS.
Unhealthy, physically inactive lifestyles increase the risk of future cardiovascular events and impaired physical fitness in individuals with schizophrenia. Insufficient literature exists to provide ...fundamental information about appropriate exercise training modality for this population. This pilot study preliminarily investigated the effects of a 12-week moderate-intensity bench-step exercise training (BSET) program on cardiopulmonary fitness, mood state, and cognition in patients with schizophrenia.
Twenty-eight patients with schizophrenia completed this study. The participants were allocated into either bench-step exercise-training (BSET;
= 14) or control (CTRL;
= 14) groups according to their preferences. The BSET group received a 12-week bench-step intervention, whereas the CTRL group did not participate in any training. The Beck Depression Inventory-II (BDI-II), 6-min walk test (6MWD), and Symbol Digit Modalities Test (SDMT) were assessed at baseline (PRE) and at the end of the intervention (POST) to determine mood state, endurance fitness, and attention, respectively.
After a 12-week BSET intervention, the 6MWD was significantly increased in the BSET (
= 0.007) but not in the CTRL (
> 0.05). The participants with BSET intervention showed a significant decrease in BDI-II at the end of the intervention (
= 0.03). However, SDMT scores were not different in both BSET and CTRL (
> 0.05).
This study demonstrated that the 12-week intervention of moderate-intensity bench-step exercise training (frequency: 1 session/week; each session of 30 min; step cadence: 96 beats/min) might effectively enhance cardiopulmonary fitness and mood state in patients with schizophrenia. However, attention did not change after the bench-step exercise intervention.
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