Symbol Digit Modalities Test Research Articles

Neurofilament and Brain Atrophy and Their Association with Cognition in Multiple Sclerosis: A 10-Year Follow-Up Study

Introduction. Cognitive impairment is an important contributor to disability in multiple sclerosis (MS). Disconnection of neuronal circuits due to axonal injury is probably an important underlying mechanism for this disability. Neurofilament light chain (NfL) is a neuron-specific constituent of axons and has gained increasing attention as a biomarker of axonal injury. Objective. To assess the association between NfL in serum (sNfL) and cerebrospinal fluid (cNfL) and cognitive function over 10 years and compare these associations with volumetric brain magnetic resonance imaging (MRI) measurements. Methods. Newly diagnosed MS patients were followed prospectively with baseline NfL and MRI as well as with clinical and cognitive assessments for up to 10 years. Results. Forty-one patients were included. Baseline sNfL correlated negatively with symbol digit modalities test (SDMT) at baseline (r=−0.45, p=0.005), year 5 (r=−0.41, p=0.017), and at year 10 (r=−0.52, p=0.008). Baseline cNfL correlated with baseline SDMT (r=−0.34, p=0.030) and SDMT at year 10 (r=−0.44, p=0.037). Baseline volumes of whole brain (r=0.476, p=0.002), gray matter (r=0.467, p=0.002), T1 (r=−0.627, p<0.001), and T2 lesion volumes (r=−0.475, p=0.002) correlated significantly with baseline SDMT. Longitudinal analyses showed that both MRI volumes and EDSS were associated with the rate of SDMT decline, whereas sNfL and cNfL were not. Conclusion. NfL levels measured in serum and cerebrospinal fluid were both associated with cognitive functioning in MS patients over a 10-year period from diagnosis. However, MRI volumes correlated strongly in addition to the rate of cognitive decline.

Utility of the Brief Assessment of Cognitive Health (BACH) computerized screening tool in identifying MS-related cognitive impairment

BackgroundCurrent guidelines recommend that individuals with MS are screened annually for processing speed deficits, often using the Symbol Digit Modalities Test (SDMT). However, given the heterogeneity of cognitive deficits in individuals with MS, other screening measures that assess a range of cognitive domains are necessary. The current cross-sectional study aimed to examine the ability of the computerized, self-administered Brief Assessment of Cognitive Health (BACH) screening measure to detect the presence of cognitive impairment in adults with MS as determined by performance on a standard neuropsychological test battery. MethodsSeventy-two individuals with MS completed the BACH and a comprehensive neuropsychological test battery. Receiver operating characteristic (ROC) analyses were conducted to investigate the ability of the BACH to identify cognitively impaired and cognitively intact individuals. ROC analyses were also conducted to compare the ability of the SDMT to discriminate between cognitively intact and cognitively impaired groups as a comparison with the BACH. ResultsCognitive impairment was observed in 56 % of the sample. The BACH showed acceptable ability to discriminate between cognitively intact and cognitively impaired groups (AUC = 0.78). Additionally, the BACH was able to adequately predict cognitive impairment in domains other than processing speed (AUC = 0.71). The SDMT also demonstrated adequate utility in identifying individuals with cognitive impairment (AUC = 0.73); however, the SDMT was not able to adequately predict cognitive impairment in domains other than processing speed (AUC = 0.56). ConclusionThe BACH showed adequate ability to detect cognitive impairment in individuals with MS. The BACH was able to identify impairments across various assessed cognitive domains, including individuals with and without processing speed deficits.

BIOLOGICAL AGE AND COGNITIVE PERFORMANCE AMONG LATE MID-LIFE WOMEN

Abstract Older biologic age, indicated by accelerated epigenetic aging, may place women at risk for poorer cognitive performance as they age. However, findings are inconsistent and based upon limited neuropsychological batteries. Studies of midlife women are few, yet women comprise two thirds of those with Alzheimer’s disease, and midlife is a critical transition and potential window for early intervention. We tested whether greater epigenetic age would be associated with poorer cognitive performance among late midlife women. 224 MsBrain study participants (average age=59 years, 82% White, 14% Black, 4% other ethnicities) underwent phlebotomy, including epigenetic aging clock estimates (GrimAge, DunedinPACE, PCPhenoAGE), and a neuropsychological battery assessing global cognitive function (Montreal Cognitive Assessment), verbal learning and memory (California Verbal Learning Test), working memory and attention (Letter Number Sequencing), letter fluency (P, R, W); semantic fluency (animal task), spatial ability (Card Rotations), processing speed (Symbol Digit Modalities Test), and perceptual speed (Finding A’s). In linear regression models controlling for age, race, and education, older PCPhenoAge was associated with poorer global cognitive performance [B(SE)=-.07(.03), p=.01], verbal memory [B(SE)=-.09(.03), p=.006], working memory [B(SE)=-.12(.03), p=.0001], attention [B(SE)=-.10(.04), p=.02], spatial ability [B(SE)=-.77(.34), p=.02], processing speed [B(SE)=-.24(.09), p=.007], and somewhat lower letter fluency [B(SE)=-.23(.13), p=.07]. GrimAge and DunedinPACE showed similar yet less consistent patterns. Interactions by race (p’s<.05) indicate that associations between older biologic age and poorer cognitive performance (verbal learning, verbal memory, processing speed) was particularly pronounced among Black women in the sample. Older biologic age is associated with poorer cognitive performance across multiple domains among late midlife women, particularly for Black women. Biologic age may serve as an early indicator of risk that could help identify women warranting early intervention to help maintain cognitive function. Supported by NIH RF1AG053504, R01AG053504, K24HL123565

Blood-based biomarkers for Alzheimer's disease and cognitive function from mid- to late life.

We investigated associations of Alzheimer's disease (AD) serum biomarkers with longitudinal changes in cognitive function from mid- to late life among women. The study population included 192 women with the median age of 53.3 years at baseline, from the Study of Women's Health Across the Nation Michigan Cohort, followed up over 14 years. Associations between baseline serum amyloid β (Aβ)42, the Aβ42/40 ratio, phosphorylated tau181 (p-tau181), and total tau with longitudinal changes in cognition were evaluated using linear mixed effects models. After adjusting for confounders, lower Aβ42/40 ratios were associated with faster declines in the Digit Span Backward Test. Higher p-tau181 also showed a borderline statistically significant association with more rapid decline in the Symbol Digit Modalities Test. Our findings suggest that mid-life serum AD biomarkers could be associated with accelerated cognitive decline from mid- to late life in women. Future studies with larger samples are needed to validate and extend our findings. This study investigates midlife serum AD biomarkers on longitudinal cognitive function changes in women. Mid-life serum AD biomarkers are associated with accelerated cognitive decline. A decrease in the Aβ42/40 ratio was associated with a faster decline in the DSB score. A higher p-tau181 concentration was associated with a faster decline in the SDMT score.

ASSOCIATION OF RAPID EYE MOVEMENT SLEEP AND APOE PROTEOTYPE TO COGNITIVE PERFORMANCE IN OLDER ADULTS

Abstract Exploring the multifaceted interaction of sleep, disease-related biomarkers and cognitive decline is of particular importance for aging populations. Sleep quality and the APOE E3/E4 allele has been linked to Alzheimer’s Disease (AD). This study aims to examine relationships between older adults’ level of cognitive performance, proportion of rapid eye movement (REM) sleep, and APOE proteotype. Analysis of sleep study data collected in an active lifestyle retirement community - The Villages, Florida was conducted using a subset of markers collected as part of a larger cognitive health study. Polysomnography, cognitive battery (Montreal Cognitive Assessment(MoCA), Trail Making Tests(TMT), Symbol Digit Modalities Test(SDMT), Psychomotor Vigilance Test(PVT)), and APOE blood-biomarker (E2/E3,E3/E3,E3/E4) data were obtained from healthy participants (n=33) aged 55-65. Descriptive statistics, multilinear regression, and ANOVA were used. Participants’ mean age was 61.9 years, with 55% being male. Cognitive test scores did not show a significant relationship with REM sleep percentage (p=0.3096). No consistent dispersion or skew was shown in box plot analysis of APOE proteotype across cognitive performance measures. Unexpectedly, although not statistically significant (p=0.396), average REM sleep percentage was higher in the APOE E3/E4 group (20.04%, Mean:75.44 minutes) as compared to the E3/E3 group (15.99%,Mean: 59.07 minutes). Proteotype E3/E4 was examined specifically due to its potential association with Alzheimer’s disease. The REM sleep proportion was lower than the average experienced on a typical night at home, possibly due to study conditions. Further research is needed examining the relationship between older adults with REM sleep insufficiency and cognitive impairment.

The Effects of Selective Serotonin Reuptake Inhibitors on Neurological and Depressive Symptoms in Multiple Sclerosis: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

Multiple sclerosis (MS) affects the central nervous system and creates plaques by demyelination of neurons. Several studies have investigated the effect of selective serotonin reuptake inhibitors (SSRIs) on MS clinical courses. The current meta-analysis was conducted to determine the effect of SSRIs on neurological and depressive symptoms of MS disease based on a systematic review and meta-analysis of randomized controlled trials. We searched the PubMed/Medline, Scopus, EMBASE, Google scholar, Web of Science, and Cochrane Library until June 2023. The effects of SSRI were assessed through indictors such as symbol digit modalities test (SDMT), expanded disability status scale (EDSS), modified fatigue impact scale (MFIS), and Beck's depression inventory/psychiatric (BDI). Considering the inclusion criteria, seven articles (including eight trials) were included in this review. The meta-analysis results demonstrated that SSRIs treatments did not have significant effects on indicators of neurological and depressive symptoms, such as SDMT (Weighted Mean Difference (WMD)=-0.87; 95% CI, -7.74, 5.99, P=0.35; I2=0.0%), EDSS (WMD=-0.05; 95% CI, -0.24, 0.14, P=0.62; I2=0.0%), MFIS (WMD=5.29; 95% CI, -18.10, 28.68, P=0.21; I2=0.0%), and BDI (WMD=-0.47; 95% CI, -2.61, 1.67, P=0.67; I2=32.05%) in patients with MS compared with controls. This study shows that the consumption of SSRIs in MS patients compared to the control group does not bring about a significant change in the indices related to neurological and depressive symptoms. Further meta-analyses are required in order to provide stronger evidence in the future.

Multi-modal neuroimaging signatures predict cognitive decline in multiple sclerosis: A 5-year longitudinal study

BackgroundCognitive impairment is a hallmark of multiple sclerosis (MS) but is usually an under-recorded symptom of disease progression. Identifying the predictive signatures of cognitive decline in people with MS (pwMS) over time is important to ensure effective preventative treatment strategies. Structural and functional brain characteristics as measured by various magnetic resonance (MR) methods have been correlated with variation in cognitive function in MS, but typically these studies are limited to a single MR modality and/or are cross-sectional designs. Here we assess the predictive value of multiple different MR modalities in relation to cognitive decline in pwMS over 5 years. MethodsA cohort of 43 pwMS was assessed at baseline and 5 years follow-up. Baseline (input) data consisted of 70 multi-modal MRI measures for different brain regions including magnetic resonance spectroscopy (MRS), diffusion tensor imaging (DTI) and standard volumetrics. Age, sex, disease duration and treatment were included as clinical inputs. Cognitive function was assessed using the Audio Recorded Cognitive Screen (ARCS) and the Symbol Digit Modalities Test (SDMT). Prediction modelling was performed using the machine learning package - GLMnet, where a penalised regression was applied to identify multi-modal signatures with the most predictive value (and the least error) for each outcome. ResultsThe multi-modal approach to neuroimaging was able to accurately predict cognitive decline in pwMS. The best performing model for change in total ARCS (tARCS) included 16 features from across the various MR modalities and explained 54 % of the variation in change over time (R2=0.54, 95 % CI=0.48–0.51). The features included nine MRS, four volumetric and two DTI parameters. The model also selected disease duration, but not treatment, as a predictive feature. By comparison, the best model for SDMT included several of the same above features and explained 39 % of the change over time (R2=0.39, 95 % CI=0.48–0.51). Conventional volumetric measures were about half as good at predicting change in tARCS score compared to the best multi-modal model (R2=0.26 95 % CI:0.22–0.29). The clinical interpretation of the best predictive model for change in tARCS showed that cognitive decline could be predicted with >90 % accuracy in this cohort (AUC=0.92, SE=0.86 - 0.94). ConclusionMulti-modal MRI signatures can predict cognitive decline in a cohort of pwMS over 5 years with high accuracy. Future studies will benefit from the inclusion of even more MR modalities e.g., functional MRI, quantitative susceptibility mapping, magnetisation transfer imaging, as well as other potential predictors e.g., genetic and environmental factors. With further validation, this signature could be used in future trials with high-risk patients to personalise the management of cognitive decline in pwMS, even in the absence of relapses.

Glymphatic function maintains sleep‐sensitive cognitive performance and predicts overnight changes in plasma amyloid β in humans

AbstractBackgroundDuring sleep, the glymphatic system facilitates rapid exchange of fluid through brain tissues, clearing solutes, including amyloid β (Aβ), tau, and α synuclein that accumulate through the course of waking activity. Glymphatic clearance is widely believed to underlie the restorative effects of sleep on cognition, and its impairment is proposed to reflect the biological basis for the corrosive effects of sleep disruption. We sought to determine if glymphatic function or sleep EEG predicted changes in cognitive performance and overnight differences in Aβ biomarker levels using a new non‐invasive investigational medical device (IMD) to measure glymphatic function by dynamic impedance spectro‐tomography.MethodEighteen healthy 50‐65 y/o participants were enrolled in a cross‐over randomized control clinical trial encompassing one night of sleep and one night of sleep deprivation. Participants were instrumented with the IMD and overnight change in brain parenchymal resistance to flow, R, was measured. Sleep EEG powerbands, slow (0.4‐1Hz), delta (1‐4Hz), beta (15‐30Hz), and time spent in N2, N3 and REM sleep were derived from the device EEG. In both sleep and sleep deprivation interventions, cognitive tests (symbol digit modality test, SDMT; psychomotor vigilance test, PVT) were administered at 7am and blood Aβ biomarkers (Aβ40; Aβ42) were taken at 10pm and 7am.ResultOvernight parenchymal resistance R predicted intraindividual paired differences (sleep – sleep deprivation) in cognitive test scores (A SDMT ρ = ‐0.65, p = 0.003; B PVT STD RT, ρ = 0.41, p = 0.095) and Aβ42 blood amyloid biomarker changes (C Aβ42 ρ = ‐0.53, p = 0.03; D Aβ40 ρ = ‐0.33, p = 0.21). Sleep EEG powerbands and time spent in N2, N3, and REM sleep were not predictive of sleep‐related changes in cognition or plasma Aβ biomarker levels.ConclusionGlymphatic function, measured continuously by dynamic impedance spectro‐tomography, predicted changes in the restorative effect of sleep on cognition and plasma Ab biomarker levels as hypothesized, but not previously demonstrated. In contrast, sleep EEG powerbands and time spent in N2, N3 and REM were not predictive. Detection of glymphatic impairment in real‐world settings may permit (i) early identification of individuals at‐risk for developing sleep‐related Alzheimer’s disease pathology, and (ii) enable precision targeted enhancement of glymphatic function to enhance glymphatic function and pathological protein clearance.

Effects of Cognitive‐motor Rhythmic Training on Executive Functions and Motor Performance in Older Adults with Mild Cognitive Impairment: A Randomized Controlled Trial

AbstractIntroductionIn recent years, prevalence of mild cognitive impairment (MCI) has increased in older adults, exacerbating the potential impact on global health. Cognitive‐motor training is an emerging treatment modality with proven benefits in enhancing both physical and cognitive functions. In recent research findings, training of musical rhythmic skills with auditory‐motor synchronization is beneficial to reactivate the brain’s sensorimotor and perceptual regions as well as to improve cognition. However, there is limited research on combining these modalities.ObjectivesThis pilot study aims to develop a pioneer program on cognitive‐motor rhythmic training (CMRT), and to investigate whether the program would improve the executive functions (EF) and hand functions of patients with MCI.MethodologyThirty patients recruited from the Hong Kong Buddhist Hospital were randomized into two groups: (i) an intervention group receiving a 6‐week training program and (ii) a waitlist control group. The program was designed with reference to the rhythm game “Taiko no Tatsujin”, in which precise timed motor responses were required to hit the circular cues against the target zone. The game was designed with progression of difficulty levels and instant feedback. Classical Cantopop songs that were familiar to Hong Kong older adults were selected. Mental flexibility, inhibitory control, working memory, visuospatial memory, verbal fluency, processing speed and problem‐solving were assessed using domain‐specific cognitive tests, while hand dexterity was measured by the Purdue Pegboard Test. Paired t‐test and ANOVA were used to examine the within group difference and the comparison between groups. The level of significance was set at P<0.05.ResultsThe analysis showed significant Time x Group interaction effects in Color Trail Test (p = 0.001), Color Word Stroop Test (P = 0.002), Digit Span Test (P<0.001), Corsi Block‐Tapping Test (P<0.001), Verbal Fluency Test (P<0.001), Symbol Digit Modalities Test (P = 0.015), Maze Test (P<0.001) and the Purdue Pegboard scores (P<0.001) compared to the control group after training.ConclusionsThe 6‐week CMRT program is effective in improving the executive functions and motor performance in patients with MCI. This innovation can serve as an affordable and quality intervention in early stages of cognitive decline.

Similarities and differences in cognition as a function of sex: A longitudinal study of healthy control participants from the Parkinson Progression Markers Initiative

AbstractBackgroundAs the global population of older adults continues to rise, there is an urgent need to understand the expected cognitive changes in healthy aging. Despite sex‐based differences in life expectancy and age‐related diseases such as Alzheimer’s disease, limited research has explicitly examined sex differences in aging. The objective of the current study was to answer three primary questions using longitudinal data for sample of healthy adults: 1) How does cognition change over time? 2) What are the sex differences in cognition? and 3) What are the sex differences in rates of cognitive change over time?MethodLongitudinal data from the healthy control group of the Parkinson’s Progression Markers Initiative was used to examine cognitive changes in healthy adult males (n = 125, mean age = 61.61, SD = 10.97) and females (n = 68, mean age = 59.44, SD = 11.56). Participants underwent annual neuropsychological testing for up to five years. A series of 2‐level linear mixed models estimated within‐person change in cognition over time (i.e., level‐1) and between‐group differences in longitudinal change trajectories as predicted by sex (i.e., level 2). Each neuropsychological measure was modeled separately as a single outcome variable, for a total of seven models.ResultStability in neuropsychological scores was seen over five years. At baseline, males scored higher on the Benton Judgement of Line Orientation Test, while females scored higher on the Symbol Digit Modalities Test, the Semantic Fluency Test, and the Hopkins Verbal Learning Test‐Revised. Rates of cognitive change over time did not significantly differ by sex. Higher age and lower education at baseline predicted lower neuropsychological scores.ConclusionStability in cognition was found across five years in a sample healthy control participants from a large multi‐site longitudinal study. Sex differences in cognition were found in several domains, including visuospatial ability, processing speed, verbal fluency, and verbal memory. However, rates of cognitive change over time did not significantly differ by sex. Higher age and lower education were predictive of lower cognitive functioning. Great intraindividual variability in cognitive trajectories was observed. Future research should continue to examine factors that predict individual trajectories of aging in healthy individuals.

Design and development of the intelligent voice recognition‐based cognitive assessment WeChat mini‐program

AbstractBackgroundEarly screening of mild cognitive impairment (MCI) is crucial for the elderly to access formal diagnosis and intervention of Alzheimer’s Disease (AD) and related dementias (ADRD) at early stages. Owing to the rapid development of artificial intelligence (AI) and voice recognition technology, the detection method using speech patterns as digital biomarkers collected by digital consumer devices can accommodate a huge demand for early and large‐scale detection. We here reported the design and development of the Shanghai Cognitive Screening (SCS) mini‐program, the first intelligent voice recognition‐based cognitive assessment WeChat mini‐program in China.MethodThe SCS mini‐program was developed based on the cognitive paradigm and classic pencil‐and‐paper neuropsychological assessments (e.g. Montreal cognitive assessment basic [MoCA‐B]). Through Automatic Speech Recognition (ASR), users speak to complete tasks including Naming, Immediate Recall, Delayed Recall, Symbol Digit Modalities Test (SDMT), Delayed RecallII, and Recognition (Figure 1). The acoustic, phonetics, and linguistic speech pattern variables would also be extracted and processed as digital biomarkers. The SCS intelligent prediction model enrolls speech pattern digital biomarkers, individual task scores, and time use variables with age, gender, and education level as linking variables, which enables to grade the user’s global cognitive function and individual cognitive domains (Figure 2).ResultAfter completing all tasks in the SCS, users can immediately read the comprehensive results which are divided into 4 categories corresponding to 4 grading intervals: “healthy” (cognitively normal), “low risk” (suspected SCD), “medium‐high risk” (suspected MCI), and “high risk” (suspected AD). We also use a radar chart with scores of cognitive domains (i.e., memory, attention, visual perception, language, and executive functions), a memory trend graph (i.e., immediate and delayed recalls), an attention persistence graph, and related advice in the automatically generated report (Figure 3).ConclusionThe SCS mini‐program is more efficient and economical compared to traditional paper‐based cognitive assessments. It is suitable for clinical cognitive assessment, remote self‐rating, and community screening for MCI and dementias among Chinese older adults and other ADRD high‐risk groups. Clinical trials are yet to be conducted to validate the accuracy and diagnostic value of the SCS WeChat mini‐program.

Symbol digit modalities test for predicting results of returning work after brain injury

Symbol digit modalities test for predicting results of returning work after brain injury

The correlation of conventional and advanced MRI findings with cognitive function in multiple sclerosis: A systematic review and meta-analysis

There are limited data on the possible association between conventional and advanced magnetic resonance imaging (MRI) findings and cognitive function in patients with multiple sclerosis (MS). Therefore, this systematic review and meta-analysis aimed to explore the correlation between MRI-derived metrics and cognitive tests in patients with MS. An electronic literature search of the PubMed, Web of Sciences, Embase, and Scopus databases was performed to identify related studies. The correlation coefficients of the MRI indices and cognitive tests were pooled. Thirteen studies were selected for inclusion of 824 patients diagnosed with MS. Most evaluated patients (60.44%) had relapsing-remitting MS (RRMS). The Paced Auditory Serial Addition Test (PASAT-3), Brief Visuospatial Memory Test (BVMT), and Symbol Digit Modalities Test (SDMT) were inversely correlated with the mean diffusivity (MD) of the brain with pooled correlation coefficient of -0.225, -0.361, and -0.438, respectively (P<0.0001). The SDMT test positively correlated with fractional anisotropy (FA) with a correlation coefficient of 0.351 (P<0.0001) and inversely correlated with T2 lesion volume with a correlation coefficient of -0.367 (P<0.0001). In the case of other tests, there was low number of studies with significant correlations being reported. We found significant correlations between some neuropsychological tests and MRI findings in patients with MS. Brain atrophy might disrupt the process of correct registration between anatomical and MRI diffusion scans. However, we did not have enough studies with exactly matched anatomical areas to evaluate correlations and we recommend that histological validation of diffusion tensor imaging (DTI) findings for brain atrophy is needed as a basis for picture processing procedures and correlation with cognition status.

Impairment of daily occupations in multiple sclerosis: analysis of neuroimaging, general and social cognition, and reserve

BackgroundMultiple Sclerosis (MS) can impact performance of daily occupations in both relapsing-remitting (RRMS) and secondary-progressive (SPMS) clinical courses. Work force participation decreases with advancing physical disability but the influence of non-motor factors, neuroimaging, and reserve have been scarcely investigated. We aimed to evaluate MRI, clinical, and cognitive (social and general) factors associated with impairment in different daily occupations and address whether cognitive and brain reserve have a positive impact on the ability to maintain these activities. MethodsWe prospectively enrolled persons with MS (PwMS) who underwent clinical examination (Expanded Disability Status Scale – EDSS; Timed 25-Foot Walk Test - T25FW; and the Nine Hole Peg Test - 9HPT), general neuropsychological assessment (Brief Repeatable Battery of Neuropsychological Tests – BRBN, including the Symbol Digit Modalities Test - SDMT), social cognition evaluation (Reading the Mind in the Eyes Test), cognitive reserve questionnaire, and MRI (FreeSurfer). We also enrolled healthy subjects for comparison as a control group. Daily occupations (employment, money management, and driving abilities) were assessed in all individuals with questionnaires. ResultsWe included 62 PwMS (32 RRMS and 30 SPMS; mean age 42.8 years; median educational time 12.75 years) and 67 controls (mean age 39.7; median educational time 12.0 years) which were similar regarding demographics, education, and socioeconomic status (p > 0.1). Most PwMS (67.7%) had work-restrictions. They also reported fewer money management and driving abilities than controls (p < 0.001). Work-restriction was associated with physical disability (p = 0.006), SDMT and BRBN performance (p = 0.035 and p = 0.031, respectively), and T2-lesion volume (p = 0.022), with large effect sizes (d > 0.75). After hierarchical linear regression, money management was associated with hand dexterity, general and social cognition, and cognitive reserve (p < 0.03). Variables associated with driving abilities included fatigue, verbal fluency, striatum volume, and brain reserve (p < 0.05). ConclusionsPwMS have more frequent work-restrictions and impairment in money management and driving abilities compared to controls. Cognitive function, physical disability, and MS-lesion burden are strongly associated with work-restriction. Social cognition can also influence financial capacity. Cognitive and brain reserve can help retain some of these daily occupations.

Association of liver fibrosis with cognitive decline in Parkinson’s disease

BackgroundCognitive decline is a common but variable non-motor manifestation of Parkinson’s disease. Chronic liver disease contributes to dementia, but its impact on cognitive performance in Parkinson’s disease is unknown. We assessed the effect of liver fibrosis on cognition in Parkinson’s disease. MethodsWe conducted a retrospective cohort study using data from the Parkinson’s Progression Markers Initiative. Our exposure was liver fibrosis at baseline, based on the validated Fibrosis-4 score. Our primary outcome was the Montreal Cognitive Assessment, and additional outcome measures were the Symbol Digit Modalities Test, the Benton Judgement of Line Orientation, the Letter-Number Sequencing Test, and the Modified Semantic Fluency Test. We used linear regression models to assess the relationship between liver fibrosis and scores on cognitive assessments at baseline and linear mixed models to evaluate the association between baseline Fibrosis-4 score with changes in each cognitive test over five years. Models were adjusted for demographics, comorbidities, and alcohol use. ResultsWe included 409 participants (mean age 61, 40 % women). There was no significant association between liver fibrosis and baseline performance on any of the cognitive assessments in adjusted models. However, over the subsequent five year period, liver fibrosis was associated with more rapid decline in scores on the Montreal Cognitive Assessment (interaction coefficient, −0.07; 95 % CI, −0.12, −0.02), the Symbol Digit Modalities Test, the Benton Judgement of Line Orientation, and the Modified Semantic Fluency Test. ConclusionIn people with Parkinson’s disease, the presence of comorbid liver fibrosis was associated with more rapid decline across multiple cognitive domains.

Networks of microstructural damage predict disability in multiple sclerosis

BackgroundNetwork-based measures are emerging MRI markers in multiple sclerosis (MS). We aimed to identify networks of white (WM) and grey matter (GM) damage that predict disability progression and cognitive worsening...

The effect of ibudilast on thalamic volume in progressive multiple sclerosis

Background: Thalamic volume loss is known to be associated with clinical and cognitive disability in progressive multiple sclerosis (PMS). Objective: To investigate the treatment effect of ibudilast on thalamic atrophy more than 96 weeks in the phase 2 trial in progressive(MS Secondary and Primary Progressive Ibudilast NeuroNEXT Trial in Multiple Sclerosis [SPRINT-MS]). Methods: A total of 231 participants were randomized to either ibudilast (n = 114) or placebo (n = 117). Thalamic volume change was computed using Bayesian Sequence Adaptive Multimodal Segmentation tool (SAMseg) incorporating T1, fluid-attenuated inversion recovery (FLAIR), and fractional anisotropy maps and analyzed with a mixed-effects repeated-measures model. Results: There was no significant difference in thalamic volumes between treatment groups. On exploratory analysis, participants with primary progressive multiple sclerosis (PPMS) on placebo had a 0.004% greater rate of thalamic atrophy than PPMS participants on ibudilast (p = 0.058, 95% confidence interval (CI) = −0.008 to <0.001). Greater reductions in thalamic volumes at more than 96 weeks were associated with worsening multiple sclerosis functional composite (MSFC-4) scores (p = 0.002) and worsening performance on the symbol digit modality test (SDMT) (p < 0.001). Conclusion: In a phase 2 trial evaluating ibudilast in PMS, no treatment effect was demonstrated in preventing thalamic atrophy. Participants with PPMS exhibited a treatment effect that trended toward significance. Longitudinal changes in thalamic volume were related to worsening of physical and cognitive disability, highlighting this outcome’s clinical importance.

Longitudinal Changes in Neuropsychological Functioning in Japanese Patients with Myotonic Dystrophy Type 1: A Five Year Follow-Up Study.

Myotonic dystrophy type 1 (DM1) is a form of muscular dystrophy that causes various symptoms, including those of the central nervous system. Some studies have reported cognitive decline in patients with DM1, although the available evidence is limited. This study aimed to describe longitudinal differences in neuropsychological function in patients with DM1. A total of 66 Japanese adult patients with DM1 were investigated using a neuropsychological battery to assess several cognitive domains, including memory, processing speed, and executive function. The patients underwent neuropsychological evaluation approximately five years after baseline (Times 1 and 2). Thirty-eight patients underwent a second neuropsychological evaluation. The participants in the Time 2 evaluation were younger than those who did not participate in Time 2. Patients showed a decline in the Mini-Mental State Examination, Trail Making Test (TMT), Block Design, and Symbol Digit Modalities Test at Time 2 (P < 0.05). Age at Time 1 was associated with a decline in TMT-A and TMT-B scores (rho = 0.57 and 0.45, respectively). These results suggest a cognitive decline in patients with DM1 and warrant further investigation into the possible effects of age-related changes.

Cerebrospinal fluid neurofilament light chains predicts early disease-activity in Multiple Sclerosis

BackgroundAmong biomarkers of axonal damage, neurofilament light chains (NFL) seem to play a major role, representing a promising and interesting tool in Multiple Sclerosis (MS). Our aim was to explore the predictive role of cerebrospinal fluid (CSF) NFL in patients with a recent diagnosis of MS, naïve to any MS therapy. MethodsWe retrospectively collected data of patients diagnosed with MS, referred to the Neurology Clinic of the University-Hospital G. Rodolico of Catania between January 1st 2005 and December 31st 2015. All patients underwent CSF collection at the time of MS diagnosis and were followed-up for at least three years afterwards. NFL levels were measured in CSF samples with Simoa NFLight advantage kit at the CRESM (University Hospital San Luigi Gonzaga, Orbassano, Torino). NFL levels were expressed as LogNFL. Symbol Digit Modalities test (SDMT) was performed at baseline, at 1-year and at 3-year follow-up. Multivariate logistic regression analysis was performed to investigate LogNFL as a potential risk factor of different clinical outcomes. Results244 MS patients (230 relapsing-remitting, RRMS; 94.3 %), with a mean age at diagnosis of 37.0 ± 11.1 years, were recruited. LogNFL did not correlate neither with EDSS score at diagnosis and at subsequent follow-up up to 12 years, nor with SDMT performed at diagnosis, at 1 year and at 3 years. LogNFL were an independent factor for the occurrence of at least one relapse during the first two years after MS diagnosis (OR = 2.75; 95 % CI 1.19–6.31; p = 0.02) and for the occurrence of gadolinium-enhanced (Gd+) lesions during the first 2 years from diagnosis at brain and spine MRI scans (OR = 3.45, 95 % CI 1.81–6.57; p < 0.001). ConclusionThe detection of CSF NFL at the time of MS diagnosis can be a useful support to predict the two-year risk of clinical and radiological relapses, thus affecting therapeutic choices in the very early phases of the disease.

Exploring the Potential of the Corpus Callosum Area as a Predictive Marker for Impaired Information Processing in Multiple Sclerosis

Early cognitive impairment (CI) detection is crucial in multiple sclerosis (MS). However, it can progress silently regardless of relapse activity and reach an advanced stage. We aimed to determine whether the corpus callosum area (CCA) is a sensitive and feasible marker for CI in MS compared to other neuroimaging markers. We assessed cognitive function in 77 MS patients using the Symbol Digit Modalities Test, Paced Auditory Serial Additions Task, Wechsler Adult Intelligence Scale-IV, and Wechsler Memory Scale-Revised. The neuroimaging markers included manually measured CCA, two diffusion tensor imaging markers, and nine volumetric measurements. Apart from volumes of the hippocampus and cerebellum, ten markers showed a significant correlation with all neuropsychological tests and significant differences between the groups. The normalized CCA demonstrated a moderate-to-strong correlation with all neuropsychological tests and successfully differentiated between the CI and cognitively normal groups with 80% sensitivity and 83% specificity. The marker had a large area under the curve and a high Youden index (0.82 and 0.63, respectively) and comparability with established cognitive markers. Therefore, the normalized CCA may serve as a reliable marker for CI in MS and can be easily implemented in clinical practice, providing a supportive diagnostic tool for CI in MS.