Impaired Information Processing Speed Research Articles

A study of the correlation between gray matter atrophy in multiple sclerosis and impairment of cognitive function domains

Objective: To quantify cerebral cortical and deep gray matter atrophy in patients with multiple sclerosis (MS) and explore its correlation with impairment in domains of cognitive function. Methods: Twenty patients with MS and 16 healthy controls (HC) matched for age, sex, and education level were included. Using FreeSurfer software, based on 3D-MRI technology, the differences in cortical thickness and deep gray matter volume between the two groups were comparatively analyzed. A neuropsychological scale that included six domains of cognitive function was scored on both study groups to analyze the correlation between cortical thickness and volume of deep gray matter in MS patients with impairment in cognitive function domains. Results: Impairment in domains of cognitive function: cognitive impairment was present in 60% MS patients in this study, mainly manifesting as impairment of verbal memory, verbal fluency, visuospatial memory, and information processing speed function (all P<0.05). Of these, the majority had impaired visuospatial memory function (55.0%), and the least number of patients had impaired information processing speed (15.0%). Changes in cortical thickness: compared with the HC group, the MS group showed that cortical atrophy was mainly concentrated in the frontoparietal region, including significant thinning of cortical thickness in the left inferior parietal gyrus, right superior frontal gyrus, and the right superior parietal gyrus (all P<0.05). Among them, atrophy of the left inferior parietal gyrus was significantly positively correlated with the impairment of verbal memory, verbal fluency, and information processing speed (all P<0.05). There was a significant positive correlation between the right superior frontal gyrus atrophy and verbal memory, verbal fluency, and visuospatial memory impairment (all P<0.05). Changes in deep gray matter volume: compared with the HC group, deep gray matter volume in the MS group decreased significantly in the bilateral thalamus, bilateral putamen, bilateral pallidum (all P<0.01), and right nucleus accumbens (P<0.05). Among them, left thalamus atrophy was significantly positively correlated with visuospatial memory impairment (r=0.45, P=0.046), and left putamen atrophy was both significantly positively correlated with visuospatial memory (r=0.45, P=0.047) and information processing speed impairment (r=0.50, P=0.026). Conclusions: Early structural brain changes in MS are dominated by gray matter atrophy. Deep gray matter is more prominent than cortical atrophy.

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

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

Effect of deep gray matter atrophy on information processing speed in early relapsing-remitting multiple sclerosis.

Cognitive dysfunction, including reduced Information processing speed (IPS), is relatively common in multiple sclerosis(MS). IPS deficits have profound effects on several aspects of patients' life. Previous studies showed that deep gray matter atrophy is highly correlated with overall cognitive impairment in MS. However, the effect of deep gray matter atrophy on IPS deficits is not well understood. In this study, we evaluated the effects of deep gray matter volume changes on IPS in people with early relapse-remitting MS (RRMS) compared to healthy control. In this case-control study, we enrolled 63 case with RRMS and 36 healthy controls. All patients were diagnosed within 6 years. IPS was evaluated using the Integrated Cognitive Assessment (ICA) test. We also performed a 1.5T MRI to evaluate deep gray matter structures. People with RRMS had lower accuracy in the ICA test (p=.01). However, the reaction time did not significantly differ between RRMS and control groups (p=.6). Thalamus volume was significantly lower in the RRMS group with impaired IPS compared to the RRMS with normal IPS and control groups (p<10-4). Other deep gray matter structures were not significantly different between the RRMS with impaired IPS group and the RRMS with normal IPS group. Some people with MS are impaired in IPS even in the early stages of the disease. Thalamic atrophy affected IPS in these patients, however atrophy in other deep gray matter structures, including caudate, putamen, globus pallidus, hippocampus, amygdala, accumbens, and cerebellum, were not significantly correlated with IPS impairment in early RRMS.

Prominent role of executive functioning on the Phonemic Fluency Test in people with multiple sclerosis.

Executive functioning (EF) can be one of the earliest, despite under-detected, impaired cognitive domains in patients with multiple sclerosis (pwMS). However, it is still not clear the role of EF on verbal fluency tests given the presence of information processing speed (IPS) deficits in pwMS. Performance of a group of 43 pwMS without IPS impairment as measured with the Symbol Digit Modalities Test (SDMT) and a group of 32 healthy controls (HC) was compared on the Phonemic and Semantic Fluency Tests. For each group, we scored the number of words generated (i) in the early time interval (i.e., first 15 sec, semi-automatic process) and (ii) in the late time interval (i.e., from 15 to 60 sec, controlled process). Globally, pwMS produced significantly fewer words than HC on the Phonemic but not on the Semantic Fluency Test. Crucially, in the Phonemic Fluency Test pwMS generated significantly fewer words than HC in the late time interval, whereas no significant difference between the two groups emerged in the early time interval. These findings suggest that executive dysfunction is the core element on the Phonemic Fluency Test also in pwMS and it deserves attention in both research and clinical practice.

Neurochemical and functional reorganization of the cognitive-ear link underlies cognitive impairment in presbycusis

Recent studies suggest that the interaction between presbycusis and cognitive impairment may be partially explained by the cognitive-ear link. However, the underlying neurophysiological mechanisms remain largely unknown. In this study, we combined magnetic resonance spectroscopy (MRS) and resting-state functional magnetic resonance imaging (fMRI) to investigate auditory gamma-aminobutyric acid (GABA) and glutamate (Glu) levels, intra- and inter-network functional connectivity, and their relationships with auditory and cognitive function in 51 presbycusis patients and 51 well-matched healthy controls. Our results confirmed reorganization of the cognitive-ear link in presbycusis, including decreased auditory GABA and Glu levels and aberrant functional connectivity involving auditory networks (AN) and cognitive-related networks, which were associated with reduced speech perception or cognitive impairment. Moreover, mediation analyses revealed that decreased auditory GABA levels and dysconnectivity between the AN and default mode network (DMN) mediated the association between hearing loss and impaired information processing speed in presbycusis. These findings highlight the importance of AN-DMN dysconnectivity in cognitive-ear link reorganization leading to cognitive impairment, and hearing loss may drive reorganization via decreased auditory GABA levels. Modulation of GABA neurotransmission may lead to new treatment strategies for cognitive impairment in presbycusis patients.

Working Memory Deficits in Multiple Sclerosis: An Overview of the Findings.

Although working memory (WM) and information processing speed (IPS) impairments in multiple sclerosis (MS) have been widely investigated, several questions, regarding the nature of these impairments and their relationship, remain unclear. The aim of this short communication article is to present an overview of our recent research findings regarding (a) the characteristics of WM impairment in MS patients and, more precisely, the degree of impairment observed in each WM’s component, i.e., phonological loop, visuospatial sketchpad, central executive, and episodic buffer and (b) the relationship between IPS and each of the four WM components, in an attempt to expand the existing rather narrow understanding of the interconnection between reduced IPS and WM impairment. Two studies of our research team are presented here and their findings are briefly discussed, highlighting the importance of further research on a specific component, namely the episodic buffer component among MS patients.

Can subjective cognitive complaints at three months post stroke predict alteration in information processing speed during the first year?

ABSTRACT Cognitive impairment, particularly slowing of information processing speed (IPS), is prevalent after stroke. However, the link between subjective cognitive complaints (SCC) and cognitive deficit remains unclear. This study evaluated the link between SCC at three months post stroke and deficit as well as objective alterations in IPS in the first year post stroke. Patients (N = 200) and healthy controls (N = 105) took part in the COMPlaints After Stroke study (COMPAS). SCC, IPS and depression were evaluated at 3 months, 1 and 2 years post stroke. The Reliable Change Index was used to assess change in IPS in the first year post. Approximately one out of three patients showed deficit in IPS irrespective of time post stroke, while a change in IPS (N = 117) over time was relatively uncommon. SCC at three months post stroke did not predict change in IPS between three months and one year post stroke, where depressive symptoms did show a link. Cross sectional data showed a deficit in IPS in a substantial number of stroke patients irrespective of the point in time. Longitudinal data revealed a further decline in a small subgroup in the first year post stroke, which was not predicted by SCC at three months post stroke. The findings show that, irrespective of time post stroke and even when stroke is relatively mild, impairment in IPS is prevalent, but cannot be predicted by the complaints patients express. The link with depressive symptoms needs more exploration.

Visual Search in Naturalistic Scenes Reveals Impaired Cognitive Processing Speed in Multiple Sclerosis.

BackgroundStandardized neuropsychological testing serves to quantify cognitive impairment in multiple sclerosis (MS) patients. However, the exact mechanism underlying the translation of cognitive dysfunction into difficulties in everyday tasks has remained unclear. To answer this question, we tested if MS patients with intact vs. impaired information processing speed measured by the Symbol Digit Modalities Test (SDMT) differ in their visual search behavior during ecologically valid tasks reflecting everyday activities.MethodsForty-three patients with relapsing-remitting MS enrolled in an eye-tracking experiment consisting of a visual search task with naturalistic images. Patients were grouped into “impaired” and “unimpaired” according to their SDMT performance. Reaction time, accuracy and eye-tracking parameters were measured.ResultsThe groups did not differ regarding age, gender, and visual acuity. Patients with impaired SDMT (cut-off SDMT-z-score < −1.5) performance needed more time to find and fixate the target (q = 0.006). They spent less time fixating the target (q = 0.042). Impaired patients had slower reaction times and were less accurate (both q = 0.0495) even after controlling for patients' upper extremity function. Exploratory analysis revealed that unimpaired patients had higher accuracy than impaired patients particularly when the announced target was in unexpected location (p = 0.037). Correlational analysis suggested that SDMT performance is inversely linked to the time to first fixation of the target only if the announced target was in its expected location (r = −0.498, p = 0.003 vs. r = −0.212, p = 0.229).ConclusionDysfunctional visual search behavior may be one of the mechanisms translating cognitive deficits into difficulties in everyday tasks in MS patients. Our results suggest that cognitively impaired patients search their visual environment less efficiently and this is particularly evident when top-down processes have to be employed.

Cerebrospinal fluid biomarkers and cognitive functions at multiple sclerosis diagnosis.

Cognitive impairment (CI) is a frequent and disabling symptom in Multiple Sclerosis (MS). Axonal damage may contribute to CI development from early stages. Nevertheless, no biomarkers are at the moment available to track CI in MS patients. We aimed to explore the correlation of cerebrospinal fluid (CSF) axonal biomarkers, in particular: light-chain neurofilaments (NFL), Tau, and Beta-amyloid protein (Abeta) in MS patients with CI at the diagnosis. 62 newly diagnosed MS patients were enrolled, and cognition was evaluated using the Brief International Cognitive Assessment for MS (BICAMS) battery. CSF NFL, Abeta, and Tau levels were determined with commercial ELISA. Patients with CI (45.1%) did not differ for demographic, clinical, and MRI characteristics (except for lower educational level), but they displayed greater neurodegeneration, exhibiting higher mean CSF Tau protein (162.1 ± 52.96pg/ml versus 132.2 ± 63.86pg/ml p:0.03). No differences were observed for Abeta and NFL. The number of impaired tests and Tau were significantly correlated (r:0.32 p:0.01). Tau was higher in particular in patients with slowed information processing speed (IPS) (p:0.006) and a linear regression analysis accounting for EDSS, MRI, and MS subtype confirmed Tau as a weak predictor of IPS and cognitive impairment. In conclusion, CI has an important burden on the quality of life of MS patients and should be looked for even at diagnosis. Axonal damage biomarkers, and in particular Tau, seem to reflect cognition impairment in the early stages.

Serum Vitamin D as a Marker of Impaired Information Processing Speed and Early Disability in Multiple Sclerosis Patients.

Slowed information processing speed (IPS) is the hallmark and first cognitive domain to be altered in multiple sclerosis (MS) patients. Insufficient serum vitamin D was previously associated with disease development, relapses, and progression, but little is reported on cognition. However, vitamin D and cognitive impairment (CI) in other neurodegenerative diseases have already been linked. We explored the possible correlation between vitamin D and IPS at diagnosis and early disability at last follow-up in 81 MS patients. At diagnosis, we collected vitamin D levels and performed a Symbol Digit Modalities Test (SDMT). Raw scores were adjusted for age, gender, and educational level. Early disability was evaluated with MS severity score (MSSS) and age-related MSSS (ARMSS). A total of 71 patients (86.58%) showed hypovitaminosis D (19.71 ± 8.76 ng/mL) and 18 patients (21.95%) had CI. Patients with CI showed severe hypovitaminosis D (p = 0.004). No patients with sufficient vitamin D levels had CI. We found a positive correlation between vitamin D levels at diagnosis and (1) SDMT raw and z-score that persisted after correction for sunlight exposure and MRI baseline characteristics, and (2) EDSS, MSSS, and ARMSS after a mean 2 year follow-up. Low vitamin D levels may affect both cognition and early disability in newly diagnosed MS patients.

OS05.4.A Do neurocognitive deficits explain the differences between brain tumour patients and their proxies assessing the patient’s I-ADL?

Abstract BACKGROUND Neurocognitive deficits are common among brain tumour patients, and may impact on patient awareness of deficits in instrumental activities in daily life (IADL). This study aimed to examine differences between patient-reported and proxy-reported assessments of the patient’s performance of IADL, and whether the level of (dis)agreement is associated with neurocognitive deficits. MATERIAL AND METHODS A phase III EORTC questionnaire measuring IADL in brain tumour patients (EORTC IADL-BN32) and six neurocognitive test measures were administered as part of a larger multicentre international study designed to develop a brain tumour specific IADL questionnaire. Bland-Altman plots and Mann-Whitney U tests were used to evaluated patient- and proxy-reported IADL on a group level. Subsequently, Mann-Whitney U tests were performed to compare patient-proxy difference scores (patient IADL score - their proxy IADL score) between patients who were considered clearly neurocognitively impaired (≥2 neurocognitive test measures; ≤2.0 SD below healthy controls) and patients who were not. Furthermore, multinomial logistic regression analyses were performed to examined which sociodemgraphic, clinical, and particularly neurocognitive variables were independently associated with patients and proxies differing in their evaluation of patient’s IADL. RESULTS Patients (N=81) and proxies (N=81), on group level, did not significantly differ on either the IADL individual item or scale scores. However, significant differences were found on patient-proxy difference scores between patients who were (N=37) and were not (N=44) considered clearly neurocognitively impaired for 10/32 individual items and one of the scales (i.e. Scale 4: Administrative tasks), all showing that the proxies of clearly neurocognitively impaired patients reported more problems relative to the patients themselves, compared to proxies of patients not clearly neurocognitively impaired. Furthermore, for each scale, a neurocognitive variable, either impaired information processing speed, cognitive flexibility, verbal fluency or the number of neurocognitive test measures impaired, was found to be independently associated with proxies reporting more problems. For 4/5 scales, a clinical variable was additionally independently associated with proxies reporting more problems. Only one variable was independently associated with patient reporting more problems, namely being in active treatment was found to be associated with patients reporting more problems on Scale 4: Administrative tasks. CONCLUSION Results imply a consistent trend of clearly neurocognitively impaired patients underreporting problems with IADL compared to their proxies. It would therefore be advised to administer both the patient- and proxy-version of the EORTC IADL-BN32, particularly if neurocognitive deficits are presumed.

A Longitudinal Study of White Matter Functional Network in Mild Traumatic Brain Injury.

Some patients after mild traumatic brain injury (mTBI) experience microstructural damages in the long-distance white matter (WM) connections, which disrupts the functional connectome of large-scale brain networks that support cognitive function. Patterns of WM structural damage following mTBI were well documented using diffusion tensor imaging (DTI). However, the functional organization of WM and its association with gray matter functional networks (GM-FNs) and its DTI metrics remain unknown. The present study adopted resting-state functional magnetic resonance imaging to explore WM functional properties in mTBI patients (108 acute patients, 48 chronic patients, 46 healthy controls [HCs]). Eleven large-scale WM functional networks (WM-FNs) were constructed by the k-means clustering algorithm of voxel-wise WM functional connectivity (FC). Compared with HCs, acute mTBI patients observed enhanced FC between inferior fronto-occipital fasciculus (IFOF) WM-FN and primary sensorimotor WM-FNs, and cortical primary sensorimotor GM-FNs. Further, acute mTBI patients showed increased DTI metrics (mean diffusivity, axial diffusivity, and radial diffusivity) in deep WM-FNs and higher-order cognitive WM-FNs. Moreover, mTBI patients demonstrated full recovery of FC and partial recovery of DTI metrics in the chronic stage. Additionally, enhanced FC between IFOF WM-FN and anterior cerebellar GM-FN was correlated with impaired information processing speed. Our findings provide novel evidence for functional and structural alteration of WM-FNs in mTBI patients. Importantly, the convergent damage of the IFOF network might imply its crucial role in our understanding of the pathophysiology mechanism of mTBI patients.

The relation of depression with structural brain abnormalities and cognitive functioning: the Maastricht study.

Individuals with depression often experience widespread and persistent cognitive deficits, which might be due to brain atrophy and cerebral small vessel disease (CSVD). We therefore studied the associations between depression, markers of brain atrophy and CSVD, and cognitive functioning. We used cross-sectional data from the population-based Maastricht study (n = 4734; mean age 59.1 ± 8.6 years, 50.2% women), which focuses on type 2 diabetes. A current episode of major depressive disorder (MDD, n = 151) was assessed by the Mini-International Neuropsychiatric Interview. Volumes of cerebral spinal fluid, white matter, gray matter and white matter hyperintensities, presence of lacunar infarcts and cerebral microbleeds, and total CSVD burden were assessed by 3 T magnetic resonance imaging. Multiple linear and logistic regression analyses tested the associations between MDD, brain markers and cognitive functioning in memory, information processing speed, and executive functioning & attention, and presence of cognitive impairment. Structural equation modeling was used to test mediation. In fully adjusted models, MDD was associated with lower scores in information processing speed [mean difference = -0.18(-0.28;-0.08)], executive functioning & attention [mean difference = -0.13(-0.25;-0.02)], and with higher odds of cognitive impairment [odds ratio (OR) = 1.60(1.06;2.40)]. MDD was associated with CSVD in participants without type 2 diabetes [OR = 1.65(1.06;2.56)], but CSVD or other markers of brain atrophy or CSVD did not mediate the association with cognitive functioning. MDD is associated with more impaired information processing speed and executive functioning & attention, and overall cognitive impairment. Furthermore, MDD was associated with CSVD in participants without type 2 diabetes, but this association did not explain an impaired cognitive profile.

Evaluation of cognitive impairment in a French sample of patients with restrictive anorexia nervosa: two distinct profiles emerged with differences in impaired functions and psychopathological symptoms

PurposeThe cognitive profiles of patients suffering from anorexia nervosa (AN) are currently explored as potential facilitating and/or maintenance factors. Specific data in restrictive AN (AN-R) remain contradictory. This study focused on women with AN-R to evaluate their cognitive functions to develop a more specific cognitive remediation program.MethodsFemale patients older than 15 years who were suffering from AN-R were recruited in a specialized unit for eating disorder management. Female healthy control (HC) participants were recruited who were matched with AN patients on age. All participants completed a cognitive evaluation (premorbid intelligence quotient (IQ), planning, information processing speed, cognitive flexibility) and a clinical evaluation (impulsivity, anxiety, depression).ResultsA total of 122 participants were included. Patients suffering from AN-R had significant impairment in information processing speed and planning. Patients exhibited significantly better cognitive flexibility than did the HC group when adjustments were made for other cognitive functions and impulsivity. Two distinct subgroups of patients were identified. The first subgroup had more marked cognitive impairment and fewer psychopathological symptoms than did the second subgroup of patients and the HC group.ConclusionOur results highlight cognitive impairment in patients with AN who had normal premorbid IQ. Two distinct profiles emerge. In clinical practice, these results open up perspectives for the development of more specific cognitive remediation programs (one specific program for cold cognitions and another specific program targeting emotions and hot cognitions). These results warrant confirmation by larger studies with a more specific evaluation of the impact of emotional status.Trial registration NTC02381639, Date of registration. March 6, 2015

Cognitive and emotional impairment in patients with chronic cerebrovascular insufficiency

Cerebrovascular disease is one of the most important problems of clinical neurology, which is a significant cause of cognitive impairment and depression. Chronic forms of cerebrovascular insufficiency are most often associated with cerebral microangiopathy or a disease of small vessels, which is characterized by the presence of lacunae, microinfarction and microbleeding, leukoaraiosis and dilated perivascular spaces. One of the main and most common clinical symptoms is vascular cognitive impairment. They are characterized by extremely variable cognitive deficits, highly dependent on the location and severity of vascular damage. However, clinical manifestations associated with impaired frontal circulation are usually observed. Recent international criteria for vascular cognitive impairment presented by the VASCOG (International Society for Vascular Behavioral and Cognitive Disorders) working group emphasize the particular importance of impaired information processing speed, attention, and/or frontal regulatory functions, often in combination with personality or emotional disorders. The frequency of vascular depression in chronic cerebrovascular insufficiency reaches 70%. The addition of affective disorders significantly aggravates the existing cognitive deficit, increases the risk of dementia. This is due to the fact that depression itself leads to the development of cognitive impairment, causes multiple functional disorders of cerebral microcirculation and a number of other mechanisms. The presence of cerebral microangiopathy underlying this pathology makes the use of drugs with vascular effects in the treatment of these patients. The use of preparations with multimodal action, in particular the combined drug and, is most preferable.

Early cognitive dysfunction as a marker for the poor course of multiple sclerosis: a prospective 12-year follow-up

Owing to the advent of current methods for the prevention of exacerbations of multiple sclerosis (MS), it has become possible to increase the period to the development of obvious persistent cerebellar and motor disorders that mainly lead to disability. This makes it possible to focus on less evident and latent symptoms, in particular on cognitive impairment (CI) that are recorded since the diagnosis of MS and slowly progress over time.Objective: to assess the prognostic capabilities of the Paced Auditory Serial Addition Test (PASAT) to identify a group of patients with early disability (10-year risk of reaching 6.5 Expanded Disability Status Scale (EDSS) scores.Patients and methods. The paper presents the data of a 12-year (2005–2018) follow-up of 36 patients having MS with and without mild CI. The patients' mean age at the time of study inclusion was 31.7 years (confidence interval (CI) 29.2–34.1; α&lt;0.05); the disease duration was 4.69 months (CI 3.31–6.08; α&lt;0.05); the EDSS scores averaged 2.51 (CI 2.23–2.82; α&lt;0.05). Severe disability (6.5 EDSS scores) was observed in 75% of cases in the presence of mild CI and in 25% of cases in the absence of mild CI; it occurred an average of 118.3 (CI 93.1–143.4; α&lt;0.05) and 141.2 (CI 126.0–156.5; α&lt;0.05) months later, respectively.Results and discussion. The findings suggest that the patients with MS in the presence of impaired information processing speed and decreased attentional function (failure to complete more than 25% of the PASAT tasks) had a significantly greater risk for persistent disability than the patients without CI or with its minimal manifestations. Limitation in walking function (4.5 EDSS scores) occurred an average of 3.5 years earlier, and its significant limitation (6.5 EDSS scores) did 2 years earlier in the severe CI group, which may be important in planning therapy.Conclusion. The presence of CI in early MS is likely to have a prognostic value in relation to the course of the disease.

Effect of dalfampridine on information processing speed impairment in multiple sclerosis.

To test a possible benefit of dalfampridine on information processing speed (IPS), a key function for cognitive impairment (CogIm) in multiple sclerosis (MS). In this randomized, double-blind, placebo-controlled trial, we included patients with a score on the Symbol Digit Modalities Test (SDMT) under the 10th percentile of the reference value. Patients were randomized in a 2:1 ratio to receive dalfampridine 10 mg or placebo twice daily for 12 weeks. They underwent a comprehensive neuropsychological evaluation at screening (T0), at the end of treatment (T1), and after a 4-week follow-up (T2). The primary endpoint was improvement in SDMT. Out of 208 patients screened, 120 were randomized to receive either dalfampridine (n = 80) or placebo (n = 40). At T1, the dalfampridine group presented an increase of SDMT scores vs placebo group (mean change 9.9 [95% confidence interval (CI) 8.5-11.4] vs 5.2 [95% CI 2.8-7.6], p = 0.0018; d = 0.60 for raw score; and 0.8 [95% CI 0.6-1] vs 0.3 [95% CI 0.0-0.5], p = 0.0013; d = 0.61 for z scores; by linear mixed model with robust standard error). The improvement was not sustained at T2. A beneficial effect of dalfampridine was observed in the Paced Auditory Serial Addition Test and in cognitive fatigue. Dalfampridine could be considered as an effective treatment option for IPS impairment in MS. 2013-002558-64 EU Clinical Trials Register. This study provides Class I evidence that for patients with MS with low scores on the SDMT, dalfampridine improves IPS.

Cerebrospinal fluid neurofilament light chain tracks cognitive impairment in multiple sclerosis.

Cognitive impairment (CI) is a disabling symptom of multiple sclerosis (MS). Axonal damage disrupts neural circuits andmay play a role in determining CI, but its detection and monitoring are not routinely performed. Cerebrospinal fluid (CSF) neurofilament light chain (NfL) is a promising marker of axonal damage in MS. To retrospectively examine the relationship between CSF NfL and CI in MS patients. CSF NfL concentration was measured in 28 consecutive newly diagnosed MS patients who underwent a neuropsychological evaluation with the Brief Repeatable Battery of Neuropsychological tests (BRBN). CSF NfL was higher in patients with overall CI (947.8 ± 400.7 vs 518.4 ± 424.7pg/mL, p < 0.01), and with impairment in information processing speed (IPS) (820.8 ± 413.6 vs 513.6 ± 461.4pg/mL, p < 0.05) and verbal fluency (1292 ± 511 vs 582.8 ± 395.4pg/mL, p < 0.05), and it positively correlated with the number of impaired BRBN tests (r = 0.48, p = 0.01) and cognitive domains (r = 0.47, p = 0.01). Multivariate analyses taking into account potential confounders confirmed these findings. CSF NfL is higher in MS patients with CI and impaired IPS and verbal fluency. Large myelinated axons injury, causing neural disconnection, may be an important determinant of CI in MS and can be reliably measured through CSF NfL.

Mindfulness and Aerobic Exercise as an Intervention for Cognitive Dysfunction Following an Acquired Brain Injury: A Pilot Study

Background: Cognitive impairments as sequelae of brain injury are common and can negatively affect activities of everyday life, participation and quality of life. Thus, finding ways to reduce cognitive impairments and ameliorate their negative impact on everyday life is an important focus of research. Aim: The aim of this pilot study was to analyse the effects of a combination of guided mindfulness and aerobic exercise on cognitive ability and mental fatigue in patients with acquired brain injury (ABI). Design: Pilot study, with a before-after design. Setting: Outpatient. Population: Twenty-one patients suffering from ABI, former patients of three rehabilitation medicine departments. Methods: The intervention comprised a structured combination of guided mindfulness program and outdoor walking, three times/week for 12 weeks. The outcome measures included assessment of information processing speed, working memory, oxygen uptake and self-reported mental fatigue. Results: The main results showed improvements in cognitive abilities related to information processing speed, perceived mental fatigue and physical capacity. Conclusions: A combination of mindfulness and physical activity can increase information processing speed and ameliorate mental fatigue. Further studies are needed to confirm our findings. Clinical Rehabilitation Impact: The combination of guided mindfulness and physical activity shows promise as a treatment modality in rehabilitation of impaired information processing speed and mental fatigue following ABI.

Examining the Inter Hemispheric Transfer Time Test: A new computerized cognitive test to incorporate into therapeutic strategy for patients with brain metastases? A pilot study

ObjectiveTo evaluate the computerized Inter Hemispheric Transfer Time Test (IHTTT), a cognitive test designed for the detection of information processing speed impairment in patients undergoing stereotactic radiation therapy for brain metastases. MethodsInclusion criteria: age ≥18 years, brain metastases treated by stereotactic radiotherapy (SRT) with dose schedule: 33 Gy in 3 fractions, solid tumour, ≥70 Karnofsky Performance Status, Mini-Mental State Evaluation (MMSE) ≥ 24, no history of stroke brain injury. Twenty-nine patients were recruited from June 2014 to April 2015. All recruited patients were administered Frontal Assessment Battery at Bedside (FAB), IHTTT and QLQ-C30 quality of life questionnaire before SRT, at one-month, six-month and one-year follow-up. The primary endpoint was Interhemispheric Transfer Index (IHTI). Secondary endpoints included Interhemispheric Transfer Time (IHTT), MMSE, FAB, and quality of life. ResultsA significant evolution of cognitive function over time was assessed by the IHTTT: IHTT = 720 ± 27 ms at baseline, 728 ± 20 at one month, 736 ± 36 at 6 months, 799 ± 111 at one-year follow-up (p = 0.0010); IHTI = 13.1 ± 31.4, 11.5 ± 24.3, 50.6 ± 57.9, 91.0 ± 59.4 (p < 0.0001). There was also a significant evolution over time for MMSE (p = 0.014) but neither for FAB score nor the quality of life scores. IHTI was strongly related to progression-free survival (p = 0.0091). ConclusionOur results suggest that IHTTT is able to detect the evolution of cognitive function over time. IHTTT could be an interesting sensitive cognitive test to include in evaluation of patients with brain metastases irradiated by SRT.