Cognitive Deficits In Multiple Sclerosis Research Articles

Repeated prefrontal tDCS for improving mental health and cognitive deficits in multiple sclerosis: a randomized, double-blind, parallel-group study

BackgroundMultiple Sclerosis (MS) is an autoimmune disease associated with physical disability, psychological impairment, and cognitive dysfunctions. Consequently, the disease burden is substantial, and treatment choices are limited. In this randomized, double-blind study, we conducted repeated prefrontal electrical stimulation in 40 patients with MS to evaluate mental health variables (quality of life, sleep difficulties, psychological distress) and cognitive dysfunctions (psychomotor speed, working memory, attention/vigilance), marking it as the third largest sample size tDCS research conducted in MS to date.MethodsThe patients were randomly assigned (block randomization method) to two groups of sham (n = 20), or 1.5-mA (n = 20) transcranial direct current stimulation (tDCS) targeting the left dorsolateral prefrontal cortex (F3) and right frontopolar cortex (Fp2) with anodal and cathodal stimulation respectively (electrode size: 25 cm2). The treatment included 10 sessions of 20 min of stimulation delivered every other day. Outcome measures were MS quality of life, sleep quality, psychological distress, and performance on a neuropsychological test battery dedicated to cognitive dysfunctions in MS (psychomotor speed, working memory, and attention). All outcome measures were evaluated at the pre-intervention and post-intervention assessments. Both patients and technicians delivering the stimulation were unaware of the type of stimulation being used.ResultsRepeated prefrontal real tDCS significantly improved quality of life and reduced sleep difficulties and psychological distress compared to the sham group. It, furthermore, improved psychomotor speed, attention, and vigilance compared to the sham protocol. Improvement in mental health outcome variables and cognitive outperformance were interrelated and could predict each other.ConclusionsRepeated prefrontal and frontopolar tDCS ameliorates secondary clinical symptoms related to mental health and results in beneficial cognitive effects in patients with MS. These results support applying prefrontal tDCS in larger trials for improving mental health and cognitive dysfunctions in MS.Trial registrationClinicalTrials.gov Identifier: NCT06401928.

An investigation of auditory processing in relapsing-remitting multiple sclerosis.

Multiple sclerosis (MS) is one of the most common neurological diseases in North America and it is frequently associated with sensory processing difficulties, cognitive deficits, and psychiatric illness. While many studies have examined cognitive deficits in MS measured by behavioural responses and neuroimaging techniques, only a few studies have examined neurophysiological measures of auditory functioning in MS, such as the mismatch negativity (MMN). The MMN is an event-related potential that indicates automatic auditory change detection. This study examined whether MMN endpoints measured by electroencephalography (EEG) differ in individuals with relapsing-remitting MS compared to healthy controls and whether the symptomatology of MS, including symptoms of depression and fatigue, are related to MMN measures. A multi-feature MMN paradigm, which includes five distinct deviant tones, was used to assess auditory cortex function in MS. There were no significant differences in MMN amplitudes or latencies between the MS and control group (p < 0.05) and corresponding effect sizes were small. However, there was a correlation between reduced MMN amplitudes in response to an intensity deviant and physician-reported disability. The intensity MMN may be more sensitive to deterioration in this population. Ultimately, this study provides a comprehensive profile of early auditory processing abilities in MS and suggests that a reduction in the MMN response may be representative of disease severity in MS.

Cognitive deficits in multiple sclerosis: Auditory and visual attention and inhibitory control

Background A growing body of evidence has been paid to the cognitive impairment in patients with multiple sclerosis (MS). However, studies concerning cognitive functions in MS have also yielded conflicting results. This study investigates the attention and inhibitory control functions in patients with MS and their relationship with other clinical features, such as depression and fatigue in these patients. Methods Participants included 80 patients with MS and 60 healthy controls. The attention and inhibitory control, fatigue, and psychiatric screening in all subjects were studied, respectively with the Integrated Visual and Auditory Continuous Performance Test (IVA-CPT), Fatigue Severity Scale (FSS), and the Hospital Anxiety and Depression Scale (HADS). Results Patients with MS performed the IVA-CPT task more poorly than the healthy control group (p < 0.001). However, multiple regression analysis did not show any significant relationship between disease duration, FSS, and HADS on attention and inhibitory control. Conclusion Inhibitory control and attention are significantly impaired in patients with MS. Finding the basics of cognitive deficits in MS have potentially important clinical implications for developing better cognitive rehabilitation strategies.

The relationship between processing speed and verbal and non-verbal new learning and memory in progressive multiple sclerosis

Objective: Processing speed (PS) deficits are the most common cognitive deficits in multiple sclerosis (MS), followed by learning and memory deficits, and are often an early cognitive problem. It has been argued that impaired PS is a primary consequence of MS, which in turn decreases learning. The current analysis examined the association between PS and learning in a large cohort of individuals with progressive MS. Methods: Baseline data from a randomized clinical trial on rehabilitation taking place at 11 centers across North America and Europe were analyzed. Participants included 275 individuals with clinically definite progressive MS (primary, secondary) consented into the trial. Results: Symbol Digit Modalities Test (SDMT) significantly correlated with California Verbal Learning Test-II (CVLT-II) (r = 0.21, p = 0.0003) and Brief Visuospatial Memory Test–Revised (BVMT-R) (r = 0.516, p < 0.0001). Receiver operating characteristic (ROC) analysis of the SDMT z score to distinguish between impaired and non-impaired CVLT-II performance demonstrated an area under the curve (AUC) of 0.61 (95% confidence interval (CI): 0.55–0.68) and a threshold of −1.62. ROC analysis between SDMT and BVMT-R resulted in an AUC of 0.77 (95% CI: 0.71–0.83) and threshold of −1.75 for the SDMT z score to predict impaired BVMT-R. Conclusion: Results indicate little ability beyond chance to predict CVLT-II from SDMT (61%), albeit statistically significant. In contrast, there was a 77% chance that the model could distinguish between impaired and non-impaired BVMT-R. Several potential explanations are discussed.

Developing the Rationale for Including Virtual Reality in Cognitive Rehabilitation and Exercise Training Approaches for Managing Cognitive Dysfunction in MS

Cognitive impairment is a common and detrimental consequence of multiple sclerosis (MS) and current rehabilitation methods are insufficient. Cognitive rehabilitation (CR) and exercise training (ET) are the most promising behavioral approaches to mitigate cognitive deficits, but effects are small and do not effectively translate to improvements in everyday function. This article presents a conceptual framework supporting the use of virtual reality (VR) as an ideal, common adjuvant traditional CR and ET in MS. VR could strengthen the effects of CR and ET by increasing sensory input and promoting multisensory integration and processing during rehabilitation. For ET specifically, VR can also help incorporate components of CR into exercise sessions. In addition, VR can enhance the transfer of cognitive improvements to everyday functioning by providing a more ecologically valid training environment. There is a clear interest in adding VR to traditional rehabilitation techniques for neurological populations, a stronger body of evidence of this unique approach is needed in MS. Finally, to better understand how to best utilize VR in rehabilitation for cognitive deficits in MS, more systematic research is needed to better understand the mechanism(s) of action of VR with CR and ET.

Visual-Attentional Load Unveils Slowed Processing Speed in Multiple Sclerosis Patients: A Pilot Study with a Tablet-Based Videogame.

Slowing in information processing speed (IPS) is the key cognitive deficit in multiple sclerosis (MS). Testing IPS in different cognitive load conditions by using computerized tools might reveal initial IPS slowness underestimated by classic paper-and-pencil tests. To investigate the extent to which IPS can be affected by increased task demands, we developed three tasks based on the manipulation of the visual-attentional load, delivered with a home-made, tablet-based videogame. Fifty-one patients with MS (pwMS), classified as having no cognitive impairment in classic paper-and-pencil tests, and 20 healthy controls (HC) underwent the videogame tasks; reaction times (RTs) and accuracy were recorded. A significant reduced performance of pwMS as compared with HC was found on the videogame tasks, with pwMS being on average slower and less accurate than HC. Furthermore, pwMS showed a significantly more pronounced decrement in accuracy as a function of the visual-attentional load, suggesting a higher susceptibility to increased task demands. Significant correlations among the Symbol Digit Modalities Test (SDMT) and the videogame mean RTs and accuracy were found, providing evidence for the concurrent validity of the videogame as a valid tool to test IPS in pwMS. The high potential that might derive from the adoption of computerized assessment tools in clinical practice should be taken into consideration and investigated further.

Peculiarities of an assessment of a cognitive efficacy in multiple sclerosis

A key cognitive deficit in multiple sclerosis (MS) is a poor efficacy of the information processing, with working memory impairments and a decreased speed of the information processing as components of formation of this poor efficacy. Despite of a sufficient number of single cognitive tests and test batteries, there are still essential knowledge gaps and methodological limitations connected with understanding and measurements of the cognitive deficit in MS. To study real reasons of changes of the cognitive efficacy in MS, a neurocognitive testing with the original computerized Set for Assessment of Cognitive Capacity and Switchability (сSACCAS), an assessment of levels anxiety/depression, and an assessment of level of fatigue were performed for 25 patients with MS (including 17 female patients) (with a mean age of 34.14 ± 2.13 years old) and 25 practically healthy persons (including 15 females) (with a mean age of 31.80 ± 2.60 years old). To determine neurophysiological correlates of the cognitive functioning, an examination of cognitive evoked potentials (CEP) was performed. An investigation of the distribution density of results of the MS patients’ testing defined 3 groups among them. These groups had differences on the time of performing of test tasks, the “real mistake ratio”, switchability, parameters of N2- and P3-components of CEP, a localization of a maximal P3 peak. The motor reaction speed was more connected with the attention and the information processing speed, than with a visual-spatial orientation, whereas the fatigue more influenced on the speed of comparison and decision making, than on the attention. In 44 % of cases, the time of reply in tests were increased by a slowing down of assessment of a stimulus modality; in 24 % of cases, a long delay of the reply was connected, besides of a low speed of cognitive processes, with impairments of a working memory. The results obtained confirmed a significance of an integrated approach to understand reasons of changes of the cognitive efficacy and to assess adequately cognitive impairments in MS. Key words: neurocognitive computerized tests, cognitive efficacy, cognitive evoked potentials, multiple sclerosis

Cognitive impairment in multiple sclerosis: lessons from cerebrospinal fluid biomarkers.

Cognitive impairment is a common clinical manifestation of multiple sclerosis, but its pathophysiology is not completely understood. White and grey matter injury together with synaptic dysfunction do play a role. The measurement of biomarkers in the cerebrospinal fluid and the study of their association with cognitive impairment may provide interesting in vivo evidence of the biological mechanisms underlying multiple sclerosis-related cognitive impairment. So far, only a few studies on this topic have been published, giving interesting results that deserve further investigation. Cerebrospinal fluid biomarkers of different pathophysiological mechanisms seem to reflect different neuropsychological patterns of cognitive deficits in multiple sclerosis. The aim of this review is to discuss the studies that have correlated cerebrospinal fluid markers of immune, glial and neuronal pathology with cognitive impairment in multiple sclerosis. Although preliminary, these findings suggest that cerebrospinal fluid biomarkers show some correlation with cognitive performance in multiple sclerosis, thus providing interesting insights into the mechanisms underlying the involvement of specific cognitive domains.

Graph Theoretic Analysis of Brain Connectomics in Multiple Sclerosis: Reliability and Relationship with Cognition.

Research suggests that disruption of brain networks might explain cognitive deficits in multiple sclerosis (MS). The reliability and effectiveness of graph theoretic network metrics as measures of cognitive performance were tested in 37 people with MS and 23 controls. Specifically, relationships with cognitive performance (linear regression against the paced auditory serial addition test-3 seconds [PASAT-3], symbol digit modalities test [SDMT], and attention network test) and 1-month reliability (using the intraclass correlation coefficient [ICC]) of network metrics were measured using both resting-state functional and diffusion magnetic resonance imaging data. Cognitive impairment was directly related to measures of brain network segregation and inversely related to network integration (prediction of PASAT-3 by small worldness, modularity, characteristic path length, R2 = 0.55; prediction of SDMT by small worldness, global efficiency, and characteristic path length, R2 = 0.60). Reliability of the measures for 1 month in a subset of nine participants was mostly rated as good (ICC >0.6) for both controls and MS patients in both functional and diffusion data, but was highly dependent on the chosen parcellation and graph density, with the 0.2–0.5 density range being the most reliable. This suggests that disrupted network organization predicts cognitive impairment in MS and its measurement is reliable for a 1-month period. These new findings support the hypothesis of network disruption as a major determinant of cognitive deficits in MS and the future possibility of the application of derived metrics as surrogate outcomes in trials of therapies for cognitive impairment.

Insulin Resistance is Related with Cognition Impairment in Multiple Sclerosis Patients

Multiple sclerosis (MS) is a chronic and progressive autoimmune disease of the central nervous system (CNS). Slowed cognitive processing speed and episodic memory decline are the most common cognitive deficits in MS, with additional difficulties in executive function, verbal fluency, and visuospatial analysis. The aim of this study was to compare the cognitive status of MS patients with and non- insulin resistant. In a cross-sectional study, 74 patients with diagnosis of relapsing remitting MS were invited to collaborate. After obtaining informed consent and recording information including time of diagnosis, waist circumference, height and weight, 5 cc of fasting blood samples were taken from patients. And blood glucose and insulin levels were measured. Cognitive status of patients was assessed using Minimal Assessment of Cognitive Function in MS (MACFIMS) questionnaire. According to Homeostatic Model Assessment of Insulin Resistance (HOMA) index more than 2.5, patients were divided into two groups with (n=28) and non-insulin resistance (n=46), then cognitive status was compared in two groups. The mean of age, duration of disease and EDSS of all participants were 40.78 ± 5.2 years, 11.56± 4.56 years and 1.68 ± 1.12 respectively. In our study, the prevalence of insulin resistance was found 37.8%. The mean scores of CVLT, CVLT-DR, COWAT, JLO tests were significantly lower in the insulin resistance group comparing to non-insulin resistance group (P<0.05). Also, the score of the CVLT, CVLT-DR, COWAT, JLO, BVMT and DKEFS tests had reverse correlation with fasting insulin levels, which was meaningful for COWAT. MS patients with insulin resistance are more disturbed in the areas of verbal memory, verbal fluency, executive function and visuospatial processing and this disorder is exacerbated by an increase in fasting blood insulin levels.

Hippocampal Neurogenesis and Neural Circuit Formation in a Cuprizone-Induced Multiple Sclerosis Mouse Model.

Cognitive impairments are key features in multiple sclerosis (MS), a progressive disorder characterized by neuroinflammation-induced demyelination in the central nervous system. To understand the neural substrates that link demyelination to cognitive deficits in MS, we investigated hippocampal neurogenesis and synaptic connectivity of adult-born neurons, which play an essential role in cognitive function. The administration and withdrawal of the combination of cuprizone and rapamycin (Cup/Rap) in C57BL/6J male mice efficiently demyelinated and remyelinated the hippocampus, respectively. In the demyelinated hippocampus, neurogenesis was nearly absent in the dentate gyrus, which was due to inhibited proliferation of neural stem cells (NSCs). Specifically, radial glia-like type 1 NSCs were shifted from a proliferative state to a mitotically-quiescent state in the demyelinated hippocampus. In addition, dendritic spine densities of adult-born neurons were significantly decreased, indicating a reduction in synaptic connections between hippocampal newborn neurons and excitatory input neurons. Concomitant with hippocampal remyelination induced by withdrawal of Cup/Rap, proliferation of type 1 NSCs and dendritic spine densities of adult-born neurons reverted to normal in the hippocampus. Our study shows that proliferation of hippocampal NSCs and synaptic connectivity of adult-born neurons are inversely correlated with the level of demyelination, providing critical insight into hippocampal neurogenesis as a potential therapeutic target to treat cognitive deficits associated with MS.SIGNIFICANCE STATEMENT To identify the neural substrates that mediate cognitive dysfunctions associated with a majority of MS patients, we investigated hippocampal neurogenesis and structural development of adult-born neurons using a Cup/Rap model, which recapitulates the hippocampal demyelination that occurs in MS patients. A shift of NSCs from a proliferatively-active state to mitotically-quiescent state dramatically decreased neurogenesis in the demyelinated hippocampus. Formation of dendritic spines on newborn neurons was also impaired following demyelination. Interestingly, the altered neurogenesis and synaptic connectivity of newborn neurons were reversed to normal levels during remyelination. Thus, our study revealed reversible genesis and synaptic connectivity of adult-born neurons between the demyelinated and remyelinated hippocampus, suggesting hippocampal neurogenesis as a potential target to normalize cognitive impairments in MS patients.

Introducing Multiple Screener: An unsupervised digital screening tool for cognitive deficits in MS

BackgroundCognitive deficits affect up to 70% of all patients with Multiple Sclerosis (MS) and have a significant impact on quality of life. Cognitive assessments need to be performed by a neuropsychologist and are often time-consuming, hampering timely identification and adequate monitoring of cognitive decline in MS. ObjectiveTo develop a time-efficient, unsupervised, digital tool to screen for cognitive deficits in MS. MethodsA digital (adjusted) version of the Brief International Cognitive Assessment for MS, including the Symbol Digit Modalities Test (SDMT, information processing speed), the California Verbal Learning Test (CVLT-II, verbal memory) and the Spatial Recall Test (SPART, visuospatial memory) was developed: Multiple Screener (intellectual property of Sanofi Genzyme).Firstly, the clarity and feasibility of the tool was confirmed by 16 patients with MS (mean age 50.9 years (SD 9.4, range 37–68). Next, in 60 healthy controls (HCs, mean age 44.5 years (SD 14.0, range 18–67), intraclass correlation coefficients (ICC) were calculated to describe how strongly the digital version resembled the paper and pencil-based assessment. Finally, 236 HCs (mean age 42.8 years (SD 12.8, range 18–69) were included to obtain norm scores for each test. ResultsICCs between digital and paper and pencil-based assessment were excellent to good (SDMT (ICC 0.79, confidence interval (CI) 0.67–0.87); CVLT-II (ICC 0.77, CI 0.64–0.85); SPART (ICC 0.61, CI 0.42–0.75)). For each test, a regression-based correction for the effect of age was applied on the raw scores before converting them to norm Z-scores. Additionally, the SDMT scores needed correction for education and the CVLT-II for education and sex (subgroups were created). ConclusionsPerformance on an adjusted, digital version of the BICAMS correlates highly with the standard paper-and-pencil based test scores in HCs. Multiple Screener is an unsupervised, digital tool, with available norm scores, ultimately allowing for easy monitoring of cognitive decline in patients with MS.

Cognitive Deficits in Multiple Sclerosis: Recent Advances in Treatment and Neurorehabilitation.

This article highlights recent progress in research on treatment and neurorehabilitation of cognitive impairment in multiple sclerosis (MS) including pharmacological interventions, physical exercise, and neuropsychological rehabilitation, both in conventional and technology-assisted settings. The most consistent evidence in terms of improvement or preservation of circumscribed cognitive scores in MS patients comes from moderately sampled randomized clinical trials on multimodal approaches that combine conventional or computerized neuropsychological training with psychoeducation or cognitive behavioral therapy. Disease-modifying treatments also appear to have beneficial effects in preventing or attenuating cognitive decline, whereas there is little evidence for agents such as donepezil or stimulants. Finally, physical exercise may yield some cognitive improvement in MS patients. Despite substantial and often promising research efforts, there is a lack of validated and widely accepted clinical procedures for cognitive neurorehabilitation in MS. Development of such approaches will require collaborative efforts towards the design of interventions that are fundamentally inspired by cognitive neuroscience, potentially guided by neuroimaging, and composed of conventional neuropsychological training and cognitive behavioral therapy as well as physical exercise and therapeutic video games. Subsequently, large-scale validation will be needed with meaningful outcome measures reflecting transfer to everyday cognitive function and maintenance of training effects.

Cognitive Fatigue, Sleep and Cortical Activity in Multiple Sclerosis Disease. A Behavioral, Polysomnographic and Functional Near-Infrared Spectroscopy Investigation.

Patients with multiple sclerosis (MS) disease frequently experience fatigue as their most debilitating symptom. Fatigue in MS partially refers to a cognitive component, cognitive fatigue (CF), characterized by a faster and stronger than usual development of the subjective feeling of exhaustion that follows sustained cognitive demands. The feeling of CF might result from supplementary task-related brain activity following MS-related demyelination and neurodegeneration. Besides, CF in MS disease might also stem from disrupted sleep. The present study investigated the association between the triggering of CF, task-related brain activity and sleep features. In a counterbalance mixed design, 10 patients with MS and 11 healthy controls were exposed twice for 16 min to a CF-inducing dual working memory updating task (TloadDback) under low or high cognitive demands conditions, counterbalanced. Considering known inter-individual differences and potential cognitive deficits in MS, the maximal cognitive load of the task was individually adapted to each participant’s own upper limits. During the experimental sessions, cortical brain activity was measured using near-infrared spectroscopy (NIRS) during the CF-induction task, and in a resting state immediately before and after. Ambulatory polysomnography recordings were obtained on the nights preceding experimental sessions. When cognitive load was individually adapted to their processing capabilities, patients with MS exhibited similar than healthy controls levels of subjectively perceived CF, evolution of performance during the task, and brain activity patterns. Linear mixed models indicate a negative association between oxygenation level changes in the dorsolateral prefrontal cortex (DLPFC) and the triggering of subjective CF in patients with MS only. Longer total sleep time was also associated with higher CF in MS patients. These results suggest that controlling for cognitive load between individuals with and without MS results in a similar task-related development of subjective CF. Besides comparable performance and cortical brain activity between groups, mixed model analyses suggest a possible association between CF, DLPFC activity and sleep duration in MS disease.

The subtleties of cognitive decline in multiple sclerosis: an exploratory study using hierarchichal cluster analysis of CANTAB results

BackgroundIt is essential to investigate cognitive deficits in multiple sclerosis (MS) to develop evidence-based cognitive rehabilitation strategies. Here we refined cognitive decline assessment using the automated tests of the Cambridge Neuropsychological Test Automated Battery (CANTAB) and hierarchical cluster analysis.MethodsWe searched for groups of distinct cognitive profiles in 35 relapsing-remitting MS outpatients and 32 healthy controls. All individuals participated in an automated assessment (CANTAB) and in a pencil and paper general neuropsychological evaluation.ResultsHierarchical cluster analysis of the CANTAB results revealed two distinct groups of patients based mainly on the Simple Reaction Time (RTI) and on the Mean Latency of Rapid Visual Processing (RVP). The general neuropsychological assessment did not show any statistically significant differences between the cluster groups. Compared to the healthy control group, all MS outpatients had lower scores for RTI, RVP, paired associate learning, and delayed matching to sample. We also analyzed the associations between CANTAB results and age, education, sex, pharmacological treatment, physical activity, employment status, and the Expanded Disability Status Scale (EDSS). Although limited by the small number of observations, our findings suggest a weak correlation between performance on the CANTAB and age, education, and EDSS scores.ConclusionsWe suggest that the use of selected large-scale automated visuospatial tests from the CANTAB in combination with multivariate statistical analyses may reveal subtle and earlier changes in information processing speed and cognition. This may expand our ability to define the limits between normal and impaired cognition in patients with Multiple Sclerosis.

Thalamic and hippocampal volume associated with memory functions in multiple sclerosis

ObjectivesAlthough multiple sclerosis (MS) has long been considered to primarily affect white matter, it is now recognized that cognitive deficits in MS are also related to neocortical, thalamic and hippocampal damage. However, the association between damage to these structures and memory deficits in MS is unclear. This study examines whether MS patients with cognitive impairment have a reduction of hippocampal and/or thalamic volumes compared to cognitively intact patients, and whether these volume reductions correlate with various aspects of memory function. MethodologyVolumetric MRI measures of thalamus and hippocampus of forty-one patients with MS were performed. The patients were divided in two groups depending on the presence or absence of cognitive impairment, based on their neuropsychological tests scores. ResultsRight hippocampal volume was found to be associated with learning, and the left thalamic volume was found to predict performance in verbal memory. Cognitively impaired patients had a tendency to have a reduced left thalamic volume compared to cognitively intact patients. ConclusionsThis study does not support a direct relationship between hippocampal atrophy and verbal memory. These results add to the growing evidence of the involvement of thalamus in cognitive impairment in MS and its association with verbal memory deficits.

Comment: Dual tasks as a sensitive measure of cognitive deficits in MS.

Dual task paradigms are gaining traction as a means of detecting subtle cognitive deficits. By dividing performance between 2 separate tasks, they can highlight early cognitive changes, possible hallmarks of later deterioration. In the literature on dementia, dual task conditions differentiate between healthy controls and those with mild cognitive impairment, despite equivalent performance in single task conditions.1 In multiple sclerosis (MS), these early markers look increasingly advantageous. Roughly half of all people with MS go on to develop cognitive impairment, and with this comes increased risk of unemployment, social difficulties, and reduced quality of life.

Cambios estructurales y funcionales del hipocampo en pacientes con esclerosis múltiple y su relación con procesos de memoria

One of the most prevalent cognitive deficits in multiple sclerosis (MS) patients relates to (both verbal and visual) information encoding, a process related the hippocampus. To assess the relationship between information learning and long-term retention processes and hippocampal volume and functional connectivity (FC) in MS patients. MS patients and a control group of healthy volunteers were assessed using the brief neuro-psychological battery, which includes tests of verbal and visual memory. Gray matter volume was assessed through the voxel based morphometry technique, and a study of seed-based FC focused on the region of ??interest (hippocampus) was also conducted. Results revealed that, as compared to the control group, MS patients display gray matter atrophy at the left hippocampus gray matter and smaller FC between left hippocampus and brainstem, cerebellum, fusiform gyrus and superior temporal gyrus. Association analyses were performed between memory tests performance and both volumetric and FC changes. Results showed a positive correlation between gray matter hippocampal (bilateral) volume and verbal memory performance of the MS group. Further, in MS patients, a positive correlation between visual memory performance and FC between the left hippocampus and several temporal regions was also found. The results of the present study reveal a relationship between structural and functional changes in the hippocampus of MS patients and their performance on verbal and visual memory tests.

Multi-parametric structural magnetic resonance imaging in relation to cognitive dysfunction in long-standing multiple sclerosis

Background: Cognitive deficits are common in multiple sclerosis. Most previous studies investigating the imaging substrate of cognitive deficits in multiple sclerosis included patients with relatively short disease durations and were limited to one modality/brain region. Objective: To identify the strongest neuroimaging predictors for cognitive dysfunction in a large cohort of patients with long-standing multiple sclerosis. Methods: Extensive neuropsychological testing and multimodal 3.0T MRI was performed in 202 patients with multiple sclerosis and 52 controls. Cognitive scores were compared between groups using Z-scores. Whole-brain, white matter, grey matter, deep grey matter and lesion volumes; cortical thickness, (juxta)cortical and cerebellar lesions; and extent and severity of diffuse white matter damage were measured. Stepwise linear regression was used to identify the strongest predictors for cognitive dysfunction. Results: All cognitive domains were affected in patients. Patients showed extensive atrophy, focal pathology and damage in up to 75% of the investigated white matter. Associations between imaging markers and average cognition were two times stronger in cognitively impaired patients than in cognitively preserved patients. The final model for average cognition consisted of deep grey matter DGMV volume and fractional anisotropy severity (adjusted R²=0.490; p<0.001). Conclusion: From all imaging markers, deep grey matter atrophy and diffuse white matter damage emerged as the strongest predictors for cognitive dysfunction in long-standing multiple sclerosis.

Role of amyloid-β CSF levels in cognitive deficit in MS

Multiple sclerosis (MS) is the most common neurological disease of the young adults. Although being long considered as a pure white matter (WM) disease, growing evidence indicates that in MS the gray matter (GM) is affected as well, and that GM pathology correlates with cognitive function deterioration in MS. Indeed, MS is increasingly recognized to cause cognitive deficits since its early stages. Therefore, the identification of a biomarker with good diagnostic and prognostic power is of great importance for monitoring and preventing cognitive impairment in MS patients. A possibility arises from the combination of two different measures of neuronal injury: the levels of amyloid-β1-42 in cerebrospinal fluid (CSF), which have been found associated with cognitive decline in Alzheimer disease (AD); the brain synaptic plasticity, which is a measure of cognitive reserve and can be explored safely in humans by means of transcranial magnetic stimulation.In this review, we discuss the relevance of amyloid-β1-42 in MS disease and its link to long-term potentiation (LTP), which is the most studied form of synaptic plasticity, providing evidence for their combined use in cognitive assessment in MS patients.