Cognitive Function In Multiple Sclerosis Patients Research Articles

Enhancing brain health: Swimming-induced BDNF release and epigenetic influence in MS female mouse models

Multiple sclerosis (MS) is a condition characterized by inflammation in the central nervous system (CNS), impacting sensory, motor, and cognitive abilities. Globally, around three million individuals are affected by MS, with up to 97,000 cases in Iran attributed to genetic predispositions along with various environmental factors like smoking. Cognitive impairment affects a significant portion of patients, ranging from 45% to 70%. This study investigates the impact of regular aerobic swimming exercise for four weeks, mild cognitive impairment induced by encephalomyelitis, and their combination on the expression of microRNA-142-3p and its correlation with the release of brain-derived neurotrophic factor (BDNF) in relation to spatial memory. Twenty-one C57BL/6 mice were divided into three groups. RT-PCR was used for microRNA expression analysis, and BDNF levels were assessed via western blotting. Clinical scores and animal weights were monitored daily. EAE induction led to an increase in microRNA-142-3p expression and a decrease in BDNF levels compared to the control group. Exercise inversed them significantly, and improved spatial memory. Our findings indicate that engaging in regular swimming exercise can counteract the up-regulation of miR-142-3p in brain tissue, which likely contributes to mild cognitive impairment induced by MS. Additionally, the increase in BDNF following exercise appears to be associated with miR-142-3p and the enhancement of cognitive function. Thus, the therapeutic benefits of exercise, particularly in releasing BDNF to improve cognitive function in MS patients, warrant consideration. Lifestyle modifications have the potential to effectively modulate environmental influences and ethnicity, underscoring their significance in MS management.

The effect of exercise on cognitive function in people with multiple sclerosis: a systematic review and meta-analysis of randomized controlled trials.

A growing body of research examining the effect of exercise on cognitive function in people with multiple sclerosis (MS), while findings of available studies were conflicting. We aimed to explore the effect of exercise on cognitive function in MS patients. For this systematic review and meta-analysis, we searched PubMed, Web of Science, EBSCO, Cochrane, and Scopus electronic databases, through July 18, 2022. Cochrane risk assessment tool was used to evaluate the methodological quality of the included literature. Twenty-one studies with a total of 23 experimental groups and 21 control groups met the inclusion criteria. There was a significant effect of exercise on improving cognitive function in MS patients, while the effect size was small (Cohen's d = 0.20, 95% CI 0.06-0.34, p < 0.001, I2 = 39.31%). Subgroup analysis showed that exercise significantly improved memory (Cohen's d = 0.17, 95% CI 0.02-0.33, p = 0.03, I2 = 7.59%). In addition, multicomponent training, exercise conducted 8weeks and 10weeks, up to 60min per session, 3 times or more per week, 180min or more per week increased cognitive function significantly. Furthermore, a worse basal MS status (defined by the Expanded Disability Status Scale) and an older age were associated with greater improvement in cognitive function. MS patients are recommended to participate in at least three multicomponent training sessions per week, with each session lasting up to 60min, and the exercise goal of 180min per week can be achieved by increasing the frequency of exercise. Exercise lasting 8 or 10weeks is best for cognitive function improvement. Additionally, a worse basal MS status, or the older the age, the greater effect on cognitive function.

Relaxation-Compensated Chemical Exchange Saturation Transfer MRI in the Brain at 7T: Application in Relapsing-Remitting Multiple Sclerosis.

Chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) can probe tissue biochemistry in vivo with high resolution and sensitivity without requiring exogenous contrast agents. Applying CEST MRI at ultrahigh field provides advantages of increasing spectral resolution and improving sensitivity to metabolites with faster proton exchange rates such as glutamate, a critical neurotransmitter in the brain. Prior magnetic resonance spectroscopy and CEST MRI studies have revealed altered regulation of glutamate in patients with multiple sclerosis (MS). While CEST imaging facilitates new strategies for investigating the pathology underlying this complex and heterogeneous neurological disease, CEST signals are contaminated or diluted by concurrent effects (e.g., semi-solid magnetization transfer (MT) and direct water saturation) and are scaled by the T1 relaxation time of the free water pool which may also be altered in the context of disease. In this study of 20 relapsing-remitting MS patients and age- and sex-matched healthy volunteers, glutamate-weighted CEST data were acquired at 7.0 T. A Lorentzian fitting procedure was used to remove the asymmetric MT contribution from CEST z-spectra, and the apparent exchange-dependent relaxation (AREX) correction was applied using an R1 map derived from an inversion recovery sequence to further isolate glutamate-weighted CEST signals from concurrent effects. Associations between AREX and cognitive function were examined using the Minimal Assessment of Cognitive Function in MS battery. After isolating CEST effects from MT, direct water saturation, and T1 effects, glutamate-weighted AREX contrast remained higher in gray matter than in white matter, though the difference between these tissues decreased. Glutamate-weighted AREX in normal-appearing gray and white matter in MS patients did not differ from healthy gray and white matter but was significantly elevated in white matter lesions. AREX in some cortical regions and in white matter lesions correlated with disability and measures of cognitive function in MS patients. However, further studies with larger sample sizes are needed to confirm these relationships due to potential confounding effects. The application of MT and AREX corrections in this study demonstrates the importance of isolating CEST signals for more specific characterization of the contribution of metabolic changes to tissue pathology and symptoms in MS.

IMPACT OF RELAPSING REMITTING MULTIPLE SCLEROSIS ON COGNITIVE FUNCTION AND SLEEP PROFILE IN PATIENTS AT ALEXANDRIA UNIVERSITY HOSPITALS

Introduction Multiple sclerosis (MS) is the most common, chronic neuroinflammatory, demyelinating and neurodegenerative disease of CNS affecting individuals in their early adult life Prevalence estimates of cognitive impairment in MS have markedly increased, 40–70% of people with MS experience neuropsychological dysfunction in one or more cognitive domains at every stage of the disease. UP to 42- 65 % of MS patients are believed to have sleep disorders. Sleep abnormalities have a deleterious impact on cognitive functions in MS patients. It is critical to assess the cognitive and sleep affection as well as the bidirectional relationship in patients with multiple sclerosis thus improve overall health and quality of life. Aim of the work: To assess the effect of different clinical variables of RRMS on cognition and sleep, as well as the relation between sleep disturbance and cognitive dysfunction in RRMS patients presented to Alexandria university hospitals..Subjects:The study was carried out on 50 subjects of confirmed Remitting relapsing MS patients with excluding Primary progressive and secondary progressive patients and patients with other associated autoimmune diseases, attending at Alexandria university hospitals.

Combined exercise training improves cognitive functions in multiple sclerosis patients with cognitive impairment: A single-blinded randomized controlled trial

Cognitive impairment is common in patients with multiple sclerosis (MS). The effects of different exercise trainings on cognitive functions in patients with MS are promising. However, the effects are not yet clear in MS patients with cognitive impairment. This study aimed to investigate the effect of combined exercise training on different cognitive functions in MS patients with cognitive impairment. Relapsing-remitting and mild disabled MS patients with cognitive impairment were randomly assigned to two groups: Exercise Group (EG, n:17) and the Control Group (CG, n:17). The EG received a combined exercise training consisting of aerobic and Pilates training in three sessions per week for 8 weeks while the CG performed the relaxation exercises at home. Cognitive functions, walking capacity, fatigue, mood, and quality of life were assessed at baseline and after eight weeks using the Brief Repeatable Battery of Neuropsychological Tests (BRB-N), Six-Minute Walk Test (6-MWT), Fatigue Impact Scale (FIS), Beck's Depression Inventory (BDI) and MS Quality of Life-54 (MSQoL-54), respectively. This study showed significant group-by-time interactions on long-term verbal memory, walking capacity, cognitive fatigue, and physical quality of life in favor of the EG (p<0.003). Moreover, verbal memory, visuospatial memory, verbal fluency, information processing speed, walking capacity, fatigue, and quality of life improved in the EG (p<0.05) while only verbal memory increased in the CG (p<0.05). Furthermore, the change in visuospatial memory was associated with the change in mental quality of life (r:0.352, p: 0.041) while the change in verbal fluency (r: -0.362, p:0.035) and processing speed (r: -0.356, p:0.039) were associated with the change in mood. Combined exercise training has beneficial effects on different cognitive functions in mild disabled RRMS patients with cognitive impairment. In addition, there is a mutual relationship in improvements in cognitive functions, mood, and quality of life after exercise.

Comparison of Cognitive and Linguistic Functions among Multiple Sclerosis Patients and Healthy Controls

Abstract Introduction: Multiple Sclerosis (MS) is an incapacitating neurological disease with diverse signs, consisting of difficult or unclear articulation of speech and cognitive and linguistic deficits. The purpose of this study was to compare the cognitive and linguistic functions among MS individuals and healthy controls. Method: The present descriptive and cross-sectional study was performed at Shahid Motahari Clinic of Shiraz, Iran, in 2018-2019. The participants were selected by using a purposeful sampling method from September 2018 to December 2018, at the MS centers of neurology departments. The Persian aphasia test was used as the research instrument to evaluate the cognitive functions in MS patients. The data were analyzed using the SPSS version 23 software. Results: The results of the present study revealed that the processing of all subscales, except for transcription, letter and word dictation, and sentence dictation, were significantly different between healthy and unhealthy individuals. Moreover, the results showed that the production of the focused sentence were worse in unhealthy individuals compared to healthy individuals (P < 0.05). Conclusion: The results of this study showed that patients with MS were involved in linguistic and cognitive problems. Language and speech therapists who interact with these patients need to be aware of cognitive-linguistic disorders and consider this in their assessment, management, and intervention.

P36-F Neurophysiological assessment of cognitive functions in patients with multiple sclerosis

Background Cognitive dysfunction concerns about 40–75% of subjects with multiple sclerosis (MS). The aim of the study was to check the usefulness of neurophysiological examinations in assessment of cognitive functions in patients with MS. Material and methods 61 relapsing-remitting MS patients and 21 healthy volunteers participated in the study. The patients were divided into two groups: A - 30 patients with short disease duration (time from first symptoms was less than 5 years); and B - 31 patients with long disease duration (time from first symptoms was more than 10 years). Neurophysiological tests were performed in all patients: event related potential (P300), somatosensory evoked potentials (SSEP), visual evoked potentials (VEP). In addition, the Hospital Anxiety and Depression Scale (HADS), the Montreal Cognitive Assessment Scale (MoCA), and the Wechsler Intelligence Scale subscales (Lacks in Pictures and Symbols of Digits) were done. Results In patients with MS the mean latencies of P100, P23 and P300 were significantly longer than compared to controls. Prolongation of P300 was associated with worse education. Patients with longer disease duration had tendency to have longer latencies of P300. An association was found between results of psychometric tests and event-related potential P300. Conclusions Event related potential (P300) is useful in clinical practice to assess cognitive functions in MS patients.

The relationship between cognitive function and body mass index in multiple sclerosis patients

BackgroundMany patients with multiple sclerosis (MS) endure cognitive impairment, which affects their everyday life and lowers their life quality. It has been demonstrated that obesity can result in poor cognitive performance in healthy individuals through various mechanisms. Therefore, we aimed at assessing the association between body mass index (BMI) and cognitive function in MS patients, using minimal assessment of cognitive functions in MS (MACFIMS) battery. MethodThis study included eighty-one patients with relapsing-remitting MS (RRMS). After collecting the demographic data, patients’ height and weight were measured in order to calculate BMI. Then, MACFIMS battery was administered in one session, after obtaining information using expanded disability status scale (EDSS). ResultsPaced Auditory Serial Addition Test (PASAT) and Symbol Digit Modalities Test (SDMT) scores were negatively correlated with BMI (P values are equal to 0.005 and 0.037, respectively). PASAT score correlated with BMI after controlling for sex, age, and EDSS, but SDMT score did not correlate. Nevertheless, no significant variation was observed in the BMI level among individuals having MS with or without cognitive deficit. ConclusionWe have shown that, BMI is associated with poor cognitive performance in some tests which, MACFIMS battery was included. This could suggest that obesity might be an important factor, which have effect on the cognitive performance.

A cross-sectional and longitudinal study evaluating brain volumes, RNFL, and cognitive functions in MS patients and healthy controls

BackgroundThe principal biomarker of neurodegeneration in multiple sclerosis (MS) is believed to be brain volume, which is associated with cognitive functions and retinal nerve fibre layer (RNFL). A cross-sectional and longitudinal assessment of the relationship between RNFL, cognitive functions and brain volume.MethodsAt baseline, relapsing patients and healthy controls underwent 1.5 T MRI to estimate the normalized volume of brain (NBV), grey (NGV), white (NWV) and peripheral grey (pNGV) matter. Cognitive functions were evaluated by BICAMS, RNFL by Spectral-Domain OCT. Patients were re-evaluated after 12 months.ResultsCognitive functions, brain volume, and RNFL differed between the group of 66 patients and that of 16 healthy controls. In the MS group, at baseline, an association was found between: p-NGV and symbol-digit (SDMT) (p = 0.022); temporal-RNFL and NBV (p = 0.007), NWV (p = 0.012), NGV (p = 0.048), and p-NGV (p = 0.021); papillo-macular bundle-RNFL and NBV (p = 0.013), NWV (p = 0.02), NGV (p = 0.049), and p-NGV (p = 0.032). Over the observational period, we found a reduction of brain volume (p < 0.001), average-RNFL (p = 0.001), temporal-RNFL (p = 0.006), and papillo-macular bundle-RNFL (p = 0.009). No association was found between OCT, MRI, and cognitive changes.ConclusionsBrain volume, cognitive functions, and RNFL are continuous measures of different neurodegenerative aspects. BICAMS and OCT have low costs and can be easily used in clinical practice to monitor neurodegeneration.

Intake of tryptophan-enriched whey protein acutely enhances recall of positive loaded words in patients with multiple sclerosis

Multiple sclerosis (MS) has physiological and/or immunological characteristics that diminish serotonin metabolism, a neurotransmitter associated with affective and cognitive functions. The aim was examine the acute and dose-dependent effects of a dietary tryptophan (TRP) enrichment on affective and cognitive functions in MS patients. We hypothesized that increased dietary availability of the amino acid TRP enhances serotonin concentrations and improves neuropsychological functions. In a double-blind, placebo-controlled, crossover study, MS patients with (n=15) and without (n=17) depressed mood ingested a whey protein mixture with 4 different amounts of TRP. Mood states, total plasma TRP and plasma TRP/ΣLNAA ratio were measured during each test session and cognitive tasks were conducted three hours after dietary intake. A fast, transient and dose-dependent increase of total plasma TRP and TRP/ΣLNAA ratio was found. Ratings of negative mood decreased over time, independent of the TRP dose. Relative to whey-only, immediate word recall and delayed recognition improved after ingestion of the lowest added TRP dose and was mainly due to better recollection for positive loaded words. Executive functions were not affected by a difference in TRP availability. A moderate addition of TRP to whey protein enhances memory processes without improving the mood state in MS. ccmo-registration number is NL32316.096.10.

The influence of age and illness duration on cognitive impairment in aging patients with relapsing-remitting multiple sclerosis (RR-MS)

The aim of this study was to dissociate age and duration of illness effects on cognitive impairment of patients with relapsing-remitting multiple sclerosis. Cognitive impairment among patients with multiple sclerosis (MS) is well known. However, few studies were devoted to assess the respective role of disease duration and age on cognitive functions in MS patients. Therefore, two studies were carried out on relapsing-remitting MS (RR-MS) patients using some tests of the BCcogSEP--a French test battery evaluating cognitive functions in MS. The cognitive deficits of RR-MS patients aged 50 years and over and whose symptoms had been present for more than 20 years were more severe than those of MS patients with a shorter illness duration (less than 10 years) or matched-age control participants. The more impaired cognitive functions were information-processing speed, episodic memory, verbal fluency and attention. On the other hand, cognitive performances of young RR-MS patients were similar to those of older RR-MS patients when all patients had the same illness duration (8 years in this study). Older patients even achieved better performance than younger ones on verbal fluency. This can be partly explained by the theory of cognitive reserve, as reported in previous cognitive aging studies. In RR-MS patients, the influence of illness duration seems to be a predominant factor in the development of cognitive impairment.

Association between smoking and cognitive impairment in multiple sclerosis.

PurposeAlthough smoking is known to cause various symptoms in multiple sclerosis (MS) patients, there have been no reports regarding the relationship between smoking and cognitive impairment in MS. Studying the effects of cigarette smoking in MS patients is imperative as there is a high prevalence of cognitive impairment in MS patients. In this study we examined the potentially deleterious effects of heavy smoking on mentation of patients with MS.Patients and methodsMS patients receiving care at the Neurology Clinic at Bezmialem Vakıf University, between the ages of 18–65 years who have at least graduated elementary school were included in the study. The Brief Repeatable Battery of Neuropsychological Tests (BRB-N) is a commonly used method to assess cognitive function in MS patients and was utilized in our study. Patients that smoked for at least 10 pack-years were considered heavy smokers.ResultsAll the patients were stratified into two groups: heavy smokers (n=20) and nonsmokers (n=24). For heavy smokers, their cognitive functioning was more impaired than that of nonsmokers (P=0.04, χ2=4.227). For patients with cognitive impairment, 78.9% of the Paced Auditory Serial Addition Test and 63.2% of the Symbol Digit Modalities Test scores were found to be lower.ConclusionPrevious reports have suggested that smoking increases the frequency of relapse among individuals with relapsing-remitting MS and accelerates disease progression in patients with progressive MS. According to the results of our study, heavy smokers had increased cognitive impairment when compared to nonsmokers. Extensive studies are necessary to further elucidate the relationship between smoking and cognitive impairment in MS patients.

Deficits in memory and visuospatial learning correlate with regional hippocampal atrophy in MS

The hippocampus has a critical role in episodic memory and visuospatial learning and consolidation. We assessed the patterns of whole and regional hippocampal atrophy in a large group of multiple sclerosis (MS) patients, and their correlations with neuropsychological impairment. From 103 MS patients and 28 healthy controls (HC), brain dual-echo and high-resolution 3D T1-weighted images were acquired using a 3.0-Tesla scanner. All patients underwent a neuropsychological assessment of hippocampal-related cognitive functions, including Paired Associate Word Learning, Short Story, delayed recall of Rey-Osterrieth Complex Figure and Paced Auditory Serial Attention tests. The hippocampi were manually segmented and volumes derived. Regional atrophy distribution was assessed using a radial mapping analysis. Correlations between hippocampal atrophy and clinical, neuropsychological and MRI metrics were also evaluated. Hippocampal volume was reduced in MS patients vs HC (p < 0.001 for both right and hippocampus). In MS patients, radial atrophy affected CA1 subfield and subiculum of posterior hippocampus, bilaterally. The dentate hilus (DG:H) of the right hippocampal head was also affected. Regional hippocampal atrophy correlated with brain T2 and T1 lesion volumes, while no correlation was found with disability. Damage to the CA1 and subiculum was significantly correlated to the performances at hippocampal-targeted neuropsychological tests. These results show that hippocampal subregions have a different vulnerability to MS-related damage, with a relative sparing of the head of the left hippocampus. The assessment of regional hippocampal atrophy may help explain deficits of specific cognitive functions in MS patients, including memory and visuospatial abilities.

Functional Brain Network Changes Associated with Maintenance of Cognitive Function in Multiple Sclerosis

In multiple sclerosis (MS) functional changes in connectivity due to cortical reorganization could lead to cognitive impairment (CI), or reflect a re-adjustment to reduce the clinical effects of widespread tissue damage. Such alterations in connectivity could result in changes in neural activation as assayed by executive function tasks. We examined cognitive function in MS patients with mild to moderate CI and age-matched controls. We evaluated brain activity using functional magnetic resonance imaging (fMRI) during the successful performance of the Wisconsin card sorting (WCS) task by MS patients, showing compensatory maintenance of normal function, as measured by response latency and error rate. To assess changes in functional connectivity throughout the brain, we performed a global functional brain network analysis by computing voxel-by-voxel correlations on the fMRI time series data and carrying out a hierarchical cluster analysis. We found that during the WCS task there is a significant reduction in the number of smaller size brain functional networks, and a change in the brain areas representing the nodes of these networks in MS patients compared to age-matched controls. There is also a concomitant increase in the strength of functional connections between brain loci separated at intermediate-scale distances in these patients. These functional alterations might reflect compensatory neuroplastic reorganization underlying maintenance of relatively normal cognitive function in the face of white matter lesions and cortical atrophy produced by MS.

Therapy-induced plasticity of cognitive functions in MS patients: Insights from fMRI

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system whose pathological mechanisms are still not completely understood. Physical as well as cognitive deterioration are consequences within the disease process that have an extensive impact on the patient’s quality of life. Therefore, understanding the functional background of spontaneous as well as induced remission is of high relevance. Studies on visualization of therapeutic effects of pharmacological or cognitive treatment by functional magnetic resonance imaging (fMRI) are still rare. From fMRI studies on focal brain lesions hypotheses on mechanisms of brain reorganization can be derived. This contribution will first give an overview of the existing studies using fMRI in MS, on cognitive decline, on cognitive treatment studies and its therapeutic effects on behavioural readouts in MS, and on therapy-induced brain plasticity and its possible visualization by fMRI. Results of a study on correlating the effects of cognitive training with changes in brain organization in patients with mild to severe cognitive impairment will be reported.

Motor assessment of upper extremity function and its relation with fatigue, cognitive function and quality of life in multiple sclerosis patients

Objectives The aim of this study was to assess the motor function of upper extremity and its relation with fatigue, cognitive function and quality of life in Multiple Sclerosis (MS) patients. Design Cross-sectional and controlled study. Setting Outpatient clinic in a university hospital. Subjects Thirty-one patients with MS (25 women, 6 men; mean age 39.74 ± 10.10 years; mean EDSS, 2.56 ± 1.91) and 30 healthy subjects (20 women, 10 men; mean age 33.56 ± 8.85 years) were enrolled into the study. Main Measures Nine-hole peg test (9-HPT) and Valpar Component Work Sample Test (VCWS-4), Upper Extremity Index (UEI), Paced Auditory Serial Addition Test (PASAT), Fatigue Severity Scale (FSS), and the Multiple Sclerosis Quality of Life-54 (MSQOL-54). Results MS patients showed significant impairment in upper extremity motor functions, cognitive function and excessive fatigue compared to controls ( p < 0.05). 9-HPT in MS group correlated with EDSS, UEI and MSQOL-54 physical health and cognitive function, whereas VCWS-4 scores (assembly right, assembly left and disassembly) correlated only with EDSS and UEI. No correlation was found between the VCWS-4 and cognitive function and fatigue in both of the groups. Compared to control group, a strong correlation existed between the 9-HPT and VCWS-4 in MS patients ( p < 0.05). Conclusion The results indicate that disability level (EDSS), UEI and cognitive function in MS patients are related with impairment in upper extremity motor function. This again contributes to an impairment in physical domain of quality of life. A strong correlation of the 9-HPT with VCWS-4 supports the use of the 9-HPT as a measure of manual dexterity and gross motor functions.

Progressive Cognitive Improvement in Multiple Sclerosis from Treatment with Electromagnetic Fields

It has long been recognized that cognitive impairment occurs in patients with multiple sclerosis (MS) particularly among patients with a chronic progressive course. MS is considered a type of “subcortical dementia” in which cognitive and behavioral abnormalities resemble those observed in patients with a frontal lobe syndrome. The Bicycle Drawing Test is employed for the neuropsychological assessment of cognitive impairment specifically that of mechanical reasoning and visuographic functioning. It also provides clues concerning the patient's organizational skills which are subserved by the frontal lobes. Extracerebral pulsed applications of picotesla flux intensity electromagnetic fields (EMFs) have been shown to improve cognitive functions in patients with MS. I present three patients with long standing symptoms of MS who, on the initial baseline, pretreatment Bicycle Drawing Test, exhibited cognitive impairment manifested by omissions of essential details and deficient organizational skills. All patients demonstrated progressive improvement in their performance during treatment with EMFs lasting from 6–18 months. The improvement in cognitive functions, which occurred during the initial phases of the treatment, was striking for the changes in organizational skills reflecting frontal lobe functions. These findings demonstrate that progressive recovery of cognitive functions in MS patients are observed over time through continued administration of picotesla flux intensity EMFs. It is believed that the beneficial cognitive effects of these EMFs are related to increased synaptic neurotransmission and that the progressive cognitive improvement noted in these patients is associated with slow recovery of synaptic functions in monoaminergic neurons of the frontal lobe or its projections from subcortical areas.