In a new study entitled “LINGO-1 antibody ameliorates myelin impairment and spatial memory deficits in experimental autoimmune encephalomyelitis mice”, scientists report that the loss of myelin in MS patients’ brains contributes to their cognitive impairment. They showed that inhibiting protein LINGO-1 can improve these cognitive deficits by promoting myelin growth, thereby establishing impairment of LINGO-1 as a potential new therapeutic avenue for cognitive deficits in MS patients.
The study was published in the journal Science Reports.
The researchers used mouse models for human MS, specifically the experimental autoimmune encephalomyelitis (EAE) mouse model, to investigate the link between myelin impairment and cognitive decline. Moreover, despite the high incidence of cognitive impairment in MS patients, the treatments available have no benefits in improving patients’ cognitive features. Hence, there is an unmet need for an effective treatment.
In the study, researchers observed that the deficits in both memory and learning skills occur at later stages of the disease. They followed previous studies suggesting that a protein called LINGO-1 (short for LRR and Ig domain containing NOGO receptor interacting protein 1) inhibits myelin production. Accordingly, the team used an antibody against LINGO-1 and discovered it significantly improved learning and memory in the EAE mouse model, while it activated the AKT/mTOR signaling pathway, a crucial regulator of myelin growth. This phenotype was accompanied by an increase and restoration of myelin basic protein (MBP) expression in the brain of these mice, a key protein in the myelination process of nerves.
These findings therefore suggest that demyelination may contribute to the learning and memory deficits of MS patients, and establish the potential action of LINGO-1 antibody as a strategy to promote myelin growth. Hence, inhibiting LINGO-1 protein is a potential future treatment for cognitive impairment in MS patients.
Source: Multiple Sclerosis News Today © BioNews Services 2015 (24/09/15)
In the first study of its kind, researchers at the Centre for BrainHealth at The University of Texas at Dallas and UT Southwestern Medical Centre found that individuals with multiple sclerosis (MS) have decreased connectivity between key regions of the brain, slowing their cognitive speed and leading to impairments in concentration, attention, memory and judgment.
The findings have been published in Neuropsychology.
“Our study is the first to really zero in on the physiology of cognitive speed, the central cognitive deficit in MS,” said Dr. Bart Rypma, Center for BrainHealth principal investigator, who also holds the Meadows Foundation Chair at UT Dallas.
“While white matter is essential to efficient network communication, white matter degradation is symptomatic of MS. This study really highlights how tightly coupled connectivity is to performance and illuminates the larger, emerging picture of white matter’s importance in human cognitive performance.”
In the study, MS patients, compared to non-MS individuals, showed weaker brain connections between the dorsolateral prefrontal cortex, which is responsible for executing goal-directed thought and action, and posterior brain regions, which carry out tasks related to cognitive speed, such as visual processing, motor execution and object recognition.
Researchers, collaborating with Dr. Elliot Frohman, director of the multiple sclerosis program and clinical center at UT Southwestern, recruited 29 participants with relapsing-remitting MS and 23 non-MS patients. Participants underwent functional magnetic resonance imaging (fMRI) while completing a test of cognitive processing speed.
Participants were given four seconds to view a nine-item key of number and symbol pairs and one number-symbol pair probe. Participants were asked to indicate whether the probe appeared in the key.
While accuracy was similar for both groups, response times for MS patients were much slower. Analysis of the fMRI data revealed that while completing this measure, MS patients showed weaker functional connections with the dorsolateral prefrontal cortex.
“These findings reveal a diffuse pattern of disconnectivity with executive areas of the brain,” said Nicholas Hubbard, the study’s lead author and a doctoral candidate at the Centre for BrainHealth working with Rypma.
“Importantly, these decreases in connectivity predicted MS-related cognitive slowing both in and out of the fMRI environment suggesting that these results were not specific to our task, but rather were able to generalize to other situations where cognitive speed is required.”
The research supports the need for therapies that target white matter structures and white matter proliferation. Rypma and Hubbard are further exploring the physiology of white matter to better understand cognitive speed reductions not only in MS patients, but also in healthy aging individuals.
Source: UT Dallas News Center © 2015 The University of Texas at Dallas (11/09/15)
A new study published in the American Journal of Occupational Therapy has found cooking can be used as a measure of activity limitation and cognitive function.
The study, Factors That Moderate Activity Limitation And Participation Restriction In People With Multiple Sclerosis, was conducted by researchers at the Kessler Foundation, a non-profit organisation focused on the field of disability and rehabilitation research.
In total, 72 MS patients were evaluated in terms of their cooking ability as a measure of their activity limitation, and employment status as a measure of their participation restriction.
All patients were assessed through neuropsychological testing of memory, visual perception, executive function and processing speed. In addition, participants completed questionnaires concerning affective symptoms, fatigue, activity and participation.
Researchers found that processing speed was the only factor significantly related to both activity and participation. When analysing specific isolated aspects, employment status was found to be significantly associated with processing speed, visual memory education level and fatigue, while cooking ability was linked to the processing speed, verbal memory and working memory.
The research team concluded that processing speed seems to be a primary cognitive factor in MS patients that can have an impact on the quality of both activity and participation in the patient’s everyday life.
“The only variable significantly related to activity and participation was processing speed,” concluded the study’s lead author Dr. Yael Goverover in a press release.
“For occupational therapists, this means that implementing strategies that improve processing speed may help people with MS maintain their daily activities and stay in the workplace. In light of the close association between cognitive factors and cooking, providers should be aware that decline in cooking skills may be sign of cognitive decline in MS.”
Source: Multiple Sclerosis News Today © BioNews Services 2015 (26/08/15)
People living with multiple sclerosis have the dice loaded against them when it comes to their decision-making ability as their condition progresses, according to a new study from the University of Alberta's Faculty of Medicine & Dentistry.
"About half of people with MS will experience cognitive defects or limitations in that capacity. Decision-making becomes important to look at in these populations," said lead author Ashley Radomski, who completed the research as part of her master's thesis.
In the study, published in BMC Neurology, people with MS took part in an assessment that involved throwing dice, which has been shown in other studies to be a standard determinant of explicit risk.
The test, The Game of Dice Task (GDT), challenges study participants to evaluate risks associated with throwing dice by choosing a combination of one, two, three or four digits as a predicted outcome of each roll. More numbers in a chosen combination means a less risky choice, but also means lower rewards for a correct guess—which, Radomski explained, can lure participants to make less advantageous choices that reveal their everyday decision-making capacity.
Esther Fujiwara, Radomski's supervisor and an associate professor in the Department of Psychiatry, helped develop the test as part of her own PhD studies. "People with MS are faced with many complex decisions on a regular basis—for example, choices about which medications to take or not take, what short- or long-term effects are desirable or undesirable, which side-effects seem acceptable or unacceptable, and so on," Fujiwara notes.
"What we found in our study is that those patients who have increased disease severity, as indicated by a particular subtype of MS or by greater structural changes in the brain, did have greater decision-making disabilities than patients who were considered less severe," Radomski said.
People with MS or their family members may find it helpful to keep a journal to help identify decision-making patterns over time, suggested Radomski, who emphasised that the journal should be discussed with the patient's doctor, nurse or neurologist for a full assessment.
Radomski also noted the rules of GDT were explained to participants at the beginning of the task, and remained consistent and on display throughout the rounds. GDT was administered as part of a two-hour standardised neuropsychological test battery to evaluate the participants' working and verbal memory, visual-spatial abilities and motor function, among other traits.
Fujiwara hopes to continue this research by examining whether stress, which has a major role in MS, affects decisions made by people living with MS more than people without MS.
"Knowing that decision-making can suffer in later-stage MS, we need to make sure to provide optimal guidance and support in making such complex decisions, and especially so for individuals in more advanced stages of the disease," she said.
Source: Medical Xpress © Medical Xpress 2011-2015, Science X network (09/07/15)
Tags: MS, multiple sclerosis, neurological disease, cognition, research
New findings published in Neuropsychology reveal decreased connectivity between network-specific brain regions are to blame for the central deficit common to the various cognitive changes associated with multiple sclerosis.
In the first study of its kind, researchers at the Centre for BrainHealth at The University of Texas at Dallas and The University of Texas Southwestern Medical Centre found that, compared to healthy controls, individuals with MS exhibit weaker brain connections between the dorsolateral prefrontal cortex and posterior brain regions. The change amounts to a breakdown in communication between the part of the brain responsible for executing goal-directed thought and action and the regions responsible for carrying out tasks related to cognitive speed such as visual processing, motor execution, and object recognition.
The researchers believe the diminished connections are likely to be the result of decreased white matter surrounding the neurons in the brain.
"Our study is the first to really zero in on the physiology of cognitive speed, the central cognitive deficit in MS," explained principal investigator Bart Rypma, PhD.
"While white matter is essential to efficient network communication, white matter degradation is symptomatic of MS. This study really highlights how tightly coupled connectivity is to performance and illuminates the larger, emerging picture of white matter's importance in human cognitive performance."
Collaborating with Elliot Frohman, MD, PhD, director of the Multiple Sclerosis Program and Clinical Centre at UT Southwestern, the study recruited 29 participants with relapsing-remitting MS and 23 age- and sex- matched healthy controls. Participants underwent functional magnetic resonance imaging (fMRI) while completing a measure of cognitive processing speed.
Participants were given four seconds to view a nine-item key of number and symbol pairs (for example '+' above the number 3) and one number-symbol pair probe. Participants were asked to indicate with a left or right thumb button press whether or not the probe appeared in the key.
While accuracy was similar for both healthy controls and individuals with MS, response times for individuals with MS were much slower. Analysis of the fMRI data revealed that while completing this measure, MS patients showed weaker functional connections with dorsolateral prefrontal cortex.
"These findings reveal a diffuse pattern of disconnectivity with executive areas of the brain," explained the study's lead author, Nicholas Hubbard.
"Importantly, these decreases in connectivity predicted MS-related cognitive slowing both in and out of the fMRI environment suggesting that these results were not specific to our task, but rather were able to generalize to other situations where cognitive speed is required."
This research supports the need for therapies that target white matter structures and white matter proliferation. Rypma and Hubbard are currently conducting research to further explore the physiology of white matter to better understand cognitive speed reductions not only in MS, but also in healthy aging individuals.
Source: EurekaAlert! Copyright © 2015 by the American Association for the Advancement of Science (AAAS) (08/07/15)
Tags: MS, multiple sclerosis, cognition, impaired concentration, attention, memory, judgment, research
Experts in Nottingham are leading a major new study into how people with multiple sclerosis (MS) could overcome problems with attention and memory associated to their condition.
The Cognitive Rehabilitation for Attention and Memory in people with Multiple Sclerosis (CRAMMS) trial will evaluate the effectiveness of new strategies to improve and compensate for these difficulties and aims to improve the quality of life for the patient.
The trial is being led by Nadina Lincoln, Professor of Clinical Psychology in the Division of Rehabilitation and Ageing at The University of Nottingham and Dr Roshan das Nair, consultant clinical psychologist at Nottingham University Hospitals NHS Trust and honorary Associate Professor in the University's Division of Rehabilitation and Ageing.
Funded by the National Institute for Health Research (NIHR) Health Technology Assessment (HTA) programme, the trial will begin recruiting participants later this month.
Professor Lincoln said: "The purpose of our research is to help people with multiple sclerosis boost their everyday memory so they can get on with their lives and do the things that people take for granted, for example remembering to pick their children up from school, turning the stove off, or knowing where they have put things.
"It will also provide them with strategies to enable them to concentrate on information without getting distracted."
Memory and attention problems are common complaints for those who have multiple sclerosis. More than 100,000 people in the UK have multiple sclerosis and of these, 50,000 will have problems with attention and memory at some stage in the progression of their condition.
Very few people with multiple sclerosis get treatment for cognitive problems in usual clinical practice, despite some evidence that cognitive rehabilitation may help reduce problems in attention and everyday forgetting. However, cognitive rehabilitation for people with multiple sclerosis has not been demonstrated to be effective or cost-effective in large-scale randomised controlled trials.
The study will be exploring the benefits of using internal memory aids, such as mnemonics -- using patterns, words and images to remember details -- and external aids, such as diaries, mobile phones and cameras. The researchers will also be looking for other imaginative ways to help improve memory and reduce forgetting.
The study is being conducted in collaboration with Swansea University, Nottingham University Hospitals NHS Trust, Sheffield Teaching Hospitals NHS Trust, The Walton Centre NHS Trust, and University Hospitals Birmingham NHS Trust.
They will recruit 400 volunteers, aged 16 to 69 years, from NHS hospitals, rehabilitation centres, multiple sclerosis charities, and web forums. About half the volunteers will then receive a 10-week group intervention at one of the study centres in Nottingham, Sheffield, Liverpool and Birmingham. The groups will focus on strategies to improve attention and to reduce memory problems in daily life. The remaining volunteers will continue to receive their existing level of care.
If this study confirms the benefits of cognitive rehabilitation it could lead to a change in clinical practice in the NHS and abroad. The researchers will also use questionnaires to determine the cost-effectiveness of this intervention, and to get feedback from those taking part in the trial to establish if intervention improved their quality of life.
Source: EurekaAlert! Copyright © 2015 by the American Association for the Advancement of Science (AAAS) (26/03/15)
Cognitive impairment is a major debilitating feature of multiple sclerosis, and is estimated to occur in more than 50% of people living with MS at some point during the disease. These cognitive impairments can appear as difficulties with learning and memory, and deterioration of executive functions, such as planning or decision-making, focusing attention, multi-tasking, and problem-solving. People living with cognitive deficits can experience greatly diminished quality of life and loss of independence while facing the realization that treatment options are few-and-far-between. There are currently no drug therapies available that can specifically treat cognitive impairments in people living with MS, and cognitive rehabilitation studies have shown mixed success to date.
One approach that is emerging as a promising strategy for treating cognitive dysfunction in MS is exercise training. There is compelling experimental evidence showing that specific types of exercise training can improve cognition in both the general population and in people with certain neurological conditions like stroke, traumatic brain injury, and schizophrenia. For people living with MS, there have been three controlled clinical trials that have examined the effects of exercise on some aspects of cognition, although the results so far have been mixed. Part of the reason for these inconclusive findings is that the types and intensities of exercise have yet to be standardized, making comparisons across studies difficult.
A study published in the Journal of Clinical and Experimental Neuropsychology by Dr. Robert Motl and colleagues examined the short-term effects of several types of aerobic and non-aerobic exercise training on cognitive performance in people living with relapsing-remitting MS.
The study was performed on 24 individuals with relapsing-remitting MS. The participants underwent assessment of disability status using the Expanded Disability Status Scale (EDSS); eligible participants needed to be able to walk with or without minimal assistance (e.g. cane or crutch) in order to be able to participate in the exercise routines.
The researchers used the modified-flanker test to assess each subject’s reaction time and accuracy in identifying a randomly-presented object while blocking out either helpful or distracting information on either side of the object. In other words, the test allowed the researchers to measure the participants’ attention and executive functions (i.e. ability to suppress information that is either related or unrelated to the task).
The procedure consisted of five sessions (one per week); the first session established the baseline for exercise endurance fitness and trained the participants in the modified-flanker test, and was followed by four testing sessions. For each testing session, participants took the modified-flanker test, followed by one of three exercises (treadmill walking, stationary bicycle, or guided yoga) or quiet rest. After completion of the exercise and a cool-down period, participants took the modified-flanker test again to determine whether the exercise training affected performance on the test. For each session, participants performed a different exercise, so that by the end of the experiment each participant performed every exercise in a random order.
The researchers measured the effects of each type of exercise on participants’ performance in the modified-flanker test, and compared that to their performance after quiet rest. They found that treadmill walking improved reaction time on the test with no improvement in accuracy compared to quiet rest; the reaction time was particularly improved in trials where the target object was surrounded by distracting information.
Both stationary bicycling and guided yoga also improved test reaction time without improving accuracy compared to quiet rest, although the reaction time improvements were not seen in trials where the target object was surrounded by distracting information.
The results of this study show that several types of exercise can improve cognitive performance and executive functions in people with relapsing-remitting MS. Treadmill walking in particular appeared to have the strongest effect on improving selective attention and blocking distracting information in this study; although the reason for this is unclear, the authors suggested that since impaired ambulation is so common in people with MS, treadmill walking perhaps stimulates those parts of the brain involved in attention to a greater degree than stationary cycling or yoga. The improvements in test performance were only seen in reaction time and not accuracy, although accuracy scores at baseline were already quite high, so there was very little room for improvement. A limitation of this study was that overall, the participants were not cognitively impaired, and it remains to be seen how people affected by MS with cognitive impairment could benefit from exercise training, as well as how to adapt exercise training in those with severe physical disability who cannot carry out these exercises.
The findings from this study contribute to a growing body of literature linking physical activity to neuroplasticity in the brain, both in the general population and in people living with MS. While the bulk of this research has looked at ways of harnessing neuroplasticity for promoting physical rehabilitation, an emerging area of study is the application of exercise interventions to improving cognitive impairment. Visit the research blog to learn more about neuroplasticity in MS.
Sandroff BM et al. (2015) Acute effects of walking, cycling, and yoga exercise on cognition in persons with relapsing-remitting multiple sclerosis without impaired cognitive processing speed. J Clin Exp Neuropsychol. 37(2):209-19
Source: MS Society of Canada © 2015 MS Society of Canada (25/03/15)
A study from a team of researchers at the Kessler Foundation provides new findings on multiple sclerosis (MS). According to the study, published in the journal Frontiers in Neurology, cognitive fatigue exhibited by MS patients is related to the length of the task they are involved in.
Fatigue is one of the most reported symptoms of Multiple Sclerosis (MS) with a prevalence estimation ranging from 70 to 90%. Cognitive fatigue can be a result of both cognitive and physical exertion, and usually presents as subjective sensations or objective changes in performance, fatigue, and fatigability.
Treating cognitive fatigue clinically is complicated because there is a poor understanding of the factors contributing to this combination of symptoms.
In their study titled “Subjective cognitive fatigue in MS depends on task length,” Joshua Sandry from the Neuropsychology and Neuroscience Research, Kessler Foundation, and colleagues examined the relationships between subjective and objective cognitive fatigue, information processing domain (PS), working memory (WM) cognitive load and time on a task in 32 patients with Multiple Sclerosis (MS). The results were compared with 24 healthy controls.
Data analysis showed that subjective cognitive fatigue was higher for the PS task, increased across time, and was higher in the MS group compared to healthy controls. Furthermore, the results revealed that subjective and objective fatigue were independent variables. Morevoer, subjective cognitive fatigue increased with the length of time spent on a task, strongly suggesting that cognitive fatigue in MS is a function of time.
The researchers indicate that this new understanding may help to inform future research studies and help clinicians conduct evaluations of cognitive fatigue in MS. This can ultimately lead to better treatment strategies to cognitive fatigue in Multiple Sclerosis.
Concerning these results, lead author Dr. Joshua Sandry said in a recent press release, “In our study, task length was the factor associated with subjective cognitive fatigue,” “which supports the hypothesis of Temporal Fatigue. This finding should be considered when designing cognitive studies in MS populations. More research is needed to look at these parameters in people with different types of MS, different levels of cognitive impairment and in more advanced stages.”
Source: Multiple Sclerosis News Today © BioNews-tx.com 2015 (23/01/15)
A 17-year longitudinal study published online ahead of print in the Multiple Sclerosis Journal found that corpus callosum area (CCA) was closely associated with cognitive decline in multiple sclerosis patients (Granberg et al., 2014). The results may point to a refreshingly uncomplicated biomarker for cognitive and physical disability in MS patients.
The researchers examined a cohort of 37 MS patients in 1996, with follow-up examinations in 2004 and 2013, to assess changes in their CCA. In order to compare CCA from patient to patient, the researchers normalised each patient’s midsagittal CCA to his or her midsagittal intracranial skull surface area. They called the resulting measurement the normalized corpus callosum area (nCCA).
In the 2004 and 2013 follow-ups, only 23 of the patients remained in the study, and the researchers compared their results with those of 23 age- and sex-matched healthy controls. At each examination the participants were assessed on the Expanded Disability Status Scale (EDSS) and they performed the Symbol Digit Modalities Test (SDMT), a measurement of processing speed.
Overall, nCCA correlated well with SDMT and EDSS scores in patients (r = 0.793, p < 0.001; r = −0.545, p < 0.001, respectively) after adjusting for disease duration, age, and sex and also adjusting for multiple comparisons. These correlations outperformed other measures of brain atrophy such as gray matter fraction and normalised lesion volume.
“I wouldn’t have expected that the simple measurements of the corpus callosum would actually outperform the volumetric measurements,” Tobias Granberg, M.D., who is a current Ph.D. candidate at Karolinska Institutet in Stockholm, Sweden, told MSDF. He said that it takes only about 45 seconds to obtain the measurement from each MRI sequence.
Although the nCCA measurements showed a strong correlation with patients’ SDMT and EDSS scores at each time point, the nCCA measurements taken in 1996 were not predictive of each patient's SDMT and EDSS scores 17 years later. Granberg and his colleagues adjusted the patients’ nCCA with their SDMT and EDSS scores at the outset and found no statistically significant relationship between nCCA and SDMT or EDSS in 2013. Granberg told MSDF that he felt the lack of statistical significance was due to the small sample size, and that future studies with larger sample sizes would show greater predictive power of nCCA.
“There are some previous studies that have used these simple measurements and have proven that they can help in deciding which patients will be going from having clinically isolated syndrome into having MS,” Granberg said.
Granberg also said that he and his colleagues are conducting a companion study to this one directly comparing corpus callosum area to the corpus callosum index, another method of measuring atrophy. He’s also testing nCCA as a way to potentially differentiate patients in the relapsing versus the progressive phase of the disease.
Corpus callosum atrophy is strongly associated with cognitive impairment in multiple sclerosis: Results of a 17-year longitudinal study. Granberg T, Martola J, Bergendal G, Shams S, Damangir S, Aspelin P, Fredrikson S, Kristoffersen-Wiberg M Mult Scler. 2014 Dec 5. PMID: 25480866. Abstract
Source: Multiple Sclerosis Discovery Forum Copyright © 2014 MGH and ACP (19/01/15)
Have you ever eaten a turkey dinner and afterwards someone says that the feeling of drowsiness is caused by the tryptophan in the meat? According to Texas A&M University Professor Dr. Nicolaas Deutz, “This story about tryptophan in turkey is just kind of a running joke, it has nothing to do with the tryptophan.” Sleepiness probably has more to do with eating a big meal, according to Deutz.
It’s not that the amino acid can’t have potent effects on the central nervous system — it simply turns out that turkey does not have unusual levels of tryptophan. Tryptophan is normally converted to the neurotransmitter serotonin. Serotonin controls sleepiness, and higher levels of serotonin seem to improve mood.
While the fable of turkey making you tired might be a joke, using tryptophan to try to improve memory problems in people with multiple sclerosis, however, is far from funny, according to Dr. Deutz. Funded by the Maastricht University Medical Center, he is studying tryptophan-enriched diets and their effect on both mood and cognition in people with the de-myelinating autoimmune disorder.
Deutz and his colleagues at Texas A&M’s Center for Translational Research in Aging and Longevity (CTRAL) have studied tryptophan depletion for several years. They have found that both memory and cognition are adversely impaired when people do not get enough tryptophan. Using brain imaging, they saw less activity in an area of the brain responsible for memory encoding — called the hippocampus — when people lacked tryptophan. In a separate study in women, they saw that mood also became worse in people with a family history of depression.
Because of these effects of tryptophan depletion, Deutz decided to try giving older people with multiple sclerosis tryptophan. He noted that although the onset of multiple sclerosis is during age 20-50, older people with the disease have particular problems with cognition and depression. He noted, “In many ways, multiple sclerosis is almost like the brain getting older on its own. The memory problems really look similar to dementia, Parkinson’s and other diseases that affect older people.”
Previous studies of tryptophan supplementation were limited by a toxic byproduct. According to the investigators of the current trial, tryptophan can now be supplied in a non-toxic form as a component of different natural proteins.
“This research has been around for nearly 30 or 40 years,” said Deutz. “What makes it new is finally bringing it to a translational/clinical level and having a practical application. We now have more tools to measure metabolism and safer ways to digest large amounts of tryptophan.”
Source: Multiple Sclerosis News Today © BioNews-tx.com 2014 (18/12/14)
The Cognitive Rehabilitation for Attention and Memory trial (CRAMMS), a major study to be conducted on patients with multiple sclerosis, was recently awarded £1,167,000 by the National Health Service (NHS), through its Health Technology Assessment (HTA) Program.
The study, which is expected to be the largest trial of its kind in the United Kingdom, is designed to examine MS patients’ cognitive rehabilitation capacities and determine if a group of cognitive rehabilitation programs is able to improve patients’ quality of life.
This symptom management clinical trial for MS is being conducted because so many patients experience difficulties in cognitive processes, including loss in memory, decision making, and concentration, and there are currently few effective treatments available for the management of these symptoms. Therefore, the CRAMMS trial is expected to be able to advance the development of new therapies to improve the lives of patients with these problems.
The trial, which is expected to occur between September of 2014 and August of 2018 at four centres in Nottingham, Sheffield, Liverpool, and Birmingham, is currently enrolling patients, who must be diagnosed with MS and between the ages of 18 and 70 years old. During the trial, participants will be enrolled over the course of 16 months and will participate in either weekly group cognitive rehabilitation sessions with a psychologist and their usual care, or just their usual care. The investigators will then evaluate and compare the effects on the two groups.
“We do not know whether taking part in the study will help but we expect that some people will find the intervention helps them cope with memory and attention problems,” the website of the trial states. “However, the information we get from this study may help us to treat people with MS and attention and memory problems better in future. There are no particular risks involved in taking part in this study.”
In addition, the trial is also expected to raise particular attention and investment into other research focused to the disease.
Source: Multiple Sclerosis News Today © Copyright 2014 BioNews Services, LLC (21/11/14)
Prematurely severe cognitive impairment in multiple sclerosis patients could be an effect of autoantibodies against the N-methyl-D-aspartate (NMDA) receptor complex, with natalizumab (Tysabri) withdrawal a potential contributor, a case report from Germany suggested.
In an MS patient who had to be confined to a nursing home at age 39 because of cognitive deficits amounting to dementia, immunoglobulin G-type antibodies to the NMDA receptor's NR1 subunit were found in cerebrospinal fluid samples, according to Klemens Ruprecht, MD, of Charité-Universitätsmedizin Berlin, and colleagues.
These autoantibodies are "the characteristic laboratory finding of anti-NMDA receptor encephalitis," they wrote online in JAMA Neurology.
When severe cognitive deficits appear at young ages, Ruprecht and colleagues concluded, they could "be related to a superimposed antibody-mediated autoimmune encephalitis."
Cognitive deficits are common in MS patients but the mechanisms underlying them are not well understood, the researchers noted. Normally these come on gradually and at later ages. However, as in the current case, occasionally such deficits appear early and progress rapidly. In such cases, clinicians should consider causes outside the MS disease process, Ruprecht and colleagues suggested.
"The diagnosis of those patients will require a high degree of clinical suspicion as cognitive symptoms are rather frequent in MS and may mask or be confounded with features of antibody-mediated encephalitides," they wrote. "Nevertheless, testing for antineuronal antibodies appears warranted in patients with MS with unusual neuropsychiatric symptoms."
Also, in the patient who was the subject of the case report, the anti-NMDA antibody pathology may have had some relation to treatment with natalizumab.
The woman was first diagnosed with MS at age 33. Her disease course was unremarkable until age 37 when she gave birth, and then rapidly developed cognitive deficits marked primarily by memory loss. She was treated aggressively with MS therapies including natalizumab, cyclophosphamide, and mitoxantrone, with no impact on the progression of cognitive decline.
At age 43, during her fourth year of nursing home residency, she underwent a complete re-evaluation that included analysis of current and stored serum and CSF samples. At that point, anti-NMDA antibodies were discovered in the CSF samples, including those taken shortly after the cognitive symptoms appeared.
The natalizumab was withdrawn 2 years after the patient started on it, out of concern for the risk of progressive multifocal leukoencephalopathy since she had also been on immunosuppressive therapy.
Five months later, she developed a "fulminant" MS relapse, the researchers indicated, which was accompanied by a spike in anti-NMDA antibody titers -- a sign that the latter may have had some connection to the natalizumab withdrawal.
Ruprecht and colleagues noted that the drug suppresses CD138-positive plasma cells. "Therefore, it seems plausible that natalizumab withdrawal facilitated entry of NMDA receptor antibody-producing plasma cells to the central nervous system," they wrote.
The patient died of urosepsis last December, almost 8 years after the onset of cognitive symptoms.
She represented only the second known case of anti-NMDA encephalitis in an MS patient, the researchers indicated, and the first in whom the antibodies targeted the receptor complex's NR1 subunit (NR2B was the target in the previous case).
But they suggested the comorbid conditions may occur more frequently than these case reports might suggest, because cognitive impairments are common in MS and clinicians may not think to look for other causes.
The study was funded by the German government. Authors reported relationships with Bayer Healthcare, Merck Serono, Biogen Idec, Novartis, Ovamed, Teva, Diamed, Genzyme, and Sanofi.
Primary source: JAMA Neurology
Source reference: Fleischmann R, et al "Severe cognitive impairment associated with intrathecal antibodies to the NR1 subunit of the N-methyl-D-aspartate receptor in a patient with multiple sclerosis" JAMA Neurology 2014; DOI: 10.1001/jamaneurol.2014.1817.
Source: Medpage Today © 2014 MedPage Today, LLC (11/11/14)
Research supports the slowed processing speed in the executive deficits found in individuals with multiple sclerosis (MS), according to a paper from the Kessler Foundation.
The investigators wanted to further explore cognitive deficits, since they affect nearly half the population of MS patients. These disabling symptoms can adversely affect patients' quality of life. Data was collected from 50 MS patients and 28 healthy controls and all patients were evaluated through executive functioning tasks both with and without a processing speed element. The tasks included the Trail Making and Wisconsin Card Sorting tests.
The researchers found the MS patients performed on tasks related to executive function compared to their healthy counterparts. While analyzing the data for speed control, the scientists discovered the differences between the healthy and MS group disappeared. The data also revealed no difference on executive tasks with non-processing speed demands.
Disease progression was also something the researchers investigated throughout this study in the MS group. For MS patients, higher atrophy was associated with greater deficits on speeded executive tasks. However, the relationship vanished when the researchers controlled for processing speed. The researchers noted there was no association between atrophy and performance when analyzing non-processing speed executive tasks.
“Our results point to slowed processing speed as the mechanism underlying deficits in executive function,” Nancy Chiaravalloti, PhD, said in a press release. “Understanding this association is an important step toward the development of effective cognitive rehabilitation strategies for individuals with MS. We should focus our efforts on 2 key domains - processing speed and memory.”
Executive deficits in MS may be explained by slow processing speed, the researchers concluded in their paper. Slowed processing speed may be a primary impairment which underlies other cognitive functions. They believe it is important to unwrap processing speed contributions to executive function, which would be an important step toward the development of appropriate treatment and rehabilitation techniques for MS patients.
"Additional neuropsychological measures should be included in future studies,” Chiaravalloti added. “We also need to focus on the contribution of specific brain pathology, such as frontal atrophy and lesion load, to executive deficits.”
Source: Rehabilitation Psychology & HCPLive Copyright HCPLive 2006-2014 (07/10/14)
Kessler Foundation scientists have shown that working memory may be an underlying mechanism of cognitive reserve in multiple sclerosis (MS).
This finding informs the relationships between working memory, intellectual enrichment (the proxy measure for cognitive reserve) and long-term memory in this population.
"Working memory mediates the relationship between intellectual enrichment and long-term memory in multiple sclerosis: An exploratory analysis of cognitive reserve" (doi: 10.1017/S1355617714000630) was published online ahead of print by the Journal of the International Neuropsychological Society on July 14. The authors are Joshua Sandry, PhD, and research scientist James F. Sumowski, PhD, of Neuropsychological & Neuroscience Research at Kessler Foundation. Dr. Sandry is a postdoctoral fellow funded by a grant from the National MS Society.
Cognitive symptoms, including deficits in long-term memory, are known to affect approximately half of individuals with MS. This study was conducted in 70 patients with MS, who were evaluated for intellectual enrichment, verbal long-term memory, and working memory capacity.
"We found that working memory capacity explained the relationship between intellectual enrichment and long-term memory in this population," said Dr Sandry. "This suggests that interventions targeted at working memory in people with MS may help build cognitive reserve to protect against decline in long-term memory."
Source: Science Codex (10/09/14)
Persons with MS may be able to improve self-awareness via task-oriented cognitive rehabilitation(26/08 14)
A new study of self-awareness by Kessler Foundation researchers shows that persons with multiple sclerosis (MS) may be able to improve their self-awareness through task-oriented cognitive rehabilitation. The study was epublished ahead of print on July 2 in NeuroRehabilitation. (Yael Goverover, Helen Genova, Hali Griswold, Nancy D. Chiaravalloti & John DeLuca: Metacognitive knowledge and online awareness in persons with multiple sclerosis doi: 10.3233/NRE-141113). Self-awareness is one's ability to recognise cognitive problems caused by brain injury. This is the first study of self-awareness in MS that includes assessment of online awareness, as well as metacognitive awareness.
Yael Goverover, PhD, OT, is a visiting scientist at Kessler Foundation. She is an associate professor at New York University. Dr. Goverover is a recipient of the National Institute on Disability and Rehabilitation Research Fellowship award (Mary Switzer Award). Drs. Genova, Chiaravalloti and DeLuca are MS researchers at Kessler Foundation.
The researchers assessed 18 people with MS and 16 healthy controls for 2 types of self-awareness - metacognitive knowledge of disabilities (or intellectual awareness) and online awareness (emergent or anticipatory awareness). They also looked at the relationships among self-awareness, functional performance and quality of life (QoL). Assessment involved the Functional Behavior Profile, questionnaires administered before and after functional tasks (purchasing cookies and airline tickets via the Internet) and the Functional Assessment of Multiple Sclerosis measure.
"Results showed that compared with controls, people with MS assessed their actual performance more realistically following completion of a task. This suggests that individuals may be able to improve their self-awareness through more experience with tasks," noted Nancy Chiaravalloti, PhD, director of Neuropsychology & Neuroscience Research at Kessler Foundation. "Research that leads to better understanding of types of self-awareness, functional outcomes and QOL will aid the development of effective assessments and rehabilitation interventions," said Dr. Chiaravalloti. "The association between online awareness and task performance in this study, for example, may have implications for cognitive rehabilitation strategies in the MS population."
Source: News-Medical.Net Copyright AZoM.com Limited 2000-2014 (26/08 14)