Objectives: To characterize the cognitive abilities of patients with primary progressive multiple sclerosis (PPMS) and relapsing-remitting multiple sclerosis (RRMS) compared with healthy controls (HCs) matched for age, sex, and education level while considering the different characteristics of PPMS and RRMS and to compare the cognitive patterns of these types of multiple sclerosis.
Methods: Forty-one patients with PPMS, 60 patients with RRMS, and 415 HCs were recruited in a cross-sectional study. Controls were divided into 20 groups according to age, sex, and education level. Participants were assessed with a large battery of neuropsychological (NP) tests that included a modified version of the Brief Repeatable Battery, the Stroop test, computerized tests from the Test of Attentional Performance battery, the numerical span test, and the Rey Complex Figure.
Results: Patients with PPMS performed worse than their matched HCs on nearly all NP tests. Patients with RRMS performed worse than matched HCs on a computerized digit-symbol substitution task and the alertness test, reaction time for visual scanning, and Paced-Auditory Serial Addition Test-3 seconds. Patients with PPMS had worse NP scores and were more impaired in cognitive domains than patients with RRMS. After controlling for Expanded Disability Status Scale score, the results remained unchanged.
Conclusion: The patients with PPMS presented with a wide range of cognitive deficits in information processing speed, attention, working memory, executive function, and verbal episodic memory, whereas the impairments in patients with RRMS were limited to information processing speed and working memory compared with their matched HCs. Cognitive deficits were more severe in patients with PPMS than in patients with RRMS.
Aurélie Ruet, MD, Mathilde Deloire, PhD, Julie Charré-Morin, Msc, Delphine Hamel, Msc and Bruno Brochet, MD
Source: Neurology © 2013 American Academy of Neurology (21/03/13)
A new computerised cognitive test for the detection of information processing speed impairment in multiple sclerosis(13/03/13)
Summary: It is well known that cognitive impairment is a prominent feature of MS. Information processing speed (IPS) impairment is the most common cognitive alteration observed in patients with MS.
This research group looked at a new IPS test called the Computerised Speed Cognitive Test (CSCT), which can be easily administered in daily clinical practice for testing IPS impairment. A group of 60 RRMS, 41 PPMS and 415 healthy controls underwent an IPS battery, which included assessment of reaction times of subsets of the Test of Attentional Performance battery, a newly developed digit/symbol substitution task, and the CSCT.
The CSCT is made up of a key displayed on the upper part of the computer screen with a list of nine symbols, with a list of nine digits displayed under this. The sequence of symbols and digits of the key are automatically generated for each session of training and testing.
The CSCT had good reliability, with a weak practice effect at the 6-month time point. There was a strong correlation between the CSCT with the Symbol Digit Modalities Test (SDMT) and with other IPS tests in patients with MS. The CSCT had the best sensitivity for predicting IPS impairment and was one of the most accurate tests among the IPS battery. This test could be used as part of a larger neuropsychological battery, as well as by neurologists in everyday practice.
BACKGROUND: Cognitive impairment in multiple sclerosis (MS) primarily applies to information processing speed (IPS).
OBJECTIVE: To evaluate psychometric properties of a new digit/symbol substitution test in healthy subjects and patients with MS, and assess its ability to detect IPS impairment in patients with MS.
METHODS: A sample of MS patients, 60 relapsing-remitting (RRMS) and 41 primary progressive MS (PPMS), and 415 healthy controls (HCs) underwent an IPS battery, including assessment of reaction times of subtests of the Test of Attentional Performance battery and a newly developed in-house digit/symbol substitution task, the Computerised Speed Cognitive Test (CSCT). The CSCT was additionally evaluated in a second cohort of 31 RRMS and 12 progressive MS patients, for comparison with the Symbol Digit Modalities Test (SDMT).
RESULTS: The CSCT had good reliability in both HCs and patients with MS. It showed a weak practice effect at the 6-month time point. This test had good ecological validity in MS patients. There was a strong correlation between the CSCT with the SDMT and with other IPS tests in patients with MS. The CSCT had the best sensitivity for predicting IPS impairment and was one of the most accurate tests among the IPS battery.
CONCLUSION: The CSCT appeared as a good candidate for detecting IPS impairment in MS patients.
Authors: Ruet A, Deloire MS, Charré-Morin J
Sources: Mult Scler. 2013 Mar 4 & Pubmed PMID: 23459569 (13/03/13)
People with multiple sclerosis (MS) who have cognitive problems, or problems with memory, attention, and concentration, have more damage to areas of the brain involved in cognitive processes than people with MS who do not have cognitive problems, according to a study published in the March 6, 2013, online issue of Neurology, the medical journal of the American Academy of Neurology.
The study used a type of MRI brain scan called diffusion tensor imaging along with regular MRI scans to compare brain measurements in 20 people with MS who had related cognitive problems, 35 people with MS who did not have cognitive problems and 30 healthy participants.
The diffusion tensor images showed that, compared to the healthy control participants, 49 percent of the investigated brain white matter had impaired integrity in those with MS and no cognitive problems, while impaired integrity was evident in 76 percent of the investigated white matter of those with MS and related cognitive problems. In the people with MS-related cognitive problems, the extra white matter dysfunction was particularly seen in areas important for cognitive skills, such as the thalamus.
"This state-of-the-art imaging technology confirms that cognitive symptoms in MS have a biological basis," said study author Hanneke E. Hulst, MSc, of VU University Medical Center in Amsterdam, the Netherlands. "The consequence of this discovery is that imaging can now be used to capture a wider spectrum of changes in the brains of people with MS, and will therefore help determine more accurately whether new treatments are helping with all aspects of the disease."
Cognitive problems are common in MS, affecting up to 65 percent of people with the disease.
Source: News-Medical.Net (07/03/12)
Studies have shown that the popular video game, Dance Dance Revolution (DDR), which requires players to coordinate their movements to the beat of music, may help improve balance and mobility in certain patient populations. Now, researchers at The Ohio State University Wexner Medical Center are the first to test the game's ability to help decrease the cognitive and physical effects of multiple sclerosis (MS).
An estimated 2.1 million people have multiple sclerosis (MS), an incurable inflammatory disease which progressively impairs nerve function in the brain and spinal cord. While studies with the elderly and Parkinson's patients have shown exercise can slow cognitive decline and improve coordination, similar information is lacking for patients with MS, leaving clinicians without data to help guide prescription of exercise programs.
"The video dancing game provides a good platform for our research because it addresses multiple issues that MS clinicians and patients face. We think our data will not only help doctors and therapists make good clinical recommendations, but provide an evidence based, in-home tool for patients that helps overcome access and cost issues associated with long term physical therapy," says Anne Kloos, PhD, PT, NCS, associate clinical professor of health and rehabilitation sciences in the Ohio State College of Medicine.
Kloos became interested in DDR as a potential therapy by conducting an earlier study of individuals with Huntington's disease. In that study, Kloos and her colleagues found that the interactive video game was a fun way to boost motivation and provide a mental and physical workout, in addition to being a convenient way to deliver physical therapy.
In early 2012, Kloos received a grant from the Ohio State Center for Clinical and Translational Science (CCTS) to examine the effects of DDR on mobility, brain plasticity and cognition in individuals with MS. In the ongoing trial, participants exercise using DDR three times a week for eight weeks. The patients' cognitive functions are tested at the beginning and end of the trial, and functional and structural magnetic resonance imaging is used to detect brain circuitry changes.
"DDR requires a lot of cognitive processing. Players must look at a screen and time their movements to the arrows on the screen," said research team member, Nora Fritz, DPT. "Incorporating DDR into standard MS treatments has the potential to improve balance, walking, cognition and motivation."
Fritz recently received a supplementary grant from the CCTS to expand the work started by Kloos, and is being mentored by both Dr. Kloos and Deborah Larsen, PhD, PT, Director of the Ohio State School of Health and Rehabilitation Sciences. With the additional funding, Fritz will investigate the differences in dual tasking abilities between individuals with MS and healthy controls and whether playing DDR will improve dual tasking abilities.
Many people diagnosed with MS feel as though they have been given a life sentence of incapacitation. Kloos and Fritz are looking to restore hope and improve the quality of life for patients suffering from this disease, something that study participants feel they are achieving.
"Participating in the study and doing the dance program has helped me feel healthier and more independent. And that is really exciting," says Tracy Blackwell, a study participant.
The trial is still enrolling patients.
Source: Science Daily Copyright © 1995-2012 ScienceDaily LLC (28/02/13)
Mental comorbidity and multiple sclerosis: validating administrative data to support population-based surveillance(07/02/13)
While mental comorbidity is considered common in multiple sclerosis (MS), its impact is poorly defined; methods are needed to support studies of mental comorbidity. We validated and applied administrative case definitions for any mental comorbidities in MS.
Using administrative health data we identified persons with MS and a matched general population cohort. Administrative case definitions for any mental comorbidity, any mood disorder, depression, anxiety, bipolar disorder and schizophrenia were developed and validated against medical records using a a kappa statistic (k). Using these definitions we estimated the prevalence of these comorbidities in the study populations.
Compared to medical records, administrative definitions showed moderate agreement for any mental comorbidity, mood disorders and depression (all k >=0.49), fair agreement for anxiety (k= 0.23) and bipolar disorder (k=0.30), and near perfect agreement for schizophrenia (k=1.0). The age-standardized prevalence of all mental comorbidities was higher in the MS than in the general populations: depression (31.7% vs. 20.5%), anxiety (35.6% vs. 29.6%), and bipolar disorder (5.83% vs. 3.45%), except for schizophrenia (0.93% vs. 0.93%).
Administrative data are a valid means of surveillance of mental comorbidity in MS. The prevalence of mental comorbidities, except schizophrenia, is increased in MS compared to the general population.
The complete article is available as a provisional PDF.
Source: Biomed Central © 2013 BioMed Central Ltd (07/02/13)
Researchers at Trinity College Dublin in collaboration with colleagues in the Department of Neurology at St Vincent's University Hospital and University College Dublin have recently reported new insights into cognitive changes in multiple sclerosis, using newly developed signal processing methods. The findings have been recently published in the international journal PlosOne.
The multidisciplinary research involved neurologists, biomedical engineers and neuropsychologists. Their focus was on cognitive impairment which affects nearly 65% of multiple sclerosis (MS) patients and can occur in the absence of physical disability.
Dysfunctions in speed of information processing, attention, memory and executive functions are most typically observed in MS patients, which have an adverse impact on daily life. It is important to recognise cognitive impairment as early as possible and to monitor its course frequently. However, neuropsychological tests to assess cognitive function can only be carried infrequently and do not provide an objective measure of cognitive impairment.
The research team was led by Professor Richard Reilly, Professor of Neural Engineering at Trinity College, and Professor Niall Tubridy, Department of Neurology at St Vincent's University Hospital. They addressed cognitive impairment assessment by developing new mathematical methods to extract information from MS subjects' scalp with electroencephalography (EEG) data that allows objective measurement of cognitive function at frequent intervals and more importantly offers new insights into the origins of this cognitive impairment in MS.
The team acquired EEG data using 128-scalp electrodes from 95 subjects (MS patients and controls subjects) while they completed a series of visual and auditory stimulus experiments. They then employed their newly developed mathematical methods to process the spatiotemporal EEG data developing a measure of cognitive function.
Professor Reilly commented that "objective, reliable EEG methods such as these developed in this study may have the potential to aid the detection and monitoring of cognitive impairment in MS, and therefore to complement clinical neuropsychological assessment."
Professor Tubridy added that "the relationship between pathological changes in the brain white and grey matter, neurophysiological and neuropsychological cognitive function is imprecisely defined in MS. This study provides new information on the impact of the cognitive impairments on the condition and will help us look for new interventions to improve the quality of life of our patients".
Professor Reilly added that "future studies will explore the neural information using new advanced data analysis methods such as approaches to model the distributed nature of EEG by incorporating activations and structural information from individual subjects' MRI image data". In addition, he said that "longitudinal studies of EEG scalp and deeper brain electrical activity spanning over several years are required to fully determine if EEG data has clinical utility in predicting the changes in cognitive function in MS".
More information: Kiiski H, Reilly RB, Lonergan R, Kelly S, O'Brien MC, et al. (2012) Only Low Frequency Event-Related EEG Activity Is Compromised in Multiple Sclerosis: Insights from an Independent Component Clustering Analysis. PLoS ONE 7(9): e45536. doi:10.1371/journal.pone.0045536
Source: Medical Xpress © Medical Xpress 2011-2012 (10/10/12)
Summary: The authors have evaluated the effects of ginkgo biloba on cognitive function in people with MS with impaired cognition.
A treatment regimen of ginkgo 120 mg twice a day did not improve cognitive performance in persons with MS.
To determine whether Ginkgo biloba extract (ginkgo) improves cognitive function in persons with multiple sclerosis (MS).
Persons with MS from the Seattle and Portland VA clinics and adjacent communities who scored 1 SD or more below the mean on one of 4 neuropsychological tests (Stroop Test, California Verbal Learning Test II [CVLT-II], Controlled Oral Word Association Test [COWAT], and Paced Auditory Serial Addition Task [PASAT]) were randomly assigned to receive either one 120-mg tablet of ginkgo (EGb-761; Willmar Schwabe GmbH & Co, Germany) or one placebo tablet twice a day for 12 weeks. As the primary outcome, we compared the performance of the 2 groups on the 4 tests at exit after adjusting for baseline performance.
Fifty-nine subjects received placebo and 61 received ginkgo; 1 participant receiving placebo and 3 receiving ginkgo were lost to follow-up. Two serious adverse events (AEs) (myocardial infarction and severe depression) believed to be unrelated to the treatment occurred in the ginkgo group; otherwise, there were no significant differences in AEs. The differences (ginkgo - placebo) at exit in the z scores for the cognitive tests were as follows: PASAT -0.2 (95% confidence interval [CI] -0.5 to 0.1); Stroop Test -0.5 (95% CI -0.9 to -0.1); COWAT 0.0 (95% CI -0.2 to 0.3); and CVLT-II 0.0 (95% CI -0.3 to 0.3); none was statistically significant.
Treatment with ginkgo 120 mg twice a day did not improve cognitive performance in persons with MS.Classification of evidence:This study provides Class I evidence that treatment with ginkgo 120 mg twice a day for 12 weeks does not improve cognitive performance in people with MS.
Authors: Lovera JF, Kim E, Heriza E, Fitzpatrick M, Hunziker J, Turner AP, Adams J, Stover T, Sangeorzan A, Sloan A, Howieson D, Wild K, Haselkorn J, Bourdette D.
Source: Neurology. 2012 Sep 5 & Pubmed PMID: 22955125 (11/09/12)
Cognitive impairment in Multiple Sclerosis (MS) is well recognized, being documented even in the earliest stages of the disease. Anticholinergic drugs (ACD) are frequently used to address bladder symptoms in this population. ACD are known for their deleterious cognitive effects in older individuals; however their potential impact on cognition has received less attention in the context of MS.
To explore possible detrimental effects of bladder-directed ACD on cognitive functioning in MS.
42 MS patients who had been on classical, bladder-directed ACD for ≥6 months were compared to 46 patients not receiving ACD, in terms of their scores on Symbol Digit Modality Test (SDMT) and Selective Reminding Test (SRT). Patients also completed questionnaires for fatigue (Modified Fatigue Impact Scale — MFIS) and depression (Beck Depression Inventory–Fast Screen – BDIFS).
Patients using ACD showed significantly lower SDMT and SRT scores compared to those not using ACD (p<0.001; t-test). The association of lower cognitive test performance with ACD usage was robust, even when other variables (like age, gender, EDSS, etc.) were considered.
Our results suggest that chronic use of classical ACD for bladder symptoms may have a negative impact on cognitive functioning in MS patients. These potential cognitive side effects need to be considered both in clinical practice and research settings.
Roxana Cruce, Reza Vosoughi, Mark S. Freedman
The Ottawa Hospital Research Institute, Ottawa, Canada
Source; Multiple Sclerosis and Related Disorders Copyright © 2012 Elsevier Inc. All rights reserved (02/07/12)
Hot days worsen cognitive function in MS(13/03/12)
Patients with MS who require high levels of cognitive functioning should consider the effect of warmer weather on their memory and processing speeds, conclude researchers who show for the first time that warm weather might affect cognitive performance as well as lesion activity in MS.
Researchers from New Jersey in the US found among a group of 45 MS patients who were tested at baseline and after 6 months, cognitive performance declined more in those for whom the weather was warmer at follow-up than at baseline.
They also conducted a crosssectional investigation, looking at 40 people with MS and 40 matched healthy controls. After controlling for disease variables, there was an association between warmer weather and worse cognitive performance, but only among the patients with MS.
Writing in Neurology, the authors said their study was “the first to formally investigate the relationship between outdoor temperature and cognition”.
They said the results have “important implications for treatment,” suggesting that lifestyle decisions by patients with MS might need to take the results into consideration.
Summer sessions at university might be a bad idea, they said as an example.
“Clinicians should carefully monitor patients with MS for heat related cognitive exacerbations, which may occur even in the absence of sensorimotor symptomology,” they wrote.
In an accompanying editorial, two experts from Boston in the US said the study provided some bad news for clinical trials.
“Now cognitive performance joins the ranks of markers subject to annual fluctuations that potentially bias clinical trials, as do relapse rates and MS lesions.”
Neurology 2012; doi: WNL.0b013e31824d5834
Source: Neurology Update (13/03/12)
In a new study published in the March issue of Radiology, functional magnetic resonance imaging (fMRI) shows that cognitive rehabilitation changes brain function and improves cognitive performance in patients with relapsing-remitting multiple sclerosis (MS).
MS is a nervous system disease affecting the brain and spinal cord. MS damages a material called the myelin sheath that surrounds and protects nerve cells. This damage disrupts messages between the brain and other parts of the body, leading to symptoms such as muscle weakness, coordination and balance difficulties, numbness, problems with vision, memory loss and other cognitive issues. MS affects women more than men and often becomes symptomatic between the ages of 20 and 40.
In relapsing-remitting MS, the most common type, patients experience a series of attacks followed by partial or complete disappearance of symptoms. The interval between relapses can range from weeks to years.
For the study, Dr. Massimo Filippi, M.D., professor of neurology at the San Raffaele Vita-Salute University and director of the "BrainMap" interdepartmental research program and the Neuroimaging Research Unit, Department of Neuroscience, Scientific Institute San Raffaele, Milan, Italy and colleagues recruited 20 patients with relapsing-remitting MS.
Patients were randomized into two groups of 10. The first group received a 12-week program of computer-assisted cognitive rehabilitation of attention and information processing and executive functions, and the second (control) group received no cognitive rehabilitation.
Aspects of the rehabilitation program included a day-planning task, which employed realistic simulations of a set of scheduled dates and duties to address the patient's ability to organize, plan and develop solution strategies; and an attention task requiring the patient to simulate driving a train, carefully observing the control panel of the train and the countryside while encountering several distractions at increasing levels of difficulty.
All of the patients underwent neuropsychological assessment and MRI exams at baseline. As compared to their performance at baseline, the patients in the treatment group improved in tests of attention and information processing and executive functions. The fMRI results showed modifications in activity in several brain regions in the rehabilitation group, compared to the non-rehabilitation group. These fMRI modifications were correlated with cognitive improvement.
Analysis after cognitive rehabilitation found no structural changes in the gray matter or normal-appearing white matter of the brain in the treatment group.
"The findings demonstrated that computer-assisted cognitive rehabilitation in patients with MS results in an improvement of the trained cognitive functions," Dr. Filippi was quoted as saying.
"However, the structural integrity of the brain's gray matter and white matter showed no modifications in these patients, suggesting an impairment of structural plasticity."
Source: Medical Breakthroughs Copyright © 2012 Ivanhoe Broadcast News, Inc (23/02/12)
Researchers at UCLA's David Geffen School of Medicine found a way to stimulate an area of the brain that can strengthen memory and it is not in pill-form interestingly enough.
“For those of us with MS who are notorious for our memory issues,” says Sierra Blankenship of Lima, “this has got to be the best news ever. Unless you have MS, or know someone with MS, you just would not believe the things that we have done or even said sometimes because of this problem.”
The area called the entorhinal cortex, the main interface between the hippocampus and neocortex, was the focus and “critically it was the stimulation at the gateway into the hippocampus, and not the hippocampus itself, that proved effective,” said Dr. Fried the school's professor of neurosurgery.
Researchers followed seven epilepsy patients who had electrodes implanted in their brains, electrodes that were there to pinpoint the area of their seizures, and they were able to monitor their brain activity while memories were being formed by using a game.
Each patient played a video game that involved the layout of a city and a taxi that would pick up passengers and drop them off at a destination found within the city. Researchers were able to see if deep-brain stimulation of the entorhinal cortex or stimulation of the hippocampus was what changed memory and they found memory was strengthened when stimulation was applied to the entorhinal cortex.
"When we stimulated the nerve fibers in the patients' entorhinal cortex during learning, they later recognized landmarks and navigated the routes more quickly," said Fried. "They even learned to take shortcuts, reflecting improved spatial memory."
The findings may see future neuroprothetic devices that would stimulate the brain during specific stages of processing and the greatest part is that strengthening the memory this way doesn't need continuous stimulation; only a “boost” for when learning would be needed.
The article talks of the millions affected by Alzheimer's and Dr. Fried himself brought up early dementia, but considering researchers at OSU were able to show losing Myelin, the coating around the nerves in the brain, was more than the loss of “just” a coating, help for memory is clearly something needed for those with MS as well.
Researchers at OSU were able to show cause and affect of demyelination and how it relates to the hippocampus.
Right now, Fried said their findings “should be interpreted with caution” because of the small number of people who were followed, but it does open a window, albeit small, of opportunity for future studies.
Either by these researchers, or others, it doesn't matter. Finding ways for millions of people to battle a part of their disease that can create such sadness and frustration is something to look forward to.
Source: Examiner.com © 2006-2012 Clarity Digital Group LLC (13/02/12)
Neuroscientists at Kessler Foundation have documented increased cerebral activation in patients with multiple sclerosis (MS) following memory retraining using the modified Story Memory Technique (mSMT). This is the first study to demonstrate that behavioral interventions can have a positive effect on brain function in people with cognitive disability caused by MS, an important step in validating the clinical utility of cognitive rehabilitation.
According to Nancy Chiaravalloti, PhD, director of Neuropsychology & Neuroscience Research at Kessler Foundation, "This demonstrates that an effective cognitive rehabilitation protocol can lead to changes in the way the brain is actually processing information." Dr. Chiaravalloti is lead author of the article, which was published online by the Journal of Neurology on January 12.
Cognitive deficits are common in MS, though few studies have examined the efficacy of memory retraining in this population. Previous research conducted at Kessler Foundation demonstrated that mSMT improves new learning and memory in MS.
The new study utilized functional magnetic resonance imaging (fMRI) to document brain activation patterns before and after memory retraining. In the double-blind, placebo-controlled, randomized clinical trial, 16 individuals were randomly assigned to treatment (n = 8) or placebo (n = 8) groups. Each underwent 10 memory retraining sessions (twice weekly for 5 weeks). After treatment, greater activation was evident on fMRI in the treatment group during performance of a memory task; no change was seen in the placebo group. Increased activation was associated with improved memory performance. These benefits may warrant third-party reimbursement for this intervention in selected patients.
The article, Increased cerebral activation after behavioral treatment for memory deficits in MS, DOI: 10.1007/s00415-011-6353-x appeared online in the Journal of Neurology on January 12, 2012. Authors are Nancy Chiaravalloti, PhD, Glenn Wylie, DPhil, Victoria Leavitt, PhD, and John DeLuca, PhD, all of Kessler Foundation, West Orange, NJ. The authors also have faculty appointments with UMDNJ-New Jersey Medical School, Newark, NJ.
Research funded by National Institutes of Health grants RO1 HD045798 & HD45798-S, National MS Society and Kessler Foundation.
Source: Science Daily Copyright © 1995-2011 ScienceDaily LLC (18/01/12)