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)
Researchers at Kessler Foundation and the Cleveland Clinic have published one of the longest longitudinal studies of cognition in multiple sclerosis (MS). The article, "Cognitive impairment in multiple sclerosis: An 18-year follow-up study," was epublished by Multiple Sclerosis and Related Disorders on April 13, 2014. Results provide insight into the natural evolution of cognitive changes over time, an important consideration for researchers and clinicians. Authors are Lauren B. Strober, PhD, of Kessler Foundation and Stephen M. Rao, PhD, Jar-Chi Lee, Elizabeth Fisher, PhD, and Richard Rudick, MD, of the Cleveland Clinic.
"While cognitive impairment is known to affect 40 to 65% of individuals with MS, few studies have followed the pattern of cognitive decline over time, which is important for understanding long-term care and outcomes associated with MS," said Dr. Strober, senior research scientist at Kessler Foundation. "Our study was based on a unique sample of 22 patients who underwent neuropsychological testing at entry into the original phase 3 clinical trial of intramuscular interferon beta-1a, and again at 18-year followup."
At baseline, 9 patients (41%) had cognitive impairment; at 18-year followup, 13 patients (59%), were found to be impaired. Significant declines over time were found in information processing speed, auditory attention, memory, episodic learning and visual construction. Decline was steeper in the unimpaired than in the impaired group, as indicated by the Symbol Digit Modalities Test (SDMT).
"These longitudinal data contribute substantially to our knowledge of the course of cognitive decline in MS," noted John DeLuca, PhD, VP of Research & Training at Kessler Foundation. "In light of the young age at diagnosis, this perspective is fundamental to the development of rehabilitation strategies that meet the needs of people dealing with the cognitive effects of MS."
The study was funded by Biogen Idec.
Source: Medical Xpress © Medical Xpress 2011-2014 (25/06/14)
Extensive White Matter Dysfunction in Cognitively Impaired Patients with Secondary-Progressive Multiple Sclerosis.
Francis PL, Chia TL, Jakubovic R, O'Connor P, Lee L, Feinstein A, Aviv RI.
BACKGROUND AND PURPOSE: Cognitive impairment is a common, disabling symptom of MS. We investigated the association between cognitive impairment and WM dysfunction in secondary-progressive multiple sclerosis using DTI.
MATERIALS AND METHODS: Cognitive performance was assessed with a standard neuropsychological battery, the Minimal Assessment of Cognitive Function in Multiple Sclerosis. Cognitive impairment was defined as scoring >1.5 standard deviations below healthy controls on ≥2 subtests. Fractional anisotropy maps were compared against cognitive status using tract-based spatial statistics with threshold-free cluster enhancement.
RESULTS: Forty-five patients with secondary-progressive multiple sclerosis (median age: 55 years, female/male: 27/18, median Expanded Disability Status Scale Score: 6.5) were prospectively recruited. Cognitively impaired patients (25/45) displayed significantly less normalized global GM and WM volumes (P = .001, P = .024), more normalized T2-weighted and T1-weighted WM lesion volumes (P = .002, P = .006), and lower WM skeleton fractional anisotropy (P < .001) than non-impaired patients. Impaired patients also had significantly lower fractional anisotropy (pcorr < .05) in over 50% of voxels within every major WM tract. The most extensively impinged tracts were the left posterior thalamic radiation (100.0%), corpus callosum (97.8%), and right sagittal stratum (97.5%). No WM voxels had significantly higher fractional anisotropy in patients with cognitive impairment compared with their non-impaired counterparts (pcorr > .05). After the inclusion of confounders in a multivariate logistic regression, only fractional anisotropy remained a significant predictor of cognitive status.
CONCLUSIONS: Cognitively impaired patients with secondary-progressive multiple sclerosis exhibited extensive WM dysfunction, though preferential involvement of WM tracts associated with cognition, such as the corpus callosum, was apparent. Multivariate analysis revealed that only WM skeleton fractional anisotropy was a significant predictor of cognitive status.
Source: AJNR Am J Neuroradiol. 2014 May 15 & Pubmed PMID: 24831599 (03/06/14)
Among adult patients with multiple sclerosis (MS), pain severity can impact performance on cognitive tests, suggesting that pain independently contributes to impaired brain function in MS.
For their pilot study presented at the American Pain Society 33rd Annual Scientific Meeting, held April 30, 2014, to May 3, 2014, in Tampa, FL, Anna L. Kratz, PhD, of the Center for Outcomes Development & Application in the Department of Physical Medicine and Rehabilitation at the University of Michigan, and Tiffany J. Braley, MD, MS, of Multiple Sclerosis and Sleep Disorders Centers in the Department of Neurology at the University of Michigan, examined the correlation between pain intensity and cognitive test scores in 40 adult patients diagnosed with MS and explored the underlying mechanisms among those elements, such as sleep duration.
While previous studies have linked pain severity to cognitive functioning in the general population and determined that cognitive dysfunction is more common in those with chronic pain, the authors said “little has been done to explore symptoms that may exacerbate cognitive dysfunction in MS, including pain,” despite the fact that approximately two-thirds of MS patients have a chronic pain condition, 25% of whom experience severe chronic pain.
Within the current research sample, 26 patients had relapsing-remitting MS, 9 had secondary-progressive MS, and 5 had primary-progressive MS. Subjects were excluded from the study if they demonstrated “severe cognitive impairment, severe depression, visual and/or hearing impairments, lack of independent mobility, use of medical treatment for obstructive sleep apnea (OSA), and drug and/or alcohol dependence,” Kratz and Braley said.
During the study’s baseline visit, the investigators calculated the patients’ PROMIS Pain Intensity and Expanded Disability Status Scale (EDSS) scores and then showed them how to use a wrist-worn accelerometer, which continuously collected data on objective sleep parameters by recording ambient light and physical movements. In order to assess the association between pain and cognitive performance with and without sleep duration as a factor, the authors conducted the Controlled Oral Word Association Test (COWAT), Judgment of Line Orientation (JLO) test, and the Symbol Digit Modalities Test (SDMT) on the patients.
When they left out sleep duration in their analysis, Kratz and Braley found “pain intensity was independently associated with poorer performance on tests of verbal fluency (COWAT), visuospatial judgment (JLO), attention, working memory, and psychomotor speed (SDMT) above and beyond the effects of age and MS-related disability.” In fact, pain severity explained 8-10% of the variance in performance across those cognitive tests.
Even after they included sleep duration, the researchers said “the associated between pain and cognitive functioning was maintained for … poorer visuospatial judgment (JLO) and verbal fluency (COWAT).” In this set of regression models, pain intensity similarly accounted for 5-10% of the deviation in cognitive test performance. Based on their findings, Kratz and Braley speculated that “pain contributes to cognitive dysfunction in MS beyond the effects of neuronal damage, cumulative neurological disability, or actigraphy-based sleep measures.” Additionally, the investigators said further research on the mechanisms underlying this association “could lead to novel advances in the management of cognitive dysfunction in MS through pain-based interventions.”
Source: HCPLive Copyright HCPLive 2006-2013 Intellisphere, LLC (07/05/14)
Multiple sclerosis researchers have found that brain reserve and cognitive reserve confer a long-term protective effect against cognitive decline. The study has been published in Neurology.
James Sumowski, PhD, lead author of the article, and John DeLuca, PhD, are at Kessler Foundation. Co-authors are from the Manhattan Memory Center, New York, NY, the San Raffaele Scientific Institute, Milan, Italy, and the University of Belgrade, Serbia. Neurology is the official journal of the American Academy of Neurology. Dr. Sumowski presented this research at the 2014 AAN conference in Philadelphia.
"Our research aims to answer these questions," explained Dr. DeLuca. "Why do some people with MS experience disabling symptoms of cognitive decline, while others maintain their cognitive abilities despite neuroimaging evidence of significant disease progression? Can the theories of brain reserve and cognitive reserve explain this dichotomy? Can we identify predictors of cognitive decline?"
In this study, memory, cognitive efficiency, vocabulary (a measure of intellectual enrichment/cognitive reserve), brain volume (a measure of brain reserve), and disease progression on MRI, were evaluated in 40 patients with MS at baseline and at 4.5-year followup. After controlling for disease progression, scientists looked at the impact of brain volume and intellectual enrichment on cognitive decline.
Results supported the protective effects of brain reserve and cognitive reserve," noted Dr. Sumowski. "Patients with greater intellectual enrichment experienced lesser degrees of cognitive decline. Those with greater brain reserve showed a protective effect for cognitive efficiency. This study not only confirms these protective effects of brain and cognitive reserve, it shows that these beneficial effects persist for years."
More information: Sumowski JF, Leavitt VM. Body Temperature Is Elevated and Linked to Fatigue in Relapsing-Remitting Multiple Sclerosis, Even Without Heat Exposure. Arch Phys Med Rehabil. 2014 Feb 20.
Sumowski JF, Coyne J, Cohen A, Deluca J.Retrieval practice improves memory in survivors of severe traumatic brain injury. Arch Phys Med Rehabil. 2014 Feb;95(2):397-400
Sumowski JF, Chiaravalloti N, Krch D, Paxton J, Deluca J. Education attenuates the negative impact of traumatic brain injury on cognitive status. Arch Phys Med Rehabil. 2013 Dec;94(12):2562-4.
Source: Medical Xpress © Medical Xpress 2011-2014 (01/05/14)
Background: The relationship between cognitive impairment and disease course and severity of multiple sclerosis (MS) is not well understood.
Objective: The aim of the study was to evaluate whether cognitive complaints in different clinical phenotypes and severity stages of MS are associated with differences in the profile of cognitive impairment.
Methods: 196 MS patients (relapsing-remitting RRMS n=138; secondary progressive SPMS n=32; primary progressive PPMS n=26) with perceived cognitive deficits underwent neuropsychological assessment with the brief repeatable battery of neuropsychological tests (BRBNT). Mood, impact of the disease, and quality of life were evaluated with self-reports.
Results: Only minor differences were observed in the cognitive impairment profile of different disease phenotypes and different disease severity stages. RRMS patients performed better only in one cognitive test of the BRBNT, than patients with progressive disease types. When RRMS, SPMS, and PPMS groups were evaluated separately, PPMS showed more pronounced cognitive impairments than RRMS and SPMS. The relationships between cognitive impairment and severity of disability as well as duration of disease were weak.
Conclusion: MS patients with cognitive complaints tend to have a relatively similar cognitive impairment profile which is not dependent on the disease course and severity.
Eija Rosti-Otajärviemail address, Juhani Ruutiainen, Heini Huhtala, Päivi Hämäläinen
Source: Multiple Sclerosis Copyright © 2014 Elsevier Inc (03/03/14)
Researchers at Kessler Foundation have studied the measurement tools used in multiple sclerosis for their effectiveness in predicting employment status. They compared the Expanded Disability Status Scale (EDSS), the Multiple Sclerosis Functional Composite (MSFC), the Paced Auditory Serial Addition Task (PASAT), and the Symbol Digit Modalities Test (SDMT), and found the SDMT effective in differentiating employed from unemployed individuals. The article, Unemployment in multiple sclerosis (MS): utility of the MS Functional Composite and cognitive testing, was published in the January 2014 issue of Multiple Sclerosis Journal (doi: 10.1177/1352458513488235). The authors are Lauren Strober, PhD, Nancy Chiaravalloti, PhD, Nancy Moore, PhD, and John DeLuca, PhD, of Kessler Foundation.
"The population with MS comprises people of working age," noted Dr. Strober, senior research scientist, "which is why factors related to employment status are a major concern for individuals and clinicians." The researchers studied 77 people with MS; 40 were employed and 37 were unemployed. To determine which factor(s) were predictive of employment status, they compared the two groups in regard to demographic factors, disease variables, MSFC, and cognitive performance. Differences were found in disease duration and progression, upper extremity function, processing speed, verbal learning and memory, and executive function. Analysis revealed the SDMT to be the only predictor of employment status, with an overall accuracy of 67%. "These findings suggest that clinical use of the SDMT may help identify those individuals who are at risk for unemployment," she explained. "This would allow clinicians to advise them on strategies for maintaining employment."
"Unemployment research is a priority at Kessler Foundation," remarked Dr. Chiaravalloti, "because maintaining employment is such an important factor in the quality of life of persons with MS."
Source: News Medical (03/02/14)
Kessler Foundation has been awarded a new grant by the US National Multiple Sclerosis (MS) Society for a pilot study of memory and learning difficulties in individuals with MS. Scientists will test the effectiveness of using of self-generated learning in a treatment intervention to improve memory and functional performance. Yael Goverover, PhD, visiting scientist in Neuropsychology & Neuroscience Research, is the study's principal investigator. Dr. Goverover, an associate professor at New York University, will work with John DeLuca, PhD, the Foundation's senior VP for Research & Training. They will test the efficacy of self-generated learning in individuals with MS who have memory and learning difficulties and in controls. The total pilot award for the one-year grant is $42,185.
"Past research has shown that items that are "self-generated" by an individual, such as words or concepts, are remembered better than items that are simply read or heard," said Dr. DeLuca. The aim of the clinical trial to demonstrate the effects of learning to use a self-generation strategy as a treatment intervention to improve performance of both laboratory tasks (e.g. words and concepts) as well as functional tasks (e.g. activities of daily living). Forty persons with MS with memory impairment, age 18 to 65, will be recruited. Half will receive self-generation training while learning different types of tasks (experimental group) and half (control group) will be asked to learn the same information using more conventional methods (e.g. repetitions).
"Self-generated learning is geared toward helping patients self-discover their own strengths and abilities while learning to use principles of self-generation independently in everyday life situations," noted Dr. DeLuca. "We anticipate that participants undergoing the self-generation-training intervention will show better memory performance, functional performance, quality of life, and satisfaction with treatment and life compared with controls."
Source: News-Medical.Net (02/01/14)
Kessler Foundation scientists correlated functional magnetic resonance imaging (fMRI) findings with the negative impact of outdoor temperature on cognitive functioning in multiple sclerosis (MS).
This study, "Warmer outdoor temperature is associated with task-related increased BOLD activation in patients with multiple sclerosis," released by Brain Imaging & Behavior corroborates the group's previous study that established that people with MS performed worse on processing speed and memory tasks during warmer outdoor temperatures versus during cooler outdoor temperatures. "Increased MS disease activity during warmer months is a recent discovery. Now, this work is the first report of brain activation associated with outdoor temperature in MS. This finding is novel and important for persons with MS who are shown to have worse cognition during warmer weather," said Victoria M. Leavitt, Ph.D., research scientist at Kessler Foundation and principal investigator for the study, funded by a grant from the National MS Society.
Kessler Foundation researchers previously demonstrated that patients with multiple sclerosis (MS) demonstrate worse cognition on warmer days. (Leavitt VM, Sumowski JF, Chiaravalloti N, DeLuca J. Warmer outdoor temperature is associated with worse cognitive status in multiple sclerosis. Neurology. 2012 Mar 27;78(13):964-8). The purpose of the current study was to identify the neurophysiological basis for worse cognition. "Here, we examined the neurophysiology underlying this temperature-cognition relationship, said Dr. Leavitt. "The association between task-related BOLD fMRI activation and outdoor temperature was investigated in 28 MS patients who demonstrated worse cognitive function on warmer days. In MS patients, warmer outdoor temperature was associated with greater BOLD activation during performance of a simple sustained attention task. The brain areas that showed greater activation on warmer days were regions typically activated by MS patients during task performance: the frontal, dorsolateral, prefrontal and parietal cortex. The relationship between outdoor temperature and cerebral activation was absent in healthy controls. Increased brain activation required by MS patients on warmer days to perform a simple task may signify neural inefficiency."
According to Dr. Sumowski, "The significant effect of warmer weather on cognition should be considered when designing and conducting clinical trials. This information might assist clinicians in choosing clinical treatment, and help researchers develop effective strategies for coping with the negative effects of weather-related effects on cognition that impact independence, education, employment and activities of daily living."
Source: Science Daily Copyright 2013 by ScienceDaily, LLC (01/11/13)
Over the course of the disease, multiple sclerosis is very often combined with a deteriorating memory and attention deficits. Researchers at the University Department of Radiology and Nuclear Medicine at the MedUni Vienna have now demonstrated by means of a meta-analysis of functional image data that increased activations in the involuntary attention system in the brain are responsible for these disorders in MS patients.
MS patients generally often have problems with fading out what is unimportant. Says head of the study Veronika Schöpf: "They are practically in continuous alarm mode." The attention system is too highly activated and also notices – for example when watching the television or when talking to someone – completely unimportant extraneous noises.
Because of this, concentrating on what is important is completely impossible or only possible to a limited extent. In addition, MS patients find it difficult to look for one specific thing and also find it. This high activation thus also leads to a poor memory and at the same time adversely affects the ability to take in new things.
In a meta-analysis in the top journal "Neuroscience & Biobehavioral Reviews" (Impact Factor 9.44) it has now been possible to prove that functional changes in the brain are responsible for these disorders and that these can also be depicted by means of functional imaging.
"In most people the centre for these activities lies in the right half of the brain, in many MS patients however it lies in the left side of the brain, as it does in many epilepsy patients," says the PhD student and primary author Kathrin Kollndorfer. This knowledge could now feed into the development of personalised treatments for people with multiple sclerosis in order to counteract these cognitive disorders in good time.
With this, the working group at the MedUni Vienna has also achieved a better generalisability of the research results so far with regard to working memory and attention in patients with multiple sclerosis. "Most studies that have so far dealt with this question by means of functional imaging have mostly examined only very small and heterogeneous samples, which clearly differ with regard to age, gender or duration of illness. We have included in our evaluation everything in studies so far," explains Veronica Schöpf.
Multiple sclerosis is an incurable, chronic inflammatory disease of the central nervous system, which develops slowly at first and in later stages leads to greater and greater physical and mental handicaps. According to figures of the Austrian Multiple Sclerosis Society (ÖMSG) about 12,500 people suffer from this disease.
Source: Health Canal (14/10/13)
High levels of educational attainment appeared to protect multiple sclerosis (MS) patients from the cognitive ravages of brain atrophy and demyelinating lesion burdens, a researcher said here.
Correlations between cognitive test results and the degree of MRI-measured brain pathology in 104 patients with MS and 33 with the pre-MS condition known as clinically isolated syndrome were markedly weaker in those in the top quartile of education compared with those in the lowest, said Daniela Pinter, PhD, of the Medical University of Graz in Austria.
In hierarchical regression models, the interactions between years of education and MRI measures of T2 lesion load and third ventricle width (indicating brain atrophy) were changed by R2=2.2 for T2 lesion volume and by R2=3.4 for third ventricle width (both P<0.05), she told attendees at the World Congress of Neurology.
These models also took account of age, sex, and disease duration.
Pinter said the findings applied across MS severity grades. "In MS patients with different phenotypes at different stages of the disease, higher education attenuated the negative effects of white matter lesion burden and thalamic atrophy on cognitive performance," she concluded.
She suggested that MS patients work to "actively enhance" their cognitive reserve before impairments set in, "in parallel to disease-modifying drugs." Such an approach should also be tested in rigorous studies, Pinter added.
Higher levels of education and other markers of an active cognitive life -- such as working in mentally challenging jobs or engagement with crossword puzzles or other "thinking games" -- have previously been established as protective in patients with Alzheimer's disease-related brain pathologies, an effect dubbed cognitive reserve. Such individuals can carry heavy burdens of beta-amyloid plaques without developing dementia.
Pinter and her colleagues hypothesized that the same concept would apply as well to MS patients, many of whom also develop cognitive impairments in parallel with increasing brain atrophy and inflammatory lesions.
They enrolled 137 patients including 33 with clinically isolated syndrome, 92 with relapsing-remitting MS, and 12 with secondary progressive MS. Overall the mean age was 36 (SD 10), though it reached 44 (SD 7) in the patients with secondary progressive disease.
Mean educational attainment was 13.1 years (SD 2.6) and was similar in the three disease-type subgroups. Mean EDSS disability scores were 1.2 in the clinically isolated syndrome group, 1.9 in those with relapsing-remitting MS, and 5.7 in those with secondary progressive disease.
Patients were administered five standard cognitive function tests, assessing verbal and visuospatial memory, attention and concentration, verbal fluency, and information processing speed. These tests together make up the Brief Repeated Battery of Neuropsychological Tests.
MRI measurements included T2 lesion volume, normalized brain volume, third ventricle width, iron accumulation in the basal ganglia, and magnetization transfer ratios in cognitively relevant brain regions.
Correlations between several of the latter measures and cognitive test results were not affected by educational attainment, Pinter noted. Only T2 lesion volume and third ventricle width showed significant interactions between the MRI metrics and education, she said.
The ameliorating effect of education on the correlation between MRI metrics and cognitive function was most pronounced for T2 lesion volume. Linear regression analyses indicated that the slope of the correlation was roughly tripled in patients in the lowest education quartile compared with the highest.
For third ventricle width, patients in the top education quartile showed almost no diminution in cognitive function with increasing atrophy. Those with in the lowest quartile, on the other hand, had sharp declines in cognition scores as their third ventricle width approached 10 mm.
Source reference: Pinter D, et al "Educational attainment moderates the effect of T2 lesion load and atrophy on cognition in multiple sclerosis" WCN 2013; Abstract 1197.
Source: MedPage Today © 2013 MedPage Today, LLC (26/09/13)