Staging and stratifying cognitive dysfunction in multiple sclerosis

BACKGROUND: The sequence in which cognitive domains become impaired in multiple sclerosis (MS) is yet to be formally demonstrated. It is unclear whether processing speed dysfunction temporally precedes other cognitive impairments, such as memory and executive function. OBJECTIVE: Determine the order in which different cognitive domains become impaired in MS and validate these findings using clinical and vocational outcomes. METHODS: In a longitudinal sample of 1073 MS patients and 306 healthy controls, we measured performance on multiple, consensus-standard, neurocognitive tests. We used an event-based staging approach to model the sequence in which cognitive domains become impaired. Linear and logistic mixed-effects models were used to explore associations between stages of impairment, neurological disability, and employment status. RESULTS: Our model suggested that the order of impairments was as follows: processing speed, visual learning, verbal learning, working memory/attention, and executive function. Stage of cognitive impairment predicted greater neurological disability, β = 0.16, SE = 0.02, p < 0.001, and probability of unemployment, β = 1.14, SE = 0.001, p < 0.001. CONCLUSION: This is the first study to introduce a cognitive staging and stratification system for MS. Findings underscore the importance of using the Symbol Digit Modalities Test in routine screening for cognitive impairment and memory testing to assess patients later in disease evolution

Application and Effectiveness of Telehealth to Support Severe Mental Illness Management: Systematic Review

Background: It is important that people with SMI receive early interventions to prevent mental health deterioration or relapse. Telecommunications and other technologies are increasingly used to assist healthcare delivery (‘telehealth’) , providing service users with immediate real-time information to improve the management of chronic health conditions. Telehealth has been found to be successful in improving management and symptoms across a number of health conditions, whilst also being acceptable to users. Initial findings suggest technology could improve quality of life in people with SMI. Objectives: This systematic review aimed to identify the variety of uses and efficacy of teleheal th technology for SMI. Methods: We systematically searched electronic databases from inception to March 2016 (MEDLINE, EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials, AMED, He alth Techno logy Assessment, CINAHL plus and NHS EED ) for randomised controlled trials (RCTs) evaluating telehealth for adults with SMI , published in English. Additional literature was identified by searching reference lists of key articles. The articles meeting the inclusion criteria were systematically reviewed and assessed for quality and risk of bias. Results: The search identified 31 eligible articles, describing 29 trials. The included studies evaluated the use of computers to deliver cognitive rehabilitation (1 5 trials), patient education (3 trials), online self- management interventions (2 trials), and to support consultations (1 trial). Virtual reality (VR) was used to simulate work and social sit uations (2 trials ) and to deliver cognitive training (1 trial). Telephones were used to prompt medication use (3 trials ) and report SMI symptoms to healthcare teams (1 trial ). Remote sensors were used to monitor medication use (1 trial). Telephone support was found effective for improving medication adherence and reducing symptom severity and inpatient days. Computer assisted cognitive rehabilitation was effective in improving cognitive function. The impact of telehealth on other outcomes was inconsistent. Few studies evaluated the 3 use of remote medication telemonitoring, VR, online self-management and computer -mediated consultations, suggesting these are novel technologies for managing SMI, although all were found effective for improving psycho social and behavioural outcomes. The results of this review should be taken in the context of varied quality in study design, with only five studies demonstrating a low risk of bias. Conclusions : A growing variety of telehealth technologies are used to support SMI. Specific types of technology have been found to be effective for som e outcomes, for example telephone prompts for medication adherence, while other types of telehealth had no benefit over traditional methods and were less acceptable to patients. Few studies found benefits for telehealth on quality of life, except for novel technologies with a limited number of trials. Further research is warranted to establish the full potential benefits of telehealth for improving quality of life in SMI, acceptability from the service user perspective, and cost-effectivenes

Cognitive performance in relapsing remitting multiple sclerosis: A longitudinal study in daily practice using a brief computerized cognitive battery

<p>Abstract</p> <p>Background</p> <p>There is need for a cognitive test battery that can be easily used in clinical practice to detect or monitor cognitive performance in patients with multiple sclerosis (MS). In order to conduct, in this patient group, a preliminary investigation of the validity and utility of a brief computerized battery, the Cognitive Drug Research (CDR) battery, we longitudinally assessed cognition in patients with relapsing remitting (RR) MS.</p> <p>Methods</p> <p>Forty-three mildly disabled, clinically active RRMS patients were repeatedly assessed with the Digit Symbol Substitution Test (DSST), Paced Auditory Serial Addition Test (PASAT) and five composite scores derived from the CDR computerized cognitive test system (CDR System): Power of Attention, Continuity of Attention, Quality of Working Memory, Quality of Episodic Memory and Speed of Memory. The Multiple Sclerosis Functional Composite (MSFC) and Expanded Disability Status Scale (EDSS) measured disability.</p> <p>Results</p> <p>The composite scores from the CDR battery generally showed excellent test-retest reliability over the repeated assessments, though was low on occasions for the Quality of Working Memory and Quality of Episodic Memory measures. The CDR measures tended to be highly correlated with other measures of cognition (DSST and PASAT) and were also strongly related to disability (EDSS and MSFC). Baseline scores indicated large impairments to visual information processing speed and attention (DSST, Cohen's d 1.1; Power of Attention d 1.4 [reaction time on tasks of focussed and sustained attention]), and a moderate impairment both to sustained attention (Continuity of Attention d 0.6) and complex information processing speed (Speed of memory d 0.7 [reaction time on tasks of working and episodic Memory]), when compared to normative data derived from healthy volunteers enrolled in a series of separate, prior clinical trials. Working memory (Quality of Working Memory) and episodic memory (Quality of Episodic Memory) were unimpaired.</p> <p>Conclusions</p> <p>Preliminary validation of the CDR System indicated that for most, but not all measures psychometric properties were adequate and the measures were related to disability (EDSS and MSFC) and other measures of cognition.</p

The clinico-radiological paradox of cognitive function and MRI burden of white matter lesions in people with multiple sclerosis: a systematic review and meta-analysis.

Moderate correlation exists between the imaging quantification of brain white matter lesions and cognitive performance in people with multiple sclerosis (MS). This may reflect the greater importance of other features, including subvisible pathology, or methodological limitations of the primary literature.To summarise the cognitive clinico-radiological paradox and explore the potential methodological factors that could influence the assessment of this relationship.Systematic review and meta-analysis of primary research relating cognitive function to white matter lesion burden.Fifty papers met eligibility criteria for review, and meta-analysis of overall results was possible in thirty-two (2050 participants). Aggregate correlation between cognition and T2 lesion burden was r = -0.30 (95% confidence interval: -0.34, -0.26). Wide methodological variability was seen, particularly related to key factors in the cognitive data capture and image analysis techniques.Resolving the persistent clinico-radiological paradox will likely require simultaneous evaluation of multiple components of the complex pathology using optimum measurement techniques for both cognitive and MRI feature quantification. We recommend a consensus initiative to support common standards for image analysis in MS, enabling benchmarking while also supporting ongoing innovation

Clinical correlates of grey matter pathology in multiple sclerosis

Traditionally, multiple sclerosis has been viewed as a disease predominantly affecting white matter. However, this view has lately been subject to numerous changes, as new evidence of anatomical and histological changes as well as of molecular targets within the grey matter has arisen. This advance was driven mainly by novel imaging techniques, however, these have not yet been implemented in routine clinical practice. The changes in the grey matter are related to physical and cognitive disability seen in individuals with multiple sclerosis. Furthermore, damage to several grey matter structures can be associated with impairment of specific functions. Therefore, we conclude that grey matter damage - global and regional - has the potential to become a marker of disease activity, complementary to the currently used magnetic resonance markers (global brain atrophy and T2 hyperintense lesions). Furthermore, it may improve the prediction of the future disease course and response to therapy in individual patients and may also become a reliable additional surrogate marker of treatment effect

Pattern of neuropsychological performance among HIV positive patients in Uganda

BACKGROUND: Few studies have examined cognitive functioning of HIV positive patients in sub-Saharan Africa. It cannot be assumed that HIV positive patients in Africa exhibit the same declines as patients in high-resource settings, since there are differences that may influence cognitive functioning including nutrition, history of concomitant disease, and varying HIV strains, among other possibilities. Part of the difficulty of specifying abnormalities in neuropsychological functioning among African HIV positive patients is that there are no readily available African normative databases. The purpose of the current study was to evaluate the pattern of neuropsychological performance in a sample of HIV positive patients in comparison to HIV negative control subjects in Uganda. METHODS: The neuropsychological test scores of 110 HIV positive patients (WHO Stage 2, n = 21; WHO Stage 3, n = 69; WHO Stage 4, n = 20) were contrasted with those of 100 control subjects on measures of attention/concentration, mental flexibility, learning/memory, and motor functioning. RESULTS: Analysis of covariance (ANCOVA) revealed significant group differences on measures of verbal learning and memory, speed of processing, attention and executive functioning between HIV seropositive and seronegative subjects. CONCLUSION: Ugandan patients with HIV demonstrated relative deficits on measures of verbal learning and memory, speed of processing, attention, and executive functioning compared to HIV negative controls. These results from a resource limited region where clades A and D are prevalent are consistent with previous findings in the developed world where clade B predominates