A much needed metric: Defining reliable and statistically meaningful change of the oral version Symbol Digit Modalities Test (SDMT).

BACKGROUND: The Symbol Digit Modalities Test (SDMT) has been recommended for use in clinical trials and outcome studies to monitor cognitive change. However, defining what is a meaningful change has been elusive for several years. OBJECTIVE: The present investigation aimed to develop methods for assessing individual-level statistically significant change on the SDMT - reliable change indices (RCIs) and standardized regression-based (SRB) equations. METHODS: A total of 219 healthy individuals completed the oral version SDMT at baseline, 6-month and 1-year follow-up. RESULTS: The SDMT demonstrated high reliability across all time points (r's = 0.83 to 0.86). Reliable change scores of 7, 8, and 10 points for the 6-month intervals represented statistically meaningful change at the 0.70, 0.80, and 0.90 confidence intervals, respectively. Over 1-year, a difference of 8, 10, and 12 was statistically meaningful at the 0.70, 0.80, and 0.90 confidence intervals, respectively. SRB equations are also provided taking into account additional factors found to be predictive of SDMT scores over time. CONCLUSION: Clinicians frequently denote a decline of 4 points on the SDMT as meaningful. Results in this large normative sample show that higher cut-points are needed to demonstrate statistically significant decline at the individual level. RCIs are provided for 6 month and one year assessment, which is typical in clinical practice and trials. SRB equations are also provided for use when applicable and may provide a more precise assessment of meaningful change.

Tired of not knowing what that fatigue score means? Normative data of the Modified Fatigue Impact Scale (MFIS).

BACKGROUND: The Modified Fatigue Impact Scale (MFIS) is one of the most common self-report measures used to assess fatigue in multiple sclerosis (MS). Despite its widespread use, there are no existing normative data for the MFIS. OBJECTIVE: The present investigation aimed to develop normative data for the MFIS in a large community sample, stratified by age, gender, and education and to compare the derived new cutoffs to an existing cutoff. METHODS: A total of 675 healthy individuals, stratified by age, gender, and education completed the MFIS. After the removal of 19 outliers, the final sample consisted of 656 individuals. Archival data of 540 individuals with MS who completed the MFIS were also included to analyze the utility of the new cutoffs. RESULTS: There were no main effects on the MFIS for gender. However, there were main effects for age and education. Specifically, younger cohorts (25-34 and 35-44) reported less physical fatigue compared to the two oldest cohorts (55-64 and 65-74). Similar effects were found for total MFIS fatigue with individuals aged 55-64 reporting greater overall fatigue than 35-44 year olds. Finally, 18-24 year olds reported significantly higher levels of cognitive fatigue compared to 35-44 and 65-74 aged cohorts. No other effects were observed for age. Individuals with higher education consistently reported less fatigue. Subsequent analyses also revealed an interaction effect for age x gender. When examining the age x gender interaction, women age 18-24 reported significantly greater levels of physical, cognitive, psychosocial, and total fatigue than their male counterparts. In contrast, men aged 65-74 reported greater physical, cognitive, and total fatigue than women their age. Comparisons of the existing cutoff of the MFIS to the new age, gender, and education specific cutoffs found either comparable or slightly higher rates of fatigue with the latter. CONCLUSION: Based on these findings, updated normative data and age, gender, and education specific cutoffs are provided. Utilization of these updated norms will result in a more accurate assessment of fatigue and will be valuable for those conducting research and/or clinical practice with individual with MS.

A new look at an old test: Normative data of the symbol digit modalities test -Oral version.

BACKGROUND: The Symbol Digit Modalities Tests (SDMT) is the most sensitive measure to multiple sclerosis (MS)-related cognitive dysfunction. However, existing normative data has been under scrutiny. Specifically, they are outdated, do not take into account gender, and are poorly stratified by education. More importantly, there exists no oral only version norms, which is typical administration among individuals with MS. OBJECTIVE: The present investigation aimed to develop updated normative data of the oral version SDMT in which age, gender, and education were taken into consideration. METHODS: A total of 675 healthy individuals, stratified by age, gender, and education completed the oral version SDMT. RESULTS: Significant effects were found for age, gender, and education, consistent with previous contentions. Specifically, performance on the SDMT tends to decline with age, with the most noticeable decline beginning in the third decade of life and continuing into the sixth decade. Women, in general perform better than men, with an average of 5.1 more points. Finally, education effects were apparent among those aged 25-54. CONCLUSION: Based on these findings, updated normative data are provided. Utilization of these updated norms will result in a much needed and more accurate assessment of processing speed for individuals with MS.

Effect of Enzogenol® Supplementation on Cognitive, Executive, and Vestibular/Balance Functioning in Chronic Phase of Concussion.

This study examined the feasibility of Enzogenol® as a potential treatment modality for concussed individuals with residual symptoms in the chronic phase. Forty-two student-athletes with history of sport-related concussion were enrolled, comparing Enzogenol® versus placebo. Testing was conducted using virtual reality (VR) and electroencephalography (EEG), with neuropsychological (NP) tasks primarily used to induce cognitive challenges. After six weeks, the Enzogenol® group showed enhanced frontal-midline theta, and decreased parietal theta power, indicating reduced mental fatigue. Subjects enrolled in the Enzogenol® group also self-reported reduced mental fatigue and sleep problems. This suggests that Enzogenol® has the potential to improve brain functioning in the chronic phase of concussion.

Unemployment among women with multiple sclerosis: the role of coping and perceived stress and support in the workplace.

Unemployment is high among individuals with multiple sclerosis (MS). Certain disease variables and demographics have been found to distinguish employed and unemployed individuals. However, these variables only account for 14-20% of the variance. Other factors, such as coping, perceived stress and social support, in the workforce have been proposed, but not yet fully examined. The purpose of the present investigation was to examine the role of known factors associated with unemployment in MS, as well as coping and perceived work stress and social support. Sixty-eight women with MS were asked about their employment status and reasons for leaving. They completed a comprehensive assessment including measures of cognition, disease symptoms, psychological functioning, coping and stress. Consistent with previous findings, certain disease and demographic variables were associated with being unemployed. In particular, women who left work due to their MS were found to be older, had a longer disease duration and progressive course, reported greater disability and fatigue, and performed worse on a cognitive measure. However, we also found that coping style distinguished those who were employed from those who left work due to their MS. In particular, those who left work reported utilizing maladaptive coping mechanisms such as behavioral disengagement and substance use. With regard to perceived work stress and support, individuals who were employed reported that job security and fellow co-workers were more of an uplift than a hassle in their lives, suggesting some benefit in employment. These findings suggest that further consideration be given to role of coping and perception of the benefit of employment among individuals with MS when making recommendations regarding work decisions.

Assessment of depression in multiple sclerosis: development of a "trunk and branch" model.

The objective of the present investigation was to improve the detection of depression in multiple sclerosis (MS). It has been hypothesized that the overlap of MS symptomatology and neurovegetative depression symptoms may lead to an over-diagnosis of depression in MS. Discerning what is depression and what is more attributable to the disease renders a complicated picture when assessing depression in medically ill people. Given this, "trunk and branch" models have been proposed. In such models "trunk" symptoms are purported to be the symptoms common to the medical condition and less likely reflective of depression. "Branch" items are those symptoms that are independent of the medical condition and likely reflect depression. In the present investigation we compared depressed individuals with MS, non-depressed individuals with MS, and non-depressed controls, to devise a "trunk and branch" model for use with individuals with MS. By identifying which symptoms are typical in MS, which exceed what is typical in MS, and which symptoms are independent of MS, but more often present in depressed individuals with MS, we hoped to present a better understanding of the nature of depression in MS.

Worsening of symptoms is associated with lower physical activity levels in individuals with multiple sclerosis.

The present study examined the relationship between the worsening of symptoms across a 3-5-year period of time and self-reported physical activity in a sample of 51 individuals with multiple sclerosis (MS). Of the 51 participants, 35 reported a worsening of symptoms over the 3-5-year period of time. The worsening of symptoms was associated with significantly and moderately lower levels of self-reported physical activity independent of depression and EDSS scores and MS-disease course (P=0.04). This study provides novel evidence that a worsening of symptoms is associated with lower levels of physical activity in individuals with MS.

[Neuropsychological evaluation in multiple sclerosis]. / Evaluación neuropsicológica en la esclerosis múltiple.

INTRODUCTION: In recent years, advances have occurred in the description of cognitive alterations in multiple sclerosis (MS) patients and the development of tools for their assessment. However, in the clinical practice, the neuropsychological assessment of these patients is often non-specific and lacks appropriate standardization. Therefore the development of neuropsychological tests and batteries sensitive and specific for detecting the cognitive alterations in MS patients has become an important subject of study. AIM. To provide a short review about the recent developments in the neuropsychological assessment of MS patients. DEVELOPMENT: We introduce and discuss various sensitive and valid tests that assess cognitive functions often altered in MS patients. In addition, because of their possible impact on cognitive performance, we also present guidelines for evaluating other frequently associated problems (such as mood disorders and fatigue) in MS patients. CONCLUSIONS: The use of sensitive and specific tests makes possible to assess the neuropsychological alterations associated with MS, however, the adaptation of such tests to languages other than English (i.e. Spanish) has just begun. Besides assessing cognitive functioning, the neuropsychological assessment of MS patients should also involve the evaluation of other variables (such as depression or fatigue) that may influence cognitive performance. Improvements in assessing these domains should help to provide better and more specific protocols for the neuropsychological evaluation of MS patients.

Pain and affective memory biases interact to predict depressive symptoms in multiple sclerosis.

A large literature supports a direct relationship between pain and depressive symptoms among various patient populations. Patients with multiple sclerosis (MS) frequently experience both pain and depression. Despite this, no relationship between pain and depression has been found in MS. The present investigation explored the relationship between pain and depression in a sample of patients with MS. Consistent with cognitive theories of depression, results supported the hypothesis that pain would only contribute to depression when MS patients exhibited a concomitant cognitive vulnerability. Cognitive vulnerability to depression was measured using a performance based affective memory bias (AMB) task. Patients with high levels of pain and negative AMB reported more depressive symptoms compared to patients with pain and positive AMB. Implications for the identification and treatment of depression in MS are discussed.

Evaluación neuropsicológica en la esclerosis múltiple / Neuropsychological evaluation in multiple sclerosis

Introducción. En los últimos años, se han logrado ciertos avances en la descripción de las alteraciones cognitivas en pacientes con esclerosis múltiple (EM) y en el desarrollo de herramientas para su evaluación. Sin embargo, en la práctica clínica, la evaluación neuropsicológica de estos pacientes suele ser inespecífica y carece de una normalización adecuada. En consecuencia, el desarrollo de tests y baterías neuropsicológicos sensibles y específicos para la detección de las alteraciones cognitivas en pacientes con EM se ha convertido en una importante línea de investigación. Objetivo. Ofrecer una breve revisión de los últimos avances en la evaluación neuropsicológica de los pacientes con EM. Desarrollo. Se presentan y se consideran distintos tests sensibles y válidos para evaluar las funciones cognitivas que con frecuencia se ven alteradas en los pacientes con EM. Además, debido a su posible impacto sobre el funcionamiento cognitivo, también se presentan unas pautas para la evaluación de otros problemas que muchas veces vienen asociados en pacientes con EM (como son los trastornos del estado de ánimo y la fatiga). Conclusiones. El uso de tests sensibles y específicos facilita la evaluación de las alteraciones neuropsicológicas asociadas a la EM; no obstante, los trabajos para adaptar este tipo de tests a otros idiomas que no sean el inglés (por ejemplo, el español) acaban de empezar. Además de evaluar el funcionamiento cognitivo, la evaluación neuropsicológica de los pacientes con EM también debe contemplar la evaluación de otras variables (como la depresión o la fatiga) que pueden influir en el funcionamiento cognitivo. Las mejoras en la evaluación de estos ámbitos deberían ayudar a proporcionar protocolos que sean mejores y más específicos para la evaluación de pacientes con EM

Introduction. In recent years, advances have occurred in the description of cognitive alterations in multiple sclerosis (MS) patients and the development of tools for their assessment. However, in the clinical practice, the neuropsychological assessment of these patients is often non-specific and lacks appropriate standardization. Therefore the development of neuropsychological tests and batteries sensitive and specific for detecting the cognitive alterations in MS patients has become an important subject of study. Aim. To provide a short review about the recent developments in the neuropsychological assessment of MS patients. Development. We introduce and discuss various sensitive and valid tests that assess cognitive functions often altered in MS patients. In addition, because of their possible impact on cognitive performance, we also present guidelines for evaluating other frequently associated problems (such as mood disorders and fatigue) in MS patients. Conclusions. The use of sensitive and specific tests makes possible to assess the neuropsychological alterations associated with MS, however, the adaptation of such tests to languages other than English (i.e. Spanish) has just begun. Besides assessing cognitive functioning, the neuropsychological assessment of MS patients should also involve the evaluation of other variables (such as depression or fatigue) that may influence cognitive performance. Improvements in assessing these domains should help to provide better and more specific protocols for the neuropsychological evaluation of MS patients

Longitudinal course of depression symptoms in multiple sclerosis.

BACKGROUND: Despite the high lifetime prevalence of depression in multiple sclerosis (MS), its longitudinal course is poorly understood. OBJECTIVE: To examine the longitudinal course of and reliable change in different depression symptom clusters in MS, and the longitudinal association of interferon beta treatment and coping with depression symptoms. METHODS: 53 MS patients were examined at two time points three years apart on the Beck Depression Inventory (BDI) and the Chicago Multiscale Depression Inventory (CMDI). RESULTS: Correlations from time 1 to time 2 for BDI, CMDI-total, CMDI-evaluative scale, and CMDI-vegetative scale were all highly significant, and reliable change indices reflected little change over time. In contrast, the correlation over time for the CMDI-mood scale was significantly lower (p<0.05) than the CMDI-evaluative and CMDI-vegetative scale correlations, and over 40% of patients showed reliable change. Patients who improved in their mood showed increased use of active coping, while patients who worsened showed decreased active coping strategies; the latter were also significantly more likely to have been taking interferon beta drugs at both time points than patients who did not change in their mood functioning. CONCLUSIONS: Mood symptoms of depression are significantly more variable over time than neurovegetative or negative evaluative symptoms in MS patients. Decreased use of active coping strategies may put patients at risk of increased depressed mood, whereas increased use of active coping may result in decreased depressed mood longitudinally. Interferon beta use may put patients at risk of increases in depressed mood.

Depression in multiple sclerosis: relationship to planning ability.

Recent research has demonstrated deficits on effortful executive tasks involving planning in multiple sclerosis (MS) patients. Given the high prevalence of depression in MS and the commonly reported link between depression and performance on executive tasks, planning impairments in MS may be associated with depression. We compared the performance of depressed and nondepressed MS patients on a planning task (Tower of London-TOL) to evaluate this hypothesis. Compared with nondepressed MS patients, depressed MS patients made significantly (p < .05) more moves and took more time per trial on the TOL. A follow-up regression analysis was conducted that included the TOL and speeded attentional/working memory task indices found to be associated with depression in MS from the authors' prior reports. This analysis revealed that 25% of the variance in depression scores was predicted by the most sensitive speeded attentional/working memory task. Furthermore, this variance overlapped completely with variance predicted by the TOL-time/trial index. The only clearly nonspeeded task index, TOL-moves per trial, was associated with unique variance (8%) in predicting MS depression scores. These results suggest that slowed information processing speed and, secondarily, deficient nonspeeded central executive skill, may be core to the cognitive deficits characteristic of depressed MS patients.

Measuring central executive functioning: what's in a reading span?

Although variations of Daneman and Carpenter's (1980) Reading Span Test (RST) have seen increasing use in both cognitive and neuropsychological research, the specific mental operations involved in performing it remain unclear. We tested 80 undergraduates to examine the extent to which speed of processing, manipulation capacity, and susceptibility to interference contributed to RST performance. The results suggest that, rather than unitary central executive or processing speed functions underlying RST performance, at least two factors, manipulation capacity and susceptibility to interference, underlie the task. Further study of RST operations may lead to a better understanding of the nature of the central executive itself.

Metamemory and tested cognitive functioning in multiple sclerosis.

Metamemory, or one's knowledge and self-report of memory ability, has been researched extensively; however, few studies have examined it in multiple sclerosis (MS). Because impairment in cognitive domains besides memory may affect memory functioning, patients may self-report problems with memory that are indicative of impairment in cognitive domains besides memory. One goal of the current study was to test this hypothesis in MS. A group of 55 MS patients were administered a variety of cognitive tasks and a self-report metamemory measure; patients' significant others were also given a metamemory measure requiring them to rate patients' memory abilities. Results indicated that patients' metamemory reports were significantly (p < .05) correlated with verbal recall, attentional, and executive tasks. Significant other ratings of patients' metamemory were correlated with verbal recall and attentional measures. Stepwise regression analyses including all relevant cognitive and demographic variables indicated that only education and Symbol Digit accounted for significant independent variance in patients' current memory reports. Our results suggest: (1) subjective complaints of memory difficulties by MS patients reflect difficulty in cognitive domains besides memory, (2) MS patient self-reports of memory difficulty are at least as accurate as significant other reports, and (3) patients with more education are more accurate in their metamemory ratings. These findings have implications not only for a better understanding of metamemory in MS, but also for more effective treatment and rehabilitation of MS patients.

Neurovegetative symptoms in multiple sclerosis: relationship to depressed mood, fatigue, and physical disability.

Some authors have suggested that when evaluating depression in multiple sclerosis (MS) patients, neurovegetative symptoms should be discounted and/or not considered, given the ostensibly high overlap between symptoms of MS (e.g., sleep disturbance, fatigue) and neurovegetative symptoms of depression. A further assertion is that inclusion of items assessing neurovegetative symptoms may artificially inflate overall depression scores and that mood scales may provide more accurate indices of depression in MS patients. The current study investigated the possibility that some neurovegetative symptoms may be specifically related to MS patients' depressed mood and are not simply indicators of physical disability and/or fatigue. Seventy-six clinically definite MS patients in the northwestern United States were administered two depression inventories and measures of physical disability and fatigue as part of a larger study. Results revealed that one neurovegetative symptom--disinterest in sex--was uniquely associated with depressed mood, and other neurovegetative symptoms were associated with both depression and fatigue but not physical disability. The present findings suggest that certain neurovegetative symptoms are differentially associated with depression, fatigue, and physical disability in MS. Routinely discounting all neurovegetative symptoms when assessing depression in MS patients may thus be unwarranted.

The ecological validity of clinical tests of memory and attention in multiple sclerosis.

Ecological validity--the degree to which clinical tests of cognitive functioning predict functional impairment--has recently become an area of interest in neuropsychology. The current study used a sample of 31 cognitively and functionally impaired multiple sclerosis (MS) patients to determine if tests commonly used to assess memory and attentional functioning in MS are ecologically valid. Two methods of improving the ecological validity of cognitive testing were employed. Stepwise multiple regression analyses suggested that tests of memory and attention more analogous to everyday tasks are better predictors of functional impairment in MS than both standard clinical tests of memory and attention, and memory questionnaires completed by the patient or a significant other. Nonetheless, both standard clinical tests and more ecologically valid tests significantly predicted functional impairment. Importantly, they were not significantly correlated with one another, suggesting that the inclusion of both types of tests in evaluating MS patients is warranted.

Depression in multiple sclerosis: relationship to working memory capacity.

Recent research has shown that depression in multiple sclerosis (MS) is associated with deficits on cognitively demanding tasks. One explanation for this relationship is that depressed MS patients may have reduced working memory capacity. The present study was designed to test this hypothesis. Depressed MS patients were compared with nondepressed MS patients and nondepressed healthy controls on a task of working memory capacity (reading span) and a short-term memory task not taxing working memory capacity (word span). In support of the capacity-reduction model, compared with the nondepressed groups, depressed MS patients performed significantly worse on reading span (p<.001) but not on word span. Additionally, reading span was significantly correlated with capacity-demanding tasks shown to be impaired in depressed MS patients in previous reports. Results suggest that depressed MS patients are characterized by limited working memory capacity and that the central executive component of the working memory system may be most affected.

Depressed mood in multiple sclerosis: relationship to capacity-demanding memory and attentional functioning.

Because it is theorized that depression results in reduced available attentional capacity that, in turn, can explain the impaired performance on capacity-demanding tasks in depressed individuals, the authors predicted that multiple sclerosis (MS) patients with depressed mood would have difficulty with these types of tasks. Twenty depressed mood MS participants were compared with 41 nondepressed mood MS participants and 8 nondepressed mood controls on 5 attentional capacity-demanding clinical memory and attentional tasks and 3 tasks with minimal capacity demands. Depressed mood MS patients performed significantly worse than both nondepressed mood groups on the 3 speeded capacity-demanding attentional measures but not on any of the tasks requiring few capacity demands, supporting the authors' predictions. The possibility that the impaired performance of depressed mood MS patients on speeded attentional tasks was mediated by reduced verbal working memory capacity, impaired deployment of executive strategies that access working memory capacity, or psychomotor slowing is explored.

Executive functions in multiple sclerosis: an analysis of temporal ordering, semantic encoding, and planning abilities.

Previous studies have consistently demonstrated impairments in conceptual reasoning and set-shifting abilities in patients with multiple sclerosis (MS). Other executive functions have been less frequently examined. We compared 44 MS patients and 48 demographically matched controls on a temporal-ordering and semantic-encoding task and on a test of planning (Tower of Hanoi). Compared with controls, MS patients experienced deficient semantic encoding and planning but unimpaired temporal-order memory. For both tasks, post hoc analyses indicated that chronic-progressive MS patients contributed most to the group differences. A combination of poor planning and slowed information-processing speed was hypothesized to have contributed to MS patients' impaired Tower of Hanoi performance. Further research is needed to explore the possible relationship between semantic-encoding and planning deficits in MS and social and occupational disabilities.