Brett A. Parmenter

Screening for cognitive impairment in multiple sclerosis using the Symbol digit Modalities Test.

Cognitive impairment is common in multiple sclerosis (MS), yet difficult to detect duringroutine neurologic examination. Therefore, briefscreening tests that identify patients who may benefit from a more thorough assessment or treatment are needed. We investigated the utility of the Symbol Digit Modalities Test (SDMT) as a screen for cognitive dysfunction because it can be administered and scored in about 5 minutes. One hundred MS patients and 50 healthy controls, matched on demographic variables, participated in the study. Examination procedures included the neuropsychological (NP) tests included in the Minimal Assessment of Cognitive Function in MS (MACFIMS) battery. Patients were considered impaired if they performed one and a half standard deviations below controls on two or more MACFIMS variables, excluding theSDMT. Bayesian statistics showed that a total score of 55 or lower onthe SDMT accurately categorized 72% of patients, yielding sensitivityof 0.82, specificity of 0.60, positive predictive value (PPV) of 0.71, and negative predictive value (NPV) of 0.73. These results suggest that the effectiveness of the SDMT as a screen for cognitive impairment in MS is roughly equal to that of other psychometric and questionnaire methods.

The utility of regression-based norms in interpreting the minimal assessment of cognitive function in multiple sclerosis (MACFIMS)

The Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS) is a consensus neuropsychological battery with established reliability and validity. One of the difficulties in implementing the MACFIMS in clinical settings is the reliance on manualized norms from disparate sources. In this study, we derived regression-based norms for the MACFIMS, using a unique data set to control for standard demographic variables (i.e., age, age2, sex, education). Multiple sclerosis (MS) patients (n = 395) and healthy volunteers (n = 100) did not differ in age, level of education, sex, or race. Multiple regression analyses were conducted on the performance of the healthy adults, and the resulting models were used to predict MS performance on the MACFIMS battery. This regression-based approach identified higher rates of impairment than manualized norms for many of the MACFIMS measures. These findings suggest that there are advantages to developing new norms from a single sample using the regression-based approach. We conclude that the regression-based norms presented here provide a valid alternative to identifying cognitive impairment as measured by the MACFIMS.

Validity of the Wisconsin Card Sorting and Delis–Kaplan Executive Function System (DKEFS) Sorting Tests in multiple sclerosis

Multiple sclerosis (MS) is a disease of the central nervous system that causes cognitive impairment with a frequency of roughly 50%. While processing speed and memory defects are most commonly observed, a substantial number of patients also have deficiency in higher executive ability. Two tests, the Wisconsin Card Sorting Test (WCST) and the Sorting Test from the Delis–Kaplan Executive Function System (DKEFS), have been recommended for evaluation of neuropsychological impairment in MS. We investigated the validity of these tests in 111 MS patients and 46 age- and education-matched controls. MS patients performed more poorly on both measures, but only the DKEFS discriminated the groups after controlling for depression. Both tests were modestly or strongly correlated with MRI indices of brain atrophy or lesion burden and discriminated between employed and disabled patients. While both tests appear to have good validity in the MS population, the availability of alternative forms makes the DKEFS an attractive alternative to the WCST, as was suggested by a consensus panel.

Working memory deficits in multiple sclerosis: Comparison between the n -back task and the Paced Auditory Serial Addition Test

Working memory (WM) deficits are common in multiple sclerosis (MS). The Paced Auditory Serial Addition Test (PASAT) is used frequently to measure WM in clinical settings. The n-back paradigm is used often in experimental studies of WM. One unique component of the n-back task is that it provides a measure of reaction time (RT), an additional behavioral index of processing speed and task difficulty. Despite the use of both tasks to measure WM, their common variance has not been documented. We tested 32 MS patients and 20 controls; performance measures were obtained for both tasks. Compared with controls, MS patients generally had poorer performance on both the PASAT and n-back task. MS patients also had slower RTs on the n-back than controls and showed more slowing than controls as a function of WM load. Correlational analyses showed a high correspondence between performance measures on the PASAT and n-back. Principal components analysis pointed to a common feature of the PASAT, n-back, and specific other neuropsychological measures, that is, processing speed. Although the PASAT and n-back were shown to have a significant amount of shared variance, each test has specific advantages and disadvantages for use in clinical populations.

Information processing deficits in multiple sclerosis: A matter of complexity

This study examined the relationship between processing speed (PS) and working memory (WM), as measured by performance on an n-back task, in relapsing-remitting multiple sclerosis (RRMS) patients. Simple PS was defined as reaction time (RT) on the 0-back task and complex PS was defined as RT on both the 1-back and 2-back tasks. Participants were administered all three n-back tasks (0-, 1-, and 2-back). Total correct responses, total dyads, and RTs were recorded. As expected, RT for all participants slowed as WM load increased. MS patients had slower RTs than controls across all tasks, and the difference between groups for RT was greatest during the 2-back task. When RT for simple PS (0-back) was parsed from the 1- and 2-back tasks, MS patients still showed impaired complex PS compared to controls. MS patients also made significantly fewer total correct responses and had fewer dyads than controls only on the 2-back task. These findings suggest that both WM and PS deficits are present in RRMS, and that as WM demand increases (from 1- to 2-back) both PS and WM deficits become more prominent.

Influence of recruitment and participation bias in neuropsychological research among MS patients.

The potential influence of recruitment context in neuropsychological (NP) research is seldom addressed in the literature. Our experience with a previous large-scale study of MS cognitive impairment led us to speculate that referral questions and motivation bias significantly impact conclusions drawn from NP testing. We re-analyzed data from Benedict et al. (2006) and compared the results obtained across three groups of patients: paid research volunteers, clinical patients undergoing evaluation for routine monitoring of cognitive status, and clinical patients referred for diagnostic clarification, determination of disability benefits, and other more complex issues. Research volunteers were significantly younger and less frequently cognitively impaired compared to the clinical groups, greatly affecting prevalence estimates (45.6 to 65.6%). Significant correlations between depression and cognitive impairment were present only among the research volunteers. NP testing significantly predicted vocational outcomes in all groups. These results suggest that greater attention should be paid to the reasons patients agree to participate in NP testing.

Fatigue – but not mTBI history, PTSD, or sleep quality – directly contributes to reduced prospective memory performance in Iraq and Afghanistan era Veterans

Abstract Objective: Memory problems that affect daily functioning are a frequent complaint among Veterans reporting a history of repetitive mild traumatic brain injury (mTBI), especially in cohorts with comorbid PTSD. Here, we test the degree to which subjective sleep impairment and daytime fatigue account for the association of PTSD and self-reported mTBI history with prospective memory. Method: 82 Veterans with and without personal history of repeated blast-related mTBI during deployment were administered the Clinician Administered PTSD Scale (CAPS), Memory for Intentions Test (MIST), Patient Health Questionnaire-9 (PHQ-9), Neurobehavioral Symptom Inventory (NSI), and the Pittsburgh Sleep Quality Index (PSQI). Relationships between self-reported mTBI, PTSD, self-reported poor sleep and daytime fatigue, and MIST performance were modeled using partial least squares structural equation modeling (PLS-SEM). Results: Reported daytime fatigue was strongly associated with poorer prospective memory performance. Poor subjective sleep quality was strongly and positively associated with reported daytime fatigue, but had no significant direct effect on prospective memory performance. PTSD diagnosis and self-reported mTBI history were only associated with prospective memory via their impact on subjective sleep quality and daytime fatigue. Conclusions: Results suggest that daytime fatigue may be a mediating factor by which both mTBI and PTSD can interfere with prospective memory. Additional attention should be given to complaints of daytime fatigue, independent of subjective sleep quality, in the clinical care of those with a self-reported history of mTBI, and/or PTSD. Further research into whether interventions that decrease daytime fatigue lead to improvement in prospective memory and subjective cognitive functioning is warranted.

Taking Mental Illness beyond the DSM-IV-TR and into a New Frontier

The awareness that cognitive deficits are associated with mental illness is not new. Indeed, what we now call schizophrenia was initially conceptualized as dementia praecox and today neuropsychological deficits have been identified as a core feature of the disease (see Green, Neuchterlein, Gold, Barch, Cohen, et al., 2004). Despite this longstanding awareness our knowledge of the neuropsychology of mental illness is still limited, in part because of the heterogeneity in how mental illness is viewed, along with diversity in how it is researched. The editors of The Neuropsychology of Mental Illness address these issues by consolidating multiple perspectives on mental illness and various research techniques in one text. By doing so they challenge the reader to think beyond criteria listed in the DSM-IV-TR (American Psychiatric Association, 2000) and to consider neuropsychological, neuroscientific, and philosophical perspectives in the conceptualization of mental illness. The book is comprised of 30 chapters divided into four sections. Section 1, entitled Neuropsychological Processes, consists of chapters that examine the neuropsychology of psychological and cognitive functions as they pertain to mental illness. Section 2, The Importance of Methods, discusses current methodology in this area of research, emphasizing the importance of valid diagnoses of psychiatric disorders as well as careful research design and test selection. This section also reviews how neurophysiology, neuroimaging, and pharmacological models of psychiatric disorders can buttress our understanding of mental illness. There also is a very thorough and up-to-date review of the nascent field of cognitive