John DeLuca

Minimal Neuropsychological Assessment of MS Patients: A Consensus Approach

Cognitive impairment is common in multiple sclerosis (MS), yet patients seen in MS clinics and neurologic practices are not routinely assessed neuropsychologically. In part, poor utilization of NP services may be attributed to a lack of consensus among neuropsychologists regarding the optimal approach for evaluating MS patients. An expert panel composed of neuropsychologists and psychologists from the United States, Canada, United Kingdom, and Australia was convened by the Consortium of MS Centers (CMSC) in April, 2001. Our objectives were to: (a) propose a minimal neuropsychological (NP) examination for clinical monitoring of MS patients and research, and (b) identify strategies for improving NP assessment of MS patients in the future. The panel reviewed pertinent literature on MS-related cognitive dysfunction, considered psychometric factors relevant to NP assessment, defined the purpose and optimal characteristics of a minimal NP examination in MS, and rated the psychometric and practical properties of 36 candidate NP measures based on available literature. A 90-minute NP battery, the Minimal Assessment of Cognitive Function in MS (MACFIMS), emerged from this discussion. The MACFIMS is composed of seven neuropsychological tests, covering five cognitive domains commonly impaired in MS (processing speed/working memory, learning and memory, executive function, visual-spatial processing, and word retrieval). It is supplemented by a measure of estimated premorbid cognitive ability. Recommendations for assessing other factors that may potentially confound interpretation of NP data (e.g., visual/sensory/motor impairment, fatigue, and depression) are offered, as well as strategies for improving NP assessment of MS patients in the future.

The contribution of MRI in assessing cognitive impairment in multiple sclerosis.

Cognitive impairment affects a large proportion of patients with multiple sclerosis (MS) and has a profound impact on their daily-life activities. Improving the knowledge of the pathophysiology of cognitive impairment in MS and of the mechanisms responsible for its evolution over time might contribute to development of better outcome measures and targets for innovative treatment strategies. Due to their ability to detect MS-related abnormalities, MRI techniques are a valuable tool to achieve these goals. Following an updated overview of the assessment methods and profile of cognitive impairment in patients with MS, this review provides a state-of-the-art summary of the main results obtained from the application of conventional and modern magnetic resonance– based techniques to quantify MS-related damage, in terms of macroscopic lesions, as well as involvement of the normal-appearing white matter and gray matter and their association with cognitive impairment. The possible role of brain cortical reorganization in limiting the clinical consequences of disease-related damage is also discussed. Finally, the utility of the previous techniques to monitor the progression of cognitive deficits over time and the efficacy of possible therapeutic strategies is considered.

Cognitive reserve moderates the negative effect of brain atrophy on cognitive efficiency in multiple sclerosis

According to the cognitive reserve hypothesis, neuropsychological expression of brain disease is attenuated among persons with higher education or premorbid intelligence. The current research examined cognitive reserve in multiple sclerosis (MS) by investigating whether the negative effect of brain atrophy on information processing (IP) efficiency is moderated by premorbid intelligence. Thirty-eight persons with clinically definite MS completed a vocabulary-based estimate of premorbid intelligence (Wechsler Vocabulary) and a composite measure of IP efficiency (Symbol Digit Modalities Test and Paced Auditory Serial Addition Task). Brain atrophy was estimated from measurements of third ventricle width using high-resolution anatomical brain magnetic resonance imaging (magnetization-prepared rapid gradient echo). In a hierarchical regression analysis controlling for age and depressive symptomatology, brain atrophy predicted worse IP efficiency (R2 = .23, p = .003) and cognitive reserve predicted better IP efficiency (R2 = .13, p = .013), but these effects were moderated by an Atrophy x Cognitive Reserve interaction (R2 = .15, p = .004). The negative effect of brain atrophy on IP efficiency was attenuated at higher levels of reserve, such that MS subjects with higher reserve were better able to withstand MS neuropathology without suffering cognitive impairment. Results help explain the incomplete and inconsistent relationship between brain atrophy and IP efficiency in previous research.

Examination of processing speed deficits in multiple sclerosis using functional magnetic resonance imaging.

Although it is known that processing speed deficits are one of the primary cognitive impairments in multiple sclerosis (MS), the underlying neural mechanisms responsible for impaired processing speed remain undetermined. Using BOLD functional magnetic resonance imaging, the current study compared the brain activity of 16 individuals with MS to 17 healthy controls (HCs) during performance of a processing speed task, a modified version of the Symbol Digit Modalities Task. Although there were no differences in performance accuracy, the MS group was significantly slower than HCs. Although both groups showed similar activation involving the precentral gyrus and occipital cortex, the MS showed significantly less cerebral activity than HCs in bilateral frontal and parietal regions, similar to what has been reported in aging samples during speeded tasks. In the HC group, processing speed was mediated by frontal and parietal regions, as well as the cerebellum and thalamus. In the MS group, processing speed was mediated by insula, thalamus and anterior cingulate. It therefore appears that neural networks involved in processing speed differ between MS and HCs, and our findings are similar to what has been reported in aging, where damage to both white and gray matter is linked to processing speed impairments.

Premorbid cognitive leisure independently contributes to cognitive reserve in multiple sclerosis

Objective: Consistent with the cognitive reserve hypothesis, higher education and vocabulary help persons with Alzheimer disease (AD) and multiple sclerosis (MS) better withstand neuropathology before developing cognitive impairment. Also, premorbid cognitive leisure (e.g., reading, hobbies) is an independent source of cognitive reserve for elders with AD, but there is no research on the contribution of leisure activity to cognition in MS. We investigated whether premorbid cognitive leisure protects patients with MS from cognitive impairment. Methods: Premorbid cognitive leisure was surveyed in 36 patients with MS. Neurologic disease severity was estimated with brain atrophy, measured as third ventricle width on high-resolution MRI. Cognitive status was measured with a composite score of processing speed and memory. Results: Controlling for brain atrophy, premorbid cognitive leisure was positively associated with current cognitive status (rp = 0.49, p < 0.01), even when controlling for vocabulary (rp = 0.39, p < 0.05) and education (rp = 0.47, p < 0.01). Also, premorbid cognitive leisure was unrelated to brain atrophy (r = 0.03, p > 0.5), but a positive partial correlation between leisure and atrophy emerged when controlling for cognitive status (rp = 0.37, p < 0.05), which remained when also controlling for vocabulary (rp = 0.34, p < 0.05) and education (rp = 0.35, p < 0.05). Conclusions: Premorbid cognitive leisure contributes to cognitive status in patients with MS independently of vocabulary and education. Also, patients with MS who engaged in more cognitive leisure were able to withstand more severe brain atrophy at a given cognitive status. Premorbid cognitive leisure is supported as an independent source of cognitive reserve in patients with MS.

Neural Correlates of Cognitive Fatigue: Cortico-Striatal Circuitry and Effort–Reward Imbalance

Recently, there has been renewed interest in the study of cognitive fatigue. It is known that fatigue is one of the most disabling symptoms in numerous neurological populations, including stroke, multiple sclerosis, Parkinson’s disease, and traumatic brain injury. Behavioral studies of cognitive fatigue are hampered by lack of correlation of self-report measures with objective performance. Neuroimaging studies provide new insight about cognitive fatigue and its neural correlates.Impairment within the cortico-striatal network, involved in effort–reward calculation, has been suggested to be critically related to fatigue. The current review surveys the recent neuroimaging literature, and suggests promising avenues for future research.

Spacing of Repetitions Improves Learning and Memory After Moderate and Severe TBI

Extensive research has determined that new learning in healthy individuals is significantly improved when trials are distributed over time (spaced presentation) compared to consecutive learning trials (massed presentation). This phenomenon known as the “spacing effect” (SE) has been shown to enhance verbal and nonverbal learning in healthy adults of different ages and in different memory paradigms (e.g., recognition, recall, etc.). The purpose of this study was to examine whether learning in adults with moderate and severe traumatic brain injury (TBI) is improved using a spacing-of-repetitions procedure. Using a within-groups design, participants with TBI (n =20) were presented a list of 115 words that were presented either once (single condition), twice consecutively (massed condition), or twice with 11 words between presentations (spaced condition). Participants were required to rank each word from 1 to 10 according to their familiarity with the word; they were not asked to “memorize” words for a later test. Word list learning was measured with a free recall test immediately following list presentation and with free recall and recognition tests after a 30-min delay. Participants recalled and recognized significantly more spaced words than massed words during this word list learning task. These results strongly indicate that the spacing of repetitions improves learning and memory in individuals who have sustained moderate to severe TBI. Implications for rehabilitation are discussed.

Retrieval practice improves memory in multiple sclerosis: clinical application of the testing effect.

The testing effect is a robust cognitive phenomenon by which memory retrieval on a test improves subsequent recall more than restudying. Also known as retrieval practice, the testing effect has been studied almost exclusively in healthy undergraduates. The current study investigated whether retrieval practice during testing leads to better delayed recall than restudy among persons with multiple sclerosis (MS), a neurologic disease associated with memory dysfunction. In a within-subjects design, 32 persons with MS and 16 demographically matched healthy controls (HC) studied 48 verbal paired associates (VPA) divided across 3 learning conditions: massed restudy (MR), spaced restudy (SR), and spaced testing (ST). Delayed VPA cued recall was measured after 45 min. There was a large main effect of learning condition (etap2 = .54, p < .001) such that both MS and HC participants produced better delayed recall for VPAs learned through ST relative to MR and SR; and SR relative to MR. This same pattern was observed for MS participants with objective memory impairment (n = 16), thereby providing the first evidence that retrieval practice improves memory more than restudy among persons with neurologically based memory impairment.

The Nature of Processing Speed Deficits in Traumatic Brain Injury: is Less Brain More?

The cognitive constructs working memory (WM) and processing speed are fundamental components to general intellectual functioning in humans and highly susceptible to disruption following neurological insult. Much of the work to date examining speeded working memory deficits in clinical samples using functional imaging has demonstrated recruitment of network areas including prefrontal cortex (PFC) and anterior cingulate cortex (ACC). What remains unclear is the nature of this neural recruitment. The goal of this study was to isolate the neural networks distinct from those evident in healthy adults and to determine if reaction time (RT) reliably predicts observable between-group differences. The current data indicate that much of the neural recruitment in TBI during a speeded visual scanning task is positively correlated with RT. These data indicate that recruitment in PFC during tasks of rapid information processing are at least partially attributable to normal recruitment of PFC support resources during slowed task processing.

Unemployment in multiple sclerosis (MS): utility of the MS Functional Composite and cognitive testing

Unemployment is a significant concern among individuals with multiple sclerosis (MS). Determinations regarding ability to work are highly dependent on measurement tools used by neurologists and allied professionals. However, little is known of the usefulness of these tools when determining issues pertaining to employment status. The purpose of the present investigation was to examine the utility of the Multiple Sclerosis Functional Composite (MSFC) and a brief cognitive test battery when examining employment status in MS. Seventy-seven individuals with MS completed the MSFC and a brief cognitive test battery. On the MSFC, unemployed individuals demonstrated worse upper extremity functioning. There was no difference on the Paced Auditory Serial Addition Task (PASAT), the sole cognitive measure of the MSFC. On cognitive testing, unemployed individuals performed worse on measures of memory, information processing speed, and executive functioning. Through logistic regression analysis, the Symbol Digit Modalities Test (SDMT) was found to be the sole predictor of employment status among the significant disease, MSFC and cognitive variables. Consistent with previous findings, logistic regression found the SDMT to be a significant predictor of employment status. Given the lack of significant group differences on the PASAT, continued consideration of replacing the PASAT with the SDMT in the MSFC appears warranted.