The relationship between subjective fatigue and cognitive fatigue in advanced multiple sclerosis

The present study examined the cognitive performance and ratings of subjective fatigue in people with advanced MS and matched healthy control participants. A continuous n-back task, involving attention (0-back), was performed at the beginning and end of one testing session; a task involving working memory (1-back) was performed at the beginning and end of another testing session. Subjective fatigue was rated at regular intervals during each session. Overall, there was limited evidence of objective cognitive fatigue in the MS group, as assessed by the change in n-back performance during the sessions. The MS group did report a greater increase, than the control group, in the level of subjective fatigue during the 1-back testing session, but change in subjective fatigue did not correlate significantly with change in cognitive performance. The implications of these findings for our understanding of cognitive fatigue in MS are discussed.     

Changes in neuropsychological test performance over the workday in multiple sclerosis

Fatigue, a common symptom of multiple sclerosis (MS), is associated with impairment in performing daily activities, poor quality of life and premature retirement from the workforce. There is little doubt that patients with MS can exhibit marked weakness and other objective signs of physical fatigue, but whether cognitive performance by patients declines more rapidly than that by controls as a function of time engaged in mental activity remains controversial. Krupp and Elkins (2000) reported more rapid deterioration of performance by MS patients on two of five cognitive measures when subjects performed 3 hr of continuously effortful tasks between baseline and posttest. Others, using shorter and less taxing interpolated tasks found similar changes in performance over time for patients and controls. In the present study participants completed a timed walk, fatigue ratings and four cognitive tests that emphasized processing novel information before they went to work and again after completing a normal workday. Patients with MS walked somewhat more slowly and performed more poorly on two of the cognitive tests, but they did not show more decline from baseline to posttest on any of these objective measures of cognitive fatigue. By contrast, subjective ratings of fatigue showed a greater increase over the day for patients than for controls. These results confirm other reports that patients' subjective ratings of their fatigue are not valid indicators of their actual performance on cognitive tests. Furthermore, laboratory studies that report "objective" cognitive fatigue in MS may utilize conditions that model the cognitive fatigue associated with the jobs patients actually perform rather poorly.     

Corpus callosum atrophy as a marker of clinically meaningful cognitive decline in secondary progressive multiple sclerosis. Impact on employment status

Cognitive impairment in Multiple Sclerosis (MS) is more frequent and pronounced in secondary progressive MS (SPMS). Cognitive decline is an important predictor of employment status in patients with MS. Magnetic Resonance Imaging (MRI) markers have been used to associate tissue damage with cognitive dysfunction. The aim of the study was to designate the MRI marker that predicts cognitive decline in SPMS and explore its effect on employment status. 30 SPMS patients and 30 healthy participants underwent neuropsychological assessment using the Trail Making Test (TMT) parts A and B, semantic and phonological verbal fluency task and a computerized cognitive screening battery (Central Nervous System Vital Signs). Employment status was obtained as a quality of life measure. Brain MRI was performed in all participants. We measured total lesion volume, third ventricle width, thalamic and corpus callosum atrophy. The frequency of cognitive decline for our SPMS patients was 80%. SPMS patients differed significantly from controls in all neuropsychological measures. Corpus callosum area was correlated with cognitive flexibility, processing speed, composite memory, executive functions, psychomotor speed, reaction time and phonological verbal fluency task. Processing speed and composite memory were the most sensitive markers for predicting employment status. Corpus callosum area was the most sensitive MRI marker for memory and processing speed. Corpus callosum atrophy predicts a clinically meaningful cognitive decline, affecting employment status in our SPMS patients.     

Integrative assessment of brain and cognitive function in post-traumatic stress disorder

The present study combined neuropsychological and electrophysiological measures to obtain a comprehensive profile of the everyday attentional and memory dysfunction reported in PTSD. The event-related potential (ERP) literature has consistently found abnormalities in late components (N2, P3) reflecting working memory (WM) function. However, the neuropsychological profile reported in the literature has considerable variation. The present study examined ERP activity in 33 PTSD participants and matched controls during a standard two-tone auditory oddball task. Neuropsychological assessment was carried out using a task battery assessing a wide range of cognitive functions. Consistent with previous work, the PTSD group showed delayed N2 latency and reduced P3 target amplitude, together with slower and less accurate target detection. Scalp topography provided evidence of widespread abnormality during WM function, but with strongest effects broadly over the left hemisphere. Neuropsychological testing found concomitant difficulties on factorial measures of verbal memory retention/access and sustained attention but enhanced performance on measures of immediate recall. This integrative pattern of effects reflects a specific impairment in the operation of working memory systems that guide ongoing, planned behavior and that facilitate the acquisition and retention of new memories.     

Ratings of subjective mental fatigue relate to cognitive performance in patients with myasthenia gravis.

We examined ratings of fatigue and cognitive performance in myasthenia gravis (MG) patients and healthy subjects. All participants were administered self-report measures of mental and physical fatigue before and after completing a demanding cognitive work battery. Change in fatigue indices was recorded and examined in relation to cognitive function. Results of the study revealed that baseline ratings of fatigue did not relate to cognitive performances for either group. By contrast, increased mental fatigue from the baseline to the post-test assessment correlated with cognitive measures for patients but not control subjects. MG patients reported that physical fatigue also increased following the work battery, but only ratings of mental fatigue correlated with cognitive performances. The results indicate that cognitive impairments may be associated with perceived fatigue in MG.     

Memory impairment in now abstinent MDMA users and continued users: a longitudinal follow-up

The authors further investigated the functional consequences of continued neurotoxicity of (+/-)3,4-methylenedioxymethamphetamine (MDMA) use. Fifteen participants who were previously given a brief neuropsychological battery were tested for a third time 2 years after baseline. At 2 years, seven participants were still using MDMA, whereas eight participants had become abstinent from MDMA since 1-year testing. Current users demonstrated further declines in memory ability; former users improved on several memory measures or remained static in performance.     

Interferon-free therapy in hepatitis C virus (HCV) monoinfected and HCV/HIV coinfected patients: effect on cognitive function,fatigue, and mental health

The efficacy and safety of interferon-free therapies for hepatitis C virus (HCV) infection have been reported. Considering the accumulating evidence for a direct central nervous system infection by HCV, we aim to evaluate the effect of direct acting antivirals (DAA) therapy on cognitive function in HCV patients. We conducted a longitudinal analysis of the cognitive performance of 22 patients (8 HCV+, 14 HCV+/HIV+) who completed neuropsychological testing at baseline and at week 12 after DAA therapy. In 20 patients, we analyzed specific attention parameters derived from an experimental testing based on the Theory of Visual Attention (TVA). Depression, fatigue, and mental health were assessed as patient reported outcomes. At baseline, 54.5% of the patients met the criteria for cognitive impairment and 40% showed impairment in TVA parameters. Follow-up analysis revealed significant improvements in the domains of visual memory/learning, executive functions, verbal fluency, processing speed, and motor skills but not in verbal learning and attention/working memory. We did not observe significant improvement in visual attention measured by TVA. Fatigue and mental health significantly improved at follow-up. Our findings indicate that successful DAA treatment leads to cognitive improvements in several domains measured by standard neuropsychological testing. The absence of improvement in TVA parameters and of significant improvement in the domain of attention/working memory might reflect the persistence of specific cognitive deficits after HCV eradication. In summary, DAA treatment seems to have a positive effect on some cognitive domains and leads to an improvement in mental health and fatigue in HCV-infected patients.     

A 3-year longitudinal study of cognitive impairment in patients with primary progressive multiple sclerosis: speed matters

BACKGROUND: The few controlled longitudinal studies of cognitive performance in MS patients all provide evidence of deterioration in at least a subset of the patients sampled. Only one of these studies has focused on primary progressive MS, and little attention has been paid to the specific domains of cognitive functioning that change over time. The present study examined three principal cognitive domains in samples of primary progressive MS patients and healthy controls followed over a period of 3 years. METHODS: A battery of neuropsychological tests that included measures of strategic problem solving, verbal memory, and information processing speed was administered annually to 24 MS patients and 25 controls. RESULTS: MS patients' performance on measures of processing speed showed significantly greater decline over the 3-year period than did that of controls. Similar results were not observed in the case of problem solving or verbal memory. There was no evidence of more dramatic decline occurring in patients who were initially classified as cognitively impaired relative to those who were unimpaired at baseline. However, this failure may have been influenced by differential attrition from the sample; more impaired patients were less likely to complete the study. CONCLUSION: Overall the results support the contention that information processing speed is the domain most sensitive to the impact of multiple sclerosis on cognitive functioning over time.     

Cognitive consequences of coexisting temporal lobe developmental malformations and hippocampal sclerosis.

OBJECTIVE: To characterize patterns of cognitive functioning in a well-defined group of patients with MRI-identified coexisting left temporal lobe developmental malformations (TLDM) and mesial temporal sclerosis (MTS), and to examine neuropsychological outcome in this dual-pathology group following epilepsy surgery. METHODS: Cognitive functioning in patients with left TLDM and MTS (n = 15) was compared with patients with isolated left MTS (n = 40). TLDM and MTS were identified by high-quality MRI protocol. Patients were administered a battery of neuropsychology tests as part of their presurgical workup for possible epilepsy surgery. Unilateral temporal lobe resection was performed on 10 of the dual-pathology patients and 34 of the isolated MTS patients. Postoperative cognitive performance was also assessed. RESULTS: Both groups displayed impairments in verbal and visual memory, language, and academic achievement. Performance on measures of psychometric intelligence, executive function, and attention were not impaired and were similar between groups. Presence of dual pathology was associated with a significantly less efficient verbal encoding strategy on the word list learning task. Postoperatively, declines were noted for both groups across tasks of verbal memory and language. Groups were not different significantly in terms of neuropsychological outcome after surgery. CONCLUSION: Patients with coexisting TLDM and MTS have impaired cognitive functioning similar to MTS patients-in particular, with regard to episodic memory and language deficits. Temporal lobe resection produces similar cognitive changes in both groups.     

Effect of type of cue,type of response,time delay and two different ongoing tasks on prospective memory functioning after acquired brain injury

Failures of prospective memory (PM) are one of the most frequent, and least studied, sequelae of brain injury. PM, also referred to as memory for intentions, is the ability to remember to carry out a future task. Successful completion of a PM task requires the ability to monitor time, keep the action to be performed periodically in awareness, remember the task to be performed, and initiate the action. Although PM has been shown to be a common difficulty after brain injury, it remains unknown which aspects of performance are impaired. In this study, the performance of 25 individuals with brain injury and that of 25 healthy participants were measured separately on the following variables: time until completion of the task, difficulty of the ongoing task being performed while waiting, whether the task to be performed is an action or is verbal, and whether the cue to perform the task is the passing of a particular amount of time (e.g., 10 minutes) or is an external cue (e.g., an alarm sounding). Individuals with brain injury demonstrated impairment compared to healthy adults on virtually all variables. PM performance was also compared to a battery of standard neuropsychological measures of attention, memory, and executive functions, and to self-report measures of PM functioning, in order to determine the underlying cognitive deficits responsible for poor PM performance, if any. PM performance was correlated with measures of executive functioning but not to self-report measures of PM functioning. Implications are discussed in terms of cognitive rehabilitation recommendations.     

The cognitive burden of multiple sclerosis in children

Little is known about the cognitive sequelae of pediatric-onset multiple sclerosis (MS). Ten pediatric patients with MS were evaluated using a comprehensive neuropsychological battery. Neuropsychological deficits were identified on measures of general cognition, language, visuomotor integration, and verbal and visual memory. Cognitive impairment occurs in children with MS, and those with longer disease duration and younger age at MS onset appear to be at greatest risk.     

Effect of type of cue, type of response, time delay and two different ongoing tasks on prospective memory functioning after acquired brain injury

Failures of prospective memory (PM) are one of the most frequent, and least studied, sequelae of brain injury. PM, also referred to as memory for intentions, is the ability to remember to carry out a future task. Successful completion of a PM task requires the ability to monitor time, keep the action to be performed periodically in awareness, remember the task to be performed, and initiate the action. Although PM has been shown to be a common difficulty after brain injury, it remains unknown which aspects of performance are impaired. In this study, the performance of 25 individuals with brain injury and that of 25 healthy participants were measured separately on the following variables: time until completion of the task, difficulty of the ongoing task being performed while waiting, whether the task to be performed is an action or is verbal, and whether the cue to perform the task is the passing of a particular amount of time (e.g., 10 minutes) or is an external cue (e.g., an alarm sounding). Individuals with brain injury demonstrated impairment compared to healthy adults on virtually all variables. PM performance was also compared to a battery of standard neuropsychological measures of attention, memory, and executive functions, and to self-report measures of PM functioning, in order to determine the underlying cognitive deficits responsible for poor PM performance, if any. PM performance was correlated with measures of executive functioning but not to self-report measures of PM functioning. Implications are discussed in terms of cognitive rehabilitation recommendations.     

The cognitive performance of patients with multiple sclerosis during periods of high and low fatigue

The objective of this study was to examine whether multiple sclerosis (MS)-related fatigue affects patients' cognitive performance. Thirty patients who had substantial fatigue in conjunction with MS and who reported marked diurnal variability in the severity of their fatigue were tested on two occasions: during a period of high fatigue and during a period of relatively low fatigue. The order of these sessions was counterbalanced across patients. During both sessions, patients completed a questionnaire concerning their present state of fatigue and a battery of neuropsychological tests of planning, selective attention, and paired associate learning. Although patients confirmed greater fatigue during the period of high fatigue and felt they had performed more poorly during this period, there were no differences in cognitive performance that could be attributed to fatigue. Instead, all subjects showed improvement from the first to the second session regardless of whether the latter entailed a period of high or low fatigue. In contrast to studies reporting fatigue-related declines in MS patients' cognitive performance, no differences in performance were found when MS patients were tested during periods of high versus low fatigue. These contrasting results, stemming from differences in experimental design, are discussed in terms of their implications for assessing cognitive function in patients with MS.     

Neuropsychological outcome after unilateral pallidotomy for the treatment of Parkinson's disease

OBJECTIVE: To assess the long term cognitive outcome of unilateral posteroventral pallidotomy (PVP) and the overall efficacy of the surgery. METHODS: Forty two (29 left and 13 right PVP) patients with Parkinson's disease underwent neurological and neuropsychological testing before PVP and at 3 and 12 months after PVP. The neuropsychological testing battery emphasised measures of verbal learning and memory, visuospatial abilities, speed of information processing, executive functioning, and affective functioning. RESULTS: All patients demonstrated motor improvements after surgery during their off state, and 86% of patients also showed improvements in motor functioning in their on state. Repeated measures ANOVA showed significant improvements in confrontational naming, visuospatial organisation, and affective functioning 3 months and 12 months after surgery, with inconsistent improvements in executive functioning 12 months post-PVP. Patients demonstrated a transient impairment in verbal memory, with verbal learning performance returning to baseline 12 months post-PVP after a significant decline 3 months after PVP. When three patients with lesions extending outside of the PVP were excluded from the analysis, a decline in verbal fluency performance after PVP was not found to be significant. Differences due to side of lesion placement were not found on any of the cognitive measures. CONCLUSIONS: In the largest long term follow up study reported to date, the cognitive changes found up to a year after PVP are minimal compared with the robust improvements in motor function. The findings highlight the need to investigate the relation between the specific fibre tracts affected by the lesions and cognitive outcome.     

Electrophysiological and behavioral effects of frontal transcranial direct current stimulation on cognitive fatigue in multiple sclerosis

Fatigue is one of the most common and debilitating symptoms affecting patients with multiple sclerosis (MS). Sustained cognitive effort induces cognitive fatigue, operationalized as subjective exhaustion and fatigue-related objective alertness decrements with time-on-task. During prolonged cognitive testing, MS patients show increased simple reaction times (RT) accompanied by lower amplitudes and prolonged latencies of the P300 event-related potential. Previous studies suggested a major role of structural and functional abnormalities in the frontal cortex including a frontal hypo-activation in fatigue pathogenesis. In the present study we investigated the neuromodulatory effect of transcranial direct current stimulation (tDCS) over the left dorsolateral prefrontal cortex (DLPFC) on objective measures of fatigue-related decrements in cognitive performance in MS patients. P300 during an auditory oddball task and simple reaction times in an alertness test were recorded at baseline, during and after stimulation. Compared to sham, anodal tDCS caused an increase in P300 amplitude that persisted after the end of stimulation and eliminated the fatigue-related increase in RT over the course of a testing session. Our findings demonstrate that anodal tDCS over the left DLPFC can counteract performance decrements associated with fatigue thereby leading to an improvement in the patient’s ability to cope with sustained cognitive demands. This provides causal evidence for the functional relevance of the left DLPFC in fatigue pathophysiology. The results indicate that tDCS-induced modulations of frontal activity can be an effective therapeutic option for the treatment of fatigue-related declines in cognitive performance in MS patients.     

Subvocal articulatory rehearsal during verbal working memory in multiple sclerosis

This study was designed to examine verbal working memory (VWM) components among multiple sclerosis (MS) patients and determine the influence of information processing speed. Of two frequently studied VWM sub-components, subvocal rehearsal was expected to be more affected by MS than short-term memory buffering. Furthermore, worse subvocal rehearsal was predicted to be specifically related to slower cognitive processing. Fifteen MS patients were administered a neuropsychological battery assessing VWM, processing speed, mood, fatigue, and disability. Participants performed a 2-Back VWM task with modified nested conditions designed to increase subvocal rehearsal (via inter-stimulus interval) and short-term memory buffering demands (via phonological similarity). Performance during these 2-Back conditions did not significantly differ and both exhibited strong positive correlations with disability. However, only scores on the subvocal rehearsal 2-Back were significantly related to performance on the remaining test battery, including processing speed and depressive symptoms. Findings suggest that performance during increased subvocal rehearsal demands is specifically influenced by cognitive processing speed and depressive symptoms.     

Computerised working memory training in healthy adults: A comparison of two different training schedules

This study compared a high intensity working memory training (45 minutes, 4 times per week for 4 weeks) with a distributed training (45 minutes, 2 times per week for 8 weeks) in middle-aged, healthy adults. The aim was to clarify whether a computerised working memory training is effective and whether intensity of training influences training outcome. To evaluate the efficacy and possible transfer effects, a neuropsychological test battery assessing short- and long-term memory, working memory, executive functions and mental speed was applied at baseline and at retest. Our results indicate that the distributed training led to increased performance in all cognitive domains when compared to the high intensity training and the control group without training. The most significant differences revealed by interaction contrasts were found for verbal and visual working memory, verbal short-term memory and mental speed. These results support the hypothesis that cognitive enhancement by cognitive intervention is effective in healthy individuals, and that a distributed training schedule is superior to a high intensity intervention.     

Cognitive decline in patients with familial Alzheimer's disease associated with E280a presenilin-1 mutation: a longitudinal study

Few longitudinal studies have been carried out to investigate the cognitive decline in early onset of familial Alzheimer's disease (FAD). In this study 12 patients with FAD (M age = 49.61 years, SD = 4.99), 10 patients with sporadic Alzheimer's disease (SAD) (M age = 71.40, SD =10.00), and 15 matched normal controls (M age = 45.01, SD = 7.24) were selected. A comprehensive neuropsychological battery was administered three times over a period of 18 months. Individuals designated as FAD met the criteria for dementia and were positive for the E280A presenilin 1 mutation. Participants with SAD met the criteria for dementia and were negative for the E280A presenilin 1 mutation. Normal control participants were the FAD patients' relatives, who were negative for the mutation. Two groups of neuropsychological instruments were administered: (1) The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychological test battery, and (2) additional neuropsychological tests of abstraction and constructional abilities. Patients with FAD were significantly impaired on all measures at the first examination except for reading of words. While the performance of the normal controls remained unchanged over the 18 months for most neuropsychological tests, the patients with FAD displayed a decline in verbal memory, language, constructional and abstraction tests. The greatest decline was observed on the Mini-Mental State Exam scores. Patients with SAD demonstrated a similar pattern of cognitive decline, but the decline was faster in FAD than in SAD participants.     

Secondary verbal memory: a potential endophenotype of schizophrenia

This study aimed at identifying neuropsychological endophenotypes of schizophrenia which met the criteria of stability and sensitivity. Twenty-six non-schizophrenic first-degree relatives together with their affected family members (all simplex-families) underwent assessment with a comprehensive neuropsychological test battery both at baseline and 13 months follow-up. Follow-up patients were in a state of stable remission. Further, 21 unrelated, demographically balanced, non-vulnerable controls were tested one at a time. A principal components analysis of our test battery resulted in four factors: (1) Vigilance, attention, and psychomotor, (2) secondary verbal memory, (3) immediate and working memory, and (3) abstraction and problem solving. At baseline testing our study revealed a pattern of selective cognitive deficits in the relative group that is less pronounced, yet qualitatively similar, to that found in the patient sample. The most severe deficits displayed both the patients and their relatives in the secondary verbal memory domain. The dysfunctions in secondary verbal memory at baseline testing significantly correlated with negative symptoms only. Secondary verbal memory deficits proved to be relatively independent of age at onset of illness, illness duration, and neuroleptic dosage. Longitudinally, dysfunctions in the patients' secondary verbal memory fluctuated over time and with negative symptoms, and persisted in remitted patients at the same level as in their relatives. In conclusion, the secondary verbal memory met the criteria of relative stability and sensitivity in our sample of simplex-families. Thus, the secondary verbal memory seems to be a potential endophenotypic marker of schizophrenia, even for cases with a hypothetically lower genetic loading.     

The therapeutic effect of treatment with RehaCom software on verbal performance in patients with multiple sclerosis

Multiple sclerosis (MS) is characterized by central nervous system lesions that lead to neurological dysfunctions including fatigue, depression and anxiety. MS is affecting almost 2.3 million people around the world, with the significant highest prevalence in the North America. MS also affects different cognitive abilities, such as attention, memory and executive functions. Furthermore, a significant impairment in verbal fluency and naming abilities in patients with MS has been reported. RehaCom, is a software that has improvement effects on cognitive functions. The goal of this research is to investigate the effect of treatment with RehaCom on verbal performance in patients with MS. To select the participants, 60 patients with MS who referred to our clinic were chosen randomly and divided into Control (n = 30) and Experimental (n = 30) groups. The participants in the experimental group were treated by RehaCom software for 10 sessions during 5 weeks (2 sessions per week and each session was 1 h). Controlled Oral Word Association Test (COWAT) and California Verbal Learning Test – Second Edition (CVLT-II), were used to assess verbal performance (verbal fluency, and verbal learning and memory) at weeks 0 (baseline), 5 (post-test) and 10 (follow-up). The results showed that, treatment with RehaCom improved verbal performance in patient with MS, at both post-test and follow-up stages. In conclusion, treatment with RehaCom cognitive rehabilitation software can improve verbal fluency, and verbal learning and memory in patient with MS, possibly by affecting the brain regions involved in language performance.