On the nature of memory disturbance in multiple sclerosis

Abstract

Thirty-seven patients with multiple sclerosis (MS) were compared to 26 normal controls of equivalent age, education, and verbal intelligence on measures of verbal learning and memory (Digit Span and Supraspan, Brown-Peterson Distractor Task, Selective Reminding Test, Story Recall, and Free Verbal Recall) and verbal fluency (Letter and Animal Fluency). The MS patients exhibited deficits on measures of secondary (long-term) memory and verbal fluency, but performed normally on measures of primary (short-term) memory, recognition memory, and rate of forgetting from secondary memory. These results suggest that the memory disturbance in MS results primarily from an impaired ability to access information from secondary memory, while encoding and storage capacity is intact. Degree of memory impairment was unrelated to length of illness, severity of disability, or self-reported depression.     

Acquisition and Storage Deficits in Multiple Sclerosis

This study examined whether verbal and visual memory impairments in multiple sclerosis (MS) are attributable to deficits in acquisition, storage, or retrieval. Volunteers with MS (n = 40) and healthy controls (n = 20) rehearsed a word list and a checkerboard pattern using a selective reminding procedure until two consecutive error-free trials were attained. Recall and recognition were assessed after 30 min and 90 min (and 1 week for verbal material) delays. The MS group required significantly more trials to attain criterion on both learning tests. Once equated for acquisition, both groups performed similarly on verbal recall and recognition. However the MS group performed significantly worse on measures of visual recall and recognition. The results suggest that the verbal memory impairment in MS is due to deficient acquisition, while the visual memory impairment in MS is attributable to deficits in acquisition and storage.     

SPECT, MRI and cognitive functions in multiple sclerosis.

Seventeen patients with relapsing remitting multiple sclerosis (MS) and mild physical disability had neuropsychological testing, magnetic resonance imaging (MRI) and single photon emission computerised tomography (SPECT) using technetium 99m (99mTc) hexamethyl-propyleneamine oxime (HMPAO). Performance in verbal fluency, naming and memory testing appeared to be impaired in MS patients compared with 17 age-sex and education matched normal controls. Weighted periventricular and confluent lesion scores and the width of the third ventricle, proved to be the most sensitive MRI measures in differentiating more cognitively impaired patients from those who were relatively unimpaired. Ratios of regional to whole brain activity, measured by SPECT, showed significant reduction in the frontal lobes and in the left temporal lobe of MS patients. A relationship was found between left temporal abnormality in 99mTc-HMPAO uptake and deficit in verbal fluency and verbal memory. Finally, asymmetrical lobar activity indicated a predominant left rather than right temporo-parietal involvement.     

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.     

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.     

Neuropsychological Measures which Discriminate Among Adults with Residual Symptoms of Attention Deficit Disorder and Other Attentional Complaints

Attention Deficit Disorder (ADD) in children is accompanied by quantifiable deficits on attentional, learning, and memory indices. Symptoms of childhood ADD persist into adulthood in many cases. However, many adults without a history of childhood ADD also complain of difficulties with attention, presumably due to other etiologies than developmental ADD. This study investigated whether performance on neuropsychological measures of attention and memory could differentiate adults with attentional complaints and history of childhood ADD from those without childhood ADD. Adults with a history of childhood ADD demonstrated reduced scores on the Paced Auditory Serial Addition Task and Delayed Free Recall on the California Verbal Learning Test as well as on a verbal fluency task relative to adults who denied attentional problems in childhood. Discriminant function analysis using verbal fluency, performance on the Wisconsin Card Sorting Test, verbal learning and recall, Digit Span Backward, and performance on the Paced Auditory Serial Addition Task as predictors correctly classified adults with and without a history of childhood ADD into diagnostic groups with 75% accuracy.     

Verbal memory and verbal fluency in adolescents with schizophrenia spectrum disorders

Aim: Although impaired verbal memory and verbal fluency are frequently found in adults with schizophrenia, there has been a paucity of studies investigating adolescents with schizophrenia. Thus, the aim of the present study was to investigate the main subcomponents of verbal memory and verbal fluency in adolescents with schizophrenia spectrum disorders. Methods: Verbal learning and memory and verbal fluency was assessed in 21 adolescents with schizophrenia spectrum disorders (mean age, 15.4 years) compared with 28 healthy adolescents (mean age, 15.1 years). Results: The patient group performed significantly below healthy controls on measures of learning, delayed recall and on a frequency estimation task. No differences between the groups were found for measures of recognition, retention, implicit memory, or susceptibility to interference. Although they had impaired delayed recall the patients remembered most of what they actually learned. The patient group was impaired on phonological and semantic fluency, but there were no differences between the groups with respect to clustering or switching on the fluency tasks, when controlling for total output. There was no disproportionate impairment in semantic, as compared to phonological fluency, in the patient group. Conclusions: Adolescents with schizophrenia spectrum disorders exhibit impairments in verbal learning and verbal fluency, which might have an impact on the individual's everyday functioning.     

Language functions in patients with multiple sclerosis

Few studies have demonstrated language impairment in patients with multiple sclerosis (MS) compared to healthy controls. The purpose of this investigation was to examine language functions, specifically naming, comprehension, and verbal fluency, in patients with MS and healthy controls to (1) determine if patients with MS demonstrate language impairment, and (2) provide clarification of MS-related language disturbance, particularly in patients with MS of differing courses. Results showed that both chronic-progressive and relapsing-remitting patients with MS performed significantly more poorly than controls on naming, aural comprehension, letter fluency, and category fluency, as well as other language-based cognitive measures. Chronic-progressive patients obtained significantly lower scores than relapsing-remitting patients on the latter three tests. The language disturbance in this MS sample may be partly explained by impairment in other verbal cognitive functions. These findings highlight the importance of assessing language abilities in patients with MS.     

Language Functions in Patients with Multiple Sclerosis

Few studies have demonstrated language impairment in patients with multiple sclerosis (MS) compared to healthy controls. The purpose of this investigation was to examine language functions, specifically naming, comprehension, and verbal fluency, in patients with MS and healthy controls to (1) determine if patients with MS demonstrate language impairment, and (2) provide clarification of MS-related language disturbance, particularly in patients with MS of differing courses. Results showed that both chronic-progressive and relapsing-remitting patients with MS performed significantly more poorly than controls on naming, aural comprehension, letter fluency, and category fluency, as well as other language-based cognitive measures. Chronic-progressive patients obtained significantly lower scores than relapsing-remitting patients on the latter three tests. The language disturbance in this MS sample may be partly explained by impairment in other verbal cognitive functions. These findings highlight the importance of assessing language abilities in patients with MS.     

Recall and recognition confabulation in psychotic and bipolar disorders: evidence for two different types without unitary mechanisms

Several forms of confabulation have been identified recently in schizophrenic patients, but it has not yet been investigated whether these forms are specific to schizophrenia. Furthermore, the origin of confabulation is unclear. The present study investigated recall and recognition confabulation and their relations with symptomatology, cognitive domains (abstraction and flexibility, verbal fluency, verbal memory, motor activity, and visual-motor processing/attention), computed tomographic (CT) measures (ventricular, cerebral, and Sylvian fissure size), and auditory event-related potentials (amplitudes and latencies of peak components in oddball paradigms) in 33 schizophrenic patients, 35 bipolar I patients, eight schizoaffective patients, and seven patients with other psychotic disorders. We found that neither type of confabulation was specific of any diagnostic group. Recall confabulation was mainly predicted by the predominance of positive symptoms, while recognition confabulation was predicted by a delay in P300 latency and the doses of antipsychotics used. Our results suggest two different mechanisms for both types of confabulation based on interference with the adequate retrieval of information and slowness in early stimulus detection.     

The effects of adjunctive topiramate on cognitive function in patients with epilepsy

PURPOSE: We investigated possible cognitive effects of topiramate (TPM) in polypharmacy on patients with intractable epilepsy. METHODS: Study 1 evaluated 22 consecutively admitted patients whose antiepileptic drugs (AEDs) on admission to the Montreal Neurological Hospital included TPM. Performance on neuropsychological tests administered on and subsequently off TPM was analyzed. Four patients also were tested before taking TPM, allowing comparisons off, then on, and then off the drug again. Measures included intellectual function, verbal and nonverbal memory, language, word and design fluency, somatosensory sensitivity, and motor skills. In Study 2, 16 patients at the Minnesota Epilepsy Group were tested first off, then on TPM with nine cognitive tasks that measured concentration, verbal fluency, language, and psychomotor speed. RESULTS: In Study 1, significant (p < or = 0.01) improvements were observed off TPM on 13 measures including verbal and nonverbal fluency and certain verbal and perceptual tasks. Notably, verbal learning and memory were unaffected; a limited effect was observed on nonverbal memory. Patients tested 3 times scored better in both tests off TPM compared with on this drug. In Study 2, declines on TPM were observed on all measures, significantly (p < or = 0.05) for tests of fluency, sustained concentration, and visual motor processing speed. CONCLUSIONS: TPM was associated with declines in fluency, attention/concentration, processing speed, language skills, and perception; working memory but not retention was affected. As the two studies used an opposite order of testing on versus off TPM, our results clearly show a performance decrement while patients are taking TPM, without respect to which condition is tested first.     

Behavioral markers for self- and other-attribution of memory: a study in patients with temporal lobe epilepsy and healthy volunteers

OBJECTIVES: The correlation between clinical measures of memory and subjectively reported memory is often poor. Regarding this we investigated in patients with temporal lobe epilepsy (TLE) whether there is evidence that persons mistake other cognitive performances for memory due to subjective memory theories. METHODS: a neuropsychological test battery comprising measures of attention, verbal/figural memory and other visual or language related functions was applied in patients with left (L-TLE, n=24) or right temporal lobe epilepsy (R-TLE, n=21) and healthy volunteers (n=20). In addition, subjective self- and other-reported memories were assessed by the subjective memory questionnaire (SMQ). RESULTS: subjective measures as well as objective measures indicate significant cognitive impairment in TLE and in L-TLE in particular. Self-reports and other-reports are interrelated but only self-reported memory correlates significantly with objective memory performance. Regression analysis indicates that self-reported memory is best predicted by word fluency followed by verbal memory and vocabulary, and other-reported memory is best predicted by word fluency, vocabulary, confrontation naming, and verbal recognition memory. DISCUSSION: The results suggest that attribution of memory refers to a subjective view of memory which is wider than its neuropsychological definition. It furthermore differs dependent on the observer's point of view. Memory is preferentially concluded from verbal behaviors. These reflect language skills and access to vocabulary rather than declarative memory. Consideration of subjective memory theories and associated attribution processes can significantly contribute to our understanding of the often-poor relationship between objective test results and subjective impairment in TLE.     

Impairment of incidental memory for frequency in patients with obsessive-compulsive disorder.

The aim of our study was to investigate whether patients with obsessive-compulsive disorder (OCD) have impaired incidental memory for frequency. Fifty-four subjects (27 OCD patients and 27 matched control subjects) performed a task assessing estimation of occurrence of previously heard words. Performance on this task was compared with other intentional verbal memory tasks (recognition, recall and learning of common words). We also correlated memory for frequency with frontal lobe tests (Wisconsin Card Sorting Test, Trail Making Tests A and B, and verbal fluency). Performance on incidental learning of frequency was significantly worse in the OCD group than in control subjects. Other verbal memory measures did not show significant differences. Performance in the frequency task correlated with verbal fluency. Although intentional verbal memories are normal in OCD patients, incidental memory for frequency is impaired, suggesting that prefrontal systems are involved in OCD.     

A pilot study of low-dose L-deprenyl in Alzheimer's disease

The use of low-dose L-deprenyl, a selective MAO-B inhibitor, in Alzheimer's disease patients has been associated previously with improvements in agitation and episodic learning and memory. Behavioral, cognitive, and regional electroencephalogram (EEG) measures were obtained in a 4-week open pilot study of 14 patients with probable Alzheimer's disease by NINCDS criteria who were administered 10 mg L-deprenyl per day. L-Deprenyl administration was associated with significant improvements on the agitation and depression factors of the Brief Psychiatric Rating Scale, the Cornell Scale for Depression in Dementia, and spouses' blind ratings. Recall improved on the Buschke Selective Reminding Task, but intrusions also tended to increase; verbal fluency decreased. Absolute EEG delta measures were selectively suppressed in the right frontal region. The pattern of changes suggests that L-deprenyl may be associated with improvement in behavioral and cognitive performance, in part through a mild behavioral disinhibiting effect.     

What is measured by verbal fluency tests in schizophrenia?

INTRODUCTION: Schizophrenia patients perform below the norm on verbal fluency tests. The causes for this are unknown, but defective memory, executive functioning and psychomotor speed may play a role. METHOD: We examined 50 patients with schizophrenia and related disorders, and 25 healthy controls with a cognitive test battery containing tests for verbal memory, executive functioning and psychomotor speed, and a categorical fluency test. RESULTS: Patients obtained significantly lower test results than the controls on most cognitive measures including the verbal fluency test. During the fluency test, they formed as many clusters, and switched as often between clusters as the controls did, but they generated fewer words per cluster. Interestingly, in the control group, fluency performance was predicted by memory and executive functioning, but not by psychomotor speed. In patients, verbal fluency was predicted by psychomotor speed, but not by memory or executive functioning. DISCUSSION: We conclude that psychomotor speed could be a crucial factor in cognition, and its influence on cognitive test performance should be considered in schizophrenia research. Furthermore, these data illustrate the importance of qualitative analysis of cognitive impairments in schizophrenia patients, as traditional cognitive tests often only provide quantitative information.     

Fluency in multiple sclerosis: which measure is best?

Tests of verbal fluency provide brief and sensitive measures of the deficits in rapidly retrieving overlearned information common in multiple sclerosis (MS). Production of words that begin with the letters F, A, and S is the verbal fluency measure most often used with patients who are fluent in English. However, because of frequency of words beginning with certain letters varies from one language to another, it is unlikely that any fixed set of letters will be appropriate for multicenter trials that involve patients who are fluent in different languages. A possible alternative involves using semantic fluency categories that contain such a large number of exemplars that no fluent speaker of any language could exhaust the category in the allotted response time. To examine the potential usefulness of semantic fluency measures, 203 MS patients and 87 healthy controls generated words that begin with F, A, or S or were exemplars of the categories animals and parts of the body. Receiver operating characteristic (ROC) curve analyses indicated that sensitivities and specificities for the three fluency measures in discriminating patients from controls were quite similar, especially if patients with global cognitive impairment were excluded.     

Cognitive dysfunction in multiple sclerosis. I. Frequency, patterns, and prediction

Previous frequency estimates of cognitive dysfunction in multiple sclerosis have ranged from 54 to 65 percent. These studies may overestimate the frequency in the general MS population, since the patients in these studies were recruited from clinic populations. In the present study, we administered a comprehensive neuropsychological test battery to 100 community-based MS patients and 100 demographically matched healthy controls. Of 31 cognitive test indices examined, 48 MS patients and five controls were impaired on four or more test indices, yielding an overall frequency rate of 43% for the MS group. The pattern of cognitive decline was not uniform: MS patients were more frequently impaired on measures of recent memory, sustained attention, verbal fluency, conceptual reasoning, and visuospatial perception, and less frequently impaired on measures of language and immediate and remote memory. We developed a brief (20-minute) screening battery empirically by selecting the four most sensitive test indices from the comprehensive battery. The brief battery yielded a sensitivity value of 71% and a specificity value of 94% in discriminating cognitively intact from impaired MS patients, as defined by the comprehensive battery. Cognitive impairment was not significantly associated with illness duration, depression, disease course, or medication usage, but was significantly (albeit weakly) correlated with physical disability.     

Fatigue and declines in cognitive functioning in multiple sclerosis

OBJECTIVE: To determine whether cognitive fatigue, defined as a decline in cognitive performance over a single testing session, could be identified in MS. METHODS: Forty-five individuals with MS and 14 healthy control participants completed a 4-hour session of cognitive testing that involved a baseline neuropsychological battery, a continuous effortful cognitive task (completing mental arithmetic problems administered on a computer), and a repeat neuropsychological battery. Self-report measures of fatigue and affect were completed before each step of the testing session. RESULTS: The pattern of change in cognitive performances over the testing session significantly differed between the MS and control participants. Individuals with MS showed declines on measures of verbal memory and conceptual planning, whereas the control participants showed improvement. Although there were no significant differences between the groups on any of the baseline cognitive measures, the MS participants performed worse than the control subjects on tests of visual memory, verbal memory, and verbal fluency that were repeated following the continuous effortful cognitive task. Both MS and control participants reported increased mental and physical fatigue across the testing session compared with their baseline values. CONCLUSION: Individuals with MS show declines in cognitive performance during a single testing session and fail to show the improvement exemplified by healthy control subjects.     

Neuropsychological performance of right- and left-frontotemporal dementia compared to Alzheimer's disease.

The performance of 16 patients with Alzheimer's disease (AD) was compared to 11 patients with right-frontotemporal dementia (FTD) and 11 patients with left-FTD on a comprehensive neuropsychological battery. Standardized scores (i.e., z scores based on normal control data) were analyzed for 5 cognitive domains. The results revealed that the AD group displayed significant impairment in visual-constructional ability relative to the two FTD groups; however, no significant difference was found between the groups on memory scores (verbal and nonverbal). Patients with left-FTD scored significantly below patients with AD on the language measures (e.g., word retrieval, verbal semantic memory), and verbal executive ability (phonemic fluency); AD patients did not differ from patients with right-FTD on these measures. Patients with right-FTD exhibited significantly more perseverative behavior than AD patients; AD patients did not differ from left-FTD patients on this parameter. These results indicate that the pattern of neuropsychological performance of AD patients is distinguishable from patients with left and right frontal frontotemporal dementia.     

Processing speed mediates the relationship between verbal memory, verbal fluency, and functional outcome in chronic schizophrenia

Verbal fluency and verbal memory have been reported to be diminished in patients with schizophrenia. These deficits could partially predict functional disability in this pathology. However, processing speed often mediates the relationship among cognitive processes in the disorder. Our goal was to analyse the influence of processing speed as mediator of the relation between verbal fluency–verbal memory and functional disability in chronic schizophrenia. We examined 90 hospitalized patients and 30 healthy controls (matched for gender, age and years of education). The neuropsychological battery included tests for verbal fluency, verbal memory, motor speed and processing speed. Outcome measures included Disability Assessment Schedule (DAS-WHO) and number of hospitalizations (NH). Results confirmed chronicity on clinical symptoms (PANSS total X = 48.94 + 14.97 PANSS negative X = 27.81 + 10.18, PANSS positive X = 23.51 + 10.81) and impairment on functional disability (DAS-WHO X = 13.62 +4.28). As expected, verbal fluency was severely impaired in patients and significantly predicted functional outcome. Immediate and Delayed Verbal Memory were also severely impaired and predicted functional outcome. However, when processing speed was entered in the regression analyses the significance of verbal fluency and verbal memory decreased significantly. Sobel's equation was significant, suggesting full mediation. Our findings suggest that processing speed may be a central factor in the relation between cognitive symptoms and functional outcome in chronic schizophrenia.