Cognitive Dysfunction In Multiple Sclerosis - 2g2

  1. The NeuroPsychiatry of Multiple Sclerosis: a review of recent developments
    Curr Opin Psychiatry 2007 May;20(3):278-85

  2. Cognitive slowing in Multiple Sclerosis is strongly associated with Brain Volume reduction
    Mult Scler 2006 Dec;12(6):760-8

  3. Cognitive patterns and progression in Multiple Sclerosis: construction and validation of percentile curves
    J Neurol NeuroSurg Psychiatry 2005 May;76(5):744-9

  4. Regional MRI lesion burden and Cognitive function in Multiple Sclerosis: A longitudinal study
    Arch Neurol 2001 Jan;58(1):115-121

  5. Altered decision-making in Multiple Sclerosis: A sign of impaired Emotional Reactivity?
    Ann Neurol 2004 Oct 4

  6. Prediction of NeuroPsychological Impairment in Multiple Sclerosis: comparison of conventional Magnetic Resonance Imaging measures of Atrophy and lesion burden
    Arch Neurol 2004 Feb;61(2):226-30

  7. A longitudinal study of Brain Atrophy and Cognitive disturbances in the early phase of Relapsing/Remitting Multiple Sclerosis
    J Neurol NeuroSurg Psychiatry 2001 Jun;70(6):773-80

  1. Cognitive Impairment in Probable Multiple Sclerosis
    J Neurol NeuroSurg Psychiatry 2003 Apr;74(4):443-6

  2. AutoBiographical Memory an advanced Multiple Sclerosis: Assessment of Episodic and personal Semantic Memory across three time spans
    J Int NeuroPsychol Soc 2002 Sep;8(6):855-60

  3. Conscious and UnConscious uses of Memory in Multiple Sclerosis
    J Neurol Sci 2002 Jun 15;198(1-2):79-85

  4. Memory in Multiple Sclerosis: contextual encoding deficits
    J Int NeuroPsychol Soc 2002 Mar;8(3):395-409

  5. Language abnormalities in Multiple Sclerosis
    Neurologia 2002 Jan;17(1):12-6

  6. MetaMemory and tested Cognitive functioning in Multiple Sclerosis
    Clin NeuroPsychol 2001 Aug;15(3):357-68

  7. Executive functions: the need for the integration of concepts
    Rev Neurol 2002 Apr 1;34(7):673-85

  8. Visual object recognition in Multiple Sclerosis
    J Neurol Sci 2001 Apr 1;185(2):77-88

  9. A comparison of Memory performance in Relapsing/Remitting, Primary/Progressive and Secondary/Progressive, Multiple Sclerosis
    NeuroPsychiatry NeuroPsychol Behav Neurol 2001 Jan;14(1):32-44

  10. Longitudinal study of Cognitive Dysfunction in Multiple Sclerosis: NeuroPsychological, NeuroRadiological, and NeuroPhysiological findings
    J Neurol NeuroSurg Psychiatry 2003 Jul;74(7):878-85

  11. Psychological and NeuroPsychological problems in Multiple Sclerosis
    Bull Acad Natl Med 2003;187(4):683-94; discussion 695-7

  12. NeoCortical volume decrease in Relapsing/Remitting MS patients with mild Cognitive Impairment
    Neurology 2004 Jul 13;63(1):89-93


Cognitive Impairment In Probable Multiple Sclerosis

Achiron A, Barak Y
J Neurol NeuroSurg Psychiatry 2003 Apr;74(4):443-6
Multiple Sclerosis Center, Sheba Medical Center, Tel Hashomer, Israel. Abarbanel Mental Health Center, Bat Yam, Israel
PMID# 12640060; UI# 22527018

To evaluate and characterise Cognitive Impairment in the very early stage of Multiple Sclerosis (MS), in which patients are still diagnosed as suffering from Probable MS.

The Brief Repeatable Battery-NeuroPsychological (BRB-N) that has been validated for MS patients was used.

Abnormal performance was defined as one standard deviation below the mean reported for healthy age matched subjects. Neurological disability and Brain Magnetic Resonance Imaging (MRI) were performed for all patients.

Correlation coefficients were calculated between disease burden variables and performance on the BRB-N.

Sixty seven patients with Probable MS were evaluated within a mean of one month of the onset of new Neurological symptoms. Evidence for the presence of Cognitive Impairment was shown in 53.7% of patients.

Verbal Abilities and Attention Span were most frequently affected. Impairment was not correlated with Neurological disability or MRI disease burden.

Prevalent Cognitive Impairment already exists at onset of MS.


AutoBiographical Memory In Advanced Multiple Sclerosis: Assessment Of Episodic And Personal Semantic Memory Across Three Time Spans

Kenealy PM, Beaumont JG, Lintern TC, Murrell RC
J Int NeuroPsychol Soc 2002 Sep;8(6):855-60
University of Surrey Roehampton, School of Psychology, Whitelands College, London, UK
PMID# 12240750

In order to investigate the status of Remote Memory, the AutoBiographical Memory Interview (AMI) was administered to 30 individuals with advanced Multiple sclerosis (MS).

In contrast to earlier studies which have shown only mild deficits in AutoBiographical Memory in those with less physical progression of the disease, about two-thirds (60%) of the present MS sample had a deficit in AutoBiographical Memory.

The presence of such a deficit was not related to age, age of onset, duration of illness, or level of physical disability, but was related to level of general Cognitive ability.

Memory for Episodic AutoBiographical incidents was more affected than for Personal Semantic information:

A temporal gradient typical of some Dementing Conditions but not before demonstrated in MS, was also observed with Memory for more recent events showing a significant decline.


Conscious And UnConscious Uses Of Memory
In Multiple Sclerosis

Seinela A, Hamalainen P, Koivisto M, Ruutiainen J
J Neurol Sci 2002 Jun 15;198(1-2):79-85
Masku Neurological Rehabilitation Centre, P.O. Box 15, FIN-21251 Masku, Finland
PMID# 12039667

Conscious and UnConscious uses of Memory and priming were studied in 30 patients with Multiple Sclerosis (MS) and 15 normal control (NC) subjects. MS patients were classified into two subgroups according to their Cognitive status;

15 of them were Cognitively Deteriorated (the MS-D group) and 15 Cognitively Preserved (the MS-P group).

A process dissociation procedure [J. Mem. Lang. 30 (1991) 513] was used to separate Conscious and UnConscious Memory performance in a word stem completion task.

The results showed that the MS-D group had deficient Conscious Memory performance, but had intact UnConscious Memory as well as priming. The MS-P group showed normal Conscious and UnConscious uses of Memory and priming.

Thus, in MS-related Cognitive decline, Conscious Memory seems to be vulnerable, whereas UnConscious Memory remains intact.

The results provide NeuroPsychological support for the distinction between Conscious and UnConscious Memory processes.

Moreover, the results show the importance of studying Cognitively homogenous MS groups as opposed to heterogenous ones, in order to find the underlying mechanisms of Memory Deficits in MS.

Interestingly, the Neural Systems needed for the UnConscious use of Memory do not seem to deteriorate even in MS patients with deficient overall Cognitive capacity.

This finding encourages the development of future rehabilitation programs, suggesting that UnConscious remembering might help MS patients with deficient Conscious Memory to cope with their daily activities.


Memory In Multiple Sclerosis:
Contextual Encoding Deficits

Thornton AE, Raz N, Tucke KA
J Int NeuroPsychol Soc 2002 Mar;8(3):395-409
Simon Fraser University, Department of Psychology, Burnaby, British Columbia, Canada
PMID# 11939698

Long-Term Memory (LTM) is one of the diverse Cognitive functions adversely affected by Multiple Sclerosis (MS). The LTM deficits have often been attributed to failure of Retrieval, whereas Encoding processes are presumed intact.

However, support for this view comes primarily from studies in which encoding and retrieval operations were not investigated systematically.

In the current study, we used an encoding specificity paradigm to examine the robustness of encoding in MS and to specifically evaluate the impact of the disease on Contextual Memory.

We hypothesized that persons with MS would exhibit a selective impairment in retrieving items from LTM when required to generate new cue-target associations at encoding, but not when cues held a strong pre-existing relationship to the targets.

The findings supported the hypotheses. We conclude that the Mnemonic deficits associated with MS affect both Encoding and Retrieval.

Specifically, problems with binding of contextual information at encoding impair effective retrieval of memories. Nonetheless, access to these memories can be gained through pre-existing associations organized in the Semantic Network.


Language Abnormalities In Multiple Sclerosis

Drake MA, Allegri RF, Carra A
Neurologia 2002 Jan;17(1):12-6
Hospital Britanico de Buenos Aires, Servicio de Neurologia, Argentina
PMID# 11834193

Patients suffering from Multiple Sclerosis (MS) have a high frequency of Cognitive Deficits. Research has demonstrated Impairments in Memory, Attention, Information-Processing Speed, and Executive Functions.

Although it has been traditionally held that Language function is commonly preserved in MS, some studies have demonstrated Language Impairment in these patients, particularly in tasks of Naming and Word-Generation.

The aim of the study was to examine Language functioning in MS, with particular interest in Naming Ability and Verbal Fluency.

Material And Methods
Thirty patients with MS, and 30 Neurologically intact normal controls, matched for age and educational level were evaluated.

As part of a wider NeuroPsychological Evaluation, all subjects were administered the Boston Naming Tests. To compare performances, a comprehensive classification of error types was devised.

MS patients showed significantly lower performance on both Linguistic measures than the control subjects.

On the Boston Naming Test, MS patients obtained significant lower scores than controls, with a high rate of Semantic errors.

Additionally, they tended to show an also high number of VisuoPerceptual errors. Low scores on Naming task correlated with low performance on Verbal Fluency.

This study reveals that Language function can be impaired in MS, and that Naming difficulties are a frequent finding.

This Naming deficit seems to have a double origin, stemming from disruption at the levels of the Perceptual and/or the Semantic Systems.


MetaMemory And Tested Cognitive Functioning In Multiple Sclerosis

Randolph JJ, Arnett PA, Higginson CI
Clin NeuroPsychol 2001 Aug;15(3):357-68
Washington State University, Pullman, USA
PMID# 11778774

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 analyzes 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
  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.


Executive Functions: The Need For
The Integration Of Concepts

Tirapu Ust rroz J, M oz C spedes JM, Pelegr n Valero C
Rev Neurol 2002 Apr 1;34(7):673-85
Servicio de NeuroPsicolog a.; Fundaci n Argibide. Asociaci n Da o Cerebral Navarra, Pamplona, 31007, Espa a
PMID# 12080519; UI# 22075613

The new Cognitive NeuroPsychology approachs have aroused an increasing interest in understanding the higher Cognitive processes as well as the Neural substrates linked to them.

Particularly, the Executive Functions, reckoned to be essential to control the information processing and to co-ordinate behavior, have received preferential treatment from specialized literature on the subject.

From Obsessive Compulsive Disorder to Schizophrenia, from Parkinson's Disease to Multiple Sclerosis, there are many reports that show the affectation of these functions in all these morbid processes.

On the other hand, the part that the PreFrontal Cortex plays in human behavior in general, and in Executive Functions in particular, constitutes one of the most important fields of research of NeuroSciences nowadays.

Thus, this Cortical Area appears closely linked to the Executive Processes, affecting different respects of the Cognitive Functions.

Working Memory, Supervisory Attentional System, Somatic Marker, Information Processing, Behavior Planning, Social Judgement, are processes which have been related to the PreFrontal Cortex activity as a structure, and to the Executive Processes as a function.

The aim of this article is to revise the concept of Executive Functions, and give rise reflections about the usefulness of the aforementioned concept and its practical applicability.

It is essential that we understand the difference between Structure and Function, Cognition and Emotion, Brain activity and behavior, category and dimension.

And between Mind and Brain, to achieve a more comprehensive approach to this concept of Executive Functions we all use, and many times find difficult to define and to understand.


Visual Object Recognition In Multiple Sclerosis

Laatu S, Revonsuo A, Hamalainen P, Ojanen V, Ruutiainen J
J Neurol Sci 2001 Apr 1;185(2):77-88
University of Turku, Centre for Cognitive NeuroScience, Turku, Finland
PMID# 11311287

Deficits in tasks measuring Visual Processing have been earlier reported in studies of MS. Yet, the nature and severity of Visual-Processing Deficits in MS remains unclear.

We used a new method in order to measure the different stages of Visual Processing in Object Recognition: Shape recognition, Familiarity recognition, Semantic categorization, and Identification with Naming.

Six two-choice reaction-time tasks were presented to 30 MS patients and 15 healthy controls. The patients were divided into Cognitively preserved and Cognitively deteriorated study groups according to their Cognitive status.

The purpose was to find out whether deficits at specific stages of Visual Processing can be found in Cognitively deteriorated MS patients.

Cognitively deteriorated MS patients did not perform as well as Cognitively preserved MS patients or healthy controls.

They were slower already at the early stage of Visual Processing where discrimination of whole objects from scrambled ones was required.

They also had higher error rates in tasks requiring object familiarity detection and object identification with Naming.

Thus, Cognitively deteriorated MS patients had difficulties in Visual Shape Recognition and Semantic-Lexical Processing.

However, variation of performances was large within both patient groups, indicating that even patients without a generalized Cognitive decline may have deficits in some stages of Visual Processing.

We suggest that because of the heterogeneity of the patients, every single case needs to be examined separately in order to identify the possible deficits in Visual Processing.


A comparison Of Memory Performance In Relapsing/Remitting, Primary/Progressive And Secondary/Progressive, Multiple Sclerosis

Gaudino EA, Chiaravalloti ND, DeLuca J, Diamond BJ
NeuroPsychiatry NeuroPsychol Behav Neurol 2001 Jan;14(1):32-44
Kessler Medical Rehabilitation Research and Education Corporation, West Orange, New Jersey 07052, USA
PMID# 11234907

The current investigation was designed to examine the influence of disease course on the specific patterns of Acquisition and Retrieval Impairments in Multiple Sclerosis (MS).

Recent investigations of Learning and Memory in MS have shown that many subjects have impaired Verbal and Visual new Learning abilities, but normal Long-Term Recall and Recognition.

However, heterogeneity in Learning and Memory abilities of subjects has been documented. Some evidence in the literature suggests that this heterogeneity may be in part attributable to clinical variables, such as disease course.

Verbal and Visual Learning and Memory tests, modified to equate MS groups with healthy controls on initial acquisition of information, were administered to 64 individuals with Clinically Definite MS:

  • Relapse/Remitting = 21
  • Primary/Progressive = 18
  • Secondary/Progressive = 25
  • 20 healthy control participants

Recall and Recognition performance then was evaluated at 30 minutes, at 90 minutes, and at 1 week for the Verbal Learning task, and at 30 minutes and at 90 minutes for the Visual Learning task.

Results indicate that the two Progressive forms of MS result in significantly greater deficits in regard to the Acquisition of new Verbal information.

With the Secondary/Progressive group showing a significantly higher failure rate in regard to meeting the Learning criterion.

Performance for Recognition measures was not significantly different among groups.

Whereas Recall performance of the Primary/Progressive group was significantly below that of the control group and of the Secondary/Progressive group.

When testing new Learning with VisuoSpatial information, individuals with Relapse/Remitting MS and Secondary/Progressive MS required more trials than control participants to learn the same amount of Visual information.

Visual Recall and Recognition performance did not differ between groups. No group differences in rates of forgetting for VisuoSpatial material was observed after equating for acquisition.

Results of the current study indicate that the primary problem in MS with regard to Memory functioning is in the acquisition of new information.

Our findings support previous research showing Verbal Memory Deficits with a Progressive disease course and VisuoSpatial Memory Deficits in Relapse/Remitting MS.

However, the detailed analysis of New Learning and Memory performed in the current study indicated that the Primary/Progressive group may be showing difficulty in their ability to use Newly Learned information.

The pattern of New Learning deficits observed between MS disease subtypes in the current study was determined to be unrelated to the duration of MS and to the physical severity of the disease.

The degree of physical disability observed in patients with MS does not appear to be related to the degree of Cognitive decline:

Because, of the distinct patterns and severity of Memory Dysfunction noted within each disease type, independent of physical disability.


Longitudinal Study Of Cognitive Dysfunction In MS:
NeuroPsychological, NeuroRadiological, And
NeuroPhysiological Findings

Piras MR, Magnano I, Canu ED, Paulus KS, Satta WM, Soddu A, Conti M, Achene A, Solinas G, Aiello I
J Neurol NeuroSurg Psychiatry 2003 Jul;74(7):878-85
University of Sassari, Institute of Clinical Neurology, Institute of Radiology, Laboratory of Epidemiology and BioStatistics, Institute of Hygiene and Preventive Medicine, Sassari, Italy
PMID# 12810771


  1. To assess Cognitive function and Cerebral Magnetic Resonance Imaging (MRI) involvement in Relapsing/Remitting Multiple Sclerosis

  2. To monitor disease evolution, Cognitive Dysfunction, and Cerebral lesion burden over time (mean 8.5 year follow up period)

  3. To study the relation between Clinical, NeuroPsychological, and MRI data

On follow up assessment, Visual and Auditory oddball Event Related Potentials (ERPs) were recorded as PsychoPhysiological evaluation of Cognitive status. Correlations between NeuroPsychological, MRI, and ERP data were also analyzed.

NeuroPsychological study assessed Verbal and Non-Verbal IQ, Deterioration Index (DI) from WAIS subtests, Conceptual Reasoning, Attention, Verbal and VisuoSpatial Short-Term and Long Term Memory.

MRI assessment detected presence of DeMyelinating lesions by using a semiquantitative method as well as Cortical and SubCortical Atrophy over time.

Attention, Short-Term and Long Term VisuoSpatial Memory were mildly impaired at baseline and remained unaltered longitudinally.

At retesting a significant worsening of Verbal Long Term Memory (p=0.023), DI presence (p=0.041) and the increase of SupraTentorial and SubTentorial MRI lesions load (p=0.001) emerged.

Expanded Disability Status scale score correlated significantly with total lesion burden at both evaluations (p=0.043 and p=0.024 respectively).

Temporal, Occipital, and Frontal Horn lesions as well as Cortical Atrophy correlated significantly with Attention and Memory Tests at baseline.

Follow up assessment revealed significant correlation between Cortical Atrophy and Attention as well as VisuoSpatial Short-Term Memory; Spatial Long Term Memory correlated significantly with lesions in body of Lateral Ventricle and Frontal Lobe.

ERP study showed P300 latency abnormalities in 75% of patients, involving specifically more Visual P300 (58.4 % of cases) than Auditory Wave (41.6 %).

Visual P300 latency and amplitude correlated significantly with DI and Auditory P300 Latency with Frontal Horn and BrainStem lesions.

These findings revealed mild Cognitive Impairment in MS patients particularly consistent with Slowing Information Processing over time.

Increased MRI lesions do not correlate with the clinical course of the disease and Cognitive Deficit evolution.

Thus, Cognitive Dysfunction could be related to disease peculiarity and not to the time course.

Correlations between P300, NeuroPsychological, and MRI findings provide further information about ERP application to examine Cognitive Impairment in MS and probably to investigate their Neural origin.


Psychological And NeuroPsychological Problems
In Multiple Sclerosis

Bequet D, Taillia H, Clervoy P, Renard JL, Flocard F
Bull Acad Natl Med 2003;187(4):683-94; discussion 695-7
Service de Neurologie, HIA du Val de Grace, 74 Boulevard de Port Royal-75005 Paris
PMID# 14556476

NeuroPsychological investigations have demonstrated that Cognitive Disorders are common (about 60%) in patients with Multiple Sclerosis.

22 patients and 22 controls participated in the study with a review of literature.

The Cognitive Dysfunction may be termed a SubCortical White Matter Dementia. The hallmarks are:

  1. Forgetfulness
  2. Reduced Information Processing Speed
  3. Impaired Attention and Slowness of Thought Processes
  4. Impaired Ability to Manipulate Acquired Knowledge

Psychiatric disturbance have also high prevalence: Emotional or personality changes, Depression. Pathological Laughing and Crying are classical but not well understood.

This intellectual and Emotional changes in Multiple Sclerosis are studied by adapted Psychometric Psychiatric examination. Correlation of Magnetic Resonance Imaging with NeuroPsychological testing is now demonstrated.

Total lesion score is the best predictor of Cognitive Deficits, also Cerebral Atrophy and lesions of the Corpus Callosum.

NeuroPsychological rehabilitation techniques and symptomatic treatments must be applied to patients with Multiple Sclerosis.


NeoCortical Volume Decrease In Relapsing/Remitting MS Patients With Mild Cognitive Impairment

Amato MP, Bartolozzi ML, Zipoli V, Portaccio E, Mortilla M, Guidi L, Siracusa G, Sorbi S, Federico A, De Stefano N
Neurology 2004 Jul 13;63(1):89-93
University of Florence, Department of Neurology, Viale Morgagni, 85-50134 Florence, Italy
PMID# 15249616

To assess NeoCortical changes and their relevance to Cognitive Impairment in early Relapsing/Remitting (RR) Multiple Sclerosis (MS).

Conventional MR was acquired in 41 patients with RR MS and 16 demographically matched Normal Control subjects (NCs).

An automated analysis tool was used with conventional T1-weighted MRI to obtain measures of Cortical Brain Volumes normalized for head size.

NeuroPsychological performance of MS patients was assessed using the Rao Brief Repeatable Battery. Relationship between volumetric MR measures and NeuroPsychological scores was assessed.

NeuroPsychological assessment allowed for the identification of 18 Cognitively preserved (MS-cp) and 23 Cognitively impaired (MS-ci) MS patients.

The whole MS sample showed lower values of Normalized Cortical Volumes (NCVs) than did the NC group (p = 0.01).

Upon grouping of MS patients according to Cognitive performance, NCV values were lower (p = 0.02) in MS-ci patients than in both MS-cp patients and NCs.

Moreover, there were positive correlations between NCV values and measures of Verbal Memory (r = 0.51, p = 0.02), Verbal Fluency (r = 0.51, p = 0.01), and Attention/Concentration (r = 0.65, p < 0.001) in MS-ci patients.

Furthermore, NCV values were decreased in patients who scored lower on a greater number of tests (r = -0.58, p < 0.01) in the MS-ci group.

None of the NeuroPsychological measures correlated to NCV values in the MS-cp patient group.

Cortical Atrophy was found only in Cognitively impaired patients.

And, was significantly correlated with a poorer performance on tests of Verbal Memory, Attention/Concentration, and Verbal Fluency.

Gray Matter pathology may contribute to the development of Cognitive Impairment in MS from the earliest stages of the disease.

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