Cognition & Cognitive Dysfunction
In Multiple Sclerosis

by: Dr. Stephen M. Rao, PhD.

  1. Cognitive dysfunction in Multiple Sclerosis: I - Frequency, patterns, and prediction
    Neurology 1991 May;41(5):685-91

  2. II - Impact on employment and social functioning
    Neurology 1991 May;41(5):692-6

  3. Guidelines for NeuroPsychological research in Multiple Sclerosis
    Arch Neurol 1990 Jan;47(1):94-7

  4. On the nature of Memory disturbance in Multiple Sclerosis
    J Clin Exp NeuroPsychol 1989 Oct;11(5):699-712

  5. Information processing speed in Multiple Sclerosis
    J Clin Exp NeuroPsychol 1989 Aug;11(4):471-7

  6. Cerebral disconnection in Multiple Sclerosis: Relationship to atrophy of the Corpus Callosum
    Arch Neurol 1989 Aug;46(8):918-20

  7. Correlation of Magnetic Resonance Imaging with NeuroPsychological testing in Multiple Sclerosis
    Neurology 1989 Feb;39(2 Pt 1):161-6

  8. NeuroPsychology of Multiple Sclerosis
    Curr Opin Neurol 1995 Jun;8(3):216-20

  9. NeuroPsychology of Multiple Sclerosis: a critical review
    J Clin Exp NeuroPsychol 1986 Oct;8(5):503-42

  10. Chronic Progressive Multiple Sclerosis. Relationship between Cerebral Ventricular size and NeuroPsychological impairment
    Arch Neurol 1985 Jul;42(7):678-82

  11. Memory disturbance in Chronic Progressive Multiple Sclerosis
    Arch Neurol 1984 Jun;41(6):625-31

  12. Hypothesis testing in patients with Chronic Progressive Multiple Sclerosis
    Brain Cogn 1984 Jan;3(1):94-104

  13. Executive Functions In Multiple Sclerosis
    NeuroPsychology 1997 Oct;11(4):535-44


Cognitive Dysfunction In Multiple Sclerosis
I. Frequency, Patterns, & Prediction

Rao SM, Leo GJ, Bernardin L, Unverzagt F
Neurology 1991 May;41(5):685-91
Dept of Neurology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226
PMID# 2027484; UI# 91226665

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
    • VisuoSpatial Perception
  • Less frequently impaired on measures of
    • Language
    • Immediate Memory
    • 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.


Cognitive Dysfunction in Multiple Sclerosis
II. Employment And Social Functioning

Rao SM, Leo GJ, Ellington L, Nauertz T, Bernardin L, Unverzagt F
Neurology 1991 May;41(5):692-6
Medical College of Wisconsin, Dept of Neurology, Milwaukee, Wisconsin 53226
PMID# 1823781; UI# 91226666

We designed a study to assess the specific contribution of Cognitive Dysfunction to Multiple Sclerosis patients' problems in daily living.

Based on the results of a comprehensive NeuroPsychological test battery, we classified 100 MS patients as either Cognitively intact (N = 52) or Cognitively impaired (N = 48).

In addition to a Neurologic Examination, MS patients completed questionnaires on Mood and Social Functioning, underwent a comprehensive in-home Occupational Therapy evaluation, and were rated by a close relative or friend regarding specific personality characteristics.

There were no significant differences between the two groups on measures of physical disability and illness duration.

    Patients in the Cognitively impaired group were
  • less likely to be working
  • engaged in fewer Social and Vocational activities
  • reported more Sexual Dysfunction
  • experienced greater difficulty in performing routine household tasks
  • exhibited more PsychoPathology than Cognitively intact patients.

These findings suggest that Cognitive Dysfunction is a major factor in determining the quality of life of patients with MS.


Guidelines For NeuroPsychological Research
In Multiple Sclerosis

Peyser JM, Rao SM, LaRocca NG, Kaplan E
Arch Neurol 1990 Jan;47(1):94-7
Univ of Vermont, Dept of Psychology, Burlington, Vermont
PMID# 2403789; UI# 90103986

Acquisition of scientific information regarding the NeuroPsychological aspects of Multiple Sclerosis has been hampered by studies using small, inadequately described patient and control samples and a wide array of Cognitive test procedures that hinder multicenter data pooling.

Based on a review of key issues of clinical need and experimental interest, research guidelines are proposed for investigations in this burgeoning research area.

The guidelines include suggestions for sampling methods, population characterization, and control groups as well as a recommended core battery of NeuroPsychological tests for use in this population.

It is hoped that these guidelines will advance knowledge about the NeuroPsychology of Multiple Sclerosis by helping to promote sound experimental design, facilitate cross-study comparison, and encourage multicenter collaborative efforts.


On The Nature Of Memory Disturbance In MS

Rao SM, Leo GJ, St Aubin-Faubert P
J Clin Exp NeuroPsychol 1989 Oct;11(5):699-712
Medical College of Wisconsin, Section of NeuroPsychology, Milwaukee, Wisconsin 53226
PMID# 2808659; UI# 90037468

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 imparied 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.


Information Processing Speed
In Multiple Sclerosis

Rao SM, St Aubin-Faubert P, Leo GJ
J Clin Exp NeuroPsychol 1989 Aug;11(4):471-7
Medical College of Wisconsin, Dept of Neurology, Milwaukee, Wisconsin 53226
PMID# 2760182; UI# 89340818

We have recently proposed that the Cognitive deficits of patients with Multiple Sclerosis (MS) share numerous characteristics associated with the syndrome of SubCortical Dementia.

One such characteristic, slowness of mental processing, was evaluated in the present study.

Thirty-six MS patients were compared to 26 normal controls of equivalent age, education, and Verbal Intelligence on the Sternberg Memory scanning test. As anticipated, the motor-involved MS patients had an overall slower reaction time than did controls.

Their scanning rate, a measure of pure Cognitive Speed, was also significantly slower than controls. These results suggest that MS patients exhibit a slowing of mental processing independent of motor involvement.


Cerebral Disconnection In Multiple Sclerosis
Relation to Corpus Callosum Atrophy

Rao SM, Bernardin L, Leo GJ, Ellington L, Ryan SB, Burg LS
Arch Neurol 1989 Aug;46(8):918-20
Medical College of Wisconsin, Dept of Neurology, Milwaukee, Wisconsin 53226
PMID# 2757533; UI# 89334638

Left Ear Suppression to DiChotically presented verbal stimuli has been observed in patients with Multiple Sclerosis (MS). Rubens and coworkers have suggested that a disconnection of the Auditory Callosal Pathways may account for this finding.

To examine this proposal on MidSagittal MR scans, we compared the performance of:

  • 28 MS patients with significant Corpus Callosum Atrophy (CCA)
  • 16 MS patients without significant CCA
  • 64 demographically matched normal control subjects on two laterality tasks:
    • Verbal Dichotic Listening
      • consonant-vowel syllables
    • Tachistiscopic Object-Naming Latency

    Results indicated that Left Ear Suppression was found only in the MS patients with CCA. Likewise, patients in the MS group with CCA were slow in responding to stimuli presented in the Left Visual Field; this effect was not observed in patients without CCA.

    These findings support the hypothesis that efficiency of Cross-Callosal information flow is reduced in MS patients with CCA.


    Correlation Of Magnetic Resonance Imaging With NeuroPsychological Testing In MS

    Rao SM, Leo GJ, Haughton VM, St Aubin-Faubert P, Bernardin L
    Neurology 1989 Feb;39(2 Pt 1):161-6
    Medical College of Wisconsin, Dept of Neurology, Milwaukee, Wisconsin 53226

    PMID# 2915783; UI# 89127811

    Previous research has suggested that Cerebral lesions observed on Magnetic Resonance Imaging (MRI) of MS patients are clinically "silent".

      We examined the validity of this assertion by correlating NeuroPsychological test performance with MRI findings in 53 MS patients. We used a semiautomated quantitation system to measure three MRI variables:
    • Total Lesion Area (TLA)
    • Ventricular-Brain Ratio (VBR)
    • Size of the Corpus Callosum (SCC)

    Stepwise multiple regression analyzes indicated that TLA was a robust predictor of Cognitive Dysfunction, particularly for measures of Recent Memory, Abstract/Conceptual Reasoning, Language, and VisuoSpatial Problem Solving.

    SCC predicted test performance on measures on mental processing speed and rapid problem solving, while VBR did not independently predict Cognitive test findings.

    These findings suggest that Cerebral lesions in MS produce Cognitive Dysfunction and that MRI may be a useful predictor of Cognitive Dysfunction.

  • #9

    NeuroPsychology Of Multiple Sclerosis

    Rao SM
    J Clin Exp NeuroPsychol 1986 Oct;8(5):503-42

    PMID# 3805250; UI# 87109734

    Multiple Sclerosis (MS) is a relatively common, Chronic Progressive Neurological illness affecting individuals primarily in the third and fourth decades of life.

    Autopsy studies indicate that the disease preferentially attacks White Matter throughout the CNS, including the Cerebral Hemispheres.

    This article reviews the current state of knowledge regarding Cognitive Dysfunction in MS and relates these findings to NeuroPathological changes.

    The view that affective disturbance may also result from Cerebral DeMyelination is presented, along with a brief discussion of MS as a prototype "SubCortical Dementia".

    Finally, methodological problems intrinsic to the study of MS are presented, and suggestions for future research are made.


    Chronic Progressive Multiple Sclerosis
    Relationship Between Cerebral Ventricular Size And NeuroPsychological Impairment

    Rao SM, Glatt S, Hammeke TA, McQuillen MP, Khatri BO, Rhodes AM, Pollard S
    Arch Neurol 1985 Jul;42(7):678-82

    PMID# 3874618; UI# 85251202

    Forty-seven patients with Chronic/Progressive Multiple Sclerosis were examined to assess the possible relationship between Cerebral Atrophy (by Computed Tomography [CT] ) and performance on NeuroPsychological tests of Memory and verbal intelligence.

    Nineteen patients were found to have mildly dilated Ventricles and another nine patients had moderate to severe Ventricular enlargement. Performance on Memory and intelligence testing was related to the degree of VentriculoMegaly.

    Three linear CT measurements were also recorded. Using this method, the width of the Third Ventricle proved to be the best indicator of intellectual and Memory Dysfunction.

    Measures of cognition and Ventricular size did not correlate with length of illness or overall disability as rated by the Kurtzke Expanded Disability Status Scale.


    Memory Disturbance In Chronic Progressive MS

    Rao SM, Hammeke TA, McQuillen MP, Khatri BO, Lloyd D
    Arch Neurol 1984 Jun;41(6):625-31

    PMID# 6721737; UI# 84202443

    Forty-four patients with Chronic/Progressive Multiple Sclerosis (MS) were compared with age- and education-matched control groups on a battery of clinical and experimental Memory measures.

    Patients with MS performed substantially below the control groups on both Immediate Learning and Delayed Recall Tasks, particularly in the Retrieval of Spatial information. The MS sample was subdivided into three groups using a cluster analytic procedure.

    One group (N = 9) performed well below expectations on Memory tasks, exhibited signs of Global Cognitive Disturbance, and had an atypical personality adjustment, characterized by irritability, social withdrawal, and apathy.

    A second group (N = 19) showed mild Memory disturbance, associated with a greater use of psychotropic medications and a higher incidence of reactive Depression.

    A third group (N = 16) performed normally on Memory measures. The three groups of patients with MS did not differ in length or overall severity of illness.


    Hypothesis Testing In Chronic Progressive MS

    Rao SM, Hammeke TA
    Brain Cogn 1984 Jan;3(1):94-104

    PMID# 6537244; UI# 85280024

    Patients with Chronic/Progressive MS (N = 38) were compared with an age and education matched medical control group (N = 19) on a visual discrimination task, designed to evaluate hypothesis testing and focusing behavior.

    Thirty-three MS patients (85%) and all control patients were able to formulate and use hypotheses, but MS patients were less likely to employ strategies leading to a correct solution.

    Furthermore, MS patients were more likely to Perseverate With One Strategy despite negative verbal feedback.

    Five MS patients were unable to formulate hypotheses. These findings suggest that MS patients have Impaired Cognitive Functioning in addition to previously reported problems with Memory.

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