Ralph H' B' Benedict, Ph'D', ABPPCN

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Detecting Cognitive Disorders in MS

• Ralph H. B. Benedict, Ph.D., ABPP-CN
• Associate Professor of Neurology and Psychiatry
• SUNY Buffalo School of Medicine
• Jacobs Neurological Institute

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Outline

• Brief History
• Update Screening for NP dysfunction
• Update Consensus NP Test Battery
• Clinical Application Integrating Cognitive
  Assessment into Routine Care

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MS MRI T2
Grade 1
Grade 2
Grade 3
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marked enfeeblement of the memory . conceptions
are formed slowly.. Charcot (1877)
22-31
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22-25
25
SET A
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SET B
15
12-19
13-19
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SET C
8-9
7-8
5
0
Language
Spatial Abilities
Attention Span
Processing Speed
Problem Solving
Memory
Adapted from Rao et al. (1991)
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NP Profiles in MS
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Third Ventricle Width (TVW)
A line is drawn through the long axis of the
third ventricle, parallel to the
inter-hemispheric fissure. The width is measured
by drawing a second line perpendicular to the
first at its midpoint, and then recording its
length.
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Brain parenchymal fraction

• Brain tissue volume (contour CSF)
• Outer contour of brain surface

BPF
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Bicaudate Ratio (BCR)

• BCR the minimum intercaudate distance divided
  by brain width along same line
• Higher BCR atrophy

Bermel et al., Arch Neurol 200259275-280
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Brain Lesion Burden or Atrophy Which MRI Measure
Best Predicts Cognitive Impairment in Multiple
Sclerosis? Benedict et al. Archives of Neurology.
2004 in press

• 37 MS patients volunteers, 28 controls matched
  age, educ, gender
• Conventional MRI T1 LV FLAIR LV TVW BCR
  BPF
• Neuropsychological Testing PASAT SDMT CVLT
  BVMT JLO WCST
• Controls Premorbid IQ North American Adult
  Reading Test (NAART) Depression Center for
  Epidemiologic Studies (CES-D)

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Benedict et al, J Neuroimaging. 2004, in press

• 31 MS patients from Benedict et al (AN 2004)
  also had informant report NPI profiles

only NPI scales correlated with cognitive
function (eg PASAT r -.53).
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Screening for Cognitive Disorders?
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Screening for MS Cognitive Impairment using a
Self-Administered 15-Item QuestionnaireBenedict
et al. Multiple Sclerosis. 2003 995-101
Phase I Item Selection/Reduction
Participants 100 consecutive clinic
patients Measure 68 Items (atten, mem, other,
pers/beh) Scale 0 (never) to 4
(severe) Procedure Reduce to 15 Items via
Rasch analysis Correlate with Cognitive
Functions Questionnaire
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MS Neuropsychological Screening Questionnaire
(MSNQ)
0 not at all 3 very often disruptive 1 rarely
no problem 4 very often greatly interferes
with life 2 occasionally, seldom a problem

• easily distracted
• lose focus when listening
• slowed problem solving
• trouble describing programs recently watched
• forgetting appointments
• forgetting what is read
• instructions repeated
• reminded to do tasks

• forgetting errands
• difficulty answering questions
• difficulty tracking two things at once
• missing the point of conversations
• difficulty controlling impulses
• laugh/cry with little cause
• talk excessively

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Screening for MS Cognitive Impairment Using a
Self-Administered 15-Item Questionnaire
Participants 50 pts (40 RR), random
recruitment Mean age 42, education 15 years
Benedict, et al. Multiple Sclerosis. 2003
995-101
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Bayesian Probabilities, Informant Report MSNQ
Sensitivity TP / patients Specificity
TN / normals Positive PP TP / positive
tests Negative PP TN / negative tests
Processing Speed and Memory Tests
Sens .83 Spec .97 PPP .91 NPP .95
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Problems?

• small sample, one center
• no controls
• no test-retest reliability

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MSNQ Cross Validation - Methods

• 85 MS pts, 40 age and education matched normal
  controls
• 80 pts with RR course
• 62 informants were spouses, known pt mean 23
  yrs
• MSNQ administered to all subjects, 40 MS retest
  at 1 week
• MACFIMS
• Depression CESD-10 BDI-FS
• Centers Jacobs Neurological Institute
• Bernard Gimbel MS Center
• UCSF
• UCHSC

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MSNQ Cross Validation - Reliability
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MSNQ Cross Validation - Validity
plt.05 plt.01
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MSNQ Cross Validation Predictive Validity
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Screening is positive, now what?
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Minimal Neuropsychological Assessment of MS
Patients A Consensus Approach Benedict et al.
Clinical Neuropsychologist, 2002.
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Process

• (1) Review Literature (MS and Psychometric Data)
• (2) Consensus Purpose of Minimal Exam
• Cognitive Domains
• Psychometric Criteria
• (3) Rank Order Candidate Tests
• (4) Propose Directions for Research

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Consensus Psychometric Criteria
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Minimal Assessment of Cognitive Function in
Multiple Sclerosis (MACFIMS)
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Practice Effects, Alternate Forms
Benedict Zgaljardic. (1998). J Clin Exp
Neuropsychol Zgaljardic Benedict. (2001).
Appl Neuropsych, in press Subjects 32 healthy
volunteers, mean age 63.3, 37 male Design Coun
terbalanced adm of 4 HVLT-R BVMT-R forms Two
week Test/Retest Interval Random assignment to
same- and alternate-form conditions
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Brief Visuospatial Memory Test - Revised
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MACFIMS Validation

• 373 MS pts (176 clinical referral)
• 59 age and education matched normal controls
• 73 pts with RR course
• MACFIMS
• Timed Ambulation, 9-H Peg,Maximum Repetition
  Rate
• CESD-10 BDI-FS
• Fatigue Severity Scale
• NEO Five Factor Inventory
• Neuropsychiatric Inventory
• MSQOL-54

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Test-Retest Reliability
Sample MS 39
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Group Discrimination
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Study Design
Vocational Status
MSQOL-54 Mental Composite
MSQOL-54 Physical Composite
Retained Significant Predictors
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Regression Analysis Results
Sample MS 120 Control 44
MSQOL-54 Physical Fatigue Severity Scale
(R20.57) Center for Epidemiologic Studies
Depression Scale (R2change0.08) EDSS
(R2change0.02) Beck Depression Inventory Fast
Screen for Medical Patients (R2change0.02) MSQOL
-54 Mental Center for Epidemiologic Studies
Depression Scale (R20.68) Fatigue Severity Scale
(R2change0.03) Vocational Status Symbol Digit
Modalities Test (Wald12.8) WCST Perseverations
(Wald7.8) NEO Personality Inventory, Informant
Report Conscientiousness (Wald6.7) Disease
Duration (Wald5.3) Judgment of Line Orientation
Test (Wald3.8)
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Patient Care?
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Neuropsychological Practice Guidelines
Routine Screening In the Office
MSNQ
Routine Minimal NP Exam
MACFIMS
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• Case HJ
• age 23, EDSS 2.5, DD 3.0 yr
• CC is fatigue
• BDI-FS borderline
• TVW3.0, BPF0.87

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• Case BK
• age 26, EDSS 4.0, DD 7.0 yr
• CC is situational, needs not met
• BDI-FS elevated
• TVW6.4, BPF0.79

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Thank You
Jacobs Neurological Institute Lawrence Jacobs,
MD Frederick Munschauer, MD Bianca Weinstock
Guttman, MD
Buffalo Neuroimaging Analysis Center Rohit
Bakshi, MD Robert Zivadinov, MD
UB Neuropsychology David Shucard, PhD Inna
Fishman, MA Janet Shucard, PhD Elizabeth Wahlig,
MA Dominic Carone, PhD Jane Braun, PhD Danielle
McCabe, MA