Neurocognitive Manifestations
in ME/CFS
Gudrun Lange, PhD
Professor
Department of Physical Medicine and
Rehabilitation, Rutgers-NJMS
Outline
• Why is it important to talk about cognitive
function in ME/CFS?
• What is the clinical presentation?
• How can cognitive dysfunction in ME/CFS
be understood?
• What is an effective neuropsychological
battery?
• What is the research evidence?
• Final thoughts
Brainfog: Common and Disabling
• Experienced as difficulties with attention,
concentration and multi-tasking
• Recognized as important: Listed as
symptom in all ME/CFS case definitions
• Serves as objective criterion for disability:
lack of validated physiological markers
Clinical Presentations
• “I feel like I’m loosing my mind…”
• “I feel like having the brain of an 80-year
old in the body of a 36-year old…”
• “I feel stupid…”
Conceptualization of Cognitive
Dysfunction
• Possible etiology of cognitive dysfunction
• Genetic
• Acquired
• Severity of cognitive dysfunction
• Severe
• Moderate
• Mild
Determination of Severity of
Cognitive Dysfunction
• Subjective
• Patient and family report
• Perception of degree of loss of cognitive
function
• Objective
• Neuropsychological evaluation
• Statistical determination of degree of loss of
cognitive function
• Behavioral observations during testing
should be taken into consideration
An effective neuropsychological
battery for ME/CFS patients
• Has to include standardized and normed
measures that
• Sufficiently and repeatedly challenge
complex information processing and multitasking
• reliably demonstrate areas of cognitive
resilience
• assess mood and anxiety
• ascertain adequate effort
Intellectual profiles in ME/CFS
WAIS-IV profile: Scores discrepant from expected
levels
Case 1
Case 2
Case 1
Analysis
Subtest Scaled Score Profile
The vertical bars represent the standard error of measurement (SEM)
Index Level Discrepancy Comparisons
Score 1
Score 2
Difference
Critical
Value
.05
VCI - PRI
VCI - WMI
VCI - PSI
PRI - WMI
112
112
112
94
94
77
65
77
18
35
47
17
7.78
8.31
11.76
8.81
Y
Y
Y
Y
9.5
0.5
1
9.2
PRI - PSI
WMI - PSI
94
77
65
65
29
12
12.12
12.47
Y
N
3
20.2
Comparison
Significant
Difference
Y/N
Base Rate
Overall Sample
Case 2
Analysis
Index Level Discrepancy Comparisons
Score 1
Score 2
Difference
Critical
Value
.05
VCI - PRI
VCI - WMI
VCI - PSI
PRI - WMI
114
114
114
107
107
111
97
111
7
3
17
-4
8.31
8.82
10.19
9.74
N
N
Y
N
30.3
45.7
19.4
36.2
PRI - PSI
WMI - PSI
107
111
97
97
10
14
11
11.38
N
Y
35.9
23.7
Comparison
Significant
Difference
Y/N
Base Rate
Ability Level

• Clinical Interview
•  Wechsler Adult Intelligence
Scale - Fourth Edition (WAISIV)
• Test of Premorbid Functioning
(TOPF)
• Beck Depression Inventory II
(BDI II)
•  Spielberger State Trait
Anxiety Questionnaire (STAI)
•  Gordon Diagnostic Test
•  Stroop Test
•  DKEFS
•
Trails
•
Verbal Fluency Test
• Paced Auditory Serial
Attention Test (PASAT)
• Wisconsin Card Sorting Test
(WCST)
•  California Verbal Learning
Test II (CVLT-II)
•  Wechsler Memory Scale Fourth Edition (WMS-IV)
•  Boston Naming Test (BNT)
• Rey Osterrieth Complex
Figure (ROCF)
•  Judgment of Line Orientation
Test (JOL)
•  Hooper Visual Organization
Test
•  Hand Dynamometer
•  Grooved Pegboard
•  Finger Tapping Test (FTT)
•  Validity Indicator Profile (VIP)
Findings on neuropsychological
exam
• Decreased attention, concentration and
slowed processing speed
• Problems sequencing pieces of information
and prioritizing their use for quick decision
making
• Limited working memory,
• less information available “online”
• Learning difficulties:
• Changes in learning strategy
• Poor absorption and recall
Neuropsychological Profile in
ME/CFS
• Profile suggests mild, subtle deficits
• Evaluation of impairment relative to
expected level of intellectual function
necessary to uncover true deficiencies
• Profile not consistent with dementia
• Generally no frank memory problem
• Profile can be differentiated from
conditions of a more focal nature
Brain Abnormalities in ME/CFS
• Lange et al., 2005
• Used verbal working memory task to
• probe brain function using fMRI
• simultaneously assessing efficient information
processing behaviorally
• Statistically controlled for age, mood, anxiety,
self-reported mental fatigue score
• Equated on prior behavioral test performance
on same task
Brain Abnormalities in ME/CFS
• Controls versus ME/CFS:
• No differences in brain activity during simple
condition
• When task demands get more complex, ME/CFS
increased involvement of
• Anterior Cingulate BA 24/32
• Left DLF BA 10/44/45/47
• Bilateral supplemental and premotor BA6/8
• Parietal regions BA 7/40
Brain Abnormalities in ME/CFS
Brain Abnormalities in ME/CFS
• Increased signal change was significantly
accounted for by ME/CFS report of mental fatigue
• Perceived mental fatigue is reflected by increased
functional recruitment of
• Left superior parietal region (BA7)
• Responsible for shifts in attention
• Bilateral supplementary and premotor regions
(BA6/8)
• Associated with automatic information processing
• maintenance of temporal order
Brain Abnormalities in ME/CFS
• No lack of effort accounted for the
differences in signal change
• To achieve behavioral performance similar
to Controls
• Brains of ME/CFS work harder when tasks
are complex
• Require efficient and quick information
processing
• Require effective online sequencing and
prioritization
Consequences of cognitive
dysfunction in ME/CFS
• Automaticity of cognitive function is often lost
• Mundane tasks become effortful
• Multi-tasking often impossible
• Considered by patients as affecting every
aspect of their lives
• Mental exertion can last for a long time
Is there an effective cognitive screen
for ME/CFS patients?
• Dementia screens and typical brief
bedside memory tests are not appropriate
• i.e. MMSE, Mini-Cog
• Suggestions:
• Serial 7s, Digit Span Sequencing
• May work if done for at least a few
minutes
• Quickly give a 6-or-7 step set of complex
driving directions and request repetition
Final thoughts
• If evaluation of cognitive function is
needed
• Refer to Clinical Neuropsychologist
knowledgeable about ME/CFS
• Much more work is needed to familiarize
Neuropsychologists with ME/CFS to
provide valid and reliable
neuropsychological assessments.