Neurocognitive Manifestations

in ME/CFS

Gudrun Lange, PhDProfessorDepartment 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 multi-tasking• reliably demonstrate areas of cognitive

resilience• assess mood and anxiety• ascertain adequate effort

Intellectual profiles in ME/CFSWAIS-IV profile: Scores discrepant from expected levels Case 1 Case 2

Case 1

Analysis

Index Level Discrepancy Comparisons

Comparison Score 1 Score 2 Difference

Critical Value .05

Significant Difference

Y / N Base Rate

Overall Sample

VCI - PRI 112 94 18 7.78 Y 9.5

VCI - WMI 112 77 35 8.31 Y 0.5

VCI - PSI 112 65 47 11.76 Y 1

PRI - WMI 94 77 17 8.81 Y 9.2

PRI - PSI 94 65 29 12.12 Y 3

WMI - PSI 77 65 12 12.47 N 20.2

Subtest Scaled Score Profile

The vertical bars represent the standard error of measurement (SEM)

Case 2

Analysis

Index Level Discrepancy Comparisons

Comparison Score 1 Score 2 Difference

Critical Value .05

Significant Difference

Y / N Base Rate

Ability Level

VCI - PRI 114 107 7 8.31 N 30.3

VCI - WMI 114 111 3 8.82 N 45.7

VCI - PSI 114 97 17 10.19 Y 19.4

PRI - WMI 107 111 -4 9.74 N 36.2

PRI - PSI 107 97 10 11 N 35.9

WMI - PSI 111 97 14 11.38 Y 23.7

• Clinical Interview• Wechsler Adult Intelligence

Scale - Fourth Edition (WAIS-IV)

• 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.