A Neuropsychologic Perspective: Cognitive
Impairments in Cancer Patients
J. Aubrey Burhart
State University of New York at
Buffalo
What is a neuropsychologist?
 A neuropsychologist is an expert in the
applied science of clinical
neuropsychology concerned with the
behavioral expression of brain dysfunction
Dimensions of Behavior
Behavior is Conceptualized in Three Systems
Cognitive
Emotionality
Executive Functions
Information-handling aspect
Concerns feelings and motivation
How behavior is expressed
What does a Neuropsychologist do?

Diagnose – Differentiate btw. Psychiatric and neurological symptoms;

Patient care and planning – Identify how the disease might affect patient’s

Rehabilitation and Treatment evaluation – provide information to
various healthcare providers regarding patient’s capacities,
defective behaviors, etc.

Research – study brain activity and its effect on behavior
distinguishing btw. 2 neurological disorders; predict outcome of a condition
behavior for family members; Assess patient’s capability for managing daily
activities and following treatment regimen; Repeated assessments at
intervals allows for tracking disease progression
Lateralization in the Brain

Left Side
Speech
 Writing
Main Language Center
 Calculation



Right Side
Spatial Construction
 Simple Language
 Copying/Drawing
Geometric Designs
 Some Musical Ability
 Odors

Major Neuropsychology Domains

Memory

Executive

Visual/Spatial

Motor

Attention/Concentration

Speech/Language

Intellectual
The Domains Defined
(Lezak, 1995)




Memory
The complex of systems by
which an organism registers,
stores, retains, and retrieves
some previous exposure to an
event or experience
Visual/Spatial
The memory for familiar routes
or for the location of objects
and places in space


Attention and
Concentration
Refers to several processes
that are related aspects of how
the organism becomes
receptive to stimuli and how it
may begin processing
incoming or attended toinformation
Definition of Domains..cont’d.




Executive
Those capacities that enable a
person to engage successfully
in independent, purposive, selfserving behavior
Motor
Primarily concerned with use
of the hands, although gait is
qualitatively assessed. Gross
and fine motor skills are
assessed to varying degrees of
precision.




Intelligence
Tendency for cerebral regions
subserving different intellectual
functions to be proportionately
developed in any one individual
Speech & Language
Refers to the understanding and
expression of language in all
realms (spoken, written, auditory).
Incl.’s quality/quantity of
spontaneous speech, aud. Comp.,
reading recognition and comp.,
writing, repetition, and
confrontation and generative
naming.
Cancer is Devastating
The incidence of cancers of the breast and lung in
women, as well as non-Hodgkin lymphoma,
melanoma of the skin, and liver in men and
women, is rising
 Lung cancer deaths in women continue to rise,
though not as effectively as before
 More people are overweight and obese, and
physical activity is increasing only slightly
 Cancer treatment spending continues to rise
along with total health care spending

Cognitive Functioning is
Essential For…
 Comprehending disease treatment and
progression
 Making informed healthcare decisions
 Adhering to a treatment regimen
 Medication compliance
 Occupational success
 Maintaining social networks
Risk Factors for Cognitive
Deficits

Disease Induced
Infections
 Pain
 Metastases to CNS
 Disturbances of
endocrinologic
system


Treatment Induced
Chemotherapy
 Radiation
 Bone marrow
transplantation
 Medications
 Biologic Response
Modifiers

All of these things can cause..

Combination treatments are often implemented which
may be more effective in combating the cancer, but poses
even greater risks of neurotoxicity for the patient
Effects of Chemotherapy on
Cognitive Functioning




Cognitive dysfunction can appear soon after treatment
initiation or as late as 10 years later
Altered cognitive functioning can be transient or
permanent
Even when cognitive function appears to be in the normal
range, low-normal functioning is associated with
previous chemotherapy treatment
There is new evidence that supports the theory that
carriers of the e4 allele of apoliprotein are at greater risk
for reduced neuropsychological performance; when
coupled with chemo treatment, their risk substantially
increases for cognitive dysfunction
Neurological complications of chemotherapy

Acute encephalopathy (begins with insomnia, rapidly
followed by a state of confusion associated with agitation

Stroke-like episodes (characterized by acute onset of
encephalopathy with fluctuating motor deficit)

Chronic encephalopathy – develops progressively for
months to years after treatment
Neurological Complications of radiation



Acute encephalopathy (headache, nausea, drowsiness,
fever)
Early-delayed Complications (2 weeks-3 or 4 months):
hypersomnia, irritability, headache, attention deficits,
memory problems
Late-delayed complications (4 months-years): radiation
necrosis, dementia syndrome, vision and/or hearing loss,
lower cranial nerve paralysis, radiation-induced tumors
Potential Mediators ?
 There have been some agents identified
that might reduce cognitive impairment:
• Erythropoietin
• Aspirin
• Methylphenidate (has demonstrated
improvement in children undergoing chemo)
What is Bone Marrow
Transplantation (BMT)?



Used to treat cancers that have not responded well to
more standard medical interventions
Bone marrow transplants involve the destruction of a
patient’s own bone marrow via chemotherapy and/or
radiation therapy, followed by infusion of new cells to
generate healthy bone marrow function
BMT can be classified as allogeneic or autologous:
• Allo – bone marrow is transferred from a donor
• Auto – replacement marrow is harvested from the patient,
cleaned from disease, and reinfused into patient
BMT patients are at high risk for cognitive
deficits

Most patients undergoing BMT receive chemotherapy or combination
chemotherapy/radiation as a preparatory regimen prior to BMT

Toxicity from high-dose chemotherapy combine with whole-body
radiation puts patient at risk for extended hospitalization,
posthospitalization recovery, and risk of death from the procedure

Neurological acute complications are frequent, including transient
drowsiness, occasional seizures, or severe encephalopathy; delayed
complications typically include mild/moderate cognitive dysfunction
with cerebral atrophy.
BMT

Studies investigating cognitive impairment in BMT
patients have used various methods of assessment
including a review of medical records, interviews, selfreported questionnaires, and standardized
neuropsychological testing

Cognitive impairment has been found to persist for
months to years following BMT
BMT


Several domains of cognitive functioning have been found
to be affected, ranging in severity from mild to severe
impairment, including memory, attention/concentration,
language, motor, and executive functioning
Most studies investigating cognitive impairment as a
result of BMT do not include a baseline assessment, lack
long-term follow-up assessment, do not include
standardized neuropsychological protocols, and lack a
measure of Quality of Life.
Research Shows…
• More than 20% of people who receive cranial irradiation
suffer significant CNS damage and neurocognitive impairment
(Levin, 1999).
• Andrykowski et al., (1992): 56% of their sample of adult
BMT candidates scored 1.5 S.D’s below the norm on
neuropsych battery
• van Dam et al., (1998): High-dose chemotherapy impairs
cognitive functioning more than standard-dose chemotherapy
on breast cancer patients
• Significant dose escalations of opioids (> or = 30%) cause
impaired psychomotor and cognitive functions in cancer
Research shows..(cont’d.)
• Chemotherapy and radiation therapy have a negative impact
on cognitive functioning (Ahles, 1998).
• In a study by Pereira et al. (1997), 44% of terminal cancer
patients had prevalent cognitive impairment upon admission
to a palliative care unit. Just prior to death, 62.1% of patients
had prevalent cognitive impairment.
• Both non-small-cell lung cancer and glioma patients suffer
from a number of condition-specific neurologic and
neuropsychologic problems that have a significant impact on
their daily lives.
Neuropsych Test
Similarities Subtest of WAIS-R
Word Fluency Subtest of Dutch Aphasia
Complex Fig.
Rey Aud. Verbal Learning
Logical Memory Subtest of WAIS-R
Behav. Ass. Of Dysexec. Functioning
Famous Faces and Events
Hopkins Verbal Learning
WM Task
Visual Verbal Learning
Autobiographical Memory Interview
Rivermead Behavioral Memory
Wechsler Memory Scale-R
Benton Visual Retention
Buscke Selective Reminding
Frequency of Neuropsych Tests used in the
Memory Domain
3
2.5
F
r
2
e
q
u 1.5
e
n
1
c
y
0.5
0
Frequency of Neuropsych Tests used to Assess
the Visual Spatial Domain
3
F
r
e
q
u
e
n
c
y
2.5
2
1.5
1
0.5
0
Facial Recognition
Judgement Line Orientation
Neuropsych Test
Line Bisection
Neuropsych Test
Sickness Impact
Profile
Hopkins Symptom
Checklist
Cog. Prob. Daily Life
Checklist
Func. Indpendence
Measures
KPS
Brian Cancer Mod.
SF-36
Activ's Daily Living
QLQ-C30
F
r
e
q
u
e
n
c
y
Func. Assess.
Cancer Therapy
Frequency of Neuropsych Tests used to Assess
the Quality of Life Domain
3
2.5
2
1.5
1
0.5
0
Freqeuncy of Neuropsych Tests used to Assess
the Motor Domain
3
2.5
F
r
e
q
u
e
n
c
y
2
1.5
1
0.5
0
Grooved Peg
Finger Oscillation
Finger Tapping
Neuropsych Test
Grip Strength
Repsy Binary
Choice
Frequency of Neuropsych Tests used to Assess
the Attention/Concentration Domain
7
6
F
r
e
q
u
e
n
c
y
5
4
3
2
1
0
Ruff 2's and 7
Digit Span
Digit Symbol
Trails A
Neuropsych Test
D2
Arrithmetic Subset
of the WIAS-R
Frequency of Neuropsych Tests used to Assess
Executive Functioning Domain
6
5
F
r
e
q
u
e
n
c
y
4
3
2
1
0
Trails B
Word Fluency
Controlled Oral Concept Shifting Wisconsin Card
Word Assoc.
Sorting
Neuropsych Test
Stroop Color
Word Proc.
Frequency of Neuropsych Tests used to Assess
the Intelligence Domain
2
1.8
F
r
e
q
u
e
n
c
y
1.6
1.4
1.2
1
0.8
0.6
0.4
0.2
0
WAIS-R
Dutch Adult Reading Test
Neuropsych Tests
Frequency of Neuropsych Tests used to Assess
the Overall Cognitive Function Domain
5
4.5
4
3.5
3
2.5
2
1.5
1
Neuropsych Test
Head Injury Symp.
Checklist
DIS
Temporal Orient.
Psych. Adust. To
Illness
Mattis Dementia
Rating
Med. Outcome Study
MMSE
BDI
STA1
0
PDI
0.5
POMS
F
r
e
q
u
e
n
c
y
Domain
Overall Cognitive
Functioning
Intelligence
Executive
Attention/Concentration
Motor
QoL
Visual/Spatial
F
r
e
q
u
e
n
c
y
Memory
Combined Frequency of Tests Used in each
Domain
25
20
15
10
5
0
•As cancer treatments become more efficacious, the
greater consideration needs to be given to choose a
treatment modality that might minimize risk for
cognitive dysfunction
•Family members are a critical component of
follow-up treatment for cancer patients/survivors;
cognitive deficits are often more apparent to others
rather than the patient themselves. Family members
should track the nature and frequency of notable
deficits
• Where is the literature concerning cognitive impairments
in other cancer populations?
• Since normal cognitive functioning is critical for
intellectual and academic development, occupational
achievement, development and maintenance of social
relationships, and appropriate self-care, why weren’t QoL
measures included in all of the studies conducted?
• If certain meds and treatments are correlated with
cognitive impairments even prior to surgical procedures,
how well informed are patients regarding their consent?
• If tamoxifen is used in the treatment of breast cancer and
has been shown to adversely effect cognition, are there
other cancer populations for which this is prescribed?