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Treatmentinduced cognitive impairments in cancer survivors: Implications for neurorehabilitation


Austin L. Errico, Ph.D. Lakeview Neurorehabilitation ... Denise Wilson OTR/L for her review of. the literature used in preparation of this presentation. ... – PowerPoint PPT presentation

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Title: Treatmentinduced cognitive impairments in cancer survivors: Implications for neurorehabilitation

Treatment-induced cognitive impairments in cancer
survivors Implications for neurorehabilitation
  • Austin L. Errico, Ph.D.
  • Lakeview Neurorehabilitation Services
  • Effingham Falls, New Hampshire
  • Independent Practice
  • Freeport, Maine

  • Denise Wilson OTR/L for her review of
  • the literature used in preparation of this
  • Marsha Martino who supported the development of
    this presentation and ongoing rehabilitative
    services for persons with acquired brain injury

Learner objectives
  • Review the literature investigating the effects
    of chemotherapy on cognitive functioning.
  • Provide an overview of diagnostic and treatment
    approaches for rehabilitating the cancer survivor
    with cognitive impairments.

  • I. Chemo brain
  • II. Overview of brain behavior relationships
  • II. Neuropsychology
  • III. Research
  • IV. What does it all mean?
  • V. Treatment
  • Cognitive remediation
  • Future clinical directions
  • VI. Areas for future research (optional)
  • VII. Questions

Other topics to cover
  • Define the meaning of life
  • Solve the nature vs. nurture question
  • Resolve the mind-brain problem
  • List all the reasons why Michael Moore and George
    W. Bush should not vacation together.

Audience objectives
  • 1.
  • 2.
  • 3.
  • 4.
  • 5.

  • The number of patients receiving multiple
    treatment agents for cancer has increased
    considerably over the last 10 years. As a result
    there is a growing number of survivors who are
    disabled by the disease as well as the

Introduction (continued)
  • In recognition of the growing number of cancer
    survivors, the National Cancer Institute
    established the Office of Cancer Survivorship
    (OCS) in 1996. The OCS has recently prioritized
    research on the late effects of cancer treatments
    including the effects on cognition.

Introduction (continued)
  • There is a growing recognition that assessment,
    counseling, and intervention strategies are of
    critical importance in enhancing a patients
    quality of life and functioning during and after
    the life-threatening illness has been treated.

  • Women with a history of breast cancer constitute
    the largest disease group in the cancer survivor
  • Studies suggest a credible dose-effect
    relationship between adjuvant chemotherapy and
    cognitive impairment. This finding is
    significant since standard chemotherapy regimens
    have increased in dose intensity during the last
    5 years.

Survivorship (continued)
  • The effects of chemotherapy on cognition have
    been most studied in patients with breast cancer
    because many are relatively young, bright and
    have high survival rates, making cognitive
    decline even more noticeable.

Survivorship (continued)
  • Nearly two-thirds of women treated with
    chemotherapy develop some level of cognitive
    problems, though most recover on their own in the
    weeks or months after treatment stops. Still, as
    many as 20 to 25 of patients may develop
    lasting problems.

Chemo brain
  • The term chemo brain is well know amongst
    patients with cancer and frequently referenced in
    published accounts of oncology survivorship.
  • I have chemo brain. I cannot concentrate
    anymore. I have lost my cognitive function. I
    used to be an accountant and be great in math,
    and I cant do that anymore.
  • I used to teach and lecture to 200 people and I
    was having trouble putting sentences together.

Chemo brain (CONTIUED)
  • Many physicians continue to attribute anxiety,
    depression and even menopause as the cause of
    their patients report of cognitive complaints.

The reality
  • Positron Emission Tomography (PET) studies have
    demonstrated that chemotherapy can cause changes
    in metabolic activity to the central nervous

The reality
An overview of brain behavior relationships
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Frontal lobe executive functioning
  • Pre-frontal lobes are the CEO of the brain
    integrates other brain structures.
  • Provides executive cognitive functioning

Functions of the prefrontal lobes
  • Eye movements and motor speech
  • Planning, prediction judgment
  • Initiation, sequencing organization
  • Self monitoring correction
  • Emotional regulation and behavioral control
  • Problem solving

Symptoms of pre-frontal lobe dysfunction
  • Apathy or emotional indifference
  • Emotional lability
  • Perseveration (repetitive thoughts and actions)
  • Discrepant behavior
  • Poor abstract thinking
  • Disinhibition
  • Distractibility

Infancy and the development of the pre-frontal
Parenthood and the regression of the pre-frontal
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Symptoms of occipital lobe dysfunction
  • Cortical blindness
  • Visual agnosia (impaired ability to recognize
    visual form)
  • Prosopagnosia (inability to recognize familiar
  • Color recognition

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Symptoms of temporal lobe dysfunction
  • Pathological rage
  • Anxiety
  • Interpersonal stickiness-viscosity
  • Sleep Disturbance
  • Paranoia

(No Transcript)
Symptoms of parietal lobe dysfunction
  • Prosopagnosia (inability to recognize familiar
  • Topographical disorientation
  • Visuospatial deficits
  • Anosagnosia (unawareness of deficit)

What is neuropsychology and why are we talking
about it here?
  • Neuropsychology is the study of brain behavior
  • Clinical neuropsychology is the applied science
    concerned with the cognitive, behavioral and
    emotional expression of brain dysfunction

Neuropsychological Assessment
  • A comprehensive assessment of cognitive,
    emotional and behavioral functions using a set of
    standardized tests and clinical procedures.
  • Provides a detailed profile of cognitive,
    emotional and behavioral strengths and weaknesses
    for an individual in comparison with
    statistically derived normative data.
  • A checkup that assess a variety of brain

Neuropsychological assessment Areas of
  • Visual, auditory tactile sensation and
  • Attention and concentration
  • Orientation, learning and memory
  • Language
  • Intelligence
  • Speed of information processing
  • Executive functions problem solving, planning,
    organization, judgment abstract reasoning
  • Personality and emotion

Research Group vs. individual
  • N1

Research Myers Abbruzzese 1992
  • Administered neuropsychological examinations to
    47 cancer patients with metastatic disease and
    significant previous chemotherapy treatment. All
    patients were at least 3 weeks post treatment

Research Myers Abbruzzese 1992 (continued)
  • Out of 15 patients 34 had cognitive deficits.
  • 53 had memory deficits
  • 47 had frontal dysfunction
  • 33 had attention difficulties
  • 40 had visual-motor scanning
  • Authors concluded that neurobehavioral
    abnormalities should be considered when
    determining the risks and benefits of cancer

Research Schagen et. al. 1998
  • Schagen et. al. studied the late
    neuropsychological effects of adjuvant
    chemotherapy given to patients with breast
  • 39 patients with breast carcinoma treated with
    adjuvant chemotherapy were examined. Results were
    compared with a group of control subjects who
    received the same surgical and radiation therapy
    with no systemic adjuvant treatment. Patients
    were examined a median of 1.9 years after

Research Schagen et. al. 1998 (continued)
  • Impairment in cognitive functioning was found in
    28 of the patients treated with chemotherapy and
    12 of the patients in the control group.
  • Cognitive impairments following chemo were noted
    in attention, mental flexibility, speed of
    information processing, visual memory and motor

Research Van Dam et al. 1998 (continued)
  • Van Dam et al. investigated the effects of high
    dose vs. standard dose chemotherapy on cognitive
    functioning in a group of woman receiving
    adjuvant treatment for high-risk breast cancer.
  • Patients were randomly assigned to receive
    either high-dose or standard dose adjuvant
    chemotherapy plus tamoxifen. They were
    administered a battery of neuropsychological
    tests. There was also a non-treatment control
    group of patients.

Research Van Dam et al. 1998 (continued)
  • Cognitive impairment was found in 32 of
    patients treated with high-dose chemotherapy, and
    in 17 of patients treated with standard-dose
    chemotherapy, and in 9 of the control patients.
  • Results were not related to anxiety,
    depression, fatigue and time since treatment.
  • Results were observed 2 years after treatment
    was completed.
  • Patients self-reported cognitive complaints
    were found to be more related to their emotional
    distress than measurable cognitive deficits.

Research Brezden et al (2000)
  • Brezden reported that women receiving adjuvant
    chemotherapy scored significantly poorer than
    healthy controls on overall cognitive
    functioning. There were no significant
    differences on measures of emotions.

Research Ahsles et al. (2002)
  • Ahsles et al. examined the neuropsychological
    effect of standard-dose systemic chemotherapy in
    long-term survivors (5 years, symptom free) of
    breast cancer and lymphoma.
  • Survivors who had been treated with systemic
    chemotherapy scored significantly lower on a
    battery of neuropsychological tests compared with
    those treated with local therapy only.
  • Differences were particularly apparent on
    measures of verbal memory and psychomotor

Research Ahsles et al. 2002
  • Ahles et al. also investigated the long-term
    effects of chemotherapy on cognition in 128
    healthy breast cancer and lymphoma survivors at
    an average of 10 years post treatment. Some of
    the study participants had undergone chemotherapy
    as part of their treatment, while others had
    received only radiation and/or surgery without
    chemotherapy. Those who had received chemotherapy
    were twice as likely to fall within the impaired

What does it all mean?
  • While many patients with cancer experience some
    kind of cognitive problem, difficulties continue
    to be under-reported by patients and
    under-diagnosed by health care professionals.
  • Cognitive impairment is often not included on the
    laundry list of potential side effects given to
    patients who are considering treatment.

What does it all mean?
  • Typical Chemotherapy side effects
  • temporary hair loss
  • fatigue
  • nausea
  • pain
  • depression
  • increased risk of infection
  • increased sun sensitivity
  • numbness or weakness in the hands and feet

What does it all mean?
  • Cognitive impairments are in the areas of
  • sustained attention (more prone to distractions)
  • alternating attention (multitasking)
  • cognitive flexibility (multitasking)
  • memory loss
  • information processing speed

What does it all mean?
  • Cognition is also effected by other symptoms
    associated with the disease and treatment
  • fatigue
  • nausea
  • pain
  • mood disturbance
  • Deficits are often subtle or mild yet significant
    enough to limit a persons productivity and

What does it all mean?
  • These impairments may limit a persons ability to
    comply with treatment protocols and make informed
    treatment decisions.
  • In children, impairments are often mild and may
    not be recognized immediately. Distractibility
    and memory deficits may mistakenly be attributed
    to laziness and low motivation.

What does it all mean?
  • Cognitive impairments do not seem to be a
    function of anxiety or depression even though
    patients with oncology are at greater risk for
    expressing symptoms of both.

  • Copeland et al, (1988) stated that children with
    cancer are at risk for academic underachievement
    because of a variety of factors such as side
    effects of treatment, school absences, and
    anxiety related to their disease.
  • For this reason, treating professionals should be
    attuned to potential problems that might develop
    and should maintain contact with school personnel
    to assure that problematic areas are managed

Intervention (continued)
  • Myers et al. (1998) reported that treatment with
    methylphenidate was associated with dramatic
    subjective and objective improvements in
    cognition and daily functioning in 30 pts with
    brain tumor.
  • Improvements were noted in the areas of mood,
    visual-motor speed, verbal memory, expressive
    speech function, executive function and fine
    motor coordination on a 10-mg dose.
  • .

Intervention (continued)
  • Certain complementary therapies can help counter
    the cognitive side effects of treatments.
  • Women who exercise experience less of the
    cognitive dysfunction associated with Tamoxifen.
    It is thought that the release of endorphins help
    attenuate the neurotoxic effects of some

Intervention (continued)
  • Researchers at the University of Texas are
    investigating whether giving the anemia drug
    Procrit before chemo can prevent cognitive damage.

Intervention (continued)
  • To date there has been one study investigating
    the efficacy of functional rehabilitation for
    cancer survivors (Cole et al., 2000). 200
    patients admitted for rehabilitation were given
    comprehensive multidisciplinary inpatient
  • All patients made gains in motor function.
    Significant gains were also made in cognitive
    function by all patients except those with
    intracranial neoplasms, central nervous system
    dysfunction and palliative rehabilitation goals.

What is cognitive neurorehabilitation and is it
helpful to cancer survivors?
  • Activities designed to facilitate and maximize
    recovery of cognitive function following injury
    to the central nervous system and to maximize
    accommodation to functional disabilities.

Is cognitive rehabilitation an effective
treatment for cancer survivors?
  • Since, in general, cancer patients have fairly
    mild focused cognitive problems, they tend to
    respond well to focused rehabilitation (Myers,

Treatment The role of neurorehabilitation
  • Neuropsychology can provide screening or
    comprehensive examinations to assess the specific
    dysfunctions underlying a patients cognitive
    impairments as well as help ferret out the role
    of emotional factors in a patients experience of
    their cognitive strengths and weaknesses.


Treatment The role of neurorehabilitation
  • PT OT can treat weakness, generalized
    de-conditioning, sensory neuropathy or other
    musculoskeletal impairments.
  • OT can help improve function when there are
    losses from upper extremity weakness due to
    peripheral neuropathy or lesions of the spinal
    cord or brain.

Treatment The role of neurorehabilitation
  • Speech therapy can assist patients who present
    with difficulties in swallowing, articulation, or
    primary language.
  • Cognitive rehabilitation implemented by a
    variety of professionals (OT, SLP, NP) is
    imperative for the design and implementation of
    compensatory mechanisms to improve efficiency and
    help minimize functional limitations.

Treatment The role of neurorehabilitation
  • Vocational rehabilitation is needed, in some
    cases, to improve productivity that may include
    volunteer work, going back to school or
    developing accommodations at work.

Areas for future research
  • Studies need to be conducted using pre-treatment
    baseline neuropsychological assessment to compare
    with baseline testing following treatment.
  • Are some people more at risk for developing
    cognitive impairment secondary to treatment than
    others (genetic markers)?

Areas for future research
  • Are there medications (e.g.Procritdrug for
    anemia) that can be taken prior to chemotherapy
    to prevent or attenuate cognitive damage?

Areas for future research (continued)
  • Are there other medications that may benefit
    patients who have cognitive deficits?
  • Longitudinal research is needed to investigate
    the effects of age on a persons ability to
    resist cognitive decline from treatment.
  • Improved research is needed on the cognitive
    effects of hormone therapy for breast cancer.

  • Now
  • Later

Other research
Research Barth et al. 1989
  • Barth examined motor and cognitive test
    performance in patients who were undergoing
    chemotherapy and radiation in a bone marrow
    transplant program. The results showed slight
    but significant changes in neuropsychological
    capacity when compared to baseline levels and
    control subjects

Research Pavol, 1995
  • Studied the neuropsychological and personality
    profiles of 25 patients with chronic leukemia
    treated with interferon alfa.
  • The group of patients receiving treatment
    performed well below expectations on tests of
    cognitive speed, verbal memory, and executive
    functions. Personality changes included
    depression, increased somatic concern, and stress
    reactions. A control group of leukemia patients
    not treated with interferon alfa had better
    cognitive speed and mood.

Research Harder et al. (2002)
  • Harder examined neuropsychological profiles and
    quality of life in 40 patients who, 2-7 years
    prior, had undergone bone marrow transplantation
    with total body irradiation.
  • Mild to moderate cognitive impairment was found
    in 24 patients or 60. Compared with healthy
    population norms, patients performed poorer on
    measures of visual memory, verbal learning and
    verbal short-term and long-term memory, attention
    or executive functions, and speed of information
  • Authors concluded that bone marrow
    transplantation may lead to persistent cognitive
    deficits in long-term adult survivors.

Research Copeland et al. 1998
  • Copeland et al. (1998) studied the immediate and
    long term neuropsychological effects of cancer
    treatment in 124 pediatric patients.
  • The authors compared neuropsychological
    performance of five groups of children who had
    received systemic chemotherapy.

Research Copeland et al. 1998 (continued)
  • Group 1 Newly diagnosed, receiving
    intrathecal chemotherapy
  • Group 2 Newly diagnosed, receiving systemic
    chemotherapy w/o CNS tx
  • Group 3 Long-term (LT) survivors who had
    received intrathecal chemotherapy
  • Group 4 LT survivors who had received
    intrathecal chemo cranial radiotherapy
  • Group 5 LT survivors who had received systemic
    chemotherapy w/o CNS tx

Research Copeland et al. 1998 (continued)
  • Long-term survivors (group 4) who received
    intrathecal chemo and cranial radiation
    demonstrated impairment in fine-motor
    functioning, arithmetic, attention, and other
    nonverbal processing skills. In contrast,
    reading and language skills appeared to be
    relatively intact. The pattern of impairment was
    suggestive of frontal-subcortical brain
  • Poorer scores in motor ability between newly
    diagnosed and long-term survivors was noted and
    believed to be due to drug-induced peripheral
    neuropathy that is believed to dissipate over