Treatmentinduced cognitive impairments in cancer survivors: Implications for neurorehabilitation

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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

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Acknowledgments

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

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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.

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Outline

• 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

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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.

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Audience objectives

• 1.
• 2.
• 3.
• 4.
• 5.

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Introduction

• 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
  interventions.

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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.

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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.

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Survivorship

• Women with a history of breast cancer constitute
  the largest disease group in the cancer survivor
  community.
• 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.

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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.

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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.

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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.

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Chemo brain (CONTIUED)

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

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The reality

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

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The reality
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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

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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

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Symptoms of pre-frontal lobe dysfunction

• Apathy or emotional indifference
• Emotional lability
• Perseveration (repetitive thoughts and actions)
• Discrepant behavior
• Poor abstract thinking
• Disinhibition
• Distractibility

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Infancy and the development of the pre-frontal
lobes
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Parenthood and the regression of the pre-frontal
lobes
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Symptoms of occipital lobe dysfunction

• Cortical blindness
• Visual agnosia (impaired ability to recognize
  visual form)
• Prosopagnosia (inability to recognize familiar
  faces)
• Color recognition

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Symptoms of temporal lobe dysfunction

• Pathological rage
• Anxiety
• Interpersonal stickiness-viscosity
• Sleep Disturbance
• Paranoia

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Symptoms of parietal lobe dysfunction

• Prosopagnosia (inability to recognize familiar
  faces)
• Topographical disorientation
• Visuospatial deficits
• Anosagnosia (unawareness of deficit)

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What is neuropsychology and why are we talking
about it here?
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Neuropsychology

• Neuropsychology is the study of brain behavior
  relationships.
• Clinical neuropsychology is the applied science
  concerned with the cognitive, behavioral and
  emotional expression of brain dysfunction

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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
  functions

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Neuropsychological assessment Areas of
examination

• Visual, auditory tactile sensation and
  perception
• 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

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Research Group vs. individual

• N1

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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

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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
  treatment.

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Research Schagen et. al. 1998

• Schagen et. al. studied the late
  neuropsychological effects of adjuvant
  chemotherapy given to patients with breast
  cancer.
• 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
  treatment.

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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
  function.

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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.

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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.

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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.

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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
  functioning.

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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
  range.

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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.

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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

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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

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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
  self-sufficiency.

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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.

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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.

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Treatment

• 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
  appropriately.

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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.
• .

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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
  chemotherapies.

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Intervention (continued)

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

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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
  rehabilitation.
• 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.

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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.

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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,
  2000)

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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.

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Treatment The role of neurorehabilitation
(continued)

• 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.

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Treatment The role of neurorehabilitation
(continued)

• 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.

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TreatmentThe role of neurorehabilitation
(continued)

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

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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)?

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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?

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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.

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Questions

• Now
• Later
• AErrico_at_lakeview.ws
• Erricoal1_at_aol.com

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Other research
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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

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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.

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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
  processing.
• Authors concluded that bone marrow
  transplantation may lead to persistent cognitive
  deficits in long-term adult survivors.

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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.

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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

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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
  dysfunction.
• 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
  time.