A Neuropsychologic Perspective: A Neuropsychologic Perspective: Cognitive Impairments in Cancer Cognitive Impairments in Cancer

PatientsPatients

J. Aubrey BurhartJ. Aubrey Burhart

State University of New York State University of New York at Buffaloat Buffalo

What is a neuropsychologist?What is a neuropsychologist?

A neuropsychologist is an expert in A neuropsychologist is an expert in the applied science of clinical the applied science of clinical

neuropsychology concerned with neuropsychology concerned with the behavioral expression of brain the behavioral expression of brain

dysfunctiondysfunction

Dimensions of BehaviorDimensions of Behavior

C ognitiveInform ation-handling aspect

Em otiona lityConcerns feelings and m otivation

Executive FunctionsHow behavior is expressed

Behav ior is C onceptualized in T hree System s

What does a Neuropsychologist do?What does a Neuropsychologist do?

Diagnose – Diagnose – Differentiate btw. Psychiatric and neurological Differentiate btw. Psychiatric and neurological symptoms; distinguishing btw. 2 neurological disorders; predict symptoms; distinguishing btw. 2 neurological disorders; predict outcome of a conditionoutcome of a condition

Patient care and planning – Patient care and planning – Identify how the disease might Identify how the disease might affect patient’s behavior for family members; Assess patient’s affect patient’s behavior for family members; Assess patient’s capability for managing daily activities and following treatment capability for managing daily activities and following treatment regimen; Repeated assessments at intervals allows for tracking regimen; Repeated assessments at intervals allows for tracking disease progressiondisease progression

Rehabilitation and Treatment evaluation – provide Rehabilitation and Treatment evaluation – provide information to various healthcare providers regarding information to various healthcare providers regarding patient’s capacities, defective behaviors, etc.patient’s capacities, defective behaviors, etc.

Research – study brain activity and its effect on behaviorResearch – study brain activity and its effect on behavior

Lateralization in the BrainLateralization in the Brain

Left SideLeft Side SpeechSpeech WritingWriting

Main Language Main Language CenterCenter

CalculationCalculation

Right SideRight Side Spatial ConstructionSpatial Construction

Simple LanguageSimple Language Copying/Drawing Copying/Drawing

Geometric DesignsGeometric Designs Some Musical AbilitySome Musical Ability

OdorsOdors

Major Neuropsychology Major Neuropsychology DomainsDomains

MemoryMemory

Visual/SpatialVisual/Spatial

Attention/Attention/ConcentrationConcentration

IntellectualIntellectual

Executive Executive

MotorMotor

Speech/LanguageSpeech/Language

The Domains Defined The Domains Defined (Lezak, 1995)(Lezak, 1995)

MemoryMemory The complex of systems by The complex of systems by

which an organism which an organism registers, stores, retains, registers, stores, retains, and retrieves some and retrieves some previous exposure to an previous exposure to an event or experienceevent or experience

Visual/SpatialVisual/Spatial The memory for familiar The memory for familiar

routes or for the location of routes or for the location of objects and places in spaceobjects and places in space

Attention and Attention and ConcentrationConcentration

Refers to several Refers to several processes that are processes that are related aspects of how related aspects of how the organism becomes the organism becomes receptive to stimuli and receptive to stimuli and how it may begin how it may begin processing incoming or processing incoming or attended to-informationattended to-information

Definition of Definition of Domains..cont’d.Domains..cont’d.

ExecutiveExecutive Those capacities that Those capacities that

enable a person to engage enable a person to engage successfully in successfully in independent, purposive, independent, purposive, self-serving behaviorself-serving behavior

MotorMotor Primarily concerned with Primarily concerned with

use of the hands, although use of the hands, although gait is qualitatively gait is qualitatively assessed. Gross and fine assessed. Gross and fine motor skills are assessed motor skills are assessed to varying degrees of to varying degrees of precision.precision.

IntelligenceIntelligence Tendency for cerebral regions Tendency for cerebral regions

subserving different subserving different intellectual functions to be intellectual functions to be proportionately developed in proportionately developed in any one individualany one individual

Speech & LanguageSpeech & Language Refers to the understanding Refers to the understanding

and expression of language in and expression of language in all realms (spoken, written, all realms (spoken, written, auditory). Incl.’s auditory). Incl.’s quality/quantity of quality/quantity of spontaneous speech, aud. spontaneous speech, aud. Comp., reading recognition and Comp., reading recognition and comp., writing, repetition, and comp., writing, repetition, and confrontation and generative confrontation and generative naming.naming.

Cancer is DevastatingCancer is Devastating

The incidence of cancers of the breast and The incidence of cancers of the breast and lung in women, as well as non-Hodgkin lung in women, as well as non-Hodgkin lymphoma, melanoma of the skin, and liver in lymphoma, melanoma of the skin, and liver in men and women, is risingmen and women, is rising

Lung cancer deaths in women continue to Lung cancer deaths in women continue to rise, though not as effectively as beforerise, though not as effectively as before

More people are overweight and obese, and More people are overweight and obese, and physical activity is increasing only slightlyphysical activity is increasing only slightly

Cancer treatment spending continues to rise Cancer treatment spending continues to rise along with total health care spendingalong with total health care spending

Cognitive Functioning is Cognitive Functioning is Essential For…Essential For…

Comprehending disease treatment Comprehending disease treatment and progressionand progression

Making informed healthcare Making informed healthcare decisionsdecisions

Adhering to a treatment regimenAdhering to a treatment regimen Medication complianceMedication compliance Occupational successOccupational success Maintaining social networksMaintaining social networks

Risk Factors for Cognitive Risk Factors for Cognitive DeficitsDeficits

Disease InducedDisease Induced InfectionsInfections PainPain Metastases to CNSMetastases to CNS Disturbances of Disturbances of

endocrinologic endocrinologic systemsystem

Treatment InducedTreatment Induced ChemotherapyChemotherapy RadiationRadiation Bone marrow Bone marrow

transplantationtransplantation MedicationsMedications Biologic Response Biologic Response

ModifiersModifiers

All of these things can All of these things can cause..cause..

Combination treatments are often implemented Combination treatments are often implemented which may be more effective in combating the which may be more effective in combating the cancer, but poses even greater risks of cancer, but poses even greater risks of neurotoxicity for the patientneurotoxicity for the patient

Effects of Chemotherapy on Effects of Chemotherapy on Cognitive FunctioningCognitive Functioning

Cognitive dysfunction can appear soon after Cognitive dysfunction can appear soon after treatment initiation or as late as 10 years latertreatment initiation or as late as 10 years later

Altered cognitive functioning can be transient or Altered cognitive functioning can be transient or permanentpermanent

Even when cognitive function appears to be in Even when cognitive function appears to be in the normal range, low-normal functioning is the normal range, low-normal functioning is associated with previous chemotherapy associated with previous chemotherapy treatmenttreatment

There is new evidence that supports the theory There is new evidence that supports the theory that carriers of the e4 allele of apoliprotein are that carriers of the e4 allele of apoliprotein are at greater risk for reduced neuropsychological at greater risk for reduced neuropsychological performance; when coupled with chemo performance; when coupled with chemo treatment, their risk substantially increases for treatment, their risk substantially increases for cognitive dysfunctioncognitive dysfunction

Neurological complications of Neurological complications of chemotherapychemotherapy

Acute encephalopathy (begins with insomnia, Acute encephalopathy (begins with insomnia, rapidly followed by a state of confusion rapidly followed by a state of confusion associated with agitationassociated with agitation

Stroke-like episodes (characterized by acute Stroke-like episodes (characterized by acute onset of encephalopathy with fluctuating motor onset of encephalopathy with fluctuating motor deficit)deficit)

Chronic encephalopathy – develops Chronic encephalopathy – develops progressively for months to years after progressively for months to years after treatmenttreatment

Neurological Complications of radiationNeurological Complications of radiation

Acute encephalopathy (headache, nausea, Acute encephalopathy (headache, nausea, drowsiness, fever)drowsiness, fever)

Early-delayed Complications (2 weeks-3 or 4 Early-delayed Complications (2 weeks-3 or 4 months): hypersomnia, irritability, headache, months): hypersomnia, irritability, headache, attention deficits, memory problemsattention deficits, memory problems

Late-delayed complications (4 months-years): Late-delayed complications (4 months-years): radiation necrosis, dementia syndrome, vision radiation necrosis, dementia syndrome, vision and/or hearing loss, lower cranial nerve and/or hearing loss, lower cranial nerve paralysis, radiation-induced tumorsparalysis, radiation-induced tumors

Potential Mediators ?Potential Mediators ?

There have been some agents There have been some agents identified that might reduce identified that might reduce cognitive impairment:cognitive impairment:• ErythropoietinErythropoietin• AspirinAspirin• Methylphenidate (has demonstrated Methylphenidate (has demonstrated

improvement in children undergoing improvement in children undergoing chemo)chemo)

What is Bone Marrow What is Bone Marrow Transplantation (BMT)?Transplantation (BMT)?

Used to treat cancers that have not responded Used to treat cancers that have not responded well to more standard medical interventionswell to more standard medical interventions

Bone marrow transplants involve the destruction Bone marrow transplants involve the destruction of a patient’s own bone marrow via of a patient’s own bone marrow via chemotherapy and/or radiation therapy, followed chemotherapy and/or radiation therapy, followed by infusion of new cells to generate healthy bone by infusion of new cells to generate healthy bone marrow functionmarrow function

BMT can be classified as allogeneic or autologous:BMT can be classified as allogeneic or autologous:• Allo – bone marrow is transferred from a donorAllo – bone marrow is transferred from a donor• Auto – replacement marrow is harvested from the Auto – replacement marrow is harvested from the

patient, cleaned from disease, and reinfused into patientpatient, cleaned from disease, and reinfused into patient

BMT patients are at high risk for BMT patients are at high risk for cognitive deficitscognitive deficits

Most patients undergoing BMT receive chemotherapy or Most patients undergoing BMT receive chemotherapy or combination chemotherapy/radiation as a preparatory combination chemotherapy/radiation as a preparatory regimen prior to BMTregimen prior to BMT

Toxicity from high-dose chemotherapy combine with Toxicity from high-dose chemotherapy combine with whole-body radiation puts patient at risk for extended whole-body radiation puts patient at risk for extended hospitalization, posthospitalization recovery, and risk of hospitalization, posthospitalization recovery, and risk of death from the proceduredeath from the procedure

Neurological acute complications are frequent, including Neurological acute complications are frequent, including transient drowsiness, occasional seizures, or severe transient drowsiness, occasional seizures, or severe encephalopathy; delayed complications typically include encephalopathy; delayed complications typically include mild/moderate cognitive dysfunction with cerebral atrophy.mild/moderate cognitive dysfunction with cerebral atrophy.

BMTBMT

Studies investigating cognitive impairment in Studies investigating cognitive impairment in BMT patients have used various methods of BMT patients have used various methods of assessment including a review of medical assessment including a review of medical records, interviews, self-reported records, interviews, self-reported questionnaires, and standardized questionnaires, and standardized neuropsychological testingneuropsychological testing

Cognitive impairment has been found to Cognitive impairment has been found to persist for months to years following BMTpersist for months to years following BMT

BMTBMT

Several domains of cognitive functioning have Several domains of cognitive functioning have been found to be affected, ranging in severity been found to be affected, ranging in severity from mild to severe impairment, including from mild to severe impairment, including memory, attention/concentration, language, memory, attention/concentration, language, motor, and executive functioningmotor, and executive functioning

Most studies investigating cognitive Most studies investigating cognitive impairment as a result of BMT do not include a impairment as a result of BMT do not include a baseline assessment, lack long-term follow-up baseline assessment, lack long-term follow-up assessment, do not include standardized assessment, do not include standardized neuropsychological protocols, and lack a neuropsychological protocols, and lack a measure of Quality of Life.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 patients (Sjogren, 1997).

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.

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•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?