A Neuropsychologic Perspective: Cognitive Impairments in Cancer Patients

1. A Neuropsychologic Perspective: Cognitive Impairments in Cancer Patients J. Aubrey Burhart State University of New York at Buffalo

2. What is a neuropsychologist? • A neuropsychologist is an expert in the applied science of clinical neuropsychology concerned with the behavioral expression of brain dysfunction

3. Dimensions of Behavior

4. What does a Neuropsychologist do? • Diagnose – Differentiate btw. Psychiatric and neurological symptoms; distinguishing btw. 2 neurological disorders; predict outcome of a condition • Patient care and planning – Identify how the disease might affect patient’s 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 • 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

5. Left Side Speech Writing Main Language Center Calculation Right Side Spatial Construction Simple Language Copying/Drawing Geometric Designs Some Musical Ability Odors Lateralization in the Brain

6. Memory Visual/Spatial Attention/Concentration Intellectual Executive Motor Speech/Language Major Neuropsychology Domains

7. 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 to-information The Domains Defined (Lezak, 1995)

8. Executive Those capacities that enable a person to engage successfully in independent, purposive, self-serving 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. Definition of Domains..cont’d.

9. 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

10. 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

11. Disease Induced Infections Pain Metastases to CNS Disturbances of endocrinologic system Treatment Induced Chemotherapy Radiation Bone marrow transplantation Medications Biologic Response Modifiers Risk Factors for Cognitive Deficits

12. 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 Encephalopathy

13. 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

14. 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

15. 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

16. Potential Mediators ? • There have been some agents identified that might reduce cognitive impairment: • Erythropoietin • Aspirin • Methylphenidate (has demonstrated improvement in children undergoing chemo)

17. 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

18. 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.

19. BMT • Studies investigating cognitive impairment in BMT patients have used various methods of assessment including a review of medical records, interviews, self-reported questionnaires, and standardized neuropsychological testing • Cognitive impairment has been found to persist for months to years following BMT

20. 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.

21. 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).

22. 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.

32. In Conclusion • 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

33. Critical Issues • 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?

34. Thanks for your attention! Any Questions?