Cognitive Dysfunction Secondary to Cancer Therapy

Background

Cognitive changes that negatively affect thinking—including memory, concentration, and behavior—are known as cognitive dysfunction (CD). CD is also referred to as cognitive impairment, cognitive changes, central neurotoxicity, cognitive impairment, or neurocognitive dysfunction¹ and is commonly referred to by cancer patients and survivors as “chemo brain” or “chemo fog.” CD has been widely reported in the professional and patient literature, yet its exact etiology in cancer patients remains unknown² and there is no consensus on its precise definition. Similar changes have been reported in patients with HIV, chronic fatigue syndrome, hepatitis C, and acquired brain injury.

Need for Studies of CD and Cancer

Cancer- and cancer treatment–related cognitive changes have been studied most widely in women undergoing treatment for breast cancer, with 17% to 75% reporting symptoms.³ However, the study of cancer-related CD is relatively new and lacks large phase 3 clinical studies to support evidence-based assessment and/or interventions. As a result, neither the National Cancer Institute (NCI) nor the National Comprehensive Cancer Network (NCCN) has yet established guidelines for the care of patients experiencing CD symptoms

Studies Suggesting Developmental Differences in Cancer-Related CD

Cognitive impairments have been well documented in children who received cancer treatment, some deficits being more noticeable 5 to 11 years after diagnosis.1 Buckwalter et al,¹ comparing 541 elderly female cancer survivors with a control group of 3,123 women, found no association between a history of cancer and poorer cognitive function or delayed verbal memory. This study suggests that since all respondents had developed their cancer after age 18, perhaps the adult brain and developing brain have different responses to cancer and treatment.^1,4

Adult Studies Suggesting Cancer-Related Differences in CD

Recently completed and ongoing studies have begun to question this concept. Silverman et al⁵ examined physical changes in the brain that occur with CD symptoms, which include memory loss, depression, inability to concentrate, and fatigue. Women with breast cancer treated with adjuvant chemotherapy were evaluated 5 to 10 years after their chemotherapy treatments and compared with a control group. On a delayed recall test, the women who received chemotherapy scored an average of 3.2 points lower than the control group. Positron emission tomographic (PET) scans of the treated women revealed changes in cerebral blood flow in regions of the frontal cortex and cerebellum, with the most significant change noted in the inferior frontal gyrus.⁵

Neurocognitive Impairments Related to Location In Brain

Site	Common Deficits
Left Hemisphere	Language Verbal memory & reasoning Right-sided strength & dexterity


Right Hemisphere	Visual perception & construction Left hemispatial inattention Left-sided strength & dexterity


Frontal lobe	Executive functions

Adapted from Baumgartner.²

Medical oncologists, radiologists, and psychologists who participated in an April 2005 workshop on CD concluded that its changes may be subtle, durable, and possibly disabling.⁶ Risk factors for CD have not been well defined, but the following list may help identify those most at risk for CD:

Central nervous system involvement from tumor
Persons with breast cancer or lymphoma who carry the e4 allele genetic mutation⁷
Increasing age
Estrogen deficiency
Certain types of chemotherapy

Cyclophosphamide
Methotrexate
5-Fluorouracil
Cytarabine
Procarbazine

Hormonal therapy
Interleukin 2 or interferon
Glucocorticosteroids

Aside from the cancer and treatment, other factors may contribute to cognitive problems:

Strees
Poor diet
Pain⁷
Sleep disturbances
Menopause
Anemia^3,8,9

Many patients find that CD resolves over time (months to years) The National Coalition for Cancer Survivorship suggests that new research may reveal CD as a lingering side effect for some patients.⁸

Assessment

The first indication of CD is the patient’s own report.² In addition to patient-provided subjective information, it is critical that nurses document objective observations of memory deficits, confusion, or altered functioning in the medical record. The Folstein Mini Mental State Examination (MMSE) (http://nursing.iupui.edu/AcademicPrograms/ASN/docs/a279Folstein.doc) can be administered in 10 minutes in any clinical setting to establish a baseline or document changes.^10,11 If the symptoms of CD are distressing to the patient, consider referral to a neuropsychologist for further objective testing of cognitive and executive function.²

Interventions

The most important intervention during patients’ reporting of CD symptoms is listening carefully to their complaints and concerns. While there are no evidence-based guidelines for CD management, the following interventions may be helpful²:

Make lists for shopping, tasks
Use a personal planner for daily schedules
Keep frequently used items (keys, cell phone, eyeglasses) in one place
Maintain a normal routine
Ensure adequate sleep, a balanced diet, and regular exercise
Consider meditation or relaxation techniques

The Oncology Nursing Society’s patient education Web site, www.cancersymptoms.org, has further suggestions for reduction of CD.¹² Chemocare, a patient support Web site, offers suggestions for promoting concentration and reducing modifiable contributing factors such as nicotine, caffeine, and other stimulants, as well as healthy stress reduction techniques.¹³ Suggestions for minimizing CD from the Lance Armstrong Foundation are available on the Livestrong Web-site.

Guidelines

There are no evidence-based guidelines for the assessment or management of cognitive dysfunction.

References

Buckwalter J, Crooks V, Petitti D. Cognitive performance of older women who have survived cancer. Intern J Neurosci. 2005;115:1307-1314.
Baumgartner K. Neurocognitive changes in cancer patients. Semin Oncol Nurs. 2004; 20:284-290
O’Shaughnessy J. Chemotherapy-related cognitive dysfunction in breast cancer. Semin Oncol Nurs. 2003;19(suppl 2):17-24
Brown PD, Buckner JC, Uhm JH, Shaw EG. The neurocognitive effects of radiation in adult low-grade glioma patients. Neuro-oncol. 2003;5:161-167.
Silverman DHS, Dy C, Castellon SA, et al. Altered frontocortical, cerebellar, and basal ganglia activity in adjuvant-treated breast cancer survivors 5-10 years after chemotherapy. Breast Cancer Res Treat. 2006 Sep 29; [Epub ahead of print]. Available at: http://springerlink.com/content/mq53511v473u2253. Accessed January 22, 2007.
Tannock I, Ahles T, Ganz P, van Dam F. Cognitive impairment associated with chemotherapy for cancer: report of a workshop. J Clin Oncol. 2004;22:223-2239
Staat K, Segatore M. The phenomenon of chemo brain. Clin J Oncol Nurs. 2005;9:713-721.
National Coalition for Cancer Survivorship. Cognitive issues. Available at: http://www.canceradvocacy.org/resources/essential/effects/cognitive.aspx. Accessed February 8, 2007.
O’ Shaughnessy J. Chemotherapy-induced cognitive dysfunction: a clearer picture. Breast Cancer. 2003;4(suppl 2):S89-S94.
Folstein MF, Folstein SE, McHugh PR. Mini-mental state: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12:189-198.
Psychological Assessment Resources, Inc. Mini-Mental State Examination. Available at: http://www.minimental.com. Accessed February 8, 2007.
Oncology Nursing Society. Cognitive dysfunction: chemo-brain prevention. Available at: http://www.cancersymptoms.org/cognitivedysfunction/prevention.shtml. Accessed February 8, 2007.
Chemocare. Chemo brain: What is chemobrain? Available at: http://www.chemocare.com/managing/chemobrain__how_to_identify_and.asp. Accessed
February 8, 2007.

Key Definitions

cerebellum — a large dorsally projecting part of the brain concerned especially with the coordination of muscles and the maintenance of bodily equilibrium; it is situated between the brain stem and back of the cerebrum and formed (in humans) of 2 lateral lobes and a median lobe

delayed recall test — assessment of the ability to verbally repeat a short list or story after a defined period of time

e4 allele — a germline mutation that has been associated with Alzheimer’s disease

executive functions — a cluster of high-order capacities, which include selective attention, behavioral planning and response inhibition, and the manipulation of information in problem-solving tasks

frontal cortex — the portion of the brain involved with reasoning, planning, abstract thought, and other complex cognitive functions in addition to motor function

frontal gyrus — any of the convolutions of the outer surface of the frontal lobe of the brain

glucocorticosteroids — any of the group of corticosteroids predominantly involved in carbohydrate fat and protein metabolism, alteration of connective tissue response to injury, and inhibition of inflammatory and allergic reactions. In humans, the most important glucocorticosteroids are cortisol (hydrocortisone) and cortisone

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