JANINE KEYSER, 48, underwent four cycles of chemotherapy with doxorubicin and cyclophosphamide to treat breast cancer. During treatment, she experienced increasing fatigue and had difficulty concentrating and multitasking at work. Then, when she began treatment with paclitaxel, she had trouble recalling names and words, and couldn't finish even simple tasks. After her third dose of paclitaxel, Ms. Keyser's cognitive deficits were so severe that she had to take a leave of absence from work. She told friends she felt like she was "in a fog" that wouldn't lift.
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During and after treatment for cancer, many patients experience cognitive impairment secondary to chemotherapy. Informally known as chemo brain, this phenomenon can be profoundly disturbing and life-altering for a patient already dealing with a cancer diagnosis. In this article, I'll explain what we know about this condition and how you can help your patient cope with it.
A poorly understood but very real phenomenon, cognitive impairment secondary to chemotherapy can affect memory, attention, and problem-solving ability. It was first identified in the 1980s, when breast cancer patients reported difficulties with cognition during and after chemotherapy. Many were soon referring to the condition as chemo brain or chemo fog. Commonly reported difficulties include:
* poor word or name recall
* difficulty staying focused
* diminished ability to learn new things
* difficulty managing daily activities
* decreased ability to multitask.1
An estimated 20% to 30% of patients undergoing chemotherapy-men and women alike-experience chemo brain. Although the brain may recover over time, research has shown that various cancer treatments can cause structural brain abnormalities that may persist for years. A genetic predisposition may be a factor for many patients.2,3
Patients are typically aware of their cognitive changes but can't emerge from the fog. They feel frustrated and helpless, adding to the burden of emotions that go with a cancer diagnosis (see Rapid recall for nurses: Tips for patient support for ways you can help them deal with cognitive problems).
Because problems may be subtle and produce no outward physical signs, chemo brain is difficult to assess. What's clear is that it can significantly impact quality of life by interfering with a patient's daily routines, family life, career, and plans for the future.
No one can predict which patients will develop cognitive impairment secondary to chemotherapy, and for those who do, severity and duration are highly variable. The time frame for the onset of cognitive impairment is also unpredictable: Changes can start as early as the first chemotherapy treatment, or may be cumulative and develop after subsequent cycles.
The duration and resolution of cognitive problems may be influenced by the patient's treatment regimen, age, and other health problems. The physical and emotional stress of diagnosis and treatment can exacerbate cognitive problems, which may worsen over the course of treatment and linger long beyond its completion.
Currently, no preventative measures are available, nor have standardized evaluation tools or effective treatments been developed. For these reasons, chemo brain can be extremely frustrating for caregivers as well as the patient.
What's behind chemo brain?
Breast cancer patients who've undergone chemotherapy are the largest group of cancer survivors, so research on chemo brain to date has focused on them.4 Studies have shown a correlation between cognitive impairment and chemotherapy, but pinpointing causes has been difficult because of differences in study design, patient characteristics, comparison groups, and chemotherapy regimens.5
Although more research is needed, the following triggers have been postulated as possible causes.
Patients getting chemotherapy drugs known to be toxic to the central nervous system (central neurotoxicity) have a greater incidence of cognitive impairment. Some drugs, such as cytarabine and methotrexate, cause neurotoxicity by crossing the blood-brain barrier and causing direct damage to neurons in the cerebral cortex. Similarly, metabolites of drugs such as ifosfamide and 5-fluorouracil can also cross the blood-brain barrier. The cerebral cortex is responsible for higher cognitive functions such as thinking, learning, problem-solving, and memory.
Patients undergoing chemotherapy should be monitored for toxicity, but standard assessment tools aren't diagnostic. Keep in mind that your patient may be struggling with cognitive impairment even if physical assessment findings and blood tests are within normal limits.
Chemotherapy drugs such as paclitaxel and vincristine can trigger an inflammatory response that indirectly affects the central nervous system. When toxic substances bypass the body's first line of defense (physical, mechanical, and biochemical barriers), the inflammatory response is activated. During the acute inflammatory response, signaling proteins called proinflammatory cytokines are released. Circulating in the bloodstream, these cytokines can penetrate the blood-brain barrier, triggering an inflammatory response in the brain. Research indicates that these cytokines can disrupt neural signaling in the part of the brain responsible for short-term memory.1
This excessive release of proinflammatory cytokines is also associated with a syndrome of physiologic and behavioral signs and symptoms known as "sickness behavior." Signs and symptoms occur 2 to 3 days after treatment and can include fever, fatigue, myalgia, anorexia, decreased ability to concentrate, and behaviors consistent with energy conservation such as sleeping.1,6
Chemotherapy agents can trigger oxidative stress when the body produces more unstable, cell-damaging substances called oxygen free radicals than it can neutralize or eliminate. The imbalance occurs when the body lacks enough antioxidants, which normally protect cells by neutralizing oxygen free radicals. Oxygen free radicals damage DNA and other key cellular components in cells throughout the body, including those in the central nervous system.1
Chemotherapy can cause bone marrow suppression and reduce red blood cell (RBC) production, resulting in anemia. Because of their level of metabolic activity, neurons have a high oxygen demand. By reducing oxygen-carrying RBCs, anemia can compromise cerebral perfusion and impair the patient's ability to think clearly.
Many chemotherapy drugs can suppress hormone production. In a young woman, this can significantly decrease the body's estrogen level and cause premature menopause. In addition, women with some types of breast cancer may be treated with drugs such as tamoxifen or raloxifene to prevent conversion of androgen to estrogen or to block estrogen from binding to cell receptors. Decreased estrogen levels can affect cognitive function because many receptors in the brain require estrogen to stimulate neuronal activity.
Medications commonly prescribed for patients with cancer, such as steroids, antiemetics, benzodiazepines, and analgesics, can affect the central nervous system and impair cognitive function. Fatigue, anxiety, and depression can impair cognition as well. The degree to which other factors impact cognition is unknown but likely to be significant.
Diminished quality of life
Most patients are prepared for well-known adverse reactions to chemotherapy treatment, such as alopecia or nausea, but few expect cognitive problems. Having trouble performing daily activities, maintaining family roles, or performing on the job can be frightening and distressing and significantly diminish the patient's quality of life. In addition, she can't be sure when normal cognitive function will return.
Educate your patient and her family that cognitive impairment is a potential treatment-related reaction to raise their awareness and provide emotional support. Encourage your patient to discuss this adverse reaction with her oncology healthcare team and give her tips for coping with cognitive dysfunction.7 (See Strategies for daily living.)
When you identify a patient at risk for cognitive impairment secondary to chemotherapy, consult with her oncology healthcare team to develop a plan of care and help her get support services she needs. For example, Ms. Keyser, the patient we met at the beginning of the article, might be referred to a neuropsychologist for help with her cognitive functions and an oncology advance practice nurse to help her deal with the emotional distress associated with a cancer diagnosis and adverse reactions to treatment. A social worker can help her with job loss, insurance matters, and other financial issues.
Emerging from the haze
Five months after completing chemotherapy, Ms. Keyser returned to work. Over the next few months, her ability to perform her duties steadily improved. Today, 3 years after completing treatment for breast cancer, she has no apparent cognitive deficits.
Until research tells us more about the causes and solutions, you can help patients like Ms. Keyser understand the risk of cognitive impairment and manage the effects.
Rapid recall for nurses: Tips for patient support
Observe. Your observations during interactions with patients may lend important information on cognitive deficits such as word recall and memory retrieval.
Ask. Inquire whether your patient has noticed any change in her ability to concentrate or to stay focused when performing a task. Is she able to multitask?
Educate. Provide information about cognitive impairment secondary to chemotherapy and give her information about coping strategies if she experiences this problem.
Identify. Determine if other factors may be contributing to her cognitive dysfunction, such as depression, stress, anemia, insomnia, or medications.
Support. Let her know that support is available to help her manage cognitive deficits. See Resources at the end of this article.
Advocate. Alert other healthcare professionals when a patient is experiencing cognitive impairment.
Validate and reassure. Validation that chemo brain is a real phenomenon will help reassure your patient, who may think she's "going crazy" or "losing it."
Strategies for daily living
Encourage your patient to keep her mind active by doing crossword puzzles or word games, or by attending lectures on subjects that interest her. To help her cope with cognitive deficits, offer these suggestions.
* Train yourself to concentrate and focus. Minimize distractions and have conversations in a quiet place.
* Set up and follow routines.
* Exercise, eat well, and pace yourself. Take breaks tailored to your concentration span and get enough rest and sleep.
* Break complex tasks into manageable pieces that you can tackle one at a time. For example, if you're cleaning your house, wash the dishes before moving on to a new task.
* Repeat information aloud after someone gives it to you. Take notes.
* Use a portable planner, personal organizer, or wall calendar to keep track of appointments and upcoming events.
* Keep a "memory notebook." Use a journal to write down your daily schedule and reminder notes about appointments and other commitments. You can also use it to keep track of signs and symptoms you want to discuss with your healthcare provider.
* Leave messages for yourself on your answering machine as reminders.
* Consider telling others what you're going through. Seek professional counseling if you feel extremely anxious or overwhelmed by your cognitive problems.7,8