Cognitive impairment, including memory loss, inability to concentrate, and difficulty multitasking, has become a widely recognized possible late effect of chemotherapy and cancer treatment. Over the past decade, research has increasingly focused on the trajectory of cognitive function during and post treatment. Many cross-sectional studies have documented impairments among women with breast cancer who received chemotherapy, in comparison to healthy controls and women treated with local therapy, and the extent of impairment has been associated with the dose intensity of chemotherapy.
Ahles and colleagues found that deficits persist for as long as 10 years post-treatment among lymphoma and breast cancer survivors with no evidence of disease. Emerging evidence implicating the role of chemotherapy in contributing to cognitive decline has led to use of the term 'chemobrain' to describe this symptom.
The first longitudinal studies examined women with breast cancer and documented decline in cognitive function during and after chemotherapy, however approximately one-third of study participants met criteria for cognitive impairment prior to chemotherapy.[4,5] This surprising finding underscored the need to consider the myriad factors that may contribute to cognitive impairments following a cancer diagnosis and cancer treatment. While a detailed review of cognitive behavioral therapy (CBT) for symptom management is outside the scope of this article, a case example will be used to illustrate its application in a woman with lymphoma who presented in acute distress and with concerns regarding 'chemobrain.'
MJ is a 43-year-old white female diagnosed with stage IE diffuse large B-cell lymphoma located in the gastrointestinal tract. During administration of her second cycle of R-CHOP, she had difficulty controlling her crying spells and she reported acute distress. She identified concerns about 'chemobrain' as one of the primary causes for her distress. A consult from this author, a clinical health psychologist, was requested to assess and manage this patient's acute distress, to evaluate the extent to which distress was contributing to the patient's concentration difficulties, and to provide her with strategies for coping with cancer-related symptoms.
This clinician assessed MJ's current symptom profile and history. MJ reported severe distress, which she rated as an 8 on a 0–10 point scale. She attributed her distress in part to her fear of cognitive impairment resulting from her chemotherapy regimen. Upon inquiry, she identified the trigger for onset of acute distress as her inability to recognize a member of the nursing staff who reportedly administered her chemotherapy at cycle 1.
MJ interpreted her inability to recognize nursing staff as a sign of 'chemobrain' and consequently experienced acute and intense anxiety about anticipated additional cognitive decline with each chemotherapy cycle. She also reported anxiety about her future capability to maintain her job responsibilities as an attorney, given the cognitive abilities required to meet the demands of her job. She reported concerns about the effects of chemotherapy on her cognitive function, as this was an anticipated side effect of treatment based on conversations with cancer survivors, and she denied noticing any prior changes in cognitive abilities.
Based on a patient-reported outcomes measure of perceived cognitive function (Functional Assessment of Cancer Therapy –Cognitive Function, FACT-Cog), MJ reported concentration difficulties several times per day and her questionnaire responses revealed significant impairment to her quality of life due to cognitive difficulties. A modified Structured Clinical Interview for the Diagnostic and Statistical Manual for Mental Disorders-IV (SCID) was administered to assess criteria for current mood and anxiety disorders.
MJ reported generalized anxiety, which she described as difficult to control and accompanied by physical symptoms (muscle tension, restlessness, difficulty with sleep onset). Anxiety was not specific to her recent lymphoma diagnosis and included worry about 'chemobrain' and the effects of R-CHOP on her long-term cognitive function. Because she had experienced these symptoms for longer than 6 months, MJ met criteria for generalized anxiety disorder (DSM-IV 300.02), and per her report she had experienced generalized anxiety for several years prior to her lymphoma diagnosis.
MJ also reported several symptoms consistent with current major depressive episode, including depressed moods, anhedonia, difficulty concentrating, frequent crying spells, excessive guilt, and hopelessness about the future. MJ and this clinician established the time of onset of her concentration difficulties as coinciding with her lymphoma diagnosis and her pursuant depressed mood and increase in anxiety. Though MJ reported fatigue and decreased appetite, these symptoms were interpreted cautiously as she was also undergoing chemotherapy.
MJ denied symptoms of other mood and anxiety disorders, including dysthymic disorder, manic episodes, post-traumatic stress disorder, and panic disorder. She was oriented to person, time, and location. Her speech did not suggest any thought disorder, and her thought processes were linear and goal-directed. She denied any auditory, visual, or tactile hallucinations, and denied delusions of persecution, grandeur, and reference. Neuropsychological evaluation was not conducted at initial assessment because MJ presented with a single episode of difficulty with facial recognition and her clinical interview did not reveal any signs or symptoms of gross cognitive dysfunction.
Summary of Treatment: Acute Symptom-Related Distress
The first step in managing cognitive impairment associated with cancer and cancer treatment is to identify and treat any medical factors that may be contributing to or exacerbating this symptom. At the time of initial assessment, this clinician consulted with the oncology healthcare team to identify and rule out common medical factors contributing to cognitive impairments (see Table 1). No major medical conditions were identified to cause cognitive deficits and there was no evidence of brain metastasis or primary brain tumors.
It is important to review the patient's medications to identify agents that may be causing or exacerbating cognitive difficulties. Based on patient interview and a review of her medication list in the electronic medical record, MJ began taking antiemetic and antianxiety medications on day 1 of cycle 1. MJ was educated about the effects of antiemetic and antianxiety medications on cognitive function. She confirmed that on cycle 1 day 1, she was given medications that can impair cognitive function.
A central tenet of cognitive behavioral therapy is that how people think affects how they feel. Therefore, causal attributions play a significant role in mediating an emotional response to an event or an experience, such as a physical symptom. The therapeutic process of collaborating with a patient to accurately attribute symptoms to their etiology, when possible, is a CBT technique called symptom reframing.
This clinician engaged MJ in guided discovery to encourage her to generate multiple hypotheses about the causes of her cognitive impairment. Her inability to recognize a member of the healthcare team from her first chemotherapy cycle was attributed to her antiemetic and antianxiety medications.
She was encouraged to alter her attribution of her memory loss from a long-term, possibly untreatable cause (eg, CNS toxicity from chemotherapy) to a transient, correctable cause (eg, short-term medication use). Reframing her symptom as transient and time-limited (short-term medication side effects) led to an immediate reduction in her acute distress.
When faced with cancer-related symptoms that are distress-generating, MJ was encouraged to engage in the same process of identifying the specific symptom (eg, 'chemobrain,' fatigue), generating several hypotheses about the potential etiology for the symptom, then evaluating the evidence supporting each of her hypotheses. This process leads to identifying potential etiologies that may be treatable (eg, anemia), therefore increasing perceived control over cancer-related symptoms. A key point is that this technique was employed after establishing rapport to ensure that MJ felt her symptom concerns had been adequately understood and were not being dismissed or trivialized.
MJ was encouraged to review her history of this symptom for evidence supporting alternative hypotheses. MJ confirmed she had only previously experienced mild, transient difficulty concentrating, and that prior to today's visit she was not aware of any episodes of significant memory loss or difficulty with facial recognition. This observation supports the likelihood that her cycle 1 day 1 medications played a large role in her difficulty recognizing her treatment nurse.
MJ was provided with education regarding the known trajectory of cognitive impairment following treatment, including aspects of this symptom that are not yet well understood, such as its mechanism and duration. When observed, for the majority of patients cognitive impairments have a gradual onset, tend to be subtle in nature, and are likely to improve in the 12 months following completion of chemotherapy. MJ reported reduced anxiety over this symptom after she was provided with education about it. She expressed the desire to proactively learn CBT strategies to manage cognitive impairments, if this symptom were to worsen during her treatment.
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