Cognitive impairment, including memory loss, inability to concentrate, and difficulty multitasking, has become a widely recognized possible late effect of chemotherapy and cancer treatment.
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.
Most Common Factors Contributing to Cognitive Impairment Among Adults With Cancer
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.
Follow-up treatment provided MJ with coping strategies for managing 'chemobrain' and her distress over this symptom, based on a CBT model. A similar approach, Memory and Attention Adaptation Training (MAAT), has been empirically evaluated. MJ was instructed to keep a daily symptom diary for 14 days to self-monitor her mild attentional difficulties and to document any new concerns related to her cognitive function, as well as related symptoms including fatigue, anxiety, and depressed moods. By keeping a symptom diary, MJ discovered a strong association between her difficulty with concentrating and her fatigue severity.
Based on this observation, MJ focused on scheduling her most demanding cognitive activities early in the day, when she has the highest energy level. MJ also planned to implement pacing strategies, to alternate physically and mentally demanding activities with brief periods of rest to maximize her function. Through her symptom diary, she discovered an association between her concentration difficulties and her overall level of anxiety. She was proivded with education on the role of the autonomic nervous system in regulating physiological arousal.
Efficiency of cognitive processing is maximized when an individual functions within the low to moderate range of physiological arousal, and difficulties with concentration are experienced when an individual is extremely anxious and overaroused.
MJ was provided with instruction in diaphragmatic breathing techniques to learn how to self-regulate her level of physiological arousal. She was instructed to practice diaphragmatic breathing on a daily basis to lower her overall level of autonomic hyperarousal. MJ was also instructed to take 5–10 diaphragmatic breaths at times when she experienced heightened anxiety, to help her transition back into the maximal range of arousal for optimal cognitive function. She was trained in relaxation techniques and provided with an audio-CD for home-based practice.
She was educated regarding strategies commonly used to compensate for problems with concentration and memory. She was encouraged to create a list of organizational strategies that she utilized previously in managing her professional responsibilities, to build on existing strengths. MJ agreed to create and maintain a calendar of upcoming events, deadlines, and scheduled activities, including medical appointments, and to retain key information through auditory repetition or by writing things down. She was encouraged to seek additional information on organizational strategies to improve cognitive efficiency (eg, creating lists, developing routines, color-coding projects).
Cognitive Behavioral Therapy (CBT) model for managing cognitive impairments
Last, MJ was encouraged to engage daily in cognitively stimulating activities (eg, crossword or other word puzzles, computer or board games, book club discussions), to regularly “exercise” her cognitive abilities. This rationale is based on emerging evidence that cognitively challenging activities may reduce the risk of dementia among older adults. MJ was encouraged to maintain a physical activity regimen as well, under the supervision of her oncology healthcare team. Physical activity is an effective intervention for cancer-related fatigue, a symptom that can exacerbate cognitive impairments, and physical activity may have direct benefits to cognitive function.[9,10]
In summary, MJ was introduced to a CBT model for managing 'chemobrain' which empowered her with skills to manage this symptom and distress secondary to coping with cancer and treatment-related symptoms (see Figure 1). The etiology of cancer-related cognitive impairments is multifactorial, so intervention should address contributing factors as illustrated in Figure 1, which is intended to be visualized as a pearl.
At the core of this 'pearl' is a grain of sand, meaning the base level of cognitive impairments that are present as a result of direct effects of cancer and cancer treatment. Additional factors, such as anxiety, anemia, reduced physical activity, and poorly managed stress exacerbate cognitive difficulties, thereby adding layers to this core and increasing the diameter of the 'pearl.' CBT approaches to symptom management focus on identifying the layers of the pearl and, when possible, implementing interventions to strip away these additional layers, thus reducing the magnitude of the target symptom.
In this case example, altering symptom interpretation, teaching stress management strategies, encouraging use of compensatory strategies, and developing a behavioral plan for increased physical activity and cognitively challenging activities were employed. This led to a reduction of MJ's severity of cognitive impairments down to the least extent possible (ie, core of the 'pearl') given her medical and treatment characteristics. One additional component of this treatment included education of family members about the most common side effects of chemotherapy, including cognitive impairments, to facilitate communication and allow family members to adjust their expectations and provide MJ with support and assistance with activities if needed. CBT principles can provide a guiding framework for members of the patient's support network.
MJ underwent an initial assessment and three follow-up visits with the clinical health psychologist. At follow-up 1 month post six cycles of R-CHOP, she reported more difficulties with “multitasking” and verbal memory in comparison to her prechemotherapy function. She said that these difficulties became more noticeable after each chemotherapy cycle. Her PET/CT indicated complete remission.
Despite experiencing more cognitive difficulties, MJ reported a significant reduction in her anxiety about her cognitive function as well as an overall decrease in her generalized anxiety. Her anxiety now was rated as a 1 on a 0–10 point scale. Her FACT-Cog subscale scores indicated an overall increase in the frequency of cognitive difficulties, however her responses indicated a decrease in impairments to quality of life resulting from these difficulties. She attributed this improvement to an increased sense of control resulting from her newly developed repertoire of coping skills (eg, diaphragmatic breathing, relaxation, cognitive reframing, and compensatory strategies).
Cognitive impairments associated with cancer and cancer treatments have been widely documented. Even among adults who appear to be cognitively intact, the perception of diminished cognitive function can be extremely distressing. Our cognitive abilities are an integral component of our identity and are how we define ourselves as uniquely human. In this light, it is comprehensible that cognitive impairments, whether reported by the patient or documented by neuropsychological assessment, significantly disrupt quality of life. Nonpharmacological strategies-including patient education, cognitive behavioral techniques, compensatory strategies, and exercise, both cognitive and physical-can be utilized to manage the difficult symptom of cognitive dysfunction. These strategies provide an increased sense of control, thereby reducing the burden of cancer.
Financial Disclosure: The author has no signifi cant fi nancial interestor other relationship with the manufacturer of any products orproviders of any service mentioned in this article.
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