Interventions coordinated by physical medicine and rehabilitation physiatrists can help patients optimize cognitive functioning during and after cancer treatment.— Arash Asher, MD
Chemotherapy-associated cognitive dysfunction, often referred to as “chemobrain” or “chemofog,” is a common occurrence during active cancer treatment and may continue after treatment is completed. However, since treatment other than chemotherapy, including radiation therapy, surgery, and hormonal therapy, also may contribute to cognitive dysfunction, the term to describe cognitive decline in cancer survivors has now been broadened to “cancer-related cognitive impairment.” Cancer-related cognitive impairment may include problems with short-term memory, executive function, attention, and information-processing speed.
Some studies suggest that up to 75% of patients treated with chemotherapy experience these symptoms during active treatment.1 A cohort of these patients, estimated to be between 20% and 30%, may continue to experience these symptoms months or years after the completion of active treatment.2 With more than 15 million cancer survivors in the United States,3 it is likely that a sizable number of these individuals will continue to struggle with cognition after cancer and its treatments, which can negatively impact their long-term quality of life. Interventions coordinated by physical medicine and rehabilitation physiatrists can help patients optimize cognitive functioning during and after cancer treatment.
Although no definitive evidence exists to support a single underlying molecular mechanism contributing to such cognitive difficulties, various biologic and psychological mechanisms have been suggested to explain the problem, including the direct neurotoxic effects of therapy, genetic predisposition, and elevated levels of proinflammatory cytokines. In addition, a number of other factors may explain the risk for persistent cognitive difficulties, including depression and anxiety; chronic stress or loneliness; medical comorbidities, such as hypothyroidism and anemia; hormonal changes from treatment, including androgen or estrogen deprivation; poor cognitive reserve due to aging or limited education; and supportive care medications, such as benzodiazepines, corticosteroids, and opioids.
Sean Smith, MD
Diagnosis and Assessment
No single symptom is pathognomonic for cancer-related cognitive impairment, and symptoms may vary from person to person. Some common symptoms include forgetfulness, word-finding difficulties, problems with executive functioning (planning, multitasking, organizing), impaired concentration or attention, and slower information-processing speed.
In general, reasoning, talents, and old memories as well as syndromes suggestive of cortical dysfunction, such as apraxia, and agnosia, are not impacted by cancer-related cognitive impairment and should alert the treating physician to explore other etiologies.
A gold standard for assessment of cancer-related cognitive impairment has yet to be established. Although researchers in the field have relied upon objective neuropsychological testing for memory functioning, including the California Verbal Learning Test, Memory Assessment Scales, and the Continuous Performance Task, there is only modest correlation between patient reports of cognitive dysfunction and objective deficits with testing. In addition, objective neuropsychological testing requires specialized training and significant time to administer; thus, it may not be pragmatic on a large-scale basis but would be appropriate in select clinical circumstances, such as for cancer survivors who continue to struggle with cognitive function 6 to 12 months after active treatment has ended.
A first step in assessing the factors contributing to patients’ cognitive difficulties may include use of a variety of clinical and laboratory tools, such as evaluation of thyroid function; a complete blood cell count to rule out anemia or infection and to check levels of vitamins B12 and D; sleep transcutaneous carbon dioxide monitoring; screening for depression; and testing for disease involvement or progression in the central nervous system.
Many experts argue that subjective assessments focusing on functioning and patients’ quality of life should be prioritized.4 In its Clinical Practice Guidelines in Oncology,5 the National Comprehensive Cancer Network® (NCCN)® suggests clinicians ascertain patients’ difficulty with attention, multitasking, word-finding, and memory by asking a series of questions:
Neuroimaging of the brain is indicated if there is concern for metastatic disease or another neurologic process. Ultimately, cancer-related cognitive impairment is a clinical diagnosis.
Physiatrists are trained to optimize the physical and mental function of patients with cancer and improve their quality of life; and they may be best situated to coordinate efforts among members of an interdisciplinary team to support oncology patients experiencing cancer-related cognitive impairment. In addition to organizing rehabilitation services for cognition difficulties, physiatrists can coordinate care for patients with ongoing cancer-related physical problems, such as lymphedema, peripheral neuropathy, musculoskeletal complications, and fatigue.
Once the assessment is completed, the NCCN suggests a number of strategies to support patients who continue experiencing symptoms5:
Benefits of Exercise
New research is providing evidence supporting the role of exercise and physical activity in helping mitigate the symptoms of cancer-related cognitive impairment. Both animal and human studies have shown that exercise leads to an increase in neurotrophic and neuroprotective factors in the brain and results in neurogenesis, increased hippocampus volume, and enhanced functioning of hippocampus-dependent cognitive abilities.
Current data on intervention studies showed preliminary positive effects of Asian-influenced movement programs, such as Yoga, and aerobic exercise in reducing subjective cognitive symptoms and inflammatory markers, including interferon, interleukin 8, and interleukin 1b in the cancer care setting.6 ■
Disclosure: Dr. Asher reported no potential conflicts of interest.
Dr. Asher is Director of Cancer Rehabilitation and Survivorship at Cedars-Sinai Medical Center in Los Angeles, California.
3. American Cancer Society: Cancer Treatment & Survivorship Facts & Figures 2016-2017. Available at https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/cancer-treatment-and-survivorship-facts-and-figures/cancer-treatment-and-survivorship-facts-and-figures-2016-2017.pdf. Accessed March 16, 2017.
5. National Comprehensive Cancer Network: NCCN Clinical Practice Guidelines in Oncology. Available at https://www.nccn.org/professionals/physician_gls/f_guidelines_nojava.asp. Accessed March 16, 2017.
6. Zimmer P, Baumann FT, Oberste M, et al: Effects of exercise interventions and physical activity behavior on cancer related cognitive impairments: A systematic review. Biomed Res Int 2016:1820954, 2016.