Chemobrain: Our Current Understanding

“Chemobrain” is the name coined to describe cognitive dysfunction arising after initiation of chemotherapy, and it appears to be on the rise.^1,2 As its prevalence grows, so too has our understanding—but many questions remain.

For many decades, cancer survivors have described problems with memory, attention, and information processing following their diagnoses and treatment, only to have their concerns dismissed.³ Beginning in the late 1990s, clinicians began to truly appreciate the cognitive decline impacting patients. Today, chemobrain is accepted as a legitimate, diagnosable condition that is experienced by many patients with cancer.⁴

Symptoms

Chemobrain is often described as a decrease in mental sharpness, particularly relating to memory and finishing tasks. Symptoms commonly cited by patients include^5,6:

• Trouble concentrating or focusing
• Trouble with word retrieval
• Trouble remembering details (ie, names and dates)
• Trouble multi-tasking
• Trouble with judgment or reasoning
• Taking longer to finish tasks (related to slower thinking and processing)

These symptoms vary in severity, but patients often report negative impacts on short- and long-term quality of life.⁷ Notably, researchers have difficulty demonstrating clinically significant cognitive impairment. The subjective experience of chemobrain is frequently discordant from objective neuropsychiatric measurements, but the reasons for this are not well understood.²

Causes

Currently, the root cause of chemobrain is unclear.⁶ Mechanistically, research experts hypothesize that chemobrain is the result of neuronal injury with inadequate repair, abnormal brain remodeling, and corresponding neuroendocrine immunologic changes. Evidence described in the literature includes alterations in the blood-brain barrier that allow increased infiltration of cytotoxic agents, and structural and functional changes in the frontal cortex and related white matter tracts, which are implicated in executive and memory function.²

In addition to chemotherapy-specific effects, cognitive dysfunction can be caused and/or worsened by many factors related to cancer diagnosis and treatment, including cancer itself, other therapies (eg, radiation therapy, hormone therapy, steroids, and anti-nausea or pain medications), surgery, low blood counts, sleep issues, infection, fatigue, nutritional deficiencies, and mental comorbidities such as depression and anxiety.⁵

The term chemobrain is therefore somewhat misleading, and some experts prefer the broader term “cancer treatment-related cognitive impairment.”¹

Prevalence and Duration

Estimates on the prevalence of chemobrain vary widely, with reports ranging from 15% to 70%.⁸ Prevalence is increasing, owing to increases in cancer survivorship.⁷

Chemobrain symptoms gradually improve in the large majority of cancer survivors after chemotherapy ends; however, some patients may take a year or more to feel normal again and others may never completely recover.^4,6

Diagnosis and Management

Currently, there are no clear guidelines for the assessment or management of chemobrain.¹ No single test exists to diagnosis the condition—it is a diagnosis of exclusion frequently made by a neuropsychologist in conjunction with a patient’s oncologist or internist.⁹

Likewise, there is no single treatment that suits all patients. Drugs such as modafinil and methylphenidate have been evaluated in small studies of cancer-treatment associated cognitive dysfunction, with variable benefits reported. Though some individuals report striking improvements, benefits are temporary and side effects are an important concern.^1,10 Coping strategies reported to help minimize chemobrain effects include^4,6:

• Memory aids: Notebooks, planners, lists, and recording devices/apps can be used to track items that come to mind
• Sufficient sleep: Poor sleep can exacerbate symptoms
• Routines: Keeping the same daily schedule may be beneficial
• Management of anxiety and depression: These co-morbid issues can compound chemobrain symptoms
• Minimizing distractions: Sound dampening environments can decrease distractions and improve concentration (eg, in the workplace)
• Physical activity: Exercise can increase mental alertness, improve mood, and decrease fatigue
• Brain exercises: Word puzzles, learning a new language, practicing a musical instrument, or taking a new class can be brain-strengthening
• Asking for help: Friends, loved ones, and employers can help with daily tasks to cut down on distractions and help save patients mental energy

Advances in Research

Research in the field of cancer-treatment related cognitive impairment is ongoing. Topics include^3,11,12:

• Which chemotherapy agents and other cancer treatments are most closely associated with cognitive impairment
• Whether cognitive rehabilitation exercises traditionally used for people with head injuries might help patients with chemobrain
• Potential genetic markers for increased vulnerability to cognitive impairment after cancer treatment
• Potential ways to prevent chemotherapy-related brain problems

Studies have shown that clinical guidelines would likely be beneficial for patients experiencing this condition.

References:

1. Moore HC. Oncology (Williston Park). 2014;28(9):797-804.
2. Wang XM. Chemobrain: a critical review and causal hypothesis of link between cytokines and epigenetic reprogramming associated with chemotherapy. Cytokine. 2014;72(1):86-96.
3. National Cancer Institute. Understanding “chemobrain” and cognitive impairment after cancer treatment. https://www.cancer.gov/about-cancer/treatment/research/understanding-chemobrain. Accessed September 2017.
4. MD Anderson Cancer Center. Chemobrain. https://www.mdanderson.org/patients-family/diagnosis-treatment/emotional-physical-effects/chemobrain.html. Accessed September 2017.
5. American Cancer Society. Chemo brain. https://www.cancer.org/treatment/treatments-and-side-effects/physical-side-effects/changes-in-mood-or-thinking/chemo-brain.html. Accessed September 2017.
6. American Society of Clinical Oncology. Chemobrain fact sheet. http://www.cancer.net/sites/cancer.net/files/asco_answers_chemobrain.pdf. Accessed September 2017.
7. American Physical Therapy Association. Chemotherapy induced cognitive impairment. http://oncologypt.org/pdfs/fact-sheets/Chemobrain%20Fact%20Sheet.pdf. Accessed September 2017.
8. Selamat MH, et al. PLoS One. 2014;9(9):e108002.
9. org. What is chemo brain? http://www.breastcancer.org/treatment/planning/ask_expert/2008_10/question_01. Accessed September 2017.
10. org. Stimulants researched for chemo brain? http://www.breastcancer.org/treatment/planning/ask_expert/2008_10/question_04. Accessed September 2017.
11. Sofis MJ, et al. Behav Brain Res. 2017;329:186-190.
12. Fred Hutchinson Cancer Research Center. Coping with “chemobrain”. https://www.fredhutch.org/en/news/center-news/2014/05/5-tips-for-combating-chemo-brain.html. Accessed September 2017.