Post-chemotherapy cognitive impairment (PCCI) (also known as chemotherapy-induced cognitive dysfunction, chemo brain or chemo fog) describes the cognitive impairment that can result from chemotherapy treatment. Approximately 20-30% of people who undergo chemotherapy experience some level of post-chemotherapy cognitive impairment. The phenomenon first came to light because of the large number of breast cancer survivors who complained of changes in memory, fluency, and other cognitive abilities that impeded their ability to function as they had pre-chemotherapy.[1]
Although the causes and existence of post-chemotherapy cognitive impairment have been a subject of debate, recent studies have confirmed that post-chemotherapy cognitive impairment is a real, measurable side-effect of chemotherapy that appears in some patients.[2] While any cancer patient may experience temporary cognitive impairment due to stress, fatigue, and depression, the long-term symptoms of PCCI are almost exclusively seen in patients treated for breast cancer, ovarian cancer, prostate cancer, and other cancers of the reproductive system.[3]
PCCI is clinically important due to the large number of women that survive breast cancer, more aggressive dosing of chemotherapeutic agents, and the use of chemotherapy as an adjuvant to other forms of treatment.[4] In some patients, fear of PCCI can impact treatment decisions. The magnitude of chemotherapy-related cognitive changes and their impact on the activities of daily living are uncertain.[5]
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PCCI affects a subset of cancer survivors,[5] though the overall epidemiology and prevalence is not well known and may depend on many factors.[6]
It generally affects about 10-40% of breast cancer patients, with higher rates among pre-menopausal women and patients that receive high-dose chemotherapy.[3]
The systems of the body most affected by chemotherapy drugs include visual and semantic memory, attention and motor coordination.[7] These effects can impair a chemotherapy patient's ability to understand and make decisions regarding treatment, perform in school or employment and can reduce quality of life.[7] Survivors often report difficulty multitasking, comprehending what they've just read, following the thread of a conversation, and retrieving words[8]
Breast cancer survivors who were treated with chemotherapy have to work harder to perform tasks than survivors whose treatment was surgical. A year after treatment the brains of cancer survivors treated with chemotherapy had physically shrunk while those of people not treated with chemotherapy had not.[9]
Post-chemotherapy cognitive impairment comes as a surprise to many cancer survivors. Often, survivors think their lives will return to normal when the cancer is gone, only to find that the lingering effects of post-chemotherapy cognitive impairment impede their efforts. Working, connecting with loved ones, carrying out day-to-day tasks—all can be very challenging for an impaired brain. Although post-chemotherapy cognitive impairment appears to be temporary, it can be quite long-lived, with some cases lasting 10 years or more.[10]
The details of PCCI's causes and boundaries are not well known.[4] Two major theories have been advanced:[3] the direct effect of chemotherapy drugs on the brain, and the role of hormones in nervous system health.
Bortezomib is known to cause neuropathy to the sensory and peripheral nervous systems that is reversible.[6] In most cases there is no known way of reducing the effects of chemotherapeutic agents related to taxanes, thalidomide and platinum-based compounds (oxaliplatin is a notable exception to the latter category - though it does cause PCCI its effects can be buffered by infusion of calcium and thought related to PCCI include the ability of the nerves to repair themselves, the ability of cells to excrete compounds, permeability of the blood-brain barrier, damage done to DNA including shortening of telomeres and cellular oxidative stress.[6]
The importance of hormones, particularly estrogen, on cognitive function is underscored by the presence of cognitive impairment in breast cancer patients before chemotherapy is begun, the similarity of the cognitive impairments to several menopausal symptoms, the increased rate of PCCI in pre-menopausal women, and the fact that the symptoms can frequently be reversed by taking estrogen.[3]
Other theories suggest vascular injury, inflammation, autoimmunity, anemia and the presence of the epsilon 4 version of the apolipoprotein E gene.[7]
PCCI is complex and factors other than the chemotherapeutic agents may impact cognitive functioning. Menopause, the biological impact of a surgical procedure with anesthesia, medications prescribed in addition to the chemotherapy, genetic predisposition, hormone therapy, emotional states (including anxiety, depression and fatigue), comorbid conditions and paraneoplastic syndrome may all co-occur and act as confounding factors in the study or experience of PCCI.[5]
Hypothesized treatment options include the use of antioxidants, cognitive behavior therapy, erythropoietin and stimulant drugs such as methylphenidate, though as the mechanism of PCCI is not well understood the potential treatment options are equally theoretical.[7]
Modafinil, approved for narcolepsy, has been used off-label in trials with people with symptoms of chemobrain. Modafinil is a wakefulness promoting agent that can improve alertness and concentration.[11] A University of Rochester study of 68 subjects had significant results. "We knew from previous studies that modafinil does alleviate problems with memory and attention, and were hoping it would do the same for breast-cancer patients experiencing chemo-brain, which it did," related the study's lead author Sadhna Kohli, Ph.D, a research assistant professor at the University of Rochester's James P. Wilmot Cancer Center.[12]
While taking estrogen will frequently reverse the symptoms,[3] this would be dangerous because of the many health risks associated with taking this hormone as a drug.
Research on PCCI is limited, and studies on the subject have often been conflicting in results, in part due to differing means of assessing and defining the phenomenon, which makes comparison and synthesis difficult.[5] Most studies have involved small samples, making generalization difficult, and there has been a focus on younger patients which makes conclusions about the largest group of cancer patients, the elderly, difficult to draw.[5]
The drug doxorubicin (adriamycin) has been investigated as a PCCI-causing agent due to its production of reactive oxygen species.[13] It has been investigated in an animal model with mice.[13][14]
While frustrating, the ultimate outcome is very good: symptoms typically disappear in about four years.[3]
The symptoms of chemobrain (a phrase coined by June Mari-Gras in 2004||fact=date=June 2009}}) were recognized by researchers in the 1980s, who typically described it as mild cognitive impairment subsequent to successful cancer treatment.[3] Some authors say that it was identified primarily in breast cancer survivor and support groups as affecting a subset of individuals treated with chemotherapy, who attributed it to the effects of the medication taken to treat their cancers.[5]
   | American Cancer Society - Chemobrain - ACS :: Chemo Brain |
| | Temporary Brain Shrinkage May Explain 'Chemobrain' - Medical News: Temporary Brain Shrinkage May Explain 'Chemobrain' - in Hematology, Chemotherapy from MedPage Today |
| | Posit Science - Posit Science Corporation | Your brain will thank you. |
| | Modafinil Relieves Cognitive Chemotherapy Side Effects - Modafinil Relieves Cognitive Chemotherapy Side Effects -- Whyche 42 (15): 31 -- Psychiatr News |
| | Cognitive impairment associated with chemotherapy for cancer: report of a workshop - JCO -- Sign In Page |
| | Chemobrain: is systemic chemotherapy neurotoxic? - Wolters Kluwer Health - Article Landing Page |
| | Neurologic complications of chemotherapy agents - Wolters Kluwer Health - Article Landing Page |
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