Post-chemotherapy cognitive impairment
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Post-chemotherapy cognitive impairment (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]
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[edit] History
Chemobrain was recognized 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.[2]
[edit] Incidence
PCCI affects a subset of breast cancer survivors,[2] though the overall epidemiology and prevalence is not well known.[3]
[edit] Cause
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.[4] The details of PCCI's causes and boundaries are not well known, with more research on the subject required to understand and treat the condition.[5] Bortezomib is known to cause neuropathy to the sensory and peripheral nervous systems that is reversible.[3] 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.[3] Other theories suggest vascular injury, inflammation, autoimmunity, anemia and the presence of the epsilon 4 version of the apolipoprotein E gene.[6]
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.[2]
[edit] Effects
The systems of the body most affected by chemotherapy drugs include visual and semantic memory, attention and motor coordination.[6] These effects can impair a chemotherapy patient's ability to understand and make decision regarding treatment, perform in school or employment and reduce quality of life.[6]
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.[7]
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.[8]
[edit] Clinical signficance
PCCI is seen as an important area of clinical interest due to the high rates of breast cancer, more aggressive dosing of chemotherapeutic agents, the use of chemotherapy as an adjuvant to other forms of treatment and higher survival rates of patients.[5] 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.[2]
[edit] Treatment
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.[6]
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.[9] 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.[10]
[edit] Research
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.[2] 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.[2]
The drug doxorubicin (adriamycin) has been investigated as a PCCI-causing agent due to its production of reactive oxygen species.[11] It has been investigated in an animal model with mice.[11][12]
[edit] See also
[edit] Footnotes
- ^ Tannock IF, Ahles TA, Ganz PA, Van Dam FS (2004). "Cognitive impairment associated with chemotherapy for cancer: report of a workshop". J. Clin. Oncol. 22 (11): 2233–9. doi:. PMID 15169812.
- ^ a b c d e f Hurria A, Somlo G, Ahles T (September 2007). "Renaming "chemobrain"". Cancer Invest. 25 (6): 373–7. doi:. PMID 17882646.
- ^ a b c Kannarkat G, Lasher EE, Schiff D (December 2007). "Neurologic complications of chemotherapy agents". Curr. Opin. Neurol. 20 (6): 719–25. doi:. PMID 17992096.
- ^ Hede K (2008). "Chemobrain is real but may need new name". J. Natl. Cancer Inst. 100 (3): 162–3, 169. doi:. PMID 18230787.
- ^ a b Taillibert S, Voillery D, Bernard-Marty C (November 2007). "Chemobrain: is systemic chemotherapy neurotoxic?". Curr Opin Oncol 19 (6): 623–7. doi:. PMID 17906463.
- ^ a b c d Nelson CJ, Nandy N, Roth AJ (September 2007). "Chemotherapy and cognitive deficits: mechanisms, findings, and potential interventions". Palliat Support Care 5 (3): 273–80. PMID 17969831.
- ^ Inagaki M, Yoshikawa E, Matsuoka Y, et al (2007). "Smaller regional volumes of brain gray and white matter demonstrated in breast cancer survivors exposed to adjuvant chemotherapy". Cancer 109 (1): 146–56. doi:. PMID 17131349.
- ^ Silverman DH, Dy CJ, Castellon SA, et al (2007). "Altered frontocortical, cerebellar, and basal ganglia activity in adjuvant-treated breast cancer survivors 5-10 years after chemotherapy". Breast Cancer Res. Treat. 103 (3): 303–11. doi:. PMID 17009108.
- ^ Doctors are finding it harder to deny "Chemobrain"The Virginian-Pilot © October 2, 2007
- ^ Modafinil Relieves Cognitive Chemotherapy Side Effects Psychiatric News, Stephanie Whyche, August 3, 2007 Volume 42 Number 15, page 31
- ^ a b Joshi G, Hardas S, Sultana R, St Clair DK, Vore M, Butterfield DA (February 2007). "Glutathione elevation by gamma-glutamyl cysteine ethyl ester as a potential therapeutic strategy for preventing oxidative stress in brain mediated by in vivo administration of adriamycin: Implication for chemobrain". J. Neurosci. Res. 85 (3): 497–503. doi:. PMID 17171703.
- ^ Tangpong J, Cole MP, Sultana R, et al (January 2007). "Adriamycin-mediated nitration of manganese superoxide dismutase in the central nervous system: insight into the mechanism of chemobrain". J. Neurochem. 100 (1): 191–201. doi:. PMID 17227439.
