Post-chemotherapy cognitive impairment ( PCCI ) (also known in the scientific community as " CRCI or Chemotherapy-Related Cognitive Impairments " and in layman terms as chemotherapy induced by cognitive dysfunction or disorder , the chemo brain , or chemo fog ) describes cognitive impairment that can result from chemotherapy treatments. Approximately 20-30% of people who undergo chemotherapy experience post-chemotherapy cognitive disorder. This phenomenon was first revealed because of the large number of breast cancer victims who complained of memory changes, fluency, and other cognitive abilities that hampered their ability to function because they had pre-chemotherapy.
Although the causes and the presence of post-chemotherapy cognitive disorders have been the subject of much debate, recent research has confirmed that post-chemotherapy cognitive impairment is a noticeable and measurable side effect of chemotherapy that occurs in some patients. While cancer patients may experience temporary cognitive impairment while undergoing chemotherapy, patients with PCCI continue to experience these symptoms long after chemotherapy is complete. PCCI is often seen in patients treated for breast cancer, ovarian cancer, prostate cancer, and other reproductive cancers, as well as other cancers that require aggressive treatment with chemotherapy.
The clinical relevance of PCCI is significant, given the increasing number of long-term cancer survivors in the population, many of whom may have been treated with aggressive doses of chemotherapeutic agents, or with chemotherapy as adjuvants for other forms of treatment. In some patients, PCCI fear may affect treatment decisions. The magnitude of cognitive changes associated with chemotherapy and its impact on daily life activities is uncertain.
Video Post-chemotherapy cognitive impairment
Symptoms
The body systems most affected by chemotherapy drugs include visual and semantic memory, motor concern and coordination. These effects can interfere with the ability of chemotherapy patients to understand and make decisions about care, work in school or work and can reduce the quality of life. Rescuers often report the difficulty of multitasking, understanding what they just read, following the conversation flow, and taking the words.
Survivors of breast cancer treated with chemotherapy may find it more difficult to perform a task than survivors whose treatment is surgical. One study showed that, a year after treatment, the cancer-suffering brains treated with chemotherapy (after surgery) were physically shrunk while people who underwent no surgery.
Post-chemotherapy cognitive impairment comes as a surprise to many cancer patients. Often, survivors think their lives will return to normal when the cancer disappears, only to find that the prolonged effects of post-chemotherapy cognitive impairment inhibit their efforts. Working, connecting with loved ones, performing everyday tasks - all can be very challenging for an impaired brain. Although post-chemotherapy cognitive disorder appears to be temporary, it can be very long-lived, with some cases lasting 10 years or more.
Maps Post-chemotherapy cognitive impairment
Proposed mechanism
The details of the causes and limits of PCCI are not well known. Two main theories have been proposed: the direct effects of chemotherapy drugs on the brain, and the role of hormones in the health of the nervous system.
PCCI is complex and factors other than chemotherapeutic agents may affect cognitive function. Menopause, the biological effects of surgical procedures with anesthesia, prescribed medications other than chemotherapy, genetic predisposition, hormone therapy, emotional states (including anxiety, depression and fatigue), comorbid conditions and paraneoplastic syndrome may all occur together and act as a confounding factor in study or PCCI experience. The chemotherapy drugs of thalidomide, epothilone such as ixabepilone, vinca alkaloids vincristine and vinblastine, taxlan paclitaxel and docetaxel, proteasome inhibitors such as bortezomib, and platinum-based cisplatin, oxaliplatin and carboplatin often cause peripheral neuropathy induced by progressive and lasting tingling, severe pain , and hypersensitivity to cold, ranging from the hands and feet and sometimes involving the arms and legs. In most cases there is no known way to reduce the effects of chemotherapeutic agents associated with taxanes, thalidomide and platinum-based compounds (oxaliplatin is an exception to the latter category - although it causes PCCI effects can be supported by calcium and PCCI-related intravenous infusions including neural self-repair, cell ability to excrete compounds, blood-brain barrier permeability, DNA damage including telomere shortening and cell oxidative stress.
The importance of hormones, especially estrogen, to cognitive functioning is underlined by the presence of cognitive impairment in breast cancer patients before chemotherapy begins, similarities in cognitive impairment for some menopausal symptoms, elevated PCCI levels in pre-menopausal women, and the fact that the symptoms can often be reversed by taking estrogen.
Other theories suggest vascular injury, inflammation, autoimmunity, anemia and the presence of epsilon 4 genes of apolipoprotein E.
Fifty-six of the 132 chemotherapy drugs approved by the FDA have been reported to induce oxidative stress. Drug doxorubicin (adriamycin) has been investigated as the causative agent of PCCI due to the production of reactive oxygen species. It has been studied in animal models with mice.
Research has revealed that nerve progenitor cells are particularly susceptible to the cytotoxic effects of chemotherapy agents. 5-fluorouracil has been shown to reduce the viability of nerve progenitor cells by 55-70% at concentrations 1? M, whereas cancer cells are exposed at 1? M of 5-fluorouracil is not affected. Other chemotherapy agents such as BCNU, cisplatin, and cytarabine also show toxicity in progenitor cells in vivo and in vitro . This is a concern because neural progenitor cells are the primary cell population that divides in the brain, causing neurons and glia.
Because of the important role that the hippocampus plays in memory, it has been the focus of numerous studies involving post-chemotherapy cognitive disorders. The hippocampus is one of the rare areas of the brain that exhibits neurogenesis. The new neurons created by the hippocampus are important for memory and learning and require brain-derived neurotrophic factors (BDNF) to form. 5-fluorouracil, a commonly used chemotherapy agent, has been shown to significantly reduce BDNF levels in mouse hippocampus. Methotrexate, an agent widely used in the treatment of breast cancer chemotherapy, also showed a persistent dose-dependent dose in hippocampal cell proliferation in rats after single intravenous drug injection. This evidence suggests that the toxicity of chemotherapy agents to cells in the hippocampus may be partly responsible for the memory impairment experienced by some patients.
Deficits in visuo-spatial, visual-motor function, and visual memory are among the symptoms seen in post-chemotherapy patients. There is evidence that this may be due to damage to the visual system rather than caused by cognitive deficits. In one study, 5-fluouracil caused ocular toxicity in 25-38% of patients treated with the drug. Methotrexate also causes ocular toxicity in 25% of patients within 2-7 days of the initial chemotherapy regimen with the drug. This evidence suggests that some visual-based cognitive deficits experienced by cancer survivors may be due to damage to ocular levels rather than cognitive processes, but most likely it is due to synergistic effects on both systems.
Treatment
Treatment options that contain hypotheses include the use of antioxidants, cognitive behavioral therapy, erythropoietin and stimulant drugs such as methylphenidate, although the PCCI mechanism is not well understood as the theoretical potential treatment option.
Modafinil, approved for narcolepsy, has been used off-label in trials with people with PCCI symptoms. Modafinil is an awareness-raising agent that can increase alertness and concentration, and studies have shown it to be effective at least among women treated for breast cancer.
While estrogen hormone supplementation may reverse the symptoms of PCCI in women treated for breast cancer, it carries a health risk, including the possibility of promoting the proliferation of estrogen-responsive breast cancer cells.
Research
Research on PCCI is limited, and studies on the subject are often contradictory in results, in part because of the different ways of assessing and defining phenomena, which make comparison and synthesis difficult. Most studies have involved small samples, making generalizations difficult. There is a focus on PCCI in younger cancer patients. This makes it difficult to draw conclusions about PCCI in the elderly.
Several recent studies have advanced the field using neuroimaging techniques. In 2005, Dr. Masatoshi Inagaki uses magnetic resonance imaging (MRI) to measure differences in brain volume between breast cancer patients affected by chemotherapy and unexposed subjects. Subjects were tested at two periods: one year after surgery, and again at three years postoperatively. Results from a first-year study found smaller volumes of gray and white matter in patients affected by chemotherapy. However, in a three-year study, both groups of breast cancer patients were observed to have the same gray and white matter volumes. Changed brain structures in chemotherapy patients provide an explanation for cognitive impairment.
Another study in 2007 investigated differences in brain structure between two adult monozygotic twins. One undergoes chemotherapy treatment for breast cancer, while others have no cancer and are not treated with chemotherapy. MRI scans are taken from both twin brains while taking part in a working memory task. The results found that the twin A (exposed to chemotherapy) experienced a wider spatial activation rate in the brain than the twin B (not exposed to chemotherapy). Twin A also reported greater difficulty than the twin B in completing memory activity. The authors of this study suggest that chemotherapy patients will generally report cognitive complaints, although they perform within normal limits on neuropsychological tasks. An MRI scan can provide evidence for this event. Chemotherapy patients may require a greater volume of neural circuits to complete neuropsychological tasks than others.
Positron Emission Tomography (PET) is also used to study post-chemotherapy cognitive disorders. In one study in 2007, scans were taken from patients exposed to adjuvant chemotherapy. Significant blood flow modified in the brain is found, especially in the frontal and cerebellum cortex. The most significant difference in blood flow is found in the inferior frontal gyrus. The authors reported metabolic breaks in this area were associated with performance on short-term memory tasks.
While post-treatment studies show significant negative adverse effects of chemotherapy on cognition, other studies suggest that there may be early vulnerability factors that may contribute to the development of cognitive impairment. These factors may include menopausal status, surgery/anesthesia, stress, genetics and fatigue, among other suspected bullies.
For a full review of Neuroimaging and chemobrain/chemofog studies, see this comprehensive review by Scherling and Smith (2013): http://www.mdpi.com/1424-8220/13/3/3169
Prognosis
While frustrating, the end result is very good: the symptoms usually disappear within about four years.
Incident
PCCI affects some of the cancer survivors, although epidemiology and overall prevalence are not well known and may depend on many factors.
It generally affects about 10-40% of breast cancer patients, with higher rates among pre-menopausal women and patients receiving high-dose chemotherapy.
History
The symptoms of PCCI were recognized by researchers in the 1980s, which typically describe them as mild cognitive impairment after successful cancer treatment. Some authors say that it is identified primarily in breast cancer survivors and support groups that affect the part of individuals treated with chemotherapy, which relate it to the effects of drugs taken to treat their cancer.
The term chemobrain appears in publications since at least 1997.
See also
- Radiation induces cognitive decline
- Cancer-related fatigue
Footnote
External links
- "Chemo Brain". American Cancer Society. April 15, 2014 . Retrieved November 27, 2015 .
- Mayo Clinic Staff (February 2, 2013). "Kemo Brain". Mayo Clinic . Retrieved November 27, 2015 .
- Brody, Jane (August 3, 2009). "The Fog Was Following Chemotherapy". Personal Health (column). The New York Times . p.Ã, D7 . Retrieved November 27, 2015 .
Source of the article : Wikipedia
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