Study background on cancer, because there is a major split between medical science and what pharma’s thought leaders have taught oncologists—for a short version.  Pharma should not be involved in the research and education processes, because pharma consistently applies tobacco ethics to maximize profits. Such is the nature of our corporate system. 

http://en.wikipedia.org/wiki/Post-chemotherapy_cognitive_impairment

Post-chemotherapy cognitive impairment

Post-chemotherapy cognitive impairment (PCCI) (also known as chemotherapy-induced cognitive dysfunction or impairment, 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.[1] 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]  While any cancer patient may experience temporary cognitive impairment while undergoing chemotherapy, patients with PCCI continue to experience these symptoms long after chemotherapy has been completed. PCCI is often seen in patients treated for breast cancer, ovarian cancer, prostate cancer, and other reproductive cancers,^[3] as well as other types of cancers requiring aggressive treatment with chemotherapy.^[4][5]  [If  this was known, few patients would take drugs that typically lengthen life only a couple of months in the clinical trials of terminal patients, and are not capable of reducing the number of cancer death for those diagnosed with an earlier stage of cancer.]  The clinical relevance of PCCI is significant, considering the increasing number of long-term cancer survivors in the population, many of whom may have been treated with aggressive dosing of chemotherapeutic agents, or with chemotherapy as an adjuvant to other forms of treatment.

Symptoms:  The systems of the body most affected by chemotherapy drugs include visual and semantic memory, attention and motor coordination.^[9] 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.^[9] Survivors often report difficulty multitasking, comprehending what they've just read, following the thread of a conversation, and retrieving words.   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, with some cases lasting 10 years or more.  Chemotherapy drugs thalidomide, the epothilones such as ixabepilone, the vinca alkaloids vincristine and vinblastine, the taxanes paclitaxel and docetaxel, the proteasome inhibitors such as bortezomib, and the platinum-based drugs cisplatin, oxaliplatin and carboplatin often cause chemotherapy-induced peripheral neuropathy, a progressive and enduring tingling numbness, intense pain, and hypersensitivity to cold, beginning in the hands and feet and sometimes involving the arms and legs.^[13][14][15] In most cases there is no known way of reducing the effects of chemotherapeutic agents related to taxanes, thalidomide and platinum-based compounds. 

Proposed Mechanisms:  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.  Other theories suggest vascular injury, inflammation, autoimmunity, anemia and the presence of the epsilon 4 version of the apolipoprotein E gene.  Fifty-six of the 132 chemotherapy agents approved by the FDA have been reported to induce oxidative stress.^[16] The drug doxorubicin (adriamycin) has been investigated as a PCCI-causing agent due to its production of reactive oxygen species.  Due to the critical role the hippocampus plays in memory, it has been the focus of various studies involving post-chemotherapy cognitive impairment. The hippocampus is one of the rare areas of the brain that exhibits neurogenesis. These new neurons created by the hippocampus are important for memory and learning and require a brain-derived neurotrophic factor (BDNF) to form. 5-fluorouracil, a commonly used chemotherapy agent, has been shown to significantly reduce the levels of BDNF in the hippocampus of the rat.^[21] Methotrexate, an agent widely used in the chemotherapy treatment of breast cancer, has also displayed a long-lasting dose dependent decrease in hippocampal cell proliferation in the rat following a single intravenous injection of the drug.^[22] This evidence suggests that chemotherapy agent toxicity to cells in the hippocampus may be partially responsible for the memory declines experienced by some patients.  5-fluorouracil has been demonstrated to reduce the viability of neural progenitor cells by 55-70% at concentrations of 1 μM, whereas cancer cell lines exposed to 1 μM of 5-fluorouracil were unaffected.  Other chemotherapy agents such as BCNU, cisplatin, and cytarabine also displayed toxicity to progenitor cells in vivo and in vitro

CHEMOBRAIN: Cognitive impairment from chemotherapy

Health News, West Virginia University, Morgantown WV at http://www.health.wvu.edu/newsreleases/news-detail.asp?ID=840

Adapted from materials provided by West Virginia University Health Science Center via Newswise

http://www.health.wvu.edu/newsreleases/news-detail.asp?ID=840

Natural estrogen (estradiol) does not stimulate the growth of breast cancer; it inhibits it and reduces the risk of developing breast cancer.  Based on pharma’s junk science the belief in estrogen receptors promoting the growth of breast cancer has been accepted.  The opposite is the case see http://jco.ascopubs.org/content/16/9/3115.short -- jk 

Morgantown, W. Va--Thanks to early diagnosis and chemotherapy, more women survive breast cancer than ever before. However, following treatment, approximately 25 percent of survivors experience mild to moderate memory, concentration and cognitive problems known as “chemobrain”.

“Several studies have investigated chemotherapy’s cause and effect on memory problems, but until now scientists had no clue what changes in the brain lead to memory loss,” Jame Abraham, M.D., director of the Comprehensive Breast Cancer Program at West Virginia University’s Mary Babb Randolph Cancer Center, said.

Abraham and his research team conducted one of the first chemobrain studies of its kind. The study documented the extent of changes to the brain’s white matter in women who received chemotherapy for breast cancer.  The preliminary study involved ten breast cancer patients who had received chemotherapy and complained of cognitive changes. A control group of nine healthy women of similar age, education and IQ, who never received chemotherapy, was also studied.  All participants were screened for medical, neurologic and psychiatric conditions that could affect brain structure or function. Participants were tested for depression, anxiety and processing speed.  Each participant also participated in a diffusion tensor imaging (DTI) MRI scan. The DTI was used to assess changes in the white matter of the brain.

“The images indicated differences in the white matter in the front part of the brain in women who had received chemotherapy,” said Marc Haut, Ph.D., of WVU’s departments of Behavioral Medicine and Psychiatry, Neurology and Radiology. “This difference in white matter correlated with how quickly the breast cancer patients could process information.”  “Women who received chemotherapy performed significantly worse in speed of processing than their counterparts in the control group,” said Abraham. “Our preliminary findings suggest that chemotherapy may change the brain and those changes affect the patient’s cognitive skills.”

Morgantown resident Sharon Palmatory, a patient of Dr. Abraham, recently finished chemotherapy treatments. She had very few side effects during chemotherapy, but after treatment experienced trouble remembering names and numbers.  “I can’t multi-task anymore; I can only focus on one thing at a time. It’s frustrating because I am used to being in control,” Palmatory said.

In some patients chemobrain can have a significant and serious affect on their everyday life.

“I feel like I’m always lagging behind in processing information,” she said. “It’s good to know that Dr. Abraham and others are studying this problem; they can let women receiving chemo know that they may experience memory loss.”

WVU researchers also concluded that changes in the white matter of the brain do not appear to be caused by depression or anxiety. Abraham and Haut are leading several chemobrain studies funded by the U.S. Department of Defense and the WVU Department of Radiology. Their article is published in Clinical Breast Cancer, Volume 8, Number 1, February 2008.

WVU co-authors include Maria Moran, Ph.D., Department of Behavioral Medicine and Psychiatry and Department of Radiology; Shannon Filburn, Clinical Trials Research Unit; and Susan Lemiuex, Center for Advanced Imaging and Department of Radiology. Hiroto Kuwabara, Ph.D., Department of Radiology at Johns Hopkins University, is also a co-author.

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Second article based on same materials

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