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Old 09-04-2008, 10:40 AM
Dross Dross is offline
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Default Curing the Mental Fog experienced by cancer patients

The famillies of loved ones with cancer are well aware that chemo causes unwelcome affects to a person's cognitive skills. Now in animal studies at West Virginia University (WVU), researchers have discovered that injections of N-acetyl cysteine (NAC), an antioxidant, can stem the memory loss that cancer drugs sometimes cause. The study has just been published in the September 2008 issue of the journal Metabolic Brain Disease.

Using adriamycin and cyclophosphamide, two commonly administered chemotherapy drugs, rats who were trained to prefer a light room to a dark one forgot their training.

When animals are treated with chemotherapy drugs, they lose memory, said Gregory Konat, Ph.D., professor of neurobiology and anatomy at WVU. When we add NAC during treatment, they don't lose memory.

NAC is a modified form of the dietary amino acid cysteine chosen for its antioxidant properties.

Jame Abraham, M.D., director of the Comprehensive Breast Cancer Program at WVU's Mary Babb Randolph Cancer Center, said that chemobrain often causes patient frustration as they feel their doctors are not taking the complaints seriously.

In the past, there was a lot of ignorance among doctors about chemo-induced cognitive problems, Dr. Abraham said. In some patients, problems can persist for up to two years.

As many as 40 percent of cancer patients undergoing chemotherapy complain of symptoms such as severe memory and attention deficits however up until now scientists felt the memory loss was attributable to the cancer rather than the drugs.

This information, coupled with MRI scans showing the differences in patients with Breast cancer before and after treatment provide a clear link between chemo and "mental fog."

At this point, we have no evidence to say that NAC is safe in patients who are getting chemotherapy, Abraham said. We need more studies to confirm the role of NAC in patients.

References

1. Konat GW et al (2008). Cognitive dysfunction induced by chronic administration of common cancer chemotherapeutics in rats. Metabolic Brain Disease. DOI 10.1007/s11011-008-9100-y

2. In addition to the Department of Neurobiology and Anatomy, researchers from WVU's Mary Babb Randolph Cancer Center and Department of Behavioral Medicine and Psychiatry collaborated on the study. The study was funded as part of a $275,000 grant over three years from the U.S. Department of Defense. Abraham is principle investigator on the studies.

[url]http://www.springer.com/biomed/neuroscience/journal/11011

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Old 10-03-2010, 07:46 PM
gdpawel gdpawel is offline
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Default Chemo Brain

There has been some recent resurgence of chemotherapy side effect research. They need to help raise consciousness about the subject of Chemo Brain. All those cancer patients ignored or just plain ridiculed all these years.

Chemo Brain is part of the language now and just to have it acknowledged makes a difference. The choice of researchers to integrate promising insights and methods remains an essential component of new paradigms of cancer treatment.

There are many reasons as to why chemobrain may occur. One is that some types of chemotherapy can cross the blood/brain barrier. Another is that the cognitive problems are created by free radicals, the toxic elements that many types of chemotherapy produce. And yet another is that some people have a genetic background that makes them more susceptible to the effects of chemotherapy. Most likely it is not just one factor but many factors that combine to set the stage for chemobrain to occur.

According to studies by Dartmouth-Hitchcock Medical Center, even standard-dose chemotherapy can negatively impact the cognitive functioning of cancer survivors up to 10 years after treatment. Reports of depression, anxiety, and fatigue, all of which can affect cognitive functioning, suggests that the differences in performance on cognitive tests were due to the chemotherapy itself, not to greater levels of depression, anxiety, and fatigue in patients who received chemotherapy.

This is one of the most recent studies:

The study showed that deterioration in brain function following breast cancer therapy has negative effects on quality of life. One of the most problematic side effects of cancer treatment, chemobrain - a range of symptoms including memory loss, inability to concentrate, difficulty thinking and other subtle cognitive changes following chemotherapy - seriously diminishes women's quality of life and daily functioning. As a result, they have to adopt a range of coping strategies to manage their restricted social and professional lives.

Breast cancer survivors tell their story in a descriptive study of the effects that cognitive impairment has on women's work, social networks and dealings with the health care profession. Dr. Saskia Subramanian from the UCLA Center for Culture and Health in the US and her colleagues have just published their work online in Springer's Journal of Cancer Survivorship.

An increasing number of women survive breast cancer, yet survival comes at a price. Mild cognitive impairment following chemotherapy, known as "chemobrain" or "chemofog" is one of the most commonly reported post-treatment symptoms by breast cancer survivors. Dr. Subramanian and colleagues' work shows that this deterioration in brain function has devastating effects on breast cancer survivors' quality of life.

Through a combination of focus groups and in-depth interviews among 74 women who had completed their course of cancer treatment at least a year earlier, the researchers gathered data on patients' medical background, treatment experience, post-treatment symptoms, reactions from medical staff and from family and friends, self-management, strength of social networks and their perceptions of themselves.

The women described a variety of cognitive changes which they found both frustrating and upsetting. Some were less able to retain material or to digest new information and recognized that they were not functioning as they once did. Others faced reduced independence, becoming limited in their ability to manage certain responsibilities or get around. These changes made women feel scared, dependent and emotionally drained.

For some, coping meant having to cut back on work and social activities. Others had more or less accepted the limitations put on their lives and resigned themselves to a diminished cognitive capacity.

The majority of women complained about the lack of acknowledgement from the medical community when they mentioned their chemobrain symptoms. Many women wished they had received some warning and only a few got answers from their physicians. Some women felt that chemobrain confused their families and friends, and young children in particular.

Chemobrain also affected women's performance at work. Because they were less able to focus, duties became more difficult and often took longer. This affected their efficiency and reduced their chances of promotion or assignment to projects.

The authors concluded: "These data underscore the very serious ways in which chemobrain can affect the life experiences of cancer survivors - emotionally, psychologically and economically. A clear understanding of the cognitive impairments experienced by survivors will aid researchers in developing targeted therapies and interventions aimed at improving or mitigating these post-treatment side effects."

Reference: Boykoff N, Moieni M, Subramanian S (2009). Confronting chemobrain: an in-depth look at survivors' reports of impact on work, social networks, and health care response. Journal of Cancer Survivorship; DOI: 10.1007/s11764-009-0098-x

Source: Journal of Cancer Survivorship

Ritalin (methylphenidate) and Cancer Fatigue

One of the most common symptoms that cancer patients experience is fatigue. Fatigue is also a common side effect of cancer chemotherapy. In one of our studies of breast cancer patients, 36 percent experienced fatigue as the principle side effect of the chemotherapy combination. Furthermore, the emotional stress associated with a cancer diagnosis can result in varying degrees of depression, also characterized by fatigue.

Studies conducted in recent years have established that cancer patients often benefit from the use of antidepressants. These can improve energy and counteract insomnia, while addressing the emotional challenges that many patients confront. While there are numerous forms of antidepressants, most function by enhancing the effects of neurotransmitters within the brain. The modern selective serotonin re-uptake inhibitors (SSRIs) are widely used in cancer patients.

Older classes of antidepressants work as direct CNS stimulants. The amphetamines and related Ritalin (methylphenidate) are CNS stimulants. Studies conducted in the last decade establish that Ritalin (methylphenidate) can be safely administered to cancer patients to counteract fatigue and depression. Indeed, Ritalin (methylphenidate) is one of the most rapidly acting antidepressants and has been used in the psychiatric literature for many years. When used appropriately the drug is well tolerated. Interestingly, it does not result in weight loss, despite its CNS stimulant effects.

While these drugs can be important adjuncts to cancer therapy, they can also be extremely toxic with such serious side effects as: paranoia, anxiety, insomnia, weight loss, hypertension, cardiac stimulation and convulsions. It is therefore extremely important that these classes of drugs be administered judiciously under the direct supervision of a trained oncologist or psychiatrist.

Source: Dr. Robert Nagourney is medical and laboratory director at Rational Therapeutics, Inc., in Long Beach, California, and an instructor of Pharmacology at the University of California, Irvine School of Medicine. He is board-certified in Internal Medicine, Medical Oncology and Hematology.
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Old 10-28-2010, 03:09 PM
gdpawel gdpawel is offline
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Default New Studies Help Better Define Cognitive Changes Due to Cancer Therapies

(Chemotherapy Advisor) - It is well known among oncology specialists that cognitive changes can occur in patients after receiving chemotherapy. These changes often involve problems with memory and concentration, where the cumulative effects have been dubbed “chemo-brain.” However, it does not appear to be chemotherapy on its own that causes these cognitive changes. Studies now suggest that it may be other cancer therapies, surgery, anesthesia, and even genetic predispositions that can result in cognitive problems for cancer survivors.

The Latest on “Chemo-brain”

“Chemo-brain may be a bit of a misnomer,” said Tim Ahles, PhD, who is a behavioral psychologist at Memorial Sloan-Kettering Cancer Center, New York, New York. Ahles and his colleagues have been studying cognitive changes in cancer survivors and they have found that a majority of patients report problems with short-term memory, difficulties in concentrating, and problems with multitasking. “Initially, we thought the cognitive changes were all due to chemotherapy, but the newer studies suggest there may be other aspects of cancer treatments that are affecting cognitive function as well.”

Radiotherapy, the process surrounding surgical procedures (ie, the use of general anesthesia) and noncytotoxic therapies, such as hormone therapies, may also play a role in the development of chemo-brain. According to Ahles, these problems may also be associated with the actual cancer, as opposed to the therapy being used to combat it. To this point, Ahles noted, “Twenty to 25% of breast cancer patients have lower cognitive functioning prior to starting treatment, so there may be something about the cancer itself.”

Researchers at the Moffitt Cancer Center in Florida have found that breast cancer survivors who have had chemotherapy, radiation, or both do not perform as well on some cognitive tests as women who have not had cancer (1). The investigators conducted a study with colleagues at the University of South Florida and the University of Kentucky that included 313 women: 62 with stage 0–II breast cancer treated with chemotherapy plus radiotherapy (CT group); 67 who received radiotherapy only (RT group; and 184 with no history of cancer (NC group).

The women in all three groups were within 5 years of age of each other, and the patients with breast cancer were matched with cancer-free women who lived in their same zip codes. All the women were tested cognitively in terms of processing speed and executive functioning, which are the two domains expected to be most affected by chemotherapy. The participants were also tested for their verbal abilities. All the women with cancer were tested 6 months after treatment and then tested again 36 months after completing treatments. The cancer-free women were also tested at 6 months and then again at 36 months (1).

Ultimately, the study showed that patients treated with chemotherapy performed worse than noncancer controls in processing speed, executive functioning, and verbal ability. In addition, the researchers found the test results for the radiotherapy-treated group to be similar to the results of those in the chemotherapy-treated group. The study also showed that the noncancer group improved in these cognitive abilities over time while the chemotherapy- and radiotherapy-treated groups did not. The researchers noted there were no differences in performance between the two groups.

The study co-investigator, Heather Jim, PhD, Assistant Professor in the Department of Health Outcomes and Behavior at the Moffitt Cancer Center, Tampa, Florida, said that there are subsets of patients with cancer who seem to do worse than other patients with the disease. Jim added that genetics, rather than a specific tumor type or treatment, may be playing a significant role in the cognitive changes patients experience after cancer therapy.

“We do think genetics are involved. Patients who may be at higher risk for Alzheimer's disease may perform worse cognitively after chemotherapy and radiation. Also, people who are older and who have less education may have lower cognitive reserves and so they may be less resilient to the insults of cancer therapy on the brain. Their brains may be less resilient,” Jim said in an interview with Chemotherapy Advisor.

Imaging Studies Better Define Brain Changes Following Cancer Therapy

Recently, researchers at West Virginia University School of Medicine used positron emission tomography combined with computed tomography (PET/CT) to detect physiologic evidence of specific brain changes following chemotherapy (2). In the study, PET/CT brain imaging results from 115 patients who had been treated with chemotherapy for breast cancer were analyzed. The investigators used special software to help discern differences in brain metabolism before and after chemotherapy. The results were correlated with patient history, neurological examinations, and chemotherapy regimens.

“Overall, what we found was that there are two areas of the brain that show decreased function in the 12 months after receiving chemotherapy. They are the two areas of the brain used for planning, organizing, sequencing, problem solving, and long-term memory,” said lead study investigator Rachel Lagos, DO, who is a diagnostic radiology resident at the West Virginia University School of Medicine, Morgantown, West Virginia. Lagos said this study demonstrated that there are specific areas of the brain—those responsible for planning and prioritizing—that use less energy following chemotherapy. Therefore, the use of PET/CT scanning, indicated Lagos, could pave the way for better tailoring therapies to individual patients, as it could be used to help facilitate clinical diagnosis and allow for earlier intervention.

Researchers in Belgium in 2012 conducted brain imaging studies that showed longitudinal changes in cognitive function and cerebral white matter integrity in women with early-stage breast cancer who underwent chemotherapy (3). The investigators studied cerebral white matter integrity before and after chemotherapy in 34 young premenopausal women, used magnetic resonance diffusion tensor imaging (DTI) combined with detailed cognitive assessments. All of the women in the trial underwent neuropsychological testing and DTI before the start of chemotherapy and 12–16 weeks after treatment. The researchers used 16 patients not exposed to chemotherapy and 19 age-matched healthy controls for a comparison. These women in the two control groups underwent the same assessments at the same matched time intervals (3).

Similar to the trial discussed earlier, the researchers found that the women who were treated with chemotherapy performed significantly worse on attention tests, psychomotor speed, and memory at 12–16 weeks after treatment. In addition, there were significant decreases in fractional anisotropy (FA), a DTI measure of white matter organization, in frontal, parietal, and occipital white matter tracts in women who underwent chemotherapy. There were no changes in FA values in both control groups. The investigators also reported that problems with attention and verbal memory correlated with mean regional FA changes in the women who underwent chemotherapy.
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Old 04-07-2011, 09:20 PM
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Hope on the Horizon?

In an interview with Chemotherapy Advisor, Steve Chui, MD, a medical oncologist with the Knight Cancer Institute at Oregon Health & Science University in Portland, Oregon said about 80% of patients who undergo chemotherapy in his practice have their cognitive problems completely dissipate within 1 year of treatment. He said malaise, fatigue, and sleep problems tend to be the most common complaints.

“Some patients are clearly worried that they are going to have severe mental problems, but I have never seen that…I worry about people refusing really beneficial treatments over perceived risks that may not even exist or are very manageable,” Dr. Chui told Chemotherapy Advisor.

Dr. Chui added that the vast majority of chemotherapy agents do not cross the blood-brain barrier. However, there are some agents that may cross the blood-brain barrier and have a direct effect on cognitive function. It is well established that most chemotherapy agents damage DNA, and researchers believe that an accumulation of DNA damage may result in deleterious brain changes; however, that is only a theory today.

Studies have also shown that patients with cognitive problems following cancer treatment can benefit from assistance from nutritionists, exercise therapists, massage therapists, and counselors. “Targeted intervention would be very beneficial for patients who are experiencing these symptoms,” Dr. Lagos told Chemotherapy Advisor. “It involves a whole team of caregivers, nurses, counselors, and radiation people. We hope this research gives this team the type of counseling and information it needs” she noted. Cognitive therapy is now routinely used to help patients with cancer who experience significant cognitive deficits following cancer treatment. Some patients are taught new skills to help compensate for their deficits.

Currently, some clinicians are trying stimulants such as methylphenidate (Ritalin) and modafinil (Provigil) to see if they can benefit patients who are having significant problems with memory and concentration following cancer treatment. "Drugs like methylphenidate are stimulants and they help to focus concentration and reduce fatigue. Fatigue is another common symptom that tracks with these cognitive problems. They (stimulants) do seem to help some people,” said Ahles.

Researchers at the Rochester School of Medicine and Dentistry, Rochester, New York, have found that modafinil may improve cognitive performance in patients with breast cancer by enhancing memory and attention skills (4). The researchers conducted a randomized clinical trial examining the effects of modafinil in reducing persistent fatigue, with secondary analyses to assess the effect of modafinil on cognitive function.

In the first phase of the study, the women received 200 mg of modafinil open-label once a day for 4 weeks. In the second phase of the study, women with a positive response following the initial trial with the drug were randomly assigned to either an additional 4 weeks of 200 mg of modafinil or placebo. Of the 82 women on the study, 76 completed the first phase of the study and 68 women completed both phases of the study (age range: 33–83 years; mean age: 54 years).

During the first phase of the study, researchers found that modafinil had a significant effect on “Speed of Memory” and “Quality of Episodic Memory.” The study showed that after week 8 postrandomization, those patients who continued on the drug showed significantly greater improvements in “Speed of Memory,” “Quality of Episodic Memory,” and mean “Continuity of Attention” compared with those patients on placebo. The investigators concluded that this approach enhanced memory and attention skills and may improve the quality of life in women who undergo chemotherapy for breast cancer.

“I think the best thing for physicians to do is to listen to the patients carefully, take their concerns seriously, and look into supportive care options for them,” said Jim.

References

1. Phillips KM, Jim HS, Small BJ, et al. Cognitive functioning after cancer treatment: a 3-year longitudinal comparison of breast cancer survivors treated with chemotherapy or radiation and noncancer controls. Cancer. 2012;118(7):1925-1932.

2. Lagos R et al. Towards diagnostic imaging of chemobrain phenomenon. Paper presented at: Annual Meeting of the Radiological Society of North America, November 27, 2012; Chicago, IL.

3. Deprez S, Amant F, Smeets A, et al. Longitudinal assessment of chemotherapy-induced structural changes in cerebral white matter and its correlation with impaired cognitive functioning. J Clin Oncol. 2012;30(3):274-281.

4. Kohli S, Fisher SG, Tra Y, et al. The effect of modafinil on cognitive function in breast cancer survivors. Cancer. 2009;115(12): 2605-2616
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Old 05-14-2011, 03:46 PM
gdpawel gdpawel is offline
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Default Neurocognitive Function Over 5 Years

Prospective Neurocognitive Function Over 5 Years After Allogeneic Hematopoietic Cell Transplantation for Cancer Survivors Compared With Matched Controls at 5 Years

Karen L. Syrjala, Samantha B. Artherholt, Brenda F. Kurland, Shelby L. Langer, Sari Roth-Roemer, JoAnn Broeckel Elrod and Sureyya Dikmen

Author Affiliations

Karen L. Syrjala, Samantha B. Artherholt, Brenda F. Kurland, and Shelby L. Langer, Fred Hutchinson Cancer Research Center; Karen L. Syrjala, Samantha B. Artherholt, JoAnn Broeckel Elrod, and Sureyya Dikmen, University of Washington School of Medicine; Shelby L. Langer, University of Washington, Seattle, WA; and Sari Roth-Roemer, Arizona Medical Psychology, Scottsdale, AZ.

Corresponding author: Karen L. Syrjala, PhD, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, D5-220, Seattle, WA 98109-1024; e-mail: [email]ksyrjala@fhcrc.org

Abstract

Purpose

Research has documented cognitive deficits both before and after high-dose treatment followed by allogeneic hematopoietic cell transplantation (HCT), with partial recovery by 1 year. This study prospectively examined the trajectory and extent of long-term cognitive dysfunction, with a focus on 1 to 5 years after treatment.

Patients and Methods

Allogeneic HCT recipients completed standardized neuropsychological tests including information processing speed (Trail Making A and Digit Symbol Substitution Test), verbal memory (Hopkins Verbal Learning Test–Revised), executive function (Controlled Oral Word Association Test and Trail Making B), and motor dexterity and speed (Grooved Pegboard). Survivors (n = 92) were retested after 80 days and 1 and 5 years after transplantation. Case-matched controls (n = 66) received testing at the 5-year time point. A Global Deficit Score (GDS) summarized overall impairment. Response profiles were analyzed using linear mixed effects models.

Results

Survivors recovered significant cognitive function from post-transplantation (80 days) to 5 years in all tests (P < .0001) except verbal recall (P > .06). Between 1 and 5 years, verbal fluency improved (P = .0002), as did executive function (P < .01), but motor dexterity did not (P > .15), remaining below controls (P < .0001) and more than 0.5 standard deviation below population norms. In GDS, 41.5% of survivors and 19.7% of controls had mild or greater deficits (NcNemar test = 7.04, P = .007).

Conclusion

Although neurocognitive function improved from 1 to 5 years after HCT, deficits remained for more than 40% of survivors. Risk factors, mechanisms and rehabilitation strategies need to be identified for these residual deficits.

Source: American Society of Clinical Oncology
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Old 11-17-2011, 06:29 PM
gdpawel gdpawel is offline
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Default Chemo Brain shows on MRI's

Prefrontal Cortex and Executive Function Impairments in Primary Breast Cancer

Shelli R. Kesler, PhD; Jamie S. Kent, MA; Ruth O’Hara, PhD

Arch Neurol. 2011;68(11):1447-1453. doi:10.1001/archneurol.2011.245

Objectives: To examine differences in prefrontal-executive function between breast cancer (BC) survivors with and without a history of chemotherapy treatment compared with healthy control women and to determine the associations between prefrontal cortex deficits and behavioral impairments, as well as certain demographic and disease variables.

Design: Observational study.

Setting: University-based research facility.

Participants: Twenty-five women with BC who had received chemotherapy, 19 women with BC who had not received chemotherapy, and 18 healthy female controls, all matched for age and other demographic variables.

Results: Women with BC demonstrated significantly reduced activation in the left middle dorsolateral prefrontal cortex and premotor cortex compared with healthy controls. The chemotherapy group also demonstrated significantly reduced left caudal lateral prefrontal cortex activation and increased perseverative errors and reduced processing speed compared with the other 2 groups. Reduced left caudal lateral prefrontal cortex activation was significantly correlated with higher disease severity and elevated subjective executive dysfunction in the chemotherapy-treated women. Older age and lower educational level were associated with increased executive function impairment in the chemotherapy group.

Conclusions: These findings provide further evidence of neurological impairment associated with primary BC irrespective of treatment history. The left caudal lateral prefrontal region may be particularly vulnerable to the effects of chemotherapy and/or disease severity and may represent a novel biomarker of subjective executive dysfunction in chemotherapy-treated women. Furthermore, negative effects of chemotherapy on brain function may be exacerbated by such factors as increased age and lower educational level.

Author Affiliations: Stanford Cancer Center, Palo Alto (Dr Kesler), and Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford (Drs Kesler and O’Hara and Ms Kent), California.

[url]http://archneur.ama-assn.org/cgi/content/abstract/68/11/1447
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Old 11-17-2011, 06:33 PM
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Default 'Chemo Brain': MRI Shows Brain Changes After Chemotherapy

'Chemo Brain': MRI Shows Brain Changes After Chemotherapy

Fran Lowry
Medscape Oncology

November 16, 2011 Breast cancer survivors who have been treated with chemotherapy show significant changes in brain activity, measured by functional magnetic resonance imaging (fMRI), according to a study published in the November issue of the Archives of Neurology.

The finding validates patients' claims of reduced cognitive function after receiving chemotherapy, a phenomenon referred to as "chemo brain," said lead author Shelli R. Kesler, PhD, from Stanford University School of Medicine in California.

"Emerging research shows that there is a biological correlate of these cognitive problems that these patients are reporting," Dr. Kesler told Medscape Medical News. "Historically, there has been some controversy as to whether these problems really exist, so looking at the brain and seeing that there are brain changes validates patients' experiences."

She added that she hopes these findings will be helpful for breast cancer survivors who are experiencing such problems, "so that they are less likely to be turned away for things like disability benefits or even to be ignored by their physicians, who sometimes tell them that they're just imagining the problem. Our study shows that there really is a problem. It's not just stress. It's not their imagination. It's a real brain change."

Performing Card-Sorting Task

In this observational study, Dr. Kesler and her team sought to ascertain differences in prefrontal executive function between 25 breast cancer survivors who underwent chemotherapy, 19 women who did not, and 18 healthy women with no history of breast cancer. All subjects were matched for age and other demographic variables.

All women underwent fMRI while performing a card-sorting task that was designed to measure prefrontal brain activation associated with executive function and while performing a control task in which they were asked to judge whether a single card was red.

All 3 groups showed a similar profile of brain activation during the fMRI tasks, including bilateral cerebellum, basal ganglia, and parietal and dorsolateral prefrontal regions.

However, the results showed that the women with breast cancer demonstrated significantly reduced activation of the left middle dorsolateral prefrontal cortex and premotor cortex, compared with the healthy women.

In addition, breast cancer survivors who received chemotherapy showed significantly reduced left caudal lateral prefrontal cortex activation, increased perseverative errors, and reduced processing speed, compared with the other 2 groups.

The researchers also found that this reduced activation in the left caudal lateral prefrontal cortex was significantly correlated with higher disease severity and self-reported executive dysfunction in the chemotherapy group.

Groundbreaking Study

Michelle C. Janelsins, PhD, from the James P. Wilmot Cancer Center, University of Rochester School of Medicine and Dentistry, in New York, told Medscape Medical News that she thinks this study is "groundbreaking, excellent, and extremely interesting."

"What is most interesting about this study is that Dr. Kesler and colleagues were looking at specific areas of the brain and trying to associate these areas with specific types of processes, such as problem solving, decision making, and planning," Dr. Janelsins said.

"We are always looking for indicators of subclinical problems that might predict longer-term impairment so that we can manage them if it looks as if the person is developing cognitive deficits," she said. "Not every single individual develops cognitive deficits; brain imaging may be a way to allow us to determine who is most at risk and who is most affected by chemotherapy for breast cancer."

"Chemo Brain" Not All in the Mind

Dr. Kesler said that older women and those who were less physically and mentally active were more likely to be cognitively affected by chemotherapy.

"Two of the things we found that predicted more cognitive dysfunction were age and cognitive reserve, so the older you are, the more vulnerable, which is not surprising since you are more vulnerable to a lot of things," she said.

"When you have been more mentally and physically active, [cognitive reserve] tends to give you more brain capacity, so when something like breast cancer and chemotherapy happens to you, you have more capacity to overcome that," she said.

Dr. Kesler hopes this research will lay the foundation for future longitudinal studies that will evaluate patients before and after chemotherapy. "These are going to be critical for figuring out this problem. It's hard to get funding to do those studies unless you have evidence such as that from our study, showing that cognitive dysfunction is a real problem."

This study was supported by the National Institutes of Health. Dr. Kesler and Dr. Janelsins have disclosed no relevant financial relationships.

Arch Neurol. 2011;68:1447-1453.
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Old 11-28-2012, 09:40 PM
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Default PET-CT Scans Reveal Chemo Brain is Real

(MedPage Today) - Chemotherapy has long been associated with cognitive decline, including loss of memory and concentration that can cause trouble with activities of daily living. Yet the exact etiology of chemo brain is difficult to determine, and some have questioned whether the phenomenon is indeed real.

In a study that was published as an abstract and presented at a conference and its data and conclusions should be considered to be preliminary until published in a peer-reviewed journal, the phenomenon known as "chemo brain" appears to to correlate with reductions in glucose metabolism in brain regions tied to cognition.

The exact mechanisms are still unclear, but the effect could be mediated through a cytokine response or by nerve demyelination.

In the single-center study of breast cancer patients who had undergone chemotherapy, there were significant changes in metabolism in the superior medial frontal gyrus and the temporal operculum as measured on PET-CT (P=0.025 and P=0.036, respectively), Rachel Lagos, DO, of the University of West Virginia, and colleagues reported during a press briefing at the Radiological Society of North America meeting.

"The good news is that we are seeing evidence on PET-CT that is diagnostic for this phenomenon," Lagos said during the briefing. "Having diagnostic criteria is going to be one of our first steps to providing relief to people receiving chemotherapy."

Lagos and colleagues took a retrospective look at 115 patients who had undergone chemotherapy for breast cancer at their facility. None had disease that had metastasized to the brain.

They used PET-CT to assess changes in brain function and calculated z-scores for changes in brain metabolism in certain regions, with patients serving as their own controls.

Overall, they found significant decreases in glucose metabolism in brain regions closely associated with symptoms of chemo brain:

Superior medial frontal gyrus: associated with mental agility and decision making (P=0.025)

Superior medial frontal gyrus, left to right difference: problem solving and sequencing (P=0.023)

Temporal operculum: long term memory (P=0.036)

"This corresponds to anecdotal evidence we're hearing from patients about how their life is being affected by chemotherapy," Lagos said.
Although the researchers did not calculate an average value for the change in z-scores of glucose metabolism pre- and post-chemotherapy, Lagos said values ranged from a decline of 2.5 to 8 points.

She said the findings reinforce that chemo brain is a disease.

The exact mechanisms are still unclear, but the effect could be mediated through a cytokine response or may have something to do with nerve demyelination.

Max Wintermark, MD, chief of neuroradiology for the University of Virginia in Charlottesville, who moderated the session during which the findings were presented, said the metabolism changes may also have something to do with the stress and anxiety of going through chemotherapy.

"It could have something to do with those changes, but more research is needed," Wintermark said, adding that the finding is reassuring for women who experience cognitive symptoms during chemotherapy.

"Instead of those symptoms being dismissed, we can see there is a substrate for them," he said. "Just to know they are not inventing those symptoms, I think that will help them go through this difficult experience."

Lagos added that acknowledging the fact that chemo brain exists is the first step toward helping patients cope with the disease, and that psychosocial therapies can be tailored to their needs, such as providing them with lists to get through their daily activities.

She added that it should be comforting for women to know that chemo brain tends to resolve once treatment is finished.

The researchers reported no conflicts of interest.

Primary source: Radiological Society of North America meeting

Source reference:
Lagos R, et al "Towards diagnostic imaging of ChemoBrain phenomenon" RSNA 2012; Abstract LL-MIS-TU2A.
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Old 04-20-2017, 12:57 PM
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Default Potential new treatment found for 'chemo brain'

MedicalNewsToday

Chemotherapy is the most commonly available form of cancer treatment, but its serious side effects are well-known. New research investigates the mechanism behind the cognitive impairment often associated with chemotherapy and offers new options for treating these adverse effects on the brain.

The National Cancer Institute estimate that there are currently 15.5 million cancer survivors in the United States.

As many as 1 in 3 patients with cancer who undergo chemotherapy experience cognitive impairment as a result of the treatment. The cognitive dysfunction associated with chemotherapy is commonly referred to as "chemo brain."

The symptoms of chemo brain include difficulty remembering things, trouble concentrating and processing information, and overall confusion. A survey of cancer survivors has shown that this population are 40 percent more likely to report cognitive issues compared with their cancer-free counterparts.

At the most recent national meeting of the American Chemical Society, University of Kansas researcher and associate professor of chemistry, Michael Johnson, presented scientific studies suggesting a potential new treatment for chemotherapy-associated cognitive impairment.

"Chemo brain is something doctors learned about because patients were complaining," Johnson says. "Symptoms include visual and verbal memory loss - so if you have a conversation with somebody, you may have difficulty recalling it. You might have attention deficit, so if you are trying to do taxes, it might be difficult to focus. It also can result in a decline in processing speed, so it may be more difficult to think on your toes. You may have trouble remembering words."

The new findings presented by Johnson examine the brain chemistry behind this cognitive dysfunction, using rodent models. The studies also suggest new ways of treating the symptoms of chemo brain.

'KU-32' drug may prevent chemo brain

One such study referenced by Johnson - conducted by him in collaboration with David Jarmolowicz of the Department of Applied Behavioral Science at the University of Kansas, and colleagues - shows that a common chemotherapy drug called 5-Fluorouracil damages the integrity of myelin, the protective layer made of fats and proteins that forms around the brain cells.

This myelin damage corresponds to neurodegenerative deficits in the hippocampus - a brain area key to learning and memory - as well as dysfunctions in the cells' mitochondria, which are the so-called powerhouses of the cells, where the nutrients are transformed into energy.

Additionally, the study - published in the journal Behavioural Brain Research - shows that chemotherapy increases levels of hydrogen peroxide in the brain and that a chemical compound called KU-32 can counter the negative effects of this excessive substance. The research shows that KU-32 can stop the chemotherapy-induced cognitive decline in rats.

Michael Johnson explains the findings:

"In our preliminary results, we found that hydrogen peroxide temporarily increases in the brains of chemotherapy-treated rats. Because hydrogen peroxide is a reactive oxygen species and potentially damaging, it may have an effect on cognitive function. Additionally, we may have a therapy that can serve as a preventative in order to treat it. We found that KU-32 prevents cognitive impairment, and our preliminary neurochemical data suggest that it may prevent increases in hydrogen peroxide production.

[url]http://www.sciencedirect.com/science/article/pii/S0166432817303145

Chemotherapy affects dopamine and serotonin

These results build on previous research carried out by Johnson and his colleagues. A recently published paper in the journal ACS Chemical Neuroscience examines the adverse effects of chemotherapy on the neurotransmitters dopamine and serotonin.

Dopamine is a major neurotransmitter that plays a key role in learning, memory, and other cognitive skills. Serotonin is largely associated with emotional states, as it helps to control mood and sleep quality, among other things.

"Dopamine is found in many regions of the brain but is particularly abundant in the striatum," Johnson says. "The striatum receives inputs from other parts of the brain, such as the cortex, and filters out the unwanted inputs while amplifying the wanted inputs, which are translated into actions. Dopamine is a key player in how the striatum responds. We felt that alterations in dopamine release due to chemo could potentially play a role in cognitive impairment."

Their study revealed that treatment with the common chemotherapy compound carboplatin impaired dopamine and serotonin release in the rats' brains. The rats treated with the drug released 42 percent less dopamine and 55 percent less serotonin than the rats that had not received the treatment.

"Serotonin is implicated in depression and cognitive function," Johnson explains. "We wanted to measure serotonin to see if this was a global effect. It turns out that serotonin is impacted as well, so it is likely that chemotherapy agents act on neurotransmitter systems other than dopamine as well and also play an important role."

Johnson notes that these findings may open up new avenues for treating chemo brain symptoms, as well as benefit research into other diseases.

"These are the first studies to our knowledge that look at what happens to neurotransmitter release events as a result of these chemotherapeutic agents. It hopefully will open up some options for treatments down the road [...] Certainly, it might be important for researchers interested in developing therapies for chemo brain as well as other disorders that might impact cognitive function. - Dr. Michael Johnson

[url]http://pubs.acs.org/doi/abs/10.1021/acschemneuro.5b00029

[url]http://www.brainfacts.org/Brain-Basics/Cell-Communication/Articles/2012/Classical-Neurotransmitters-Brain-Communicators

Citation: Ana Sandolu Medical News Today. 17 Apr. 2017
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