Cancer & the brain

A pilot study involving 22 breast cancer patients currently receiving chemotherapy (mean age 54), has found that those with higher levels of inflammatory biomarkers did significantly worse on tests for short-term visual memory. One particular biomarker — tumor necrosis factor-alpha (as reflected through its two soluble receptors, TNFRI and TNFRII) — was the strongest indicator of cognitive problems.

The findings are consistent with an earlier study involving 174 breast cancer patients evaluated before chemotherapy, which found that higher levels of those biomarkers were associated with worse memory, and another study of 49 patients, which found that higher levels of sTNFRII were associated with more memory complaints after chemotherapy.

Cognition was assessed using the Cambridge Neuropsychological Test Automated Battery (CANTAB), looking at those domains previously reported to be affected in cancer survivors: visual memory, executive functioning, attention, verbal memory, and cognitive processing.

Almost all the patients were Caucasian and college-educated.

http://www.futurity.org/chemo-brain-cancer-1631232-2/

Williams, AnnaLynn M. et al. 2018. Associations between inflammatory markers and cognitive function in breast cancer patients receiving chemotherapy. Journal of Neuroimmunology, 314, 17-23. Full text available at https://www.jni-journal.com/article/S0165-5728(17)30198-4/fulltext

Patel, S.K., Wong, A.L., Wong, F.L., Breen, E.C., Hurria, A., Smith, M. et al. 2015. Inflammatory biomarkers, comorbidity, and neurocognition in women with newly diagnosed breast cancer. J. Natl. Cancer Inst., 107.

Ganz, P.A., Bower, J.E., Kwan, L., Castellon, S.A., Silverman, D.H., Geist, C. et al. 2013. Does tumor necrosis factor-alpha (TNF-alpha) play a role in post-chemotherapy cerebral dysfunction?. Brain Behav. Immun., 30, S99–108.

Chemo-brain common among women with breast cancer

A study involving 581 breast cancer patients and 364 healthy age-matched people (mean age 53) has found that women with breast cancer reported significantly greater cognitive difficulties for up to six months after chemotherapy. Cognitive difficulties were evaluated using FACT-Cog, an assessment that examines a person's own perceived impairment as well as cognitive impairment perceived by others.

Compared to healthy controls, the FACT-Cog scores of women with breast cancer were 45% lower at outset. This difference increased substantially after chemotherapy (see graph). The first assessment after chemotherapy was at 4.8 months, with the second 6 months after that (i.e, nearly a year after chemotherapy). Patients were also much more likely to report significant cognitive decline from diagnosis to the first post-chemotherapy assessment (45.2% vs 10.4% of the controls), and from prechemotherapy to second post-chemotherapy assessment (36.5% v 13.6%).

Having more anxiety and depressive symptoms at the outset, and having lower cognitive reserve (assessed by a reading score), were significantly associated with lower scores.

Those who received hormone therapy and/or radiation treatment after chemotherapy had similar cognitive problems to women who received chemotherapy alone.

Chemobrain a product of dysfunction in dopamine & serotonin release?

A rat study suggests one reason for chemo-brain is an effect of chemotherapy on the neurotransmitters dopamine and serotonin. Both of these are important for both mood and cognition.

After giving carboplatin (commonly used with breast, bladder, colon and other cancers) to rats over four weeks, researchers found that the release and uptake of both dopamine and serotonin in their brains became impaired, although overall levels didn’t change. The rats also showed impaired cognition.

Exercise helps memory for breast cancer survivors

A role for dopamine and serotonin in chemo-brain is consistent with findings that anxiety and depression are risk factors for chemo-brain. No surprise then, that a study has found that physical exercise helps improve cognition in breast cancer survivors.

The study used self-reported data from 1,477 breast cancer survivors, as well as from accelerometers worn by 362 of the women. It found that breast cancer survivors who did more moderate or vigorous physical activity (including brisk walking, biking, jogging, or an exercise class) had fewer subjective memory problems.

Higher levels of physical activity were associated with lower levels of fatigue and distress, and higher levels of physical confidence. The researchers suggest that exercise reduces subjective memory problems via these factors.

Cognitive-behavioral therapy may help

A cognitive-behavioral therapy called "Memory and Attention Adaptation Training" (MAAT), which helps cancer survivors to increase their awareness of situations where memory problems can arise and to develop skills to either prevent memory failure or to compensate for memory dysfunction, has been trialed in a small randomized study involving 47 Caucasian breast cancer survivors. The patients were an average of four years post-chemotherapy.

The participants were either assigned to eight visits of MAAT (30 to 45 minutes each visit) or supportive talk therapy for the same length of time. Both treatments were delivered over a videoconference network between health centers.

MAAT participants reported significantly fewer memory problems as well as improved processing speed two months after treatment. They also reported much less anxiety about cognitive problems.

https://www.eurekalert.org/pub_releases/2017-01/uorm-caw010317.php

http://www.eurekalert.org/pub_releases/2016-05/acs-ih052516.php

http://www.futurity.org/exercise-breast-cancer-memory-1200372-2/

http://www.eurekalert.org/pub_releases/2016-05/w-ctm050216.php

A six-week study involving 619 cancer patients has found that those who took part in a simple home-based exercise program significantly reduced their cognitive impairment ('chemo-brain'). The EXCAP (Exercise for Cancer Patients) was developed by the researchers some years ago, and this evaluation was a phase III randomized study for early-stage chemotherapy patients. Half the group were given standard care (no exercise during chemotherapy), while the others were given instruction to walk daily and carry out low-to-moderate resistance band training for 10 minutes, 5 days a week.

This very modest increase in exercise (the 'no-exercise' group walked on average 3,800 steps a day, while the excap group walked on average 5,000 steps) had significant effects:

  • lower levels of inflammation
  • less brain 'fogginess'
  • fewer memory problems
  • greater mobility.

Exercisers who received chemotherapy in 2-week cycles reported the greatest benefits, compared to other timing cycles.

http://www.futurity.org/exercise-chemotherapy-932492/

http://www.urmc.rochester.edu/news/story/index.cfm?id=4333

The findings were presented at the American Society of Clinical Oncology (ASCO) annual meeting on June 1, by Karen Mustian.

The issue of ‘chemo-brain’ — cognitive impairment following chemotherapy — has been a controversial one. While it is now (I hope) accepted by most that it is, indeed, a real issue, there is still an ongoing debate over whether the main cause is really the chemotherapy. A new study adds to the debate.

The study involved 28 women who received adjuvant chemotherapy for breast cancer, 37 who received radiotherapy, and 32 age-matched healthy controls. Brain scans while doing a verbal working memory task were taken before treatment and one month after treatment.

Women who underwent chemotherapy performed less accurately on the working memory task both before treatment and one month after treatment. They also reported a significantly higher level of fatigue. Greater fatigue correlated with poorer test performance and more cognitive problems, across both patient groups and at both times (although the correlation was stronger after treatment).

Both patient groups showed reduced function in the left inferior frontal gyrus, before therapy, but those awaiting chemotherapy showed greater impairment than those in the radiotherapy group. Pre-treatment difficulty in recruiting this brain region in high demand situations was associated with greater fatigue after treatment.

In other words, reduced working memory function before treatment began predicted how tired people felt after treatment, and how much their cognitive performance suffered. All of which suggests it is not the treatment itself that is the main problem.

But the fact that reduced working memory function precedes the fatigue indicates it’s not the fatigue that’s the main problem either. The researchers suggest that the main driver is level of worry —worry interfered with the task; level of worry was related to fatigue. And worry, as we know, can reduce working memory capacity (because it uses up part of it).

All of which is to say that support for cancer patients aimed at combating stress and anxiety might do more for ‘chemo-brain’ than anything else. In this context, I note also that there have been suggestions that sleep problems have also been linked to chemo-brain — a not unrelated issue!

Cimprich, B. et al. 2012. Neurocognitive impact in adjuvant chemotherapy for breast cancer linked to fatigue: A Prospective functional MRI study. Presented at the 2012 CTRC-AACR San Antonio Breast Cancer Symposium, Dec. 4-8

Cancer survivors who underwent chemotherapy often suffer long-term cognitive problems. Until now, most research has been occupied with establishing that this is in fact the case, and studies investigating how to help have been rare. I recently reported on studies suggesting that help with sleep problems and stress can be beneficial. It has also been suggested that exercise can help. None of these suggestions are special to cancer survivors (although cancer survivors may well be one of several groups that derive particular benefit). Similarly, a new study investigates another familiar approach to improving cognitive decline.

The pilot study involved 82 post-menopausal breast cancer survivors (average age 56) who had received chemotherapy and who were worried about their cognitive abilities. The women were randomly assigned to one of three groups: one group received memory training adapted from the ACTIVE (Advanced Cognitive Training for Independent and Vital Elderly) trial; another received processing speed training using Posit Science’s Insight program (commercially available); the third was a wait-listed control group.

Training consisted of ten 1-hour small-group (3-5 people) sessions over 6-8 weeks. Memory training involved learning strategies and applying them to word lists, sequences, and texts. Strategies included mnemonic techniques, as well as instruction in principles of meaningfulness, organization, visualization, and association. Strategies were taught and practiced in the first five sessions, and further practiced in the remaining sessions.

In the Insight program, stimulus duration is progressively shortened during a series of progressively more difficult information-processing tasks, such as time-order judgment, discrimination, spatial-match, forward-span, instruction-following, and narrative-memory tasks. Exercises automatically adjust to maintain an 85% correct rate.

Both programs proved beneficial. The memory training group showed significant improvement in immediate and delayed memory, which was maintained at the two-month follow-up. There was of course individual variability: 39% showed significant improvement on immediate memory (compared to 18% of controls) and 42% on delayed memory (compared to 11% of controls). While the group as a whole didn’t show significant improvement in processing speed, some 73% of the group showed reliable improvement at the two-month follow-up.

The Insight group showed significant improvement on both memory and processing speed. Some 68% improved processing speed (compared to 43% of controls). But note that at the 2-month follow-up, the 67% of the Insight group is not that much greater than the 61% of the controls (demonstrating very clearly the benefits of even the small amount of practice received in testing) and is in fact less than the 73% of the memory group.

The Insight group also showed significant improvement in memory. At two-month follow-up, some 30% of the Insight group had improved immediate memory (compared to the 18% of controls), and 33% had improved delayed memory (vs 11%).

Both training programs had a positive effect on perceived cognitive functioning and symptom distress (mood, anxiety, fatigue), and there was no difference between the groups in terms of satisfaction with the training (both groups were very satisfied).

The researchers concluded that, while both training programs were promising, the dual effect of processing speed training (on memory as well as processing speed) argued for its broader benefits.

However, I note that, although the size of the effect of memory training on processing speed was too small to reach statistical significance, the fact that the number of participants showing reliable improvement was greater than that of the Insight group points to an equally broad effect of memory training. If the memory training was supplemented by a small amount of practice on tasks designed to boost processing speed, it would seem to me that this might produce greater cognitive benefits than the processing speed training. Indeed, the Insight program was, I believe, first developed in the context of the ACTIVE program, and I have, of course, talked before about the value of training that includes multiple domains.

Still, the main message of this study should not be overlooked: it demonstrates that many cancer survivors suffering from cognitive decline can improve their cognitive performance through training and practice.

Women who received a once-standard type of chemotherapy regimen for breast cancer between 1976 and 1995 have been found to score worse on cognitive tests than women who never had cancer. Specifically, they tended to have lower scores on tests of immediate and delayed verbal memory, executive function, information processing speed, and psychomotor speed. The difference was comparable to some six years of age-related decline.

CMF chemotherapy was the standard of care for breast cancer worldwide from the 1970s through the 1990s. Some of the chemicals (shown to be associated with impaired learning and memory in animal studies) are still commonly incorporated in modern chemotherapeutic regimens for breast cancer.

The study compared the performance of 196 women who had received CMF chemotherapy to that of 1,509 women enrolled in the Rotterdam Study. All participants were aged 50-80 at the beginning of the study. Factors such as age, education, and depression score were taken into account in the analysis.

For more about the effects of chemotherapy on cognition

A recent study of cancer survivors has found that many survivors still suffer moderate to severe problems with pain, fatigue, sleep, memory and concentration three to five years after treatment has ended.

The study included 248 survivors of breast, colorectal, lung and prostate cancer. The survivors were primarily female and white, and most were more than five years post-diagnosis. Cognitive difficulties were reported by 13%. The other most common symptoms were fatigue (16%), disturbed sleep (15%), and pain (13%). Two assessments were made, one month apart. The similar results indicate these symptoms tend to be chronic.

The researchers pointed to the need for education programs to help survivors transition from treatment to life as a cancer survivor, and the need for clinicians and researchers to develop better ways to address sleep problems, fatigue and lasting difficulties with memory and concentration.

One activity that could be part of a post-treatment program is t'ai chi.  A recent pilot study involving 23 women with a history of chemotherapy has found better cognitive and physical functioning after 10 weeks participating in a 60-minute t’ai chi class twice a week. Before and after the intervention, participants completed tests of memory, executive functioning, language, and attention, as well as tests of balance and self-report questionnaires of neuropsychological complaints, stress and mood, and fatigue.

However, though I’m a big fan of t’ai chi, I do have to note that without a control group, allowing the passing of time and the effects of any sort of group activity to be taken into account, it’s hard to draw any real conclusions from this.

Still, some support for this finding can be found in a recent meta-analysis of research investigating the benefits of t'ai chi for any improvement of medical conditions or clinical symptoms. This review found that the only clear evidence is in relation to fall prevention and improving psychological health. So, only middling support for t'ai chi, but the affirmation of its benefit for psychological health does support the potential value of this meditational practice for cancer survivors.

The findings of the first study were presented June 4 at the 2011 American Society of Clinical Oncology Annual Meeting in Chicago.

[2320] Reid-Arndt, S. A., Matsuda S., & Cox C. R.
(Submitted).  Tai Chi effects on neuropsychological, emotional, and physical functioning following cancer treatment: A pilot study.
Complementary Therapies in Clinical Practice. In Press, Corrected Proof,

[2319] Lee, M S., & Ernst E.
(2011).  Systematic reviews of t'ai chi: an overview.
British Journal of Sports Medicine.

A study involving 1426 long-term survivors of childhood cancer (survivors of eight different childhood cancers who were treated between 1970 and 1986) has revealed cognitive impairment in over a fifth. Those who reported problems sleeping or frequent daytime sleepiness and fatigue were three to four times more likely to have attention and memory problems.

Additionally, those who were taking antidepressants were 50% more likely to report attention problems and 70% more likely to report memory problems.

The findings emphasize the need for help in sleep hygiene for this group.

Confirming earlier indications from small studies, a very large nationwide survey has found that people who have had cancer are 40% more likely to experience memory problems that interfere with daily functioning.

The U.S. study involved nearly 10,000 people aged 40 and older, of whom 1,305 (13.3%) reported they had cancer or a history of cancer. Of these, 14% answered yes to the question "Are you limited in any way because of difficulty remembering or because you experience periods of confusion?" Of those who did not have a history of cancer, 8% answered yes to this question.

The degree to which these memory problems are related to the treatment or to the cancer itself (or even perhaps to the experience of having cancer) is one that needs further investigation, but the researcher suggests the finding points to memory issues being more common among cancer sufferers than realized, and recommends that cognitive assessment should be a standard part of cancer treatment.

The study is noteworthy in including all cancers, rather than focusing on one. Nevertheless, I hope that we eventually see a published paper (these results were presented at conference) that also analyses the data in terms of different cancers, different treatments, and length of time since the cancer.

Earlier reports on ‘chemobrain’, and possible ways to help

Results were presented at the Third AACR Conference on The Science of Cancer Health Disparities.

Over the years I’ve reported on a number of studies investigating the effect of chemotherapy on the brain. A new study uses brain imaging, before and after treatment for breast cancer, to show that there is an anatomic basis for “chemobrain” complaints. The study, involving 17 breast cancer patients treated with chemotherapy after surgery, 12 women with breast cancer who did not undergo chemotherapy after surgery, and 18 women without breast cancer, found that gray matter density decreased in the frontal lobe, temporal lobe, cerebellum and right thalamus, shortly after chemotherapy.

The areas affected are consistent with memory and executive functions like multi-tasking and processing speed being the most typically affected functions. Post-surgery scans were carried out at one month, and at one year. Gray matter density in most women had improved by one year after chemotherapy ended.

Many survivors of childhood cancer experience cognitive problems as a result of their treatment. The drug methylphenidate (marketed under several names, the best known of which is Ritalin) has previously been shown to help attention problems in such survivors in the short term. Now a new study demonstrates that it can also be of benefit in the long term.

The study tested attention, social skills and behavior in survivors who had been on the drug for a year, comparing them to a similar group of unmedicated survivors. Although the drug did not lead to a significant gain in measured academic skills in math, reading and spelling, many did show improvements to attention that put them back in the normal range.

Nevertheless, the results also emphasize the need for other approaches, given that many did not benefit from the drug, and some may not be good candidates for medical or other reasons. The treatment group included 35 survivors of brain tumors and 33 of acute lymphoblastic leukemia (ALL). Any who suffered from ADHD before their cancer were excluded from the study.

Older news items (pre-2010) brought over from the old website

Helping 'chemobrain'

Mouse study points to possible treatment for chemobrain

A mouse study has found that four commonly used chemotherapy drugs disrupt neurogenesis, and that the condition could be partially reversed with the growth hormone IGF-1. Surprising the researchers, both the drugs which cross the blood-brain barrier (cyclophosphamide and fluorouracil) and the two that don’t (paclitaxel and doxorubicin) reduced neurogenesis, with fluorouracil producing a 15.4% reduction, compared to 22.4% with doxorubicin, 30.5% with cyclophosphamide, 36% with paclitaxel. A second study of a single high dose of cyclophosphamide, a mainstay of breast cancer treatment, resulted in a 40.9% reduction. Administration of the experimental growth hormone IGF-1 helped in all cases, but was more effective with the high dose.
[448] Gross, R. A., Janelsins M. C., Roscoe J. A., Berg M. J., Thompson B. D., Gallagher M. J., et al.
(2010).  IGF-1 partially restores chemotherapy-induced reductions in neural cell proliferation in adult C57BL/6 mice.
Cancer Investigation. 28(5), 544 - 553.
http://www.eurekalert.org/pub_releases/2009-12/uorm-usr121709.php

Stem cells restore cognitive abilities impaired by brain tumor treatment

A rat study has found that transplanted stem cells restored learning and memory to normal levels four months after radiotherapy. This compares with a greater than 50% decline in cognitive function in those rats that didn’t receive the therapy. Cranial irradiation is a common treatment for brain tumors.
[803] Acharya, M. M., Christie L. - A., Lan M. L., Donovan P. J., Cotman C. W., Fike J. R., et al.
(2009).  Rescue of radiation-induced cognitive impairment through cranial transplantation of human embryonic stem cells.
Proceedings of the National Academy of Sciences. 106(45), 19150 - 19155.
http://www.eurekalert.org/pub_releases/2009-11/uoc--scr110509.php

Exercise can aid recovery after brain radiation

A mouse study has found that exercise can prevent a decline in memory after whole-brain radiation treatment. Mice that had radiation plus access to a running wheel did as well at remembering where an escape hole in maze was as normal mice that didn't exercise. Irradiated mice that had no access to an exercise wheel eventually showed no particular preference for the section of the maze with the escape hole. The irradiated mice who didn’t exercise also showed depressive-like behavior, while those who exercised did not.
Wong-Goodrich, S.J. et al. 2009. Exercise promotes recovery from cognitive dysfunction, depressive-like behavior, and loss of hippocampal neurogenesis following whole-brain irradiation in adult mice. Presented October 20 at the annual Society for Neuroscience meeting in Chicago.
http://www.eurekalert.org/pub_releases/2009-10/dumc-eca101309.php

Potential remedy for the 'mental fog' in cancer patients

A rat study has found that injections of the antioxidant N-acetyl cysteine (a modified form of the dietary amino acid cysteine), fully prevented the memory loss induced by the commonly used chemotherapy drugs adriamycin and cyclophosphamide. The findings suggest that the cause of impairment is oxidative stress. More research will be needed to determine the safety of NAC for chemotherapy patients.
[846] Konat, G. W., Kraszpulski M., James I., Zhang H-T., & Abraham J.
(2008).  Cognitive dysfunction induced by chronic administration of common cancer chemotherapeutics in rats.
Metabolic Brain Disease. 23(3), 325 - 333.
http://www.eurekalert.org/pub_releases/2008-09/s-prf090408.php

Anastrozole does not impair cognition in postmenopausal women at risk of breast cancer

Trials have demonstrated that anastrozole is superior to tamoxifen in preventing breast cancer recurrence, and contralateral breast cancer in postmenopausal women, however other research has suggested that women receiving endocrine therapies show significantly poorer performance on verbal memory and processing tasks. In a substudy of the International Breast Intervention Study (IBIS II), which was specifically designed to investigate the clinical benefit of anastrozole, given daily for 5 years, as a primary chemopreventive treatment, cognitive function was assessed at baseline and at 6 and 24 months after the start of treatment. There were no significant differences between the anastrozole group and the placebo group in attention or memory, however, at 24 months significantly more women in the anastrozole group reported hot flushes. I note the recent study indicating the number of hot flushes in postmenopausal women is correlated with cognitive impairment.
[640] Jenkins, V. A., Ambroisine L. M., Atkins L., Cuzick J., Howell A., & Fallowfield L. J.
(2008).  Effects of anastrozole on cognitive performance in postmenopausal women: a randomised, double-blind chemoprevention trial (IBIS II).
The Lancet Oncology. 9(10), 953 - 961.
http://www.eurekalert.org/pub_releases/2008-09/l-adn082908.php

Narcolepsy drug alleviates post-chemotherapy fogginess

A trial involving 68 breast cancer survivors suffering from ‘chemo-brain’ has had positive results with modafinil (Provigil), a drug that promotes wakefulness. The women who took modafinil for eight weeks reported major improvements in memory, concentration and learning.
The findings were presented on June 3 at the American Society of Clinical Oncology meeting in Chicago.
http://www.eurekalert.org/pub_releases/2007-06/uorm-bpa052207.php

Diabetes drug shows promise for preventing brain injury from radiation therapy

Hope for preventing the memory and learning problems that cancer patients often experience after whole-brain radiation treatments comes from a rat study. Rats receiving the diabetes drug piolitazone (Actos®) before, during and after radiation treatments did not experience cognitive impairment. The drug is thought to work by preventing inflammation.
[1156] Zhao, W., Payne V., Tommasi E., Diz D. I., Hsu F-C., & Robbins M. E.
(2007).  Administration of the peroxisomal proliferator-activated receptor gamma agonist pioglitazone during fractionated brain irradiation prevents radiation-induced cognitive impairment.
International Journal of Radiation Oncology, Biology, Physics. 67(1), 6 - 9.
Full text available at http://tinyurl.com/37xglp
http://www.eurekalert.org/pub_releases/2007-01/wfub-dds011007.php

Possible treatment found for 'chemobrain'

A common consequence of chemotherapy is memory problems, confusion and difficulty in concentrating ("chemobrain"). While nearly all breast and ovarian cancer patients receiving chemotherapy or radiation treatments seem to suffer chemobrain, 61% continue to experience memory problems long after their cancer treatment has stopped. A new study involving 154 cancer survivors suggests a possible new treatment using the drug dexmethyphenidate (d-MPH). The drug significantly reduced fatigue and improved memory.
Results of the study were presented to the annual meeting of the American Society of Clinical Oncology.
http://www.eurekalert.org/pub_releases/2005-06/uoc-ptf060705.php

Estrogen boosts memory in men with prostate cancer

A new study suggests that high doses of estrogen may improve long-term memory and decrease feelings of confusion in men whose testosterone levels have been lowered to treat advanced prostate cancer. The findings suggest that hormone deprivation, prostate cancer or a combination of the two significantly impair verbal memory, while estrogen therapy significantly improves verbal memory performance. Hormone deprivation appears to slow working memory performance, but did not affect accuracy. Supplementation with estrogen did not affect working memory.
Beer, T.M. & Janowsky, J. 2004. High dose estrogen may enhance memory in men with prostate cancer. Presented at the American Society for Clinical Oncology annual meeting in New Orleans, La. on June 6.
http://www.eurekalert.org/pub_releases/2004-06/ohs-ebm060604.php
 

Evidence for 'chemobrain'

Childhood brain tumors permanently impact cognition & lifestyle

A survey involving 785 CNS cancer survivors, 5,870 survivors of non-CNS cancers (such as leukemia, Hodgkin's disease, and bone tumors), and 379 siblings of CNS cancer survivors, sent at least 16 years after diagnosis, has found that CNS cancer survivors reported significantly greater neurocognitive dysfunction than their siblings and survivors of other types of cancer. Moreover, these problems were linked to lower achievement in education and in full-time employment and income, as well as less chance of being married. The worst problems were found in those who had tumors in the cortex, and those who had cranial radiation treatment.
Ellenberg, L. et al. 2009. Neurocognitive Status in Long-Term Survivors of Childhood CNS Malignancies: A Report From the Childhood Cancer Survivor Study. Neuropsychology, 23 (6), 705-717.
Full text available at http://www.apa.org/journals/releases/neu-23-6-705.pdf
http://www.eurekalert.org/pub_releases/2009-11/apa-bti102709.php

Whole-brain radiation therapy for tumors results in worse cognitive function

In a randomised controlled trial, 58 patients with one to three brain tumors were treated either with stereotactic radiosurgery (SRS) plus whole-brain radiotherapy (WBRT), or with SRS alone. Those who were randomly assigned to SRS plus WBRT were more likely to show a significant drop on a verbal learning & memory test at 4 months than patients randomly assigned to SRS alone (52% vs 24%, despite patients in the SRS alone group having a higher overall brain tumour recurrence rate. This finding persisted at 6-month follow-up. However, tumors didn’t recur in 73% of patients in the SRS plus WBRT group at 1 year, compared with 27% of patients who received SRS alone. Mortality rates were also higher in the SRS alone group. Despite this, the authors advise against WBRT because it causes more of decline in brain function — but point to the need for close clinical monitoring in that case (but see report below).
[1211] Maor, M. H., Chang E. L., Wefel J. S., Hess K. R., Allen P. K., Lang F. F., et al.
(2009).  Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial.
The Lancet Oncology. 10(11), 1037 - 1044.
Full Article at: http://press.thelancet.com/tlowbrt.pdf 
http://www.eurekalert.org/pub_releases/2009-10/l-aow100109.php
http://www.eurekalert.org/pub_releases/2009-10/uotm-srp100509.php

Increased risk of cognitive problems for brain cancer patients who have whole brain radiation

A six-year study of 58 cancer patients with tumors that have spread to the brain has found that those who had whole brain radiation as well as stereotactic radiosurgery (SRS) had more than double the risk of developing learning and memory problems compared to those who only had stereotactic radiosurgery. The trial was halted when interim results showed that patients who received both had a 49% decline in learning and memory functioning at four months, while those who underwent stereotactic radiosurgery alone experienced only a 23% decline in neurocognitive functioning. Nearly half of the patients who had both treatments lost the ability to recall five words from the same list over three attempts.
The study was presented September 22, 2008, at the American Society for Therapeutic Radiology and Oncology's 50th Annual Meeting in Boston.
http://www.eurekalert.org/pub_releases/2008-09/asft-cpe091508.php

Chemotherapy may not affect memory in breast cancer patients

A study that tested 30 women with breast cancer repeatedly before each cycle of chemotherapy and one month after the final cycle, comparing them to healthy controls, found the women with breast cancer had slight problems in attention and learning skills before chemotherapy started. Only three women (10%) developed cognitive problems during chemotherapy, and interestingly, these were not the women who reported that they had problems.
Another study compared 40 women with breast cancer not yet treated, 27 women who had recently had a breast biopsy that was not cancerous, and 20 breast cancer survivors who had completed treatment at least one year before. On tests of working memory and spatial learning, the women recently diagnosed with breast cancer performed about the same as the women with the recent benign biopsy, but both groups were slower and less accurate than the breast cancer survivors. The results suggest the cognitive difficulties may be related to stress as a result of the diagnosis and other quality-of-life factors.
The studies were presented at the American Academy of Neurology Annual Meeting in Chicago, April 12–19.
http://www.eurekalert.org/pub_releases/2008-04/aaon-cmn040208.php

Chemotherapy's damage to the brain identified

On the other hand, studies have shown that upwards of 82% of breast cancer patients report that they suffer from some form of cognitive impairment, and that a significant proportion of these (reports range from 15-20% to 50%) have lingering cognitive problems a year or more after treatment. And following their demonstration that three common chemotherapy drugs used to treat a wide range of cancers are more toxic to healthy brain cells than the cancer cells they were intended to treat, researchers have now found in cell and mouse studies that the widely used chemotherapy drug 5-fluorouracil (5-FU) is associated with a progressing collapse of support cells that are responsible for producing myelin. The next step will be to find out why some patients are vulnerable to this, and others not.
[935] Han, R., Yang Y. M., Dietrich J., Luebke A., Mayer-Pröschel M., & Noble M.
(2008).  Systemic 5-fluorouracil treatment causes a syndrome of delayed myelin destruction in the central nervous system.
Journal of Biology. 7(4), 12 - 12.
Full text available at http://jbiol.com/content/7/4/12
http://www.eurekalert.org/pub_releases/2008-04/uorm-rdc041708.php

Cognitive deficits among cancer patients insufficiently recognized problem

A survey of 471 cancer patients has found that the cognitive impairment experienced by 14 to 45% of cancer patients can be long-lasting and severely affect their personal and professional lives. Patients report that the lack of concentration, short-term memory loss, difficulty with word recall and the inability to organize or multi-task have led to significant problems at home and in the workplace. 42% described their doctors as dismissive or indifferent when it came to addressing their concerns.
To view the executive summary, visit www.hurricanevoices.org/today/cognition.
http://www.eurekalert.org/pub_releases/2007-10/hvbc-cdl100107.php

How whole-brain radiation might cause dementia

Whole-brain radiation is widely used to treat recurrent brain tumors as well as to prevent other cancers from spreading to the brain. About a half of patients later develop progressive memory problems. A new study has now identified changes in brain chemistry that may be responsible. Using middle-aged rats, researchers found changes in brain receptors for the neurotransmitter glutamate. The changes may impair synaptic communication.
The research was reported at the annual meeting of the Radiation Research Society in Philadelphia.
http://www.eurekalert.org/pub_releases/2006-11/wfub-ssp103006.php

Common cancer treatments toxic to healthy brain cells

A new study may explain ‘chemo-brain’ (cognitive dysfunction following chemotherapy). The study reveals that common drugs used to treat cancer are far more toxic to healthy brain cells than cancer cells — typical exposure levels killed 70-100% of brain cells but just 40-80% of the cancer cells. Moreover, the healthy cells continued to die for at least six weeks after treatment. Now the task is to find out how to protect healthy cells from the drugs.
The full article is available at: http://jbiol.com/content/5/7/22
[568] Dietrich, J., Han R., Yang Y., Mayer-Pröschel M., & Noble M.
(2006).  CNS progenitor cells and oligodendrocytes are targets of chemotherapeutic agents in vitro and in vivo.
Journal of Biology. 5(7), 22 - 22.
http://www.eurekalert.org/pub_releases/2006-11/uorm-cct112806.php

Chemotherapy temporarily affects the brain

A new study has found that although significant regions of the brain associated with cognitive function were significantly smaller in breast cancer patients within 12 months of receiving adjuvant chemotherapy, after three years, there were no differences in these regions between those who had received chemotherapy and those who had not.
[418] Uchitomi, Y., Inagaki M., Yoshikawa E., Matsuoka Y., Sugawara Y., Nakano T., 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 - 156.
http://www.eurekalert.org/pub_releases/2006-11/jws-cta112006.php

Chemo drugs for treating breast cancer may cause changes in cognitive function

A study involving female mice confirms the existence of "chemobrain", finding mild to moderate learning and memory deficits in mice receiving methotrexate and 5-fluorouracil (5FU), two drugs widely used in women to prevent recurrence of breast cancer. The deficits extended only to those types of memory that involve the hippocampus or the frontal lobes (spatial memory and working memory, in this instance). The study only looked at short-term effects (2—4 weeks).
[1069] Winocur, G., Vardy J., Binns M. A., Kerr L., & Tannock I.
(2006).  The effects of the anti-cancer drugs, methotrexate and 5-fluorouracil, on cognitive function in mice.
Pharmacology Biochemistry and Behavior. 85(1), 66 - 75.
http://www.eurekalert.org/pub_releases/2006-10/b-cdf102706.php

Brain scans reveal 'chemobrain' no figment of the imagination

A PET study of 21 women who had undergone surgery to remove breast tumors five to 10 years earlier found that the 16 who had been treated with chemotherapy regimens near the time of their surgeries to reduce the risk of cancer recurrence had specific alterations in activity of frontal cortex, cerebellum, and basal ganglia compared to 5 breast cancer patients who underwent surgery only, and 13 control subjects who did not have breast cancer or chemotherapy. The alterations suggested the chemotherapy patients’ brains were working harder to recall the same information.
[542] Ganz, P. A., Silverman D. H. S., Dy C. J., Castellon S. A., Lai J., Pio B. S., et al.
(2007).  Altered frontocortical, cerebellar, and basal ganglia activity in adjuvant-treated breast cancer survivors 5-10 years after chemotherapy.
Breast Cancer Research and Treatment. 103(3), 303 - 311.
http://www.eurekalert.org/pub_releases/2006-10/uoc--bn092906.php

Cancer survivors may be at higher risk for cognitive dysfunction

A study involving 702 cancer survivors and their cancer-free twins has found that cancer survivors are twice as likely to develop cognitive problems as individuals who have never been treated for cancer. About 15% of the cancer survivors showed cognitive dysfunction. The study did not involve patients who had tumors involving the central nervous system. A follow-up study is planned, to compare those who received different treatments for their cancer.
[284] Heflin, L. H., Meyerowitz B. E., Hall P., Lichtenstein P., Johansson B., Pedersen N. L., et al.
(2005).  Cancer as a risk factor for long-term cognitive deficits and dementia.
Journal of the National Cancer Institute. 97(11), 854 - 856.
http://www.eurekalert.org/pub_releases/2005-05/uosc-csm052705.php 

Impaired neuromotor function following cancer treatment can improve

A study of 142 patients who had blood disorders and who underwent hematopoietic cell transplant (preceded by high-dose chemotherapy) found that, at three months after transplant, patients experienced a significant decline in all cognitive and motor functions tested. By one year, however, the neuromotor functions for most patients had come back to the level experienced before the transplant, with the exception of two capabilities: grip strength and motor dexterity. Patients who had no chemotherapy or chemotherapy with only hydroxyurea prior to the transplant and those who did not receive certain immune suppressants were better off.
Syrjala, K.L., Dikmen, S., Langer, S.L., Roth-Roemer, S. & Abrams, J.R. 2004. Neuropsychologic changes from before transplantation to 1 year in patients receiving myeloablative allogeneic hematopoietic cell transplant. Blood, 104, 3386-3392.
http://www.eurekalert.org/pub_releases/2004-11/asoh-inf110804.php

New radiation therapy of brain tumors in children spares cognitive functions

The second phase of a clinical trial for ependymoma (a malignant brain tumor that occurs predominately in children) suggests a radiation therapy technique called conformal radiation therapy (CRT) allows young patients to enjoy normal development of their cognitive functions. About 75% of the 88 children treated for ependymoma with CRT did not experience progression of their cancer after three years, and their cognitive development was not significantly impaired by radiation therapy. Although radiation treatment is more effective than chemotherapy for brain tumors, physicians have been reluctant to use it because of fears of impairing cognitive development in young children.
[637] Boop, F. A., Sanford R. A., Merchant T. E., Mulhern R. K., Krasin M. J., Kun L. E., et al.
(2004).  Preliminary Results From a Phase II Trial of Conformal Radiation Therapy and Evaluation of Radiation-Related CNS Effects for Pediatric Patients With Localized Ependymoma.
J Clin Oncol. 22(15), 3156 - 3162.
http://www.eurekalert.org/pub_releases/2004-08/sjcr-3io080504.php

Cognitive dysfunction found in women with breast cancer prior to treatment

The first study to evaluate cognitive skills prior to chemotherapy has found significant deficits in neuropsychological function in breast cancer patients before undergoing chemotherapy, and suggests the incidence of "chemobrain," a widely reported side effect in women undergoing treatment for breast cancer, may be overestimated. The study found 35% of the women demonstrated baseline cognitive impairment with significant deficits in verbal learning and memory prior to chemotherapy. Psychomotor processing speed and attention, non-verbal memory, naming, complex visual tasks and hand fine motor dexterity also trended toward significant impairment compared to the controls.
[544] Wefel, J. S., Lenzi R., Theriault R., Buzdar A. U., Cruickshank S., & Meyers C. A.
(2004).  'Chemobrain' in breast carcinoma?: a prologue.
Cancer. 101(3), 466 - 475.
http://www.eurekalert.org/pub_releases/2004-06/jws-scw061604.php

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