10_05_2006. Chemotherapy causes changes in the brain's metabolism and blood flow that can last as long as 10 years, a discovery that may explain the mental fog and confusion that affect many cancer survivors, researchers said on Thursday. The researchers, from the University of California, Los Angeles, found that women who had undergone chemotherapy five to 10 years earlier had lower metabolism in a key region of the frontal cortex.

Women treated with chemotherapy also showed a spike in blood flow to the frontal cortex and cerebellum while performing memory tests, indicating a rapid jump in activity level, the researchers said in a statement about their study.

"The same area of the frontal lobe that showed lower resting metabolism displayed a substantial leap in activity when the patients were performing the memory exercise," said Daniel Silverman, the UCLA associate professor who led the study.

"In effect, these women's brains were working harder than the control subjects' to recall the same information," he said in a statement.

Experts estimate at least 25 percent of chemotherapy patients are affected by symptoms of confusion, so-called chemo brain, and a recent study by the University of Minnesota reported an 82 percent rate, the statement said.

"People with 'chemo brain' often can't focus, remember things or multitask the way they did before chemotherapy," Silverman said. "Our study demonstrates for the first time that patients suffering from these cognitive symptoms have specific alterations in brain metabolism."

The study, published on Thursday in the online edition of Breast Cancer Research and Treatment, tested 21 women who had surgery to remove breast tumors, 16 of whom had received chemotherapy and five who had not.

The researchers used positron emission tomography scans to compare the brain function of the women. They also compared the scans with those of 13 women who had not had breast cancer or chemotherapy.

Positron emission tomography creates an image of sections of the body using a special camera that follows the progress of an injected radioactive tracer.

Researchers used the scans to examine the women's resting brain metabolism as well as the blood flow to their brains as they did a short-term memory exercise.

Silverman said the findings suggested PET scans could be used to monitor the effects of chemotherapy on brain metabolism. Since the scans already are used to monitor patients for tumor response to therapy, the additional tests would be easy to add, he said.

Acute and late onset cognitive dysfunction associated with chemotherapy in women with breast cancer

The University of Texas M. D. Anderson Cancer Center, Section of Neuropsychology, Department of Neuro-Oncology, Houston, Texas

Growing evidence supports cognitive dysfunction associated with standard dose chemotherapy in breast cancer survivors. We determined the incidence, nature, and chronicity of cognitive dysfunction in a prospective longitudinal randomized phase 3 treatment trial for patients with T1-3, N0-1, M0 breast cancer receiving 5-fluorouracil, doxorubicin, and cyclophosphamide with or without paclitaxel.

Forty-two patients underwent a neuropsychological evaluation including measures of cognition, mood, and quality of life. Patients were scheduled to be assessed before chemotherapy, during and shortly after chemotherapy, and 1 year after completion of chemotherapy.

Before chemotherapy, 21% (9 of 42) evidenced cognitive dysfunction. In the acute interval, 65% (24 of 37) demonstrated cognitive decline. At the long-term evaluation, 61% (17 of 28) evidenced cognitive decline after cessation of treatment. Within this group of patients, 71% (12 of 17) evidenced continuous decline from the acute interval, and, notably, 29% (5 of 17) evidenced new delayed cognitive decline. Cognitive decline was most common in the domains of learning and memory, executive function, and processing speed. Cognitive decline was not associated with mood or other measured clinical or demographic characteristics, but late decline may be associated with baseline level of performance.

CONCLUSIONS:

Standard dose systemic chemotherapy is associated with decline in cognitive function during and shortly after completion of chemotherapy. In addition, delayed cognitive dysfunction occurred in a large proportion of patients. These findings are consistent with a developing body of translational animal research demonstrating both acute and delayed structural brain changes as well as functional changes associated with common chemotherapeutic agents such as 5-flouorouracil. Cancer 2010. © 2010 American Cancer Society.

Neurocognitive performance in breast cancer survivors exposed to adjuvant chemotherapy and tamoxifen. Castellon SA,  J Clin Exp Neuropsychol. 2004 Oct;26(7):955-69.   Department of Psychiatry & Biobehavioral Sciences, UCLA School of Medicine, Los Angeles, CA, USA. scastell@ucla.edu

The primary aim of the current study was to examine whether neurocognitive functioning among breast cancer survivors (BCS) exposed to systemic adjuvant chemotherapy differs from that seen among BCS who did not receive chemotherapy. The performance of each of these BCS groups was compared to a demographically matched comparison group without history of breast cancer, a group not included in the majority of previous cognitive functioning studies. We also sought to explore whether usage of the anti-estrogen drug tamoxifen, a common component of breast cancer treatment, was related to neurocognitive functioning. Finally, we wished to examine the relationship between subjective report of cognitive functioning and objective performance on neurocognitive measures among BCS. Fifty-three survivors of breast cancer (all between 2-5 years after diagnosis and initial surgical removal of cancerous tissue) and 19 healthy non-BCS comparison subjects were administered a comprehensive neurocognitive battery, and measures of mood, energy level, and self-reported cognitive functioning. Those BCS who received adjuvant chemotherapy performed significantly worse in the domains of verbal learning, visuospatial functioning, and visual memory than BCS treated with surgery only. Those who received both chemotherapy and tamoxifen showed the greatest compromise. Although patients who received chemotherapy (with and without tamoxifen) performed worse than those treated with surgery only on several domains, neither group was significantly different from demographically matched comparison subjects without a history of breast cancer. Finally, we found no relationship between subjective cognitive complaints and objective performance, although cognitive complaints were associated with measures of psychological distress and fatigue. We highlight ways in which these data converge with other recent studies to suggest that systemic chemotherapy, especially in combination with tamoxifen, can have adverse yet subtle effects on cognitive functioning.

Cognitive functioning after adjuvant chemotherapy and/or radiotherapy for early-stage breast carcinoma. Donovan.  Cancer. 2005 Dec 1;104(11):2499-507 Psychosocial and Palliative Care Program, Moffitt Cancer Center and Research Institute, Tampa, Florida 33612, USA.

BACKGROUND: Evidence suggests that women diagnosed with early-stage breast carcinoma may experience cognitive problems as a consequence of adjuvant chemotherapy treatment. The present study was conducted to examine whether there are differences in cognitive performance and cognitive complaints between women treated with and without chemotherapy for TNM Stage 0 to II breast carcinoma. METHODS: As part of a larger study on quality of life, women were recruited with newly diagnosed Stage 0 to II breast carcinoma scheduled to be treated with chemotherapy plus radiotherapy (n = 60) or radiotherapy only (n = 83). Six months after the completion of treatment, participants were administered a standard neuropsychologic battery to assess cognitive performance and a self-report measure to assess perceived cognitive problems. RESULTS: There were no statistically significant differences between women who received chemotherapy and those who did not with regard to their average performance on tests of episodic memory, attention, complex cognition, motor performance, or language. Likewise, there were no significant differences between the treatment groups in the prevalence of impairment in each of these cognitive domains. Women who underwent chemotherapy also did not report significantly more problems with cognitive functioning than women treated without chemotherapy. CONCLUSIONS: The findings failed to confirm previous reports suggesting adjuvant chemotherapy is associated with problems in cognitive functioning among women who receive treatment for Stage 0 to II breast carcinoma. Future research should use prospective longitudinal research designs incorporating appropriate comparison groups to further explore this issue.