Chemotherapy causes changes to the brain's metabolism and blood flow that can linger at least 10 years after the last dose of chemotherapy.

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

Positron emission tomography (PET) was used to scan the brains of 21 women who had undergone surgery to remove breast tumors 5-10 years earlier.  Sixteen of them had been treated with chemotherapy regimens near the time of their surgeries to reduce the risk of cancer recurrence.  PET images were compared to PET scans from 18 control patients who had not received chemotherapy.  As the women performed a series of short-term memory tasks, we measured blood flow to their brains, and then ran a scan of the patients' resting brain metabolism after the women finished the memory tests. 

The PET scans showed a link between chemobrain symptoms and lower metabolism in a key region of the frontal cortex, such that the lower the patient's resting brain metabolism rate was, the more difficulty she had performing a short-term memory test.  The scans also revealed that blood flow to the frontal cortex and cerebellum spiked as the chemotherapy subjects performed the memory tests, indicating a rapid jump in these brain regions' activity level.  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.  In effect, these women's brains were working harder than the control subjects' to recall the same information. 

Finally, it was discovered that patients who underwent hormonal therapy in addition to chemotherapy displayed changes to their basal ganglia, a part of the brain that works to bridge thought and action.  On average, these women showed an 8% drop in resting metabolism in this brain region. 

Our team recently received funding from the United States National Institutes of Health to carry out an expanded study, following a larger number of patients prospectively and longitudinally, from the time of their initial chemotherapy shortly after diagnosis, continuing for several years afterwards.  If the results of the present study are borne out, then in the future this type of neuroimaging could be used to monitor the effects of chemotherapy on brain function, similar to the way that MUGA scans are presently being used to monitor the effects of some chemotherapy agents on heart function, potentially guiding treatment to minimize adverse impact on neuropsychological abilities.

 

Bibliographic reference:

Silverman DH et al.: "Altered frontocortical, cerebellar, and basal ganglia activity in adjuvant-treated breast cancer survivors 5-10 years after chemotherapy", Breast Cancer Res Treat. 2006 Sep 29

 

Dan Silverman

Department of Molecular and Medical Pharmacology, University of California, David Geffen School of Medicine, Los Angeles, CA, USA