Chemotherapy-Induced Changes in Brain Structure Correlate with Cognitive Dysfunction

JHOP - March 2012, VOL 2 NO 1 - From the Literature, From the Literature
Robert J. Ignoffo, PharmD, FASHP, FCSHP, FHOPA
Clinical Professor Emeritus
University of California, San Francisco
Professor of Pharmacy
College of Pharmacy, Touro University–California
Mare Island, Vallejo, CA

Background: Women with breast cancer often complain of cognitive difficulties after chemotherapy. Findings from several cross-sectional and longitudinal studies of women who receive chemotherapy for breast cancer have confirmed a correlation between impaired memory and other cognitive functions and chemotherapy. This study investigated the link between chemo­therapy-induced structural changes in the brain and cognitive function.

Design: This Dutch study of 69 premenopausal women compared 34 women (mean age, 43.7 years) with early-stage breast cancer who received chemotherapy with 16 women (mean age, 43.1 years) with early-stage breast cancer who did not receive chemotherapy and 19 matched healthy controls (mean age, 43.8 years). Before treatment initiation and at 3- to 4-month intervals, all participants underwent neuropsychologic testing involving attention, concentration, memory, executive functioning, cognitive/psychomotor processing speed, and self-reported cognitive functioning. In addition, the cerebral white matter of all participants was analyzed via magnetic resonance diffusion tensor imaging, which enables the visualization and characterization of the white matter architecture.

Summary: Baseline testing revealed similar results among all 3 groups, but paired t-test analyses showed that the chemotherapy group scored significantly worse on attention, concentration, psychomotor speed, and memory tests 3 to 4 months after treatment than at baseline (P <.05). By contrast, the 2 control groups performed significantly better at 3 to 4 months than at baseline (P <.05) in those domains, a result consistent with a learning effect. In addition, in the chemotherapy group, fractional anisotropy (a measure of the water molecule diffusion in the white matter tissue) was significantly lower in the frontal, parietal, and occipital white matter tracts after treatment than at baseline, whereas in the 2 control groups, the baseline and posttreatment measurements were the same. A correlation analysis revealed that the decline in the attention and verbal memory domains in the neuropsychologic tests in the chemotherapy group correlated with the observed changes in fractional anisotropy (P <.05).

Takeaway: This appears to be the first study of the pathophysiology of chemotherapy-induced cognitive impairment. The study correlated cognitive impairment with tests that could determine if chemotherapy could cause direct damage to brain white matter. Thirty-four patients received chemotherapy consisting of adjuvant fluorouracil, epirubicin, and cyclophosphamide. Cog­nitive deficits included decreased attention and verbal memory and were observed fairly rapidly, within 4 months of treatment. The investigators demonstrated changes in white matter structure after the institution of chemotherapy. The study results were partially confounded by the use of tamoxifen in 18 patients, beginning at 7 months into the study; tamoxifen may impair cognitive function.

This study provides valuable new information on chemotherapy-induced cognitive dysfunction. With the use of these new tests for cognition, future studies may lead to effective agents to prevent this side effect.

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

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