Control volunteers needed
for Research
Study of Chemotherapy Side Effects . . .
Breast Cancer Information. . .
Funded by: National Institute on Aging
Time Period: 07/04 - 06/09
Abstract
Objectives: The purpose of this project is to study the effects of adjuvant chemotherapy on
cognitive functioning among older women with breast cancer, and to test hypotheses regarding risk factors and a possible
mechanism for this impairment. Although it has appeared for some time that high dose chemotherapy may impair cognition,
there is a growing literature that suggests that certain aspects of cognition are impaired by standard-dose chemotherapy.
Complaints about problems with memory and concentration are common among women undergoing treatment, and the syndrome is
colloquially referred to as "chemobrain." It is a significant factor affecting quality of life (QOL). The problem may
be especially noteworthy among older women, who already may have some cognitive impairment secondary to the aging process
itself, or associated with various comorbid medical disorders that could affect cognition. The issue has not been studied
to date in older women, and little is known about the natural history of cognitive impairment among women on chemotherapy
generally. We hypothesize that women with disorders that compromise cerebral vasculature (e.g., diabetes, hypertension)
may be especially at risk, due to a mild impairment of the blood-brain barrier (BBB). In addition, we will indirectly
assess the hypothesis that the infiltration of pro-inflammatory cytokines across the endothelial cell layer in brain
capillaries may impair cognition by producing an inflammatory condition in the white matter, especially periventricularly.
Methods: We are studying four groups (n = 85 in each) of women in a repeated-measures design—older
women (age 60 and older) with cancer on adjuvant therapy, older women with cancer who decline adjuvant therapy, women aged
45-59 with breast cancer on adjuvant therapy, and a group of age- and education-matched healthy control subjects. We
conduct cognitive assessments at baseline (prior to treatment), three months after completion of chemotherapy, and nine
months after chemotherapy, focusing in particular on cognitive abilities frequently associated with white matter disease
(e.g., working memory, attention, executive functioning). We acquire T2-weighted MRI data on a subsample of each group
(n = 21 per group) at each time point in order to measure the volume of affected white matter. We draw blood to measure
the level of the peripheral pro-inflammatory cytokines Interleukin-1 and Interleukin-6 (IL-1 and IL-6), and Tumor Necrosis
Factor alpha (TNF-a). We also assess the level of C-reactive protein (CRP), a general measure of inflammation. In our
analyses, we plan to assess the prevalence and nature of cognitive impairment and MRI anomalies among older women. We will
use mixed effects models to evaluate the contribution of vascular risk factors (e.g., diabetes, hypertension) to the
incidence, severity, and persistence of cognitive deficits, and to assess the contribution of cytokine level of cognitive
deficits and white matter hyperintensities on T2 imaging.
Key Staff: Grigsby, Bennett, Brega, Conway, Baillie, Fleshner, Simoneau