Journal
BRAIN BEHAVIOR AND IMMUNITY
Volume 30, Issue -, Pages S117-S125Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbi.2012.05.007
Keywords
Adjuvant chemotherapy; APOE genotype; Brain; Breast cancer; BRIEF-A; Executive function; Frontal lobes; Magnetic resonance imaging; Neuroimaging; Voxel-based morphometry
Categories
Funding
- National Institutes of Health
- National Cancer Institute [R01 CA101318, P30 CA082709, R25 CA117865]
- National Center for Research Resources [U54 RR025761, C06 RR020128, S10 RR027710]
- National Institute on Aging [F30 AG039959, R01 AG019771, P30 AG010133, U24 AG021886]
- Indiana Economic Development Corporation [87884]
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Cognitive changes related to cancer and its treatment have been intensely studied, and neuroimaging has begun to demonstrate brain correlates. In the first prospective longitudinal neuroimaging study of breast cancer (BC) patients we recently reported decreased gray matter density one month after chemotherapy completion, particularly in frontal regions. These findings helped confirm a neural basis for previously reported cognitive symptoms, which most commonly involve executive and memory processes in which the frontal lobes are a critical component of underlying neural circuitry. Here we present data from an independent, larger, more demographically diverse cohort that is more generalizable to the BC population. BC patients treated with (N= 27) and without (N= 28) chemotherapy and matched healthy controls (N = 24) were scanned at baseline (prior to systemic treatment) and one month following chemotherapy completion (or yoked intervals for non-chemotherapy and control groups) and APOE-genotyped. Voxel-based morphometry (VBM) showed decreased frontal gray matter density after chemotherapy, as observed in the prior cohort, which was accompanied by self-reported difficulties in executive functioning. Gray matter and executive symptom changes were not related to APOE epsilon 4 status, though a somewhat greater percentage of BC patients who received chemotherapy were epsilon 4 allele carriers than patients not treated with chemotherapy or healthy controls. These findings provide confirmatory evidence of frontal morphometric changes that may be a pathophysiological basis for cancer and treatment-related cognitive dysfunction. Further research into individual risk factors for such changes will be critical for development of treatment and prevention strategies. (C) 2012 Elsevier Inc. All rights reserved.
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