2. Department of Neurology, Center for Patient Care and Outcomes Research, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
3. The Center for Patient Care and Outcomes Research, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
4. The Schey Center for Cognitive Neuroimaging, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA.
Background: The use of aromatase inhibitor (AI) therapy is increasing due to efficacy in decreasing breast cancer recurrence. There are theoretical reasons for concern about the effects of AI's on cognition, but few empiric studies have addressed this issue. We sought to assess cognitive function in relation to AI exposure.
Methods: Patients aged 65 or older at the time of an incident early-stage breast cancer underwent a battery of neuropsychological tests, as well as functional magnetic resonance imaging (fMRI) during an N-back cognitive task, which incrementally varies working memory load. Of 22 subjects, 11 had been treated with an AI for a mean of 37 months (AI group); 11 had no-AI exposure (no-AI group). The groups had similar distributions of age and educational achievement; no subject had received chemotherapy.
Results: The AI group did not differ significantly from the no-AI group on neuropsychological test scores. However there was a trend toward worse cognitive function among the AI subjects, who demonstrated worse performance on all 12 tests with a Cohen's d effect size of 0.3 or greater. During fMRI testing, the AI group failed to exhibit the expected pattern of increased regional blood oxygenation as the complexity of the working memory task increased. In contrast, the no-AI group showed the normally expected pattern of increased oxygenation as the demands on working memory increased.
Conclusions: This study suggests the possibility of adverse effects of AI exposure on cognition, and suggests that fMRI may be sensitive to early changes in cognitive performance.
Keywords: Breast cancer, aromatase inhibitors, cognition, memory, fMRI