Functional Magnetic Resonance Imaging (fMRI) was used to examine brain activity in women with early stage Breast Cancer (BC) and to compare their neural profiles to a matched control group. This was accomplished as participants performed two working memory tasks, before and at two time points following the chemotherapy intervention of the BC group. Nineteen BC patients between the ages of 18 and 65 years were recruited from the Ottawa Hospital Regional Cancer Centre. The nineteen control participants were matched on sex, language, age and education. The results, from whole brain analyses, show significant differences in neural activity between BC patients and matched control participants during both verbal and visuospatial working memory tasks, before and right after chemotherapy. However, these differences were no longer observed one year post chemotherapy for verbal WM processing. Performance results were not significantly different between groups until the third imaging sessions when patients made significantly more errors of omission than controls for both tasks. Importantly, mood, anxiety and fatigue all played significant roles in the observed findings demonstrating the multifaceted nature of the impact of both cancer and chemotherapy on neural function during working memory. This is one of the first fMRI studies to measure neural activations during cognitive performance both before and after chemotherapy in BC patients and a control group while controlling for many potentially confounding variables. While BC patients should be made aware of the potential cognitive challenges they might face before, during and shortly after treatment, they can also feel reassured that these impairments may not be long lasting.

Advances in cancer treatment have led to increasing numbers of survivors left to struggle with the long-term adverse effects of disease and treatment. Many possible effects have been described including anxiety, depression, as well as physical side effects and consequences of cancer treatment. One particular adverse effect that is frequently reported but often overlooked in clinical practice is disturbances of cognitive functioning. Cancer-related cognitive impairment (CRCI) is a growing area of research with important clinical implications for current patients and survivors. Despite a huge increase in this research endeavour in the last 20 years, many important questions remain unanswered due, in large part, to methodological limitations of many of the studies. The overall goal of this dissertation is to critically examine previous CRCI research from a methodological perspective. It will explore limitations and confounds in this research and provide suggestions for improving future work. This dissertation is comprised of three manuscripts, a critical literature review and two original papers, addressing specific research questions. The first original paper addresses the disparity between the results of objective (performance-based) and subjective (self-report) measures of cognition that is typically observed in samples of cancer patients, using multilevel modeling to explore the hypothesis that this is due to failure to address measures of change over time. Despite negative findings, the methodological approach taken to this research question provided greater evidence for this subjective-objective disparity as well as methodological suggestions for future studies. The second original paper explores the sensitivity and validity of a computerized cognitive test for measuring CRCI to determine if it might be an appropriate alternative to traditional, resource-intensive neuropsychological testing. This study found that, although the computerized measure of cognitive functioning was not sensitive enough to detect changes at the individual level or within specific domains, it was sensitive to changes in cognitive functioning at the group level suggesting its usefulness as a screening tool in research settings. By addressing methodological limitations of research to date and, specifically, the two issues identified above, this dissertation aims to a) make recommendations to help improve the quality of future research, b) validate the cognitive complaints of cancer patients, and c) improve access to cognitive assessments leading to increased detection and treatment of cognitive side effects and improvement in quality of life of cancer survivors.

Functional Magnetic Resonance Imaging (fMRI) was used to examine brain activity in women with early stage Breast Cancer (BC) and to compare their neural profiles to a matched control group. This was accomplished as participants performed two working memory tasks, before and at two time points following the chemotherapy intervention of the BC group. Nineteen BC patients between the ages of 18 and 65 years were recruited from the Ottawa Hospital Regional Cancer Centre. The nineteen control participants were matched on sex, language, age and education. The results, from whole brain analyses, show significant differences in neural activity between BC patients and matched control participants during both verbal and visuospatial working memory tasks, before and right after chemotherapy. However, these differences were no longer observed one year post chemotherapy for verbal WM processing. Performance results were not significantly different between groups until the third imaging sessions when patients made significantly more errors of omission than controls for both tasks. Importantly, mood, anxiety and fatigue all played significant roles in the observed findings demonstrating the multifaceted nature of the impact of both cancer and chemotherapy on neural function during working memory. This is one of the first fMRI studies to measure neural activations during cognitive performance both before and after chemotherapy in BC patients and a control group while controlling for many potentially confounding variables. While BC patients should be made aware of the potential cognitive challenges they might face before, during and shortly after treatment, they can also feel reassured that these impairments may not be long lasting.

Indiana University-Purdue University Indianapolis (IUPUI) / Only one third of older breast cancer survivors (BCS) meet national physical activity (PA) guidelines. Theories of self-regulation and research with older adults suggest that executive function (EF) plays an important role in PA, yet the impact of lower EF on older survivors’ PA is unknown. My project addressed this gap using secondary data from the Thinking and Living with Cancer (TLC) cohort study, which examined cognitive function among older BCS pre-treatment, followed every 12 months, and contemporaneously assessed matched controls. My first aim was to test two hypotheses regarding EF change and PA and determine if these relationships differ between BCS and controls. My hypotheses were: 1) EF decline from baseline to 12 months will predict lower PA at 24 months, and 2) lower PA at 12 months will predict EF decline from 12 to 24 months. My second aim was to explore whether the effects of EF change on PA in BCS differed based on risk factors for accelerated cognitive decline (i.e., older age, more advanced cancer stage, comorbidity, and APOE ε4 genotype). The TLC study measured EF with neuropsychological tests and PA with the International Physical Activity Questionnaire-Short Form. For aims 1 and 2, I used multiple regression with multiple imputation. Primary results showed no significant effect of EF change from baseline to 12 months on PA at 24 months (β=-0.01, p=0.88) and no significant group (BCS vs. controls) by EF interaction (β=-0.05, p=0.33). Separate models in BCS and controls showed similar findings. In the entire sample, PA at 12 months significantly predicted EF change from 12 to 24 months (β=0.17, p=0.01), but there was no significant group by PA interaction (β=-0.06, p=0.54). Separate analyses by group found a significant effect of PA for controls (β=0.07, p=0.02), but not for BCS (β=0.05, p=0.27). Regarding the second aim, there were no significant interactions between EF change and the proposed risk factors on PA. Findings were largely inconsistent with theory and prior research. Continued research in this area will inform future exercise interventions to improve physical and cognitive health for the growing population of older cancer survivors.