Lifting the fog on 'chemobrain' : a prospective cohort study of chemotherapy-related cognitive changes in women with early breast cancer
Date
2013
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Lacey, Rachel
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The purpose of this prospective study was to evaluate whether women treated with chemotherapy for early breast cancer would show significantly poorer cognitive functioning following treatment than women not treated with chemotherapy. A comprehensive clinical neuropsychological assessment designed to be sensitive to mild cognitive impairment and change in six cognitive domains was conducted in order to uncover any profile of chemotherapy-related cognitive impairment. Women with early breast cancer scheduled to receive adjuvant chemotherapy completed a detailed assessment: before commencing chemotherapy; after completing chemotherapy; and again 9 months later. A control group of women with early breast cancer not receiving chemotherapy were tested at matched timepoints. Prior to the group analysis, a multivariate statistical approach called Principal Components Analysis (PCA) was used to examine the entire set of relationships among neuropsychological outcome measures within a cognitive domain. This enabled the underlying dimensions that explain the correlations among the set of measures to be identified. From this a smaller set of neuropsychologically meaningful summarized outcome measures were derived, using the first principal component summary score, for use in subsequent analyses involving ANOVA and regression. Two approaches were used for the analyses of individual deficits. For the first, individual test scores were screened for 'cognitive complications' at each timepoint, defined as a score of more than two standard deviations below the mean of age-standardized normative data for each test. An overall 'lower than expected performance' score was also calculated for each individual from the mean of all scores that were one and a half standard deviations below their estimated premorbid intelligence. Findings from the group analyses provided limited support at the 95% confidence level for the hypothesis that women treated with chemotherapy would demonstrate significantly worse cognitive functioning over a 9-month post treatment follow-up period relative to women not treated with chemotherapy for breast cancer. Only verbal recall discriminability, derived from new more sensitive measures of verbal recall accuracy and discrimination, displayed a significant interaction effect. However, when groupings with interaction effects that showed trends towards significance were examined, a profile of chemotherapy-related cognitive impairment was revealed within verbal learning and memory, and executive functions. This trend was not found at the domain level of executive functions but was revealed at the nested subgroup level, namely in verbal fluency, flexibility and reasoning, and visual cognitive flexibility. Factors that increased the vulnerability of women to decline included lower premorbid IQ, clinical anxiety or mood disorders at baseline, hormonal therapy following chemotherapy, and chemotherapy-induced adverse events, such as neutropenia. For the first time in a prospective study the results of the group analyses were supported by the findings from the individual analyses. The current study unveiled a complex interaction of pre-treatment cognitive reserve and cognitive resilience with chemotherapy-related cumulative threshold effects on cognitive outcome following chemotherapy. The cognitive reserve threshold appears to be lowered by the cumulative effects of chemotherapy and acute adverse events, like neutropenia, and hormonal therapy, but individual threshold differences are moderated by cognitive reserve and cognitive resilience.
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