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ABSTRACT: OBJECTIVE: The purpose of this study was to determine if cognition progressively worsens with cumulative chemotherapy exposure. We reasoned that the demonstration of such a 'dose-response' relationship would help to establish whether cognitive changes are caused by neurotoxic effects of chemotherapy or whether they are due to other confounding factors such as mood and pre-treatment differences in cognition. METHODS: Sixty women with early stage breast cancer, aged 65 years or younger with no previous history of cancer or chemotherapy, were matched to 60 healthy women on age and education. Neuropsychological assessment was conducted after surgery but prior to commencing chemotherapy and then again following each chemotherapy cycle in patients and at yoked intervals in healthy controls. We used multilevel modeling to assess change over time in an overall cognitive summary score as well as domain-specific cognitive scores. RESULTS: After controlling for baseline performance, age, education, and mood, the chemotherapy group showed a significant progressive decline over time relative to a matched healthy control group in an overall cognitive summary score, as well as in working memory, processing speed, verbal memory, and visual memory scores. A linear model best fit the trajectory of cognitive change over the course of treatment in the chemotherapy group supporting a dose-response hypothesis. CONCLUSIONS: These results are in keeping with a dose-response relationship and provide the most compelling clinical evidence to date that cognitive decline is caused by chemotherapy exposure. Copyright © 2012 John Wiley & Sons, Ltd.
Psycho-Oncology 08/2012; · 3.34 Impact Factor
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ABSTRACT: Prechemotherapy neuroimaging data are lacking in posttreatment cognitive impairment studies. Breast cancer patients and noncancer controls were scanned prior to chemotherapy during a response inhibition task. Task reaction times and error rates, as well as neuropsychological tests, hospital records, and salivary biomarkers, were investigated, yielding no significant group differences. Significant group differences observed for the functional magnetic resonance imaging (fMRI) data depended on the type of analysis performed, most consistently implicating widespread attenuated activations in patients. The patient group also revealed considerable variability in task-related brain activity. These pretreatment differences highlight the need to understand the effects of confounding variables before considering posttreatment effects. Role of the funding source: The Canadian Breast Cancer Foundation has funded this project. Their contribution was solely financial support.
Journal of Clinical and Experimental Neuropsychology 03/2012; 34(5):543-60. · 2.13 Impact Factor
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ABSTRACT: Introduction: Cognitive deficits are a side-effect of chemotherapy, however pre-treatment research is limited. This study examines neurofunctional differences during working memory between breast cancer (BC) patients and controls, prior to chemotherapy. Methods: Early stage BC females (23), scanned after surgery but before chemotherapy, were individually matched to non-cancer controls. Participants underwent functional magnetic resonance imaging (fMRI) while performing a Visuospatial N-back task and data was analyzed by multiple group comparisons. fMRI task performance, neuropsychological tests, hospital records, and salivary biomarkers were also collected. Results: There were no significant group differences on neuropsychological tests, estrogen, or cortisol. Patients made significantly fewer commission errors but had less overall correct responses and were slower than controls during the task. Significant group differences were observed for the fMRI data, yet results depended on the type of analysis. BC patients presented with increased activations during working memory compared to controls in areas such as the inferior frontal gyrus, insula, thalamus, and midbrain. Individual group regressions revealed a reverse relationship between brain activity and commission errors. Conclusion: This is the first fMRI investigation to reveal neurophysiological differences during visuospatial working memory between BC patients pre-chemotherapy and controls. These results also increase the knowledge about the effects of BC and related factors on the working memory network. Significance: This highlights the need to better understand the pre-chemotherapy BC patient and the effects of associated confounding variables.
Frontiers in Human Neuroscience 01/2011; 5:122. · 2.34 Impact Factor
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ABSTRACT: To explore the heterogeneity of mild traumatic brain injury (mTBI).
Hospital-based prospective follow-up study of 125 patients with mTBI sub-divided into 'severity' sub-groups on the basis of GCS scores (GCS of 15 = mild sub-group; GCS of 13-14 = moderate sub-group). Post-traumatic amnesia (PTA) duration (30 minutes used as a cut-off) was also used to define group membership for secondary analyses. The follow-up assessment consisted of a brief neuropsychological battery as well as measures of neurobehavioural functioning, community integration and post-concussive symptomatology. CT scanning was also obtained when clinically relevant.
The two mTBI sub-groups, as defined by GCS scores, did not differ with respect to post-concussive symptomatology, neurobehavioural symptoms, neuropsychological performance or CT scan abnormalities. In contrast, when group membership was redefined on the basis of PTA, the two sub-groups differed significantly with respect to intracranial abnormalities and report of aggressive or disinhibited behaviours at the 6-month mark.
While the notion of heterogeneity in mTBI was not supported when severity was based on GCS scores, there was partial support when PTA duration was used as a measure of severity.
Brain Injury 10/2009; 23(11):879-87. · 1.36 Impact Factor
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ABSTRACT: In spite of the fact that reaction time (RT) measures are sensitive to the effects of traumatic brain injury (TBI), few RT procedures have been developed for use in standard clinical evaluations. The computerized test of information processing (CTIP) [Tombaugh, T. N., & Rees, L. (2000). Manual for the computerized tests of information processing (CTIP). Ottawa, Ont.: Carleton University] was designed to measure the degree to which TBI decreases the speed at which information is processed. The CTIP consists of three computerized programs that progressively increase the amount of information that is processed. Results of the current study demonstrated that RT increased as the difficulty of the CTIP tests increased (known as the complexity effect), and as severity of injury increased (from mild to severe TBI). The current study also demonstrated the importance of selecting a non-biased measure of variability. Overall, findings suggest that the CTIP is an easy to administer and sensitive measure of information processing speed.
Archives of Clinical Neuropsychology 01/2007; 22(1):25-36. · 2.18 Impact Factor
