Study protocol of the Aerobic exercise and CogniTIVe functioning in women with breAsT cancEr (ACTIVATE) trial: a two-arm, two-centre randomized controlled trial.

BACKGROUND: Up to 75% of women diagnosed with breast cancer report chemotherapy-related cognitive changes (CRCC) during treatment, including decreased memory, attention, and processing speed. Though CRCC negatively impacts everyday functioning and reduces overall quality of life in women diagnosed with breast cancer, effective interventions to prevent and/or manage CRCC are elusive. Consequently, women seldom receive advice on how to prevent or manage CRCC. Aerobic exercise is associated with improved cognitive functioning in healthy older adults and adults with cognitive impairments. Accordingly, it holds promise as an intervention to prevent and/or manage CRCC. However, evidence from randomized controlled trials (RCTs) supporting a beneficial effect of aerobic exercise on CRCC is limited. The primary aim of the ACTIVATE trial is to evaluate the impact of supervised aerobic exercise on CRCC in women receiving chemotherapy for breast cancer. METHODS: The ACTIVATE trial is a two-arm, two-centre RCT. Women diagnosed with stage I-III breast cancer and awaiting neo-adjuvant or adjuvant chemotherapy are recruited from hospitals in Ottawa (Ontario) and Vancouver (British Columbia), Canada. Recruits are randomized to the intervention group (aerobic exercise during chemotherapy) or the wait-list control group (usual care during chemotherapy and aerobic exercise post-chemotherapy). The primary outcome is cognitive functioning as measured by a composite cognitive summary score (COGSUM) of several neuropsychological tests. Secondary outcomes are self-reported cognitive functioning, quality of life, and brain structure and functioning (measured by magnetic resonance imaging (MRI)/functional MRI and electroencephalography). Assessments take place pre-chemotherapy (pre-intervention), mid-way through chemotherapy (mid-intervention/mid-wait period), end of chemotherapy (post-intervention/post-wait period; primary endpoint), 16-weeks post-chemotherapy, and at 1-year post-baseline. DISCUSSION: Aerobic exercise is a promising intervention for preventing and/or managing CRCC and enhancing quality of life among women diagnosed with breast cancer. The ACTIVATE trial tests several novel hypotheses, including that aerobic exercise can prevent and/or mitigate CRCC and that this effect is mediated by the timing of intervention delivery (i.e., during versus post-chemotherapy). Findings may support prescribing exercise during (or post-) chemotherapy for breast cancer and elucidate the potential role of aerobic exercise as a management strategy for CRCC in women with early-stage breast cancer. TRIAL REGISTRATION: The trial was registered with the ClinicalTrials.gov database ( NCT03277898 ) on September 11, 2017.

A Hypothesis-Generating Study Using Electrophysiology to Examine Cognitive Function in Colon Cancer Patients.

INTRODUCTION: The purpose of this study was to describe the trajectory of cognitive function using neuropsychological tests and electrophysiological measures in individuals receiving 5FU/oxaliplatin chemotherapy for colon cancer. METHODS: A total of 10 participants were tested at baseline (within 3 weeks of starting chemotherapy), 6 months (coinciding with the end of chemotherapy treatment), and 12 months (approximately 6 months post-chemotherapy). Participants completed neuropsychological tests and electrophysiology recordings of P300 event-related potential (ERP) elicited by a sustained attention to response task paired with experience sampling of attentional states (subjective reports of on-task or mind wandering). RESULTS: No change in mean neuropsychological test performance was observed. Comparison of mean P300 ERP amplitudes as a function of attentional states (on-task vs. mind wandering) revealed no main effect of attentional state observed at baseline or 6 months, but a significant effect of attention was observed at 12 months, consistent with effects observed in healthy individuals. CONCLUSIONS: Future studies can consider sustained attention constructs when studying cognitive function in colon cancer patients.

Patient perspectives of the experience of a computerized cognitive assessment in a clinical setting.

INTRODUCTION: Computerized assessments are becoming widely accepted in the clinical setting and as a potential outcome measure in clinical trials. To gain patient perspectives of this experience, the aim of the present study was to investigate patient attitudes and perceptions of the Cognigram [Cogstate], a computerized cognitive assessment. METHODS: Semi-structured interviews were conducted with 19 older adults undergoing a computerized cognitive assessment at the University of British Columbia Hospital Clinic for Alzheimer Disease and Related Disorders. Thematic analysis was applied to identify key themes and relationships within the data. RESULTS: The analysis resulted in three categories: attitudes toward computers in healthcare, the cognitive assessment process, and evaluation of the computerized assessment experience. The results show shared views on the need for balance between human and computer intervention, as well as room for improvement in test design and utility. DISCUSSION: Careful design and user-testing should be made a priority in the development of computerized assessment interfaces, as well as reevaluating the cognitive assessment process to minimize patient anxiety and discomfort. Future research should move toward continuous data capture within clinical trials and ensuring instruments of high reliability to reduce variance.

Altered neural activation during prepotent response inhibition in breast cancer survivors treated with chemotherapy: an fMRI study.

While impairments in executive functions have been reported in breast cancer survivors (BCS) who have undergone adjuvant chemotherapy, only a limited number of functional neuroimaging studies have associated alterations in cerebral activity with executive functions deficits in BCS. Using fMRI, the current study assessed the neural basis underlying a specific facet of executive function, namely prepotent response inhibition. 12 BCS who self-reported cognitive problems up to 3 years following cancer treatment and 12 female healthy comparisons (HC) performed the Stroop task. We compared their neural activation between the incongruent and neutral experimental conditions. Relative to the HC group, BCS showed lower blood-oxygen level dependent signal in several frontal regions, including the anterior cingulate cortex, a region critical for response inhibition. Our data indicates reduced neural activation in BCS during a prepotent response inhibition task, providing support for the prevailing notion of neural alterations observed in BCS treated with chemotherapy.

C-TOC (Cognitive Testing on Computer): investigating the usability and validity of a novel self-administered cognitive assessment tool in aging and early dementia.

INTRODUCTION: Cognitive Testing on Computer (C-TOC) is a novel computer-based test battery developed to improve both usability and validity in the computerized assessment of cognitive function in older adults. METHODS: C-TOC's usability was evaluated concurrently with its iterative development to version 4 in subjects with and without cognitive impairment, and health professional advisors representing different ethnocultural groups. C-TOC version 4 was then validated against neuropsychological tests (NPTs), and by comparing performance scores of subjects with normal cognition, Cognitive Impairment Not Dementia (CIND) and Alzheimer disease. C-TOC's language tests were validated in subjects with aphasic disorders. RESULTS: The most important usability issue that emerged from consultations with 27 older adults and with 8 cultural advisors was the test-takers' understanding of the task, particularly executive function tasks. User interface features did not pose significant problems. C-TOC version 4 tests correlated with comparator NPT (r=0.4 to 0.7). C-TOC test scores were normal (n=16)>CIND (n=16)>Alzheimer disease (n=6). All normal/CIND NPT performance differences were detected on C-TOC. Low computer knowledge adversely affected test performance, particularly in CIND. C-TOC detected impairments in aphasic disorders (n=11). DISCUSSION: In general, C-TOC had good validity in detecting cognitive impairment. Ensuring test-takers' understanding of the tasks, and considering their computer knowledge appear important steps towards C-TOC's implementation.

Scientific and ethical features of English-language online tests for Alzheimer's disease.

INTRODUCTION: Freely accessible online tests for the diagnosis of Alzheimer's disease (AD) are widely available. The objective of this study was to evaluate these tests along three dimensions as follows: (1) scientific validity; (2) human-computer interaction (HCI) features; and (3) ethics features. METHODS: A sample of 16 online tests was identified through a keyword search. A rating grid for the tests was developed, and all tests were evaluated by two expert panels. RESULTS: Expert analysis revealed that (1) the validity of freely accessible online tests for AD is insufficient to provide useful diagnostic information; (2) HCI features of the tests are adequate for target users, and (3) the tests do not adhere to accepted ethical norms for medical interventions. DISCUSSION: The most urgent concerns raised center on the ethics of collecting and evaluating responses from users. Physicians and other professionals will benefit from a heightened awareness of these tools and their limitations today.

Neuropsychological subgroups of cognitively-impaired-not-demented (CIND) individuals: delineation, reliability, and predictive validity.

The objectives of the present investigation were to determine whether subgroups of Cognitively-Impaired-Not-Demented (CIND) individuals with distinct neuropsychological profiles exist in two independent samples, and whether subgroup membership is related to diagnostic outcome over periods of 2 to 5 years. A series of cluster analyses was performed on ipsative factor z-scores derived from principal component analyses. Five subgroups were identified in the Base Sample (n = 461): Verbal Dysfunction, Verbal/Visuospatial Dysfunction, Memory/Verbal Dysfunction, Memory Dysfunction, and Visuospatial Dysfunction. This five-cluster solution was replicated in an independent sample of CIND individuals (n = 166). The highest rates of conversion to dementia were observed in the Memory Dysfunction and Memory/Verbal Dysfunction subgroups. The Verbal Dysfunction subgroup was most likely to show improvement in cognitive status. The cognitive heterogeneity of the CIND condition must be taken into account in future research focusing on the early identification of dementia.

Neuropsychological characterization of cognitively-impaired-not-demented (CIND) individuals: clinical comparison data.

The primary objective of the present investigation was to characterize the neuropsychological test performance of a large sample of clinic-referred individuals diagnosed as Cognitively-Impaired-Not-Demented (CIND). Participants classified as Not-Cognitively-Impaired (NCI; n = 68) differed from CIND individuals (n = 205) on a number of demographic, clinical, and neuropsychological measures. A backward stepwise logistic regression analysis revealed that measures of learning and memory, visuoconstruction abilities, and cognitive flexibility provided the best discrimination between NCI and CIND participants. Clinical comparison data for CIND participants were generated for various demographically defined groups. The amount of inter-test scatter (highest minus lowest sample-based z-score) and the overall number of cognitive impairments (impairment being defined as performance equal to or greater than 1 standard deviation below the sample mean) in CIND individuals are reported. The results support the impression that CIND is a cognitively heterogeneous condition.