Neuroimaging studies have begun to uncover the neural substrates of cancer and treatment-related cognitive dysfunction, but the time course of these changes in the years following chemotherapy is unclear. This study analyzed multimodality 3T MRI scans to examine the structural and functional effects of chemotherapy and post-chemotherapy interval (PCI) in a cohort of breast cancer survivors (BCS; n=24; PCI mean 6, range 3–10 y) relative to age- and education-matched healthy controls (HC; n=23). Assessments included voxel-based morphometry (VBM) for gray matter density (GMD) and fMRI for activation profile during a 3-back working memory task. The relationships between brain regions associated with PCI and neuropsychological performance, self-reported cognition, and oxidative and direct DNA damage as measured in peripheral lymphocytes were assessed in secondary analyses. PCI was positively associated with GMD and activation on fMRI in the right anterior frontal region (Brodmann Areas 9 and 10) independent of participant age. GMD in this region was also positively correlated with global neuropsychological function. Memory dysfunction, cognitive complaints, and oxidative DNA damage were increased in BCS compared to HC. Imaging results indicated lower fMRI activation in several regions in the BCS group. BCS also had lower GMD than HC in several regions, and in these regions GMD was inversely related to oxidative DNA damage and learning and memory neuropsychological domain scores. This is the first study to show structural and functional effects of PCI and to relate oxidative DNA damage to brain alterations in BCS. The relationship between neuroimaging and cognitive function indicates the potential clinical relevance of these findings. The relationship with oxidative DNA damage provides a mechanistic clue warranting further investigation.

Sensitive measures of neuropsychological function were adapted to a telephone administration format for use in a large survey of quality of life in breast cancer survivors (BCS). Healthy controls (HC) and BCS were recruited from the community and administered the same neuropsychological test battery on two occasions separated by 1 week. Subjects were randomly assigned to conditions, stratified by diagnosis: In-person at Time-1 and In-person at Time-2 (P-P); Telephone at Time-1 and Telephone at Time-2 (T-T); T-P; and P-T. Four cognitive (Rey Auditory Verbal Learning Test, Controlled Oral Word Association, Digit Span, Symbol Digit) and two self-report measures (Squire Memory Self-Report Scale, Center for Epidemiological Studies Depression Scale) were used. The 106 subjects were randomized (54 HC and 52 BCS). Test-retest reliabilities (intraclass correlations) did not differ significantly by condition across the cognitive or self-report measures and ranged from moderate to near perfect (r's .43-.93; p's < .05). Mean scores at Time-1, practice effects (Time-1 to Time-2), and standard errors of measurement were comparable between In-person and Telephone administration formats. Results suggest that memory, attention, information processing speed, verbal fluency, and self-report of mood and memory can be measured reliably and precisely over the telephone.

The cognitive function of breast cancer survivors (BC, n = 52) and individually-matched healthy controls (n = 52) was compared on a battery of sensitive neuropsychological tests. The BC group endorsed significantly higher levels of subjective memory loss and scored significantly worse than controls on learning and delayed recall indices from the Rey Auditory Verbal Learning Test (AVLT). Defining clinically significant impairment as scores at or below the 7th percentile of the control group, the rate of cognitive impairment in the BC sample was 17% for total learning on the AVLT, 17% for delayed recall on the AVLT, and 25% for either measure. Findings indicate that a sizeable percentage of breast cancer survivors have clinically significant cognitive impairment.

The purpose of this study was to examine the prevalence and factors associated with objective and subjective cognitive dysfunction in older breast cancer survivors (BCS). Materials and Methods: This cross-sectional descriptive study leveraged previously collected data from older BCS (n = 335). Separate linear regression models were used to determine relationships between demographic factors (age, education), medical factors (comorbidities), disease factors (time since diagnosis, cancer stage), cancer-related symptoms (depressive symptoms, anxiety, fatigue, sleep disturbance) and cognitive dysfunction measures, including objective learning, delayed recall, attention, executive function-working memory, verbal fluency and subjective attentional function. Results: Cognitive dysfunction was prevalent with up to 18.6% of older BCS experiencing mild-moderate dysfunction (1.5 standard deviations below mean of non-cancer controls) in at least one cognitive domain. Poor to moderate subjective attentional function was reported by 26% of older BCS. More depressive symptoms were significantly related to poorer cognitive function including learning (p < .01), delayed recall (p < .05), verbal fluency (p < .001), and subjective attentional function (p < .001) but not attention and executive function-working memory. Age, education, anxiety, and fatigue were also negatively associated with cognitive function in some models (p < .05-0.001). Conclusion:Cognitive dysfunction is common among older BCS and depressive symptoms, anxiety, and fatigue are related factors. Importantly, depressive symptoms were not only related to self-report, but also to cognitive performance. Healthcare providers should be aware of and assess for related factors and cognitive dysfunction itself in older BCS even years after diagnosis and treatment thorough geriatric assessment. Future longitudinal research is needed to discern these relationships.

BackgroundDelirium affects nearly 70% of older adults hospitalized in the intensive care unit (ICU), and many of those will be left with persistent cognitive impairment or dementia. There are no effective and scalable recovery models to remediate ICU-acquired cognitive impairment and its attendant elevated risk for dementia or Alzheimer disease (AD). The Improving Recovery and Outcomes Every Day after the ICU (IMPROVE) trial is an ongoing clinical trial which evaluates the efficacy of a combined physical exercise and cognitive training on cognitive function among ICU survivors 50 years and older who experienced delirium during an ICU stay. This article describes the study protocol for IMPROVE.MethodsIMPROVE is a four-arm, randomized controlled trial. Subjects will be randomized to one of four arms: cognitive training and physical exercise; cognitive control and physical exercise; cognitive training and physical exercise control; and cognitive control and physical exercise control. Facilitators administer the physical exercise and exercise control interventions in individual and small group formats by using Internet-enabled videoconference. Cognitive training and control interventions are also facilitator led using Posit Science, Inc. online modules delivered in individual and small group format directly into the participants’ homes. Subjects complete cognitive assessment, mood questionnaires, physical performance batteries, and quality of life scales at baseline, 3, and 6 months. Blood samples will also be taken at baseline and 3 months to measure pro-inflammatory cytokines and acute-phase reactants; neurotrophic factors; and markers of glial dysfunction and astrocyte activation.DiscussionThis study is the first clinical trial to examine the efficacy of combined physical and cognitive exercise on cognitive function in older ICU survivors with delirium. The results will provide information about potential synergistic effects of a combined intervention on a range of outcomes and mechanisms of action.Trial registrationClinicalTrials.gov, NCT03095417. Registered on 23 March 2017. Last updated on 15 May 2017.Electronic supplementary materialThe online version of this article (10.1186/s13063-018-2569-8) contains supplementary material, which is available to authorized users.