Chemotherapy-induced amenorrhea: a prospective study of brain activation changes and neurocognitive correlates

Chemotherapy-induced amenorrhea (CIA) often occurs in pre- and peri-menopausal BC patients, and while cancer/chemotherapy and abrupt estrogen loss have separately been shown to affect cognition and brain function, studies of the cognitive effects of CIA are equivocal, and its effects on brain function are unknown. Functional MRI (fMRI) during a working memory task was used to prospectively assess the pattern of brain activation and deactivation prior to and one month after chemotherapy in BC patients who experienced CIA (n=9), post-menopausal BC patients undergoing chemotherapy (n=9), and pre- and post-menopausal healthy controls (n=6 each). Neurocognitive testing was also performed at both time points. Repeated measures general linear models were used to assess statistical significance, and age was a covariate in all analyses. We observed a group-by-time interaction in the combined magnitudes of brain activation and deactivation (p = 0.006): the CIA group increased in magnitude from baseline to post-treatment while other groups maintained similar levels over time. Further, the change in brain activity magnitude in CIA was strongly correlated with change in processing speed neurocognitive testing score (r=0.837 p=0.005), suggesting this increase in brain activity reflects effective cognitive compensation. Our results demonstrate prospectively that the pattern of change in brain activity from pre- to post-chemotherapy varies according to pre-treatment menopausal status. Cognitive correlates add to the potential clinical significance of these findings. These findings have implications for risk appraisal and development of prevention or treatment strategies for cognitive changes in CIA

Longitudinal assessment of cognitive changes associated with adjuvant treatment for breast cancer: the impact of APOE and smoking

PURPOSE: This study examined the association of post-treatment changes in cognitive performance, apolipoprotein E (APOE), and smoking in breast cancer patients treated with adjuvant therapy. PARTICIPANTS AND METHODS: Breast cancer patients treated with chemotherapy (N = 55, age = 51.9 ± 7.1, education = 15.7 ± 2.6) were evaluated with a battery of neuropsychological tests prior to chemotherapy and at 1, 6, and 18 months post-chemotherapy. Matched groups of breast cancer patients not exposed to chemotherapy (N = 68, age = 56.8 ± 8.3, education = 14.8 ± 2.2) and healthy controls (N = 43, age = 53.0 ± 10.1, education = 15.2 ± 2.6) were evaluated at similar intervals. APOE epsilon 4 carrier status (APOE4+) and smoking history were also evaluated. RESULTS: The detrimental effect of APOE4+ genotype on post-treatment cognitive functioning was moderated by smoking history, that is, patients without a smoking history had significantly lower performance on measures of processing speed and working memory compared with those with a smoking history and healthy controls. Exploratory analyses revealed that APOE4+ patients without a smoking history who were exposed to chemotherapy showed a decline in performance in processing speed, compared with patients with a smoking history. A similar but less pronounced pattern was seen in the no chemotherapy group (primarily endocrine treatment). For working memory, the APOE4+ by smoking interaction was observed in the no chemotherapy group only. CONCLUSIONS: The association between APOE status, breast cancer treatment, and cognitive functioning was moderated by smoking history suggesting that both chemotherapy and endocrine therapy interact with APOE status and smoking to influence cognition. A putative mechanism is that smoking corrects a deficit in nicotinic receptor functioning and dopamine levels in APOE4+ individuals

The effect of long-term Aronia melanocarpa extract supplementation on cognitive performance, mood, and vascular function: A randomized controlled trial in healthy, middle-aged individuals

Cognitive decline is associated with lifestyle-related factors such as overweight, blood pressure, and dietary composition. Studies have reported beneficial effects of dietary anthocyanins on cognition in older adults and children. However, the effect of anthocyanin-rich Aronia melanocarpa extract (AME) on cognition is unknown. Therefore, this study aimed to determine the effect of long-term supplementation with AME on cognitive performance, mood, and vascular function in healthy, middle-aged, overweight adults. In a randomized double-blind placebo-controlled parallel study, 101 participants either consumed 90 mg AME, 150 mg AME, or placebo for 24 weeks. The grooved pegboard test, number cross-out test, and Stroop test were performed as measures for psychomotor speed, attention, and cognitive flexibility. Mood was evaluated with a visual analogue scale, serum brain-derived neurotrophic factor (BDNF) was determined, and vascular function was assessed by carotid ultrasounds and blood pressure measurements. AME improved psychomotor speed compared to placebo (90 mg AME: change = -3.37; p = 0.009). Furthermore, 150 mg AME decreased brachial diastolic blood pressure compared to 90 mg AME (change = 2.44; p = 0.011), but not compared to placebo. Attention, cognitive flexibility, BDNF, and other vascular parameters were not affected. In conclusion, AME supplementation showed an indication of beneficial effects on cognitive performance and blood pressure in individuals at risk of cognitive decline

Positive affective functioning in anhedonic individuals' daily life:Anything but Flat and Blunted

Background Anhedonia, the decreased interest and pleasure, is often described as 'flat' or 'blunted' positive affect (PA). Yet, little is known about PA functioning in anhedonic individuals' daily lives. The current study investigates PA reactivity to pleasurable experiences in anhedonia together with its relevant temporal dynamics (i.e., variability, instability, and inertia), and expands current knowledge by exploring the role of arousal therein. Methods: Using the Experience Sampling Method (ESM), we collected 90 assessments of real-life PA experiences across 30 days in 18-24 year old individuals with anhedonia (N = 69) and without anhedonia (N = 69). Results: Multilevel analyses showed that anhedonia was associated with less intense pleasure experience, and lower levels of PA. Contrary to predictions from laboratory research and depression theory, individuals with anhedonia showed more variability and less stability in PA, and no signs of blunted PA reactivity. In fact, when exploring high and low arousal PA, individuals with anhedonia showed a slightly stronger reactivity to pleasurable experiences in high-arousal PA but not low-arousal PA. Limitations: We did not control for previous pleasure experiences and, instead of the last positive event, accumulation of positive events may have determined the change in high-arousal PA. Conclusions: Individuals with anhedonia are likely less 'flat' or 'blunted' than generally thought. Although replication is warranted, impairments in high-arousal positive emotions may be of particular interest in the clinical treatment of anhedonia

Ice drilling on Skytrain Ice Rise and Sherman Island, Antarctica

AbstractTo understand the long-term climate and glaciological evolution of the ice sheet in the region bordering the Weddell Sea, the British Antarctic Survey has undertaken a series of successful ice core projects drilling to bedrock on Berkner Island, James Ross Island and the Fletcher Promontory. A new project, WACSWAIN, seeks to increase this knowledge by further drilling to bedrock on two further ice rises in this region. In a single-season project, an ice core was recovered to bedrock at 651 m on Skytrain Ice Rise using an ice core drill in a fluid-filled borehole. In a second season, a rapid access drill was used to recover ice chips to 323 m on Sherman Island in a dry borehole, though failing to reach the bedrock which was at an estimated depth of 428 m.Royal Society ER

Continuous flow analysis methods for sodium, magnesium and calcium detection in the Skytrain ice core

AbstractDissolved and particulate sodium, magnesium and calcium are analyzed in ice cores to determine past changes in sea ice extent, terrestrial dust variability and atmospheric aerosol transport efficiency. They are also used to date ice cores if annual layers are visible. Multiple methods have been developed to analyze these important compounds in ice cores. Continuous flow analysis (CFA) is implemented with instruments that sample the meltstream continuously. In this study, CFA with ICP-MS (inductively coupled-plasma mass spectrometry) and fast ion chromatography (FIC) methods are compared for analysis of sodium and magnesium. ICP-MS, FIC and fluorescence methods are compared for analysis of calcium. Respective analysis of a 10 m section of the Antarctic WACSWAIN Skytrain Ice Rise ice core shows that all of the methods result in similar levels of the compounds. The ICP-MS method is the most suitable for analysis of the Skytrain ice core due to its superior precision (relative standard deviation: 1.6% for Na, 1.3% for Mg and 1.2% for Ca) and sampling frequency compared to the FIC method. The fluorescence detection method may be preferred for calcium analysis due to its higher depth resolution (1.4 cm) relative to the ICP-MS and FIC methods (~4 cm).European Research Counci

Reliable change in neuropsychological assessment of breast cancer survivors

BACKGROUND: The purpose of this study was to enhance the current understanding and interpretation of longitudinal change on tests of neurocognitive function in individuals with cancer. Scores on standard neuropsychological instruments may be impacted by practice effects and other random forms of error. METHODS: The current study assessed the test-retest reliability of several tests and overarching cognitive domains comprising a neurocognitive battery typical of those used for research and clinical evaluation using relevant time frames. Practice effect-adjusted reliable change confidence intervals for test-retest difference scores based on a sample of patient-matched healthy controls are provided. RESULTS: By applying reliable change confidence intervals to scores from two samples of breast cancer patients at post-treatment follow-up assessment, meaningful levels of detectable change in cognitive functioning in breast cancer survivors were ascertained and indicate that standardized neuropsychological instruments may be subject to limitations in detection of subtle cognitive dysfunction over clinically relevant intervals, especially in patient samples with average to above average range baseline functioning. CONCLUSIONS: These results are discussed in relation to reported prevalence of cognitive change in breast cancer patients along with recommendations for study designs that enhance detection of treatment effects

Surface-controlled reversal of the selectivity of halogen bonds

Intermolecular halogen bonds are ideally suited for designing new molecular assemblies because of their strong directionality and the possibility of tuning the interactions by using different types of halogens or molecular moieties. Due to these unique properties of the halogen bonds, numerous areas of application have recently been identified and are still emerging. Here, we present an approach for controlling the 2D self-assembly process of organic molecules by adsorption to reactive vs. inert metal surfaces. Therewith, the order of halogen bond strengths that is known from gas phase or liquids can be reversed. Our approach relies on adjusting the molecular charge distribution, i.e., the σ-hole, by molecule-substrate interactions. The polarizability of the halogen and the reactiveness of the metal substrate are serving as control parameters. Our results establish the surface as a control knob for tuning molecular assemblies by reversing the selectivity of bonding sites, which is interesting for future applications

Cognitive effects of cancer and its treatments at the intersection of aging: what do we know; what do we need to know?

There is a fairly consistent, albeit non-universal body of research documenting cognitive declines after cancer and its treatments. While few of these studies have included subjects aged 65 years and older, it is logical to expect that older patients are at risk of cognitive decline. Here, we use breast cancer as an exemplar disease for inquiry into the intersection of aging and cognitive effects of cancer and its therapies. There are a striking number of common underlying potential biological risks and pathways for the development of cancer, cancer-related cognitive declines, and aging processes, including the development of a frail phenotype. Candidate shared pathways include changes in hormonal milieu, inflammation, oxidative stress, DNA damage and compromised DNA repair, genetic susceptibility, decreased brain blood flow or disruption of the blood-brain barrier, direct neurotoxicity, decreased telomere length, and cell senescence. There also are similar structure and functional changes seen in brain imaging studies of cancer patients and those seen with "normal" aging and Alzheimer's disease. Disentangling the role of these overlapping processes is difficult since they require aged animal models and large samples of older human subjects. From what we do know, frailty and its low cognitive reserve seem to be a clinically useful marker of risk for cognitive decline after cancer and its treatments. This and other results from this review suggest the value of geriatric assessments to identify older patients at the highest risk of cognitive decline. Further research is needed to understand the interactions between aging, genetic predisposition, lifestyle factors, and frailty phenotypes to best identify the subgroups of older patients at greatest risk for decline and to develop behavioral and pharmacological interventions targeting this group. We recommend that basic science and population trials be developed specifically for older hosts with intermediate endpoints of relevance to this group, including cognitive function and trajectories of frailty. Clinicians and their older patients can advance the field by active encouragement of and participation in research designed to improve the care and outcomes of the growing population of older cancer patients

Oncologist use of the Adjuvant! model for risk communication: a pilot study examining patient knowledge of 10-year prognosis

<p>Abstract</p> <p>Background</p> <p>Our purpose was to collect preliminary data on newly diagnosed breast cancer patient knowledge of prognosis before and after oncology visits. Many oncologists use a validated prognostic software model, Adjuvant!, to estimate 10-year recurrence and mortality outcomes for breast cancer local and adjuvant therapy. Some oncologists are printing Adjuvant! screens to use as visual aids during consultations. No study has reported how such use of Adjuvant! printouts affects patient knowledge of prognosis. We hypothesized that Adjuvant! printouts would be associated with significant changes in the proportion of patients with accurate understanding of local therapy prognosis.</p> <p>Methods</p> <p>We recruited a convenience sample of 20 patients seen by 2 senior oncologists using Adjuvant! printouts of recurrence and mortality screens in our academic medical center. We asked patients for their estimates of local therapy recurrence and mortality risks and counted the number of patients whose estimates were within ± 5% of Adjuvant! before and after the oncology visit, testing whether pre/post changes were significant using McNemar's two-sided test at a significance level of 5%.</p> <p>Results</p> <p>Two patients (10%) accurately estimated local therapy recurrence and mortality risks before the oncology visit, while seven out of twenty (35%) were accurate afterwards (p = 0.125).</p> <p>Conclusion</p> <p>A majority of patients in our sample were inaccurate in estimating their local therapy recurrence and mortality risks, even after being shown printouts summarizing these risks during their oncology visits. Larger studies are needed to replicate or repudiate these preliminary findings, and test alternative methods of presenting risk estimates. Meanwhile, oncologists should be wary of relying exclusively on Adjuvant! printouts to communicate local therapy recurrence and mortality estimates to patients, as they may leave a majority of patients misinformed.</p