‘Hearts and minds’: association, causation and implication of cognitive impairment in heart failure

The clinical syndrome of heart failure is one of the leading causes of hospitalisation and mortality in older adults. An association between cognitive impairment and heart failure is well described but our understanding of the relationship between the two conditions remains limited. In this review we provide a synthesis of available evidence, focussing on epidemiology, the potential pathogenesis, and treatment implications of cognitive decline in heart failure. Most evidence available relates to heart failure with reduced ejection fraction and the syndromes of chronic cognitive decline or dementia. These conditions are only part of a complex heart failure-cognition paradigm. Associations between cognition and heart failure with preserved ejection fraction and between acute delirium and heart failure also seem evident and where data are available we will discuss these syndromes. Many questions remain unanswered regarding heart failure and cognition. Much of the observational evidence on the association is confounded by study design, comorbidity and insensitive cognitive assessment tools. If a causal link exists, there are several potential pathophysiological explanations. Plausible underlying mechanisms relating to cerebral hypoperfusion or occult cerebrovascular disease have been described and it seems likely that these may coexist and exert synergistic effects. Despite the prevalence of the two conditions, when cognitive impairment coexists with heart failure there is no specific guidance on treatment. Institution of evidence-based heart failure therapies that reduce mortality and hospitalisations seems intuitive and there is no signal that these interventions have an adverse effect on cognition. However, cognitive impairment will present a further barrier to the often complex medication self-management that is required in contemporary heart failure treatment

The vulnerability of rules in complex work environments: dynamism and uncertainty pose problems for cognition

Many complex work environments rely heavily on cognitive operators using rules. Operators sometimes fail to implement rules, with catastrophic human, social and economic costs. Rule-based error is widely reported, yet the mechanisms of rule vulnerability have received less attention. This paper examines rule vulnerability in the complex setting of airline transport operations. We examined ‘the stable approach criteria rule’, which acts as a system defence during the approach to land. The study experimentally tested whether system state complexity influenced rule failure. The results showed increased uncertainty and dynamism led to increased likelihood of rule failure. There was also an interaction effect, indicating complexity from different sources can combine to further constrain rule-based response. We discuss the results in relation to recent aircraft accidents and suggest that ‘rule-based error’ could be progressed to embrace rule vulnerability, fragility and failure. This better reflects the influence that system behaviour and cognitive variety have on rule-based response. Practitioner Summary: In this study, we examined mechanisms of rule vulnerability in the complex setting of airline transport operations. The results suggest work scenarios featuring high uncertainty and dynamism constrain rule-based response, leading to rules becoming vulnerable, fragile or failing completely. This has significant implications for rule-intensive, safety critical work environments

Incorporating development of a patient-reported outcome instrument in a clinical drug development program: examples from a heart failure program.

BackgroundPatient-reported outcome (PRO) measures can be used to support label claims if they adhere to US Food & Drug Administration guidance. The process of developing a new PRO measure is expensive and time-consuming. We report the results of qualitative studies to develop new PRO measures for use in clinical trials of omecamtiv mecarbil (a selective, small molecule activator of cardiac myosin) for patients with heart failure (HF), as well as the lessons learned from the development process.MethodsConcept elicitation focus groups and individual interviews were conducted with patients with HF to identify concepts for the instrument. Cognitive interviews with HF patients were used to confirm that no essential concepts were missing and to assess patient comprehension of the instrument and items.ResultsDuring concept elicitation, the most frequently reported HF symptoms were shortness of breath, tiredness, fluid retention, fatigue, dizziness/light-headedness, swelling, weight fluctuation, and trouble sleeping. Two measures were developed based on the concepts: the Heart Failure Symptom Diary (HF-SD) and the Heart Failure Impact Scale (HFIS). Findings from cognitive interviews suggested that the items in the HF-SD and HFIS were relevant and well understood by patients. Multiple iterations of concept elicitation and cognitive interviews were needed based on FDA request for a broader patient population in the qualitative study. Lessons learned from the omecamtiv mecarbil PRO/clinical development program are discussed, including challenges of qualitative studies, patient recruitment, expected and actual timelines, cost, and engagement with various stakeholders.ConclusionDevelopment of a new PRO measure to support a label claim requires significant investment and early planning, as demonstrated by the omecamtiv mecarbil program

Frontostriatal Maturation Predicts Cognitive Control Failure to Appetitive Cues in Adolescents

Adolescent risk-taking is a public health issue that increases the odds of poor lifetime outcomes. One factor thought to influence adolescents' propensity for risk-taking is an enhanced sensitivity to appetitive cues, relative to an immature capacity to exert sufficient cognitive control. We tested this hypothesis by characterizing interactions among ventral striatal, dorsal striatal, and prefrontal cortical regions with varying appetitive load using fMRI scanning. Child, teen, and adult participants performed a go/no-go task with appetitive (happy faces) and neutral cues (calm faces). Impulse control to neutral cues showed linear improvement with age, whereas teens showed a nonlinear reduction in impulse control to appetitive cues. This performance decrement in teens was paralleled by enhanced activity in the ventral striatum. Prefrontal cortical recruitment correlated with overall accuracy and showed a linear response with age for no-go versus go trials. Connectivity analyses identified a ventral frontostriatal circuit including the inferior frontal gyrus and dorsal striatum during no-go versus go trials. Examining recruitment developmentally showed that teens had greater between-subject ventral-dorsal striatal coactivation relative to children and adults for happy no-go versus go trials. These findings implicate exaggerated ventral striatal representation of appetitive cues in adolescents relative to an intermediary cognitive control response. Connectivity and coactivity data suggest these systems communicate at the level of the dorsal striatum differentially across development. Biased responding in this system is one possible mechanism underlying heightened risk-taking during adolescence

Cognitive ability and continuous measures of relative hand-skill. a note

This note re-examines a finding by Crow et al. (1998) that equal skill of right and left hands is associated with deficits in cognitive ability. This is consistent with the idea that failure to develop dominance of one hemisphere is associated with various pathologies such as learning difficulties. Using the same data source but utilising additional data, evidence is found of a more complex relationship between cognitive ability and relative hand skill.

Sliding Window Spectrum Sensing for Full-Duplex Cognitive Radios with Low Access-Latency

In a cognitive radio system the failure of secondary user (SU) transceivers to promptly vacate the channel can introduce significant access-latency for primary or high-priority users (PU). In conventional cognitive radio systems, the backoff latency is exacerbated by frame structures that only allow sensing at periodic intervals. Concurrent transmission and sensing using self-interference suppression has been suggested to improve the performance of cognitive radio systems, allowing decisions to be taken at multiple points within the frame. In this paper, we extend this approach by proposing a sliding-window full-duplex model allowing decisions to be taken on a sample-by-sample basis. We also derive the access-latency for both the existing and the proposed schemes. Our results show that the access-latency of the sliding scheme is decreased by a factor of 2.6 compared to the existing slotted full-duplex scheme and by a factor of approximately 16 compared to a half-duplex cognitive radio system. Moreover, the proposed scheme is significantly more resilient to the destructive effects of residual self-interference compared to previous approaches.Comment: Published in IEEE VTC Spring 2016, Nanjing, Chin

A Rebound Effect After Stereotype Threat?

Two studies investigated a potential cognitive mediator for stereotype threat, a phenomenon whereby the mere threat of confirming a negative stereotype results in a performance deficit. It was hypothesized that people attempt to suppress stereotypes in memory during threatening situations, consuming cognitive resources, but that the suppression is released after the threatening situation has ended. This results in a “rebound effect” and a subsequent increase in stereotyped thought. The experiments failed to find a significant stereotype threat effect when examined individually, but when the data from the experiments were aggregated aggregated, a performance deficit was found. However, because of the failure to find a significant performance deficit in any one experiment, the results to not directly bear on any potential rebound effect

Addressing the selective role of distinct prefrontal areas in response suppression: A study with brain tumor patients

The diverging evidence for functional localization of response inhibition within the prefrontal cortex might be justified by the still unclear involvement of other intrinsically related cognitive processes like response selection and sustained attention. In this study, the main aim was to understand whether inhibitory impairments, previously found in patients with both left and right frontal lesions, could be better accounted for by assessing these potentially related cognitive processes. We tested 37 brain tumor patients with left prefrontal, right prefrontal and non-prefrontal lesions and a healthy control group on Go/No-Go and Foreperiod tasks. In both types of tasks inhibitory impairments are likely to cause false alarms, although additionally the former task requires response selection and the latter target detection abilities. Irrespective of the task context, patients with right prefrontal damage showed frequent Go and target omissions, probably due to sustained attention lapses. Left prefrontal patients, on the other hand, showed both Go and target omissions and high false alarm rates to No-Go and warning stimuli, suggesting a decisional rather than an inhibitory impairment. An exploratory whole-brain voxel-based lesion-symptom mapping analysis confirmed the association of left ventrolateral and dorsolateral prefrontal lesions with target discrimination failure, and right ventrolateral and medial prefrontal lesions with target detection failure. Results from this study show how left and right prefrontal areas, which previous research has linked to response inhibition, underlie broader cognitive control processes, particularly involved in response selection and target detection. Based on these findings, we suggest that successful inhibitory control relies on more than one functionally distinct process which, if assessed appropriately, might help us to better understand inhibitory impairments across different pathologies