Education is power: preserving cognition in the UK Biobank

Introduction: Dementia is a debilitating syndrome characterized by the gradual loss of memory and cognitive function. Although there are currently limited, largely symptomatic treatments for the diseases that can lead to dementia, its onset may be prevented by identifying and modifying relevant life style risk factors. Commonly described modifiable risk factors include diet, physical inactivity, and educational attainment. Importantly, however, to maximize the utility of our understanding of these risk factors, tangible and meaningful changes to policy must also be addressed. Objectives: Here, we aim to identify the mechanism(s) by which educational attainment influences cognition. Methods: We investigated data from 502,357 individuals (Mage = 56.53, SDage = 8.09, 54.40% female) from the UK Biobank cohort via Structural Equation Modelling to illustrate links between predictor variables (i.e., Townsend Deprivation Index, coastal distance, greenspace, years of education), covariates (i.e., participant age) and cognitive function as outcome variables (i.e., pairs-matching, trail-making task B, fluid intelligence). Results: Our model demonstrated that higher education was associated with better cognitive performance (ps  Conclusion: Accordingly, our model evinces the mediating effect of socioeconomic and environmental factors on the relationship between years of education and cognitive function. These results further demonstrate the utility and necessity of adapting public policy to encourage equitable access to education and other supports in deprived areas

A single bout of passive exercise mitigates a mental fatigue-induced inhibitory control deficit

Sustained cognitive effort associated with the psychomotor vigilance task (PVT) increases objective and subjective measures of mental fatigue and elicits a post-PVT inhibitory control deficit. In contrast, passive exercise wherein an individual’s limbs are moved via an external force (i.e., mechanically driven cycle ergometer flywheel) provides a postexercise inhibitory control benefit linked to an exercise-based increase in cerebral blood flow. Here, we examined whether passive exercise performed concurrently with the PVT ‘blunts’ an inhibitory control deficit. On separate days, participants (N = 27) completed a 20 min PVT protocol (control condition) and same duration PVT protocol paired with passive cycle ergometry (passive exercise condition). Prior to (i.e., baseline), immediately after and 30 min after each condition inhibitory control was assessed via the antisaccade task. Antisaccades require a goal-directed eye movement (i.e., saccade) mirror-symmetrical to a target and provide an ideal tool for evaluating task-based changes in inhibitory control. PVT results showed that vigilance (as assessed via reaction time: RT) during control and passive exercise conditions decreased from the first to last 5 min of the protocol and increased subjective ratings of mental fatigue. As well, in the control condition, immediate (but not 30-min) post-intervention antisaccade RTs were longer than their baseline counterparts–a result evincing a transient mental fatigue-based inhibitory control deficit. For the passive exercise condition, immediate and 30-min post-intervention antisaccade RTs were shorter than their baseline counterparts and this result was linked to decreased subjective ratings of mental fatigue. Thus, passive exercise ameliorated the selective inhibitory control deficit associated with PVT-induced mental fatigue and thus provides a potential framework to reduce executive dysfunction in vigilance-demanding occupations

Acute stress imparts a transient benefit to task-switching that is not modulated following a single bout of exercise

Introduction: Cognitive flexibility represents a core component of executive function that promotes the ability to efficiently alternate—or “switch”—between different tasks. Literature suggests that acute stress negatively impacts cognitive flexibility, whereas a single bout of aerobic exercise supports a postexercise improvement in cognitive flexibility. Here, we examined whether a single bout of aerobic exercise attenuates a stress-induced decrement in task-switching. Materials and Methods: Forty participants (age range = 19–30) completed the Trier Social Stress Test (TSST) and were randomized into separate Exercise or Rest groups entailing 20-min sessions of heavy intensity exercise (80% of heart rate maximum via cycle ergometer) or rest, respectively. Stress induction was confirmed via state anxiety and heart rate. Task-switching was assessed prior to the TSST (i.e., pre-TSST), following the TSST (i.e., post-TSST), and following Exercise and Rest interventions (i.e., post-intervention) via pro- (i.e., saccade to veridical target location) and antisaccades (i.e., saccade mirror-symmetrical to target location) arranged in an AABB task-switching paradigm. The underlying principle of the AABB paradigm suggests that when prosaccades are preceded by antisaccades (i.e., task-switch trials), the reaction times are longer compared to their task-repeat counterparts (i.e., unidirectional prosaccade switch-cost). Results: As expected, the pre-TSST assessment yielded a prosaccade switch cost. Notably, post-TSST physiological measures indicated a reliable stress response and at this assessment a null prosaccade switch-cost was observed. In turn, post-intervention assessments revealed a switch-cost independent of Exercise and Rest groups. Conclusion: Accordingly, the immediate effects of acute stress supported improved task-switching in young adults; however, these benefits were not modulated by a single bout of aerobic exercise

Feedback-Driven Radiology Exam Report Retrieval with Semantics

Clinical documents are vital resources for radiologists to have a better understanding of patient history. The use of clinical documents can complement the often brief reasons for exams that are provided by physicians in order to perform more informed diagnoses. With the large number of study exams that radiologists have to perform on a daily basis, it becomes too time-consuming for radiologists to sift through each patient\u27s clinical documents. It is therefore important to provide a capability that can present contextually relevant clinical documents, and at the same time satisfy the diverse information needs among radiologists from different specialties. In this work, we propose a knowledge-based semantic similarity approach that uses domain-specific relationships such as part-of along with taxonomic relationships such as is-a to identify relevant radiology exam records. Our approach also incorporates explicit relevance feedback to personalize radiologists information needs. We evaluated our approach on a corpus of 6,265 radiology exam reports through study sessions with radiologists and demonstrated that the retrieval performance of our approach yields an improvement of 5% over the baseline. We further performed intra-class and inter-class similarities using a subset of 2,384 reports spanning across 10 exam codes. Our result shows that intra-class similarities are always higher than the inter-class similarities and our approach was able to obtain 6% percent improvement in intra-class similarities against the baseline. Our results suggest that the use of domain-specific relationships together with relevance feedback provides a significant value to improve the accuracy of the retrieval of radiology exam reports

The indirect relationship between sleep and cognition in the PREVENT Cohort: Identifying targets for intervention

Introduction As the global population ages, the economic, societal, and personal burdens associated with worsening cognition and dementia onset are growing. It is therefore becoming ever more critical to understand the factors associated with cognitive decline. One such factor is sleep. Adequate sleep has been shown to maintain cognitive function and protect against the onset of chronic disease, whereas sleep deprivation has been linked to cognitive impairment and the onset of depression and dementia. Objectives Here, we aim to identify and explore mechanistic links between several sleep parameters, depressive symptoms and cognition in a cohort of middle-aged adults. Methods We investigated data from the PREVENT dementia programme via structural equation modelling to illustrate links between predictor variables, moderator variables, and two cognitive constructs (i.e., Executive Function and Memory). Results Our model demonstrated that sleep quality, and total hours of sleep were related to participants’ depressive symptoms, and that, participant apathy was related to higher scores on the Epworth Sleepiness and Lausanne NoSAS Scales. Subsequently, depressive symptoms, but not sleep or apathy ratings, were associated with Executive Function. Conclusions We provide evidence for an indirect relationship between sleep and cognition mediated by depressive symptoms in a middle-aged population. Our results provide a base from which cognition, dementia onset, and potential points of intervention, may be better understood

The indirect relationship between sleep and cognition in the PREVENT cohort: identifying targets for intervention

Introduction: As the global population ages, the economic, societal, and personal burdens associated with worsening cognition and dementia onset are growing. It is therefore becoming ever more critical to understand the factors associated with cognitive decline. One such factor is sleep. Adequate sleep has been shown to maintain cognitive function and protect against the onset of chronic disease, whereas sleep deprivation has been linked to cognitive impairment and the onset of depression and dementia. Objectives: Here, we aim to identify and explore mechanistic links between several sleep parameters, depressive symptoms and cognition in a cohort of middle-aged adults. Methods: We investigated data from the PREVENT dementia programme via structural equation modeling to illustrate links between predictor variables, moderator variables, and two cognitive constructs (i.e., Executive Function and Memory). Results: Our model demonstrated that sleep quality, and total hours of sleep were related to participants' depressive symptoms, and that, participant apathy was related to higher scores on the Epworth Sleepiness and Lausanne NoSAS Scales. Subsequently, depressive symptoms, but not sleep or apathy ratings, were associated with Executive Function. Conclusions: We provide evidence for an indirect relationship between sleep and cognition mediated by depressive symptoms in a middle-aged population. Our results provide a base from which cognition, dementia onset, and potential points of intervention, may be better understood

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Postexercise executive function benefits and cerebral blood flow: in the lab and at home

A single bout of aerobic exercise improves executive function; however, the mechanism, or mechanisms, supporting this improvement remain unclear. One candidate mechanism is an exercise-mediated increase in cerebral blood flow (CBF) that enhances the efficiency of executive-related frontoparietal networks. To evaluate the link between exercise, CBF and executive function, three separate experiments were conducted. In the first study, separate 10-min sessions of moderate-to-heavy-intensity aerobic exercise, and a hypercapnic environment (i.e., 5% CO2) were implemented. The hypercapnic condition was included because it increases CBF independent of the metabolic demands of exercise. The second study investigated whether exercise intensity-specific changes in CBF differentially influence the magnitude of a postexercise executive function benefit. Accordingly, I measured CBF in conditions wherein participants completed separate 10-min sessions of light- (i.e., 25 Watts: W), moderate- (i.e., 80% estimated lactate threshold: LT), and heavy-intensity (i.e., 15% of the difference between LT and V̇O2peak) aerobic exercise. The third study measured CBF during separate passive and active light-intensity exercise conditions and evaluated putative immediate and sustained executive function benefits. My final study (i.e., Study 4) was developed to meet the challenges associated with COVID-related research restrictions and hence developed and evaluated an at-home tablet-based assessment of postexercise executive function. The first three studies demonstrated that an increase in CBF independent of the metabolic demands of exercise was associated with a postexercise improvement in executive function. The fourth study demonstrated that an at-home executive function assessment provides a reliable means to identify single bout postexercise benefits to executive function. The findings from my dissertation provide further evidence indicating that CBF is a candidate mechanism supporting postexercise executive function and demonstrate the utility of a novel executive function assessment that may be implemented in populations that are demo- and geographically under-represented in exercise neuroscience research

Evaluating the efficacy of an iPad® app in determining a single bout of exercise benefit to executive function

We examined the efficacy and feasibility of an iPad® app used at-home in identifying a postexercise benefit to executive function. The iPad® app required simple reaching movements mirror-symmetrical to an exogenously presented target (i.e., antipointing) and is a task that lab-based behavioral and neuroimaging work has shown to provide a valid measure of the response inhibition component of executive function. Fifty English-speaking individuals (18 female, age range 18-26 years of age) completed the iPad® app before and immediately after a 20-min session of heavy-intensity aerobic exercise, and on a separate day completed the app prior to and following a 20-min non-exercise control condition. Results showed antipointing reaction times (RTs) in the exercise condition decreased by an average of 18 ms postexercise (p z = 0.90), whereas control condition pre- and post-assessment RTs did not reliably differ (p = 0.12, dz = 0.22) and were within an equivalence boundary (p < 0.005). Further, pre-assessment exercise and control condition antipointing RTs were within an equivalence boundary (p < 0.05). Accordingly, a simple iPad® app provides the requisite resolution to detect subtle executive function benefits derived from a single bout of exercise