Variance In Cognitive Performance Research Articles

Prognosis for Persistent Post Concussion Symptoms using a Multifaceted Objective Gait and Balance Assessment Approach

BackgroundConcussion prognosis is a challenging clinical task. Identification of measures useful for persistent symptom risk can help optimize treatment pathways and allow clinicians to offer appropriate anticipatory guidance. Research QuestionCan a multifaceted single/dual-task postural control assessment within one week of a diagnosed concussion identify the odds of developing persistent post-concussion symptoms (PPCS; symptoms that persist for more than 28 days post-concussion)? MethodsWe conducted a prospective cohort study of youth and young adult athletes who were evaluated within 7 days of injury, and followed until they no longer reported concussion symptoms. Participants were grouped into those who developed PPCS and those who did not. During the initial evaluation, participants completed a postural control evaluation in single/dual-task conditions. We calculated six gait performance variables (in single/dual-task conditions), nine quiet stance performance variables, and three cognitive task performance (standing and walking) variables. We conducted between-group comparisons to identify candidate PPCS prognostic variables, and multivariable models to adjust for covariates (age, post-injury evaluation time, history of concussion, and BMI). ResultsSixty-six participants completed the study: 24% reported PPCS (mean age = 16.9 ± 3.5 years; 50% female; evaluated 4.2 ± 1.9 days post-injury) and 74% (mean age = 18.3 ± 3.0 years; 52% female; evaluated 3.5 ± 1.6 days post-injury) did not. Between-group comparisons indicated greater dual-task transverse plane center-of-mass (COM) range of motion (ROM) (13.1 ± 4.3 vs. 9.9 ± 2.5 degrees; p = 0.013) and lateral step variability (5.1 ± 1.4 vs. 4.0 ± 1.2 cm; p = 0.003) for the PPCS group relative to the no PPCS group. After multivariable modeling, dual-task transverse plane COM ROM (adjusted odds ratio = 1.34, 95% CI = 1.07, 1.68) and lateral step variability (adjusted odds ratio = 1.85, 95% CI = 1.13, 3.05) were significantly associated with PPCS. SignificanceDual-task transverse plane movement and lateral step variability demonstrate viable prognostic ability for PPCS among youth and young adult athletes and, along with other established factors, may add incremental value to PPCS prognosis models.

Sulcal Morphology of the Lateral Prefrontal Cortex Predicts Individual Differences in Cognitive Development

The human cortex folds in distinctive and predictable patterns of gyri and sulci (LaGuen et al., 2018). Deep primary sulci emerge early, while comparatively shallow tertiary sulci appear later and deepen through development. Due to their morphological variability and protracted development, a classic, but largely untested, hypothesis situates tertiary sulci as functional landmarks for cognition in slower developing cortical regions (Sanides, 1964). Here we extend this hypothesis to cognitive development and predict that morphological features of tertiary, but not primary, latPFC sulci will be associated with reasoning ability in children, as reasoning is a cognitive process known to heavily tax the latPFC.Cortical morphometric analyses were performed on high resolution T1‐weighted MPRAGE anatomical scans in 65 participants ages 6–18, randomly sampled from an existing dataset (see Wendelken et al., 2017). This dataset was further divided into Discovery (N =37) and Replication (N = 28) samples. Cortical surface reconstructions were generated using Freesurfer.14 sulci in LatPFC were manually defined from recently proposed definitions (Petrides, 2019). 1,829 labels (14 labels per hemisphere, per subject) were assessed across both samples for mean sulcal depth, maximum sulcal depth, and cortical thickness. Each participant also performed a matrix reasoning task.To investigate the relationship between sulcal morphology and cognition, we employed a data‐driven approach using nested cross‐validation to relate sulcal depth to reasoning performance in the Discovery sample. We first conducted a LASSO‐regression as a regularization technique to select only sulci that are relevant to reasoning performance. Only two tertiary sulci showed a significant relationship with reasoning skill. Using a leave‐one‐out cross‐validation procedure, we then predicted individuals’ reasoning performance from the depth of these two relevant sulci, with age included as a covariate in the model. This model explained 50.4% (RMSE: 2.32) of the variance in performance on the matrix reasoning task, which was higher than models with either a) age as the sole predictor or b) the depth of both these tertiary sulci and the surrounding primary sulci as predictors. Finally, we used the model defined in the Discovery sample to predict reasoning performance in our Replication sample and found that we can predict performance with high accuracy (R2cv= 0.55; RMSE = 2.99) in this independent sample. Our findings demonstrate for the first time that tertiary latPFC sulci can be identified reliably in children, and provide strong evidence for tertiary sulci as sources of individual variability in cognitive performance. The results corroborate prior research on the importance of latPFC development for higher cognition, and demonstrate that precise anatomical parcellations in individual subjects can provide valuable insights into relationships between cortical anatomy and cognitive development.Support or Funding InformationNational Science Foundation (Grant BCS1558585). Jacobs Foundation Research Fellow Health (R01 NS057156). NIMH (R01 MH091109). National Institute of Child Health and Human Development (R01HD067254).

Heterogeneous Indicators of Cognitive Performance and Performance Variability Across the Lifespan.

Reaction time (RT) and RT variability are core components of cognitive performance that can be captured through brief and easy-to-administer tasks of simple RT and choice RT. The current study aims to describe age-related differences in cognitive performance, toward better characterizing normative performance across the lifespan. We examined mean and variability of response times on a simple RT and choice RT tasks in a large and diverse web-based sample (10,060 visitors to TestMyBrain.org). We also examined lifespan-related differences in response time variability using multiple different approaches (raw variability, mean scaled variability, and mean residualized variability). These analyses revealed significant heterogeneity in the patterns of age-related differences in performance, across metrics and within different estimates of the same metric. Based on segmented regression analysis, age of peak performance differed significantly across metrics, with young adults having the best performance based on measures of median RT, middle age adults at peak on certain measures of RT variability (standard deviation and coefficient of variability), and older adults showing the best performance based on accuracy and mean-corrected RT variability. Our results indicate that no single measure of cognitive performance and performance variability produces the same findings with respect to age related change, with further work needed to establish the validity of particular metrics for different applications.

Second-generation long-acting injections anti-psychotics improve executive functions in patients with schizophrenia: a 12-month real-world study

Background: The main purpose of this study was to assess possible modifications of cognitive performance among schizophrenia patients treated with long-acting injectable antipsychotics (LAIs) of second generation anti-psychotics (SGAs). Our hypothesis is that the shift from the oral formulation to the LAI formulation of SGAs drugs improves the cognitive performance. The secondary objective was to carry out a head to head comparison of two different SGA-LAI treatments [i.e., 1-month Paliperidone Palmitate (PP1M), monthly Aripiprazole (Ari-LAI)] in our study with an independent and real-world setting.Methods: The sample comprised 32 participants who were consecutively recruited over 12 months. Seventeen patients treated with Ari-LAI and 10 treated with PP1M completed psychopathological, neuropsychological and functional assessments. Group differences were explored through chi-squared and t-tests, as appropriate. GLM Repeated Measures were used to study variations of cognitive performance along 12 months and to test differences between drugs.Results: We found an effect of time on the outcomes investigated but this did not depend on the type of LAI used.Conclusions: In comparison with the previous oral treatment with SGAs, patients showed a significant improvement in neurocognitive function after 12 months of treatment with SGA-LAI. Furthermore, there were no differences between the SGA-LAI regimens.Key pointsThe main purpose of this study was to assess possible modification of cognitive performance of patients with Schizophrenia treated with second generation long-acting injectable antipsychotics (SGA-LAIs).The secondary objective was to carry out a head to head comparison of two different SGA-LAIs: Paliperidone Palmitate 1-Month (PP1M) and Aripiprazole Monthly (Ari-LAI).Patients showed a significant improvement in neurocognitive function after 12 months of treatment with SGA-LAI.There were no differences between the SGA-LAI regimens.From a practical point of view, switching to LAI formulation seems to produce further social and cognitive improvements in patients who had already benefitted from oral SGA therapy.

Developmental Genes and Regulatory Proteins, Domains of Cognitive Impairment in Schizophrenia Spectrum Psychosis and Implications for Antipsychotic Drug Discovery: The Example of Dysbindin-1 Isoforms and Beyond.

Alongside positive and negative symptomatology, deficits in working memory, attention, selective learning processes, and executive function have been widely documented in schizophrenia spectrum psychosis. These cognitive abnormalities are strongly associated with impairment across multiple function domains and are generally treatment-resistant. The DTNBP1 (dystrobrevin-binding protein-1) gene, encoding dysbindin, is considered a risk factor for schizophrenia and is associated with variation in cognitive function in both clinical and nonclinical samples. Downregulation of DTNBP1 expression in dorsolateral prefrontal cortex and hippocampal formation of patients with schizophrenia has been suggested to serve as a primary pathophysiological process. Described as a “hub,” dysbindin is an important regulatory protein that is linked with multiple complexes in the brain and is involved in a wide variety of functions implicated in neurodevelopment and neuroplasticity. The expression pattern of the various dysbindin isoforms (-1A, -1B, -1C) changes depending upon stage of brain development, tissue areas and subcellular localizations, and can involve interaction with different protein partners. We review evidence describing how sequence variation in DTNBP1 isoforms has been differentially associated with schizophrenia-associated symptoms. We discuss results linking these isoform proteins, and their interacting molecular partners, with cognitive dysfunction in schizophrenia, including evidence from drosophila through to genetic mouse models of dysbindin function. Finally, we discuss preclinical evidence investigating the antipsychotic potential of molecules that influence dysbindin expression and functionality. These studies, and other recent work that has extended this approach to other developmental regulators, may facilitate identification of novel molecular pathways leading to improved antipsychotic treatments.

Variability in Executive Control Performance Is Predicted by Physical Activity.

Physical activity (PA) promotes neurogenesis and has neuroprotective effects on the brain, bolstering the structural and functional resources necessary for improved cognitive functioning. Intraindividual variability (IIV) in cognitive performance is linked to neuropsychological structure and functional ability. Despite evidence of the neurogenerative and neuroprotective effects of PA, limited investigation into the link between PA and IIV has been conducted. Across three studies we investigate the effect of PA on IIV in reaction time (RT) on three modified Flanker Tasks. The International PA Questionnaire was used to evaluate PA while the Attention Network Test (ANT) and two additional modified Flanker Tasks were used to assess executive control and attentional performance. RT coefficients of variation (RTCV) were calculated for each participant by dividing the standard deviation by the mean RT for each stimuli condition. Analysis revealed that basic RT was not associated with PA nor was PA predictive of IIV on the modified Flanker Tasks. However, three consistent findings emerged from analysis of the ANT. First, RTCV and moderate PA were positively related, such that more self-reported moderate PA was associated with greater IIV. Conversely, RTCV and vigorous PA were negatively related. Finally, when controlling for the effects of PA on IIV in young adults, variability decreases as age increases. In sum, PA is predictive of IIV on attentional and executive control tasks in young adults, though only at particular intensities and on certain tasks, indicating that task type and cognitive load are important determinants of the relationship between PA and cognitive performance. These findings are consistent with prior literature that suggests that the role of PA in young adults is reliant on specific interventions and measures in order to detect effects more readily found in adolescent and aging populations.

Microstructural damage of white-matter tracts connecting large-scale networks is related to impaired executive profile in alcohol use disorder.

Alcohol Use Disorders (AUD) is associated with negative consequences on global functioning, likely reflecting chronic changes in brain morphology and connectivity. Previous attempts to characterize cognitive impairment in AUD addressed patients' performance in single domains, without considering their cognitive profile as a whole. While altered cognitive performance likely reflects abnormal white-matter microstructural properties, to date no study has directly addressed the relationship between a proxy of patients' cognitive profile and microstructural damage. To fill this gap we aimed to characterize the microstructural damage pattern, and its relationship with cognitive profile, in treatment-seeking AUD patients. Twenty-two AUD patients and 18 healthy controls underwent a multimodal MRI protocol including diffusion tensor imaging (DTI), alongside a comprehensive neurocognitive assessment. We used a principal component analysis (PCA) to identify superordinate components maximally explaining variability in cognitive performance, and whole-brain voxelwise analyses to unveil the neural correlates of AUD patients' cognitive impairment in terms of different white-matter microstructural features, i.e. fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD). PCA revealed a basic executive component, significantly impaired in AUD patients, associated with tasks tapping visuo-motor processing speed, attention and working-memory. Within a widespread pattern of white-matter damage in patients, we found diverse types of relationship linking WM microstructure and executive performance: (i) in the whole sample, we observed a linear relationship involving MD/RD metrics within both 'superficial' white-matter systems mediating connectivity within large-scale brain networks, and deeper systems modulating their reciprocal connections; (ii) in AUD patients vs. controls, a performance-by-group interaction highlighted a MD/AD pattern involving two frontal white-matter systems, including the genu of corpus callosum and cingulum bundle, mediating structural connectivity among central executive, salience and default mode networks. Alterations of prefrontal white-matter pathways are suggestive of abnormal structural connectivity in AUD, whereby a defective interplay among large-scale networks underpins patients' executive dysfunction. These findings highlight different directions for future basic and translational research aiming to tailor novel rehabilitation strategies and assess their functional outcomes.

Physical Activity, Sports Practice, and Cognitive Functioning: The Current Research Status.

The evidence for the benefits of physical activity on cognitive functioning has increased in recent years. Although the relationship between these variables has been analyzed for decades, the development of evaluation techniques has resolved several issues and advanced this area of knowledge. Moreover, several authors have pointed out the association between the cognitive functioning of athletes and their performance in competition. These recent studies suggest that some specific cognitive abilities of athletes could help them become more effective and improve their chances of success. The objective of this paper was to identify the most relevant advances in these areas of study and to highlight more promising lines of research for the next few years. We have discussed findings from the application of different physical activity programs as well as the most significant cognitive performance variables for sports practice. The limitations of the findings were also discussed.

Medial temporal lobe white matter pathway variability is associated with individual differences in episodic memory in cognitively normal older adults

Significant evidence demonstrates that aging is associated with variability in cognitive performance, even among individuals who are cognitively normal. In this study, we examined measures from magnetic resonance imaging and cerebrospinal fluid (CSF) to investigate which measures, alone or in combination, were associated with individual differences in episodic memory performance. Using hierarchical linear regressions, we compared the ability of diffusion tensor imaging (DTI) metrics, CSF measures of amyloid and tau, and gray matter volumes to explain variability in memory performance in a cohort of cognitively normal older adults. Measures of DTI microstructure were significantly associated with variance in memory performance, even after accounting for the contribution of the CSF and magnetic resonance imaging gray matter volume measures. Significant associations were found between DTI measures of the hippocampal cingulum and fornix with individual differences in memory. No such relationships were found between memory performance and CSF markers or gray matter volumes. These findings suggest that DTI metrics may be useful in identifying changes associated with aging or age-related diseases.

Variation in cognitive function over time in Gaucher disease type 3.

To identify relevant efficacy parameters essential in designing clinical trials for brain-penetrant therapies for Gaucher disease, we evaluated cognitive function longitudinally in 34 patients with Gaucher disease type 3 seen at the NIH Clinical Center. Individuals were tested with age-appropriate Wechsler Intelligence Scales administered between 1 and 18 times over 29 years. Variation in all IQ domains was not linear with time and was best characterized with the coefficient of variation (SD/mean) for each individual. Mixed-effects regressions were used to determine whether IQ was associated with clinical features. Models were controlled for variation in test version, participant identification, and test administrator. Mean verbal, performance, and full-scale IQs were 81.77, 75.98, and 82.02, respectively, with a consistent discrepancy between verbal and performance IQs. Mean (SD) verbal, performance, and full-scale coefficient of variations were 0.07 (0.04), 0.09 (0.05), and 0.06 (0.02), respectively. IQ varied about a mean, with no clear trajectory, indicating no clear patterns of improvement or decline over time. EEG lateralization and behavioral issues were consistently associated with IQ. The observed variation in IQ in Gaucher disease type 3 across the cohort and within single individuals over time may be characteristic of other neuronopathic diseases. Therefore, to reliably use IQ as an efficacy measure in any clinical trial of neurotherapeutics, a normal variation range must be established to assess the clinical relevance of any IQ change.

Exploring Relationships Among Peripheral Amyloid Beta, Tau, Cytokines, Cognitive Function, and Psychosomatic Symptoms in Breast Cancer Survivors.

Accelerated brain aging has been proposed to explain cancer-related cognitive impairment, but empirical evidence for this relationship is lacking. The purpose of this study was to evaluate amyloid beta (Aβ) and tau, biomarkers of neurodegeneration, in relation to cognition in breast cancer survivors (BCSs). We explored relationships among peripheral concentrations of Aβ42, Aβ-40, tau, and cytokines; cognitive function; and psychosomatic symptoms in a cohort of BCSs post-chemotherapy. This secondary analysis of a cross-sectional study was conducted with 65 BCSs. Serum total Aβ-42, Aβ-40, and tau levels were measured with single molecule array technology. Cytokines (interleukin [IL]-6, tumor necrosis factor [TNF]-α, granulocyte-macrophage colony-stimulating factor [GM-CSF], interferon [IFN]-g, IL-10, IL-12, IL-13, IL1-b, IL-2, IL-4, IL-5, IL-7, and IL-8) were simultaneously measured in serum using multiplex assays. Cognitive function was measured with five standardized neuropsychological tests and psychosomatic symptoms (stress, loneliness, anxiety, depressive symptoms, fatigue, sleep quality, and daytime sleepiness) with self-report questionnaires. Data analyses included correlations and random forest regression (RFR). Significant correlations were identified among hip-to-waste ratio, number of treatment modalities, Aβ-42, Aβ-40, and tau levels (rs = .27-.35, ps < .05). RFR modeling including Aβ-42, Aβ-40, tau, and cytokines as features explained significant variance in cognitive function (R2 = .71, F = 9.01, p < .0001) and psychosomatic symptoms (R2 = .74, F = 10.22, p < .0001). This study suggests that neurodegenerative biomarkers interact with cytokines to influence cognitive functioning and psychosomatic symptoms in BCSs following chemotherapy, but additional research is needed.

SHORT-TERM INTRAINDIVIDUAL DYNAMICS OF HEART RATE AND COGNITIVE FUNCTIONING IN OLDER ADULTS

Short-term intraindividual variability in cognition can provide insights into the underlying processes that cannot be captured by only examining mean levels (MacDonald et al., 2003). This variability is often dependent on a number of individual or contextual characteristics. Thus, modeling the heterogeneity of the within-person variance and including meaningful covariates to account for why individuals are more variable on some occasions than others is an alternate way to understand process. The present study utilized a 14-day intensive measurement design to examine the effects of fluctuations in daily heart rate on variability in cognitive performance. Fifty-five older adults (Mage = 70.1 years) completed daily cognitive tasks and measures of well-being, while also wearing an accelerometer to capture physical activity, sleep, and continuous heart rate. Data were examined with a mixed effects location scale model (Hedeker et al., 2008; Rast et al., 2012), which incorporates both an individual’s measured level (location) and their variability around that level (scale). Both the location and the scale are permitted to be random such that on any given occasion an individual may deviate from their typical level and they may also deviate from their typical amount of variability. In this way, the location scale model allows for the heterogeneity of the variance in cognition to be modeled and accounted for with other covariates. Results revealed that there were significant amounts of variability in daily heart rate and cognition across 14 days. The impact of heart rate variability on cognitive performance will be discussed.

Cue-based decision rules of cleaner fish in a biological market task

To develop an evolutionary theory of social decision making, we require an understanding of how individuals utilize environmental cues to form decision rules. We exposed ‘cleaner’ fish (bluestreak cleaner wrasse, Labroides dimidiatus) to a biological market task, where giving priority to an ephemeral (i.e. ‘visitor’ client) food plate, over a permanent (i.e. ‘resident’ client) plate, doubled the food reward. Previously published experiments revealed that adult cleaners from a complex social environment regularly solved this task and outperformed adult cleaners from a simple social environment as well as juveniles from both habitat types. In these studies, plates were differentiated by colour and/or colour pattern. However, client size is another potentially useful cue that may be used by cleaners to solve the biological market task in nature, as visitor clients are typically larger than resident clients. Here, we tested cleaners in a setting where plates differed only in size and not colour/pattern: the majority of cleaners exhibited a spontaneous preference for inspecting larger plates or were more likely to reach the task-solving criterion if the visitor plate was larger. All cleaners were able to solve the task when we incorporated both size and colour/pattern cues; however, only cleaners from the complex social environment settled on the more precise colour/pattern cue. In contrast, cleaners from the simple social environment relied on size as the primary, yet less precise, cue to solve the task. In conclusion, our results strongly suggest that intraspecific variation in the performance of cleaners in the biological market task is based on variation in the relative salience of available cues and correlates with variation in a cleaner's natural social environment. Variation in the relative salience of available cues may therefore explain a portion of the intra- and interspecific variance in cognitive performance and social behaviour documented in other animal species.

Association between cognitive performance and SYT1-rs2251214 among women with cocaine use disorder.

The SNP rs2251214 of the SYT1 gene was recently associated with externalizing phenotypes, including ADHD and cocaine use disorder (CUD). Here, we investigated whether SYT1-rs2251214 could also be implicated with cognitive performance variations among women with CUD. Results showed that G homozygous (n = 146) have lower cognitive performance in the Stroop, Trail Making and Matrix Reasoning tests compared with A-allele carriers (n = 64), suggesting that rs2251214 may influence the severity of cognitive impairments in CUD.

Pain interference may be an important link between pain severity, impairment, and self-reported disability in participants with wrist/hand pain

Study DesignCross-sectional. IntroductionPain severity, sensory and motor impairment, and psychological (distress and anxiety) and social factors have previously been related to self-reported disability in persons with wrist and hand pain. Purpose of the studyThe purpose of this study to determine the relative contribution of pain severity, measures of impairment (sensory and motor function), psychosocial factors, and pain interference on self-reported disability experienced by persons with heterogeneous orthopedic injuries and conditions of the wrist and hand. MethodsMeasures of disability and pain severity as well as measures of sensory (pressure pain thresholds, joint position sense), motor (grip strength, Purdue pegboard), and cognitive performance (Stroop test) and psychosocial variables related to pain and participation (West Haven-Yale Multidimensional Pain Inventory) were administered to 60 participants with wrist and hand pain. Pearson product correlations controlled for age and sex, and multiple linear regression was performed to determine the relationship between measures of impairment, pain severity, psychosocial variables, and pain interference with self-reported disability assessed with the Disability of Arm, Shoulder and Hand (DASH) questionnaire. ResultsThe best-fitting regression model with DASH scores entered as the dependent variable (F4,50 = 28.8, P < .01) included MPI Pain Interference (β = −0.54), Life Control (β = −0.16), Purdue pegboard scores (β = −0.32), and Stroop test times (β = 0.21). Pain Interference had the strongest correlation with self-reported disability (adjusted R2 = 0.67, P < .01). ConclusionPain interference appears to be an important factor explaining the link between impairment, pain severity, and self-reported disability. Addressing pain interference may be important to improve outcomes in this population.

Beyond C4: Analysis of the complement gene pathway shows enrichment for IQ in patients with psychotic disorders and healthy controls

Variation in cognitive performance, which strongly predicts functional outcome in schizophrenia (SZ), has been associated with multiple immune-relevant genetic loci. These loci include complement component 4 (C4A), structural variation at which was recently associated with SZ risk and synaptic pruning during neurodevelopment and cognitive function. Here, we test whether this genetic association with cognition and SZ risk is specific to C4A, or extends more broadly to genes related to the complement system. Using a gene-set with an identified role in "complement" function (excluding C4A), we used MAGMA to test if this gene-set was enriched for genes associated with human intelligence and SZ risk, using genome-wide association summary statistics (IQ; N = 269 867, SZ; N = 105 318). We followed up this gene-set analysis with a complement gene-set polygenic score (PGS) regression analysis in an independent data set of patients with psychotic disorders and healthy participants with cognitive and genomic data (N = 1000). Enrichment analysis suggested that genes within the complement pathway were significantly enriched for genes associated with IQ, but not SZ. In a gene-based analysis of 90 genes, SERPING1 was the most enriched gene for the phenotype of IQ. In a PGS regression analysis, we found that a complement pathway PGS associated with IQ genome-wide association studies statistics also predicted variation in IQ in our independent sample. This association (observed across both patients and controls) remained significant after controlling for the relationship between C4A and cognition. These results suggest a robust association between the complement system and cognitive function, extending beyond structural variation at C4A.

The genetic relationship between educational attainment and cognitive performance in major psychiatric disorders

Cognitive deficits are a core feature of psychiatric disorders like schizophrenia and bipolar disorder. Evidence supports a genome-wide polygenic score (GPS) for educational attainment (GPSEDU) can be used to explain variability in cognitive performance. We aimed to identify different cognitive domains associated with GPSEDU in a transdiagnostic clinical cohort of chronic psychiatric patients with known cognitive deficits. Bipolar and schizophrenia patients from the PsyCourse cohort (N = 730; 43% female) were used. Likewise, we tested whether GPSs for schizophrenia (GPSSZ) and bipolar disorder (GPSBD) were associated with cognitive outcomes. GPSEDU explained 1.5% of variance in the backward verbal digit span, 1.9% in the number of correctly recalled words of the Verbal Learning and Memory Test, and 1.1% in crystallized intelligence. These effects were robust to the influences of treatment and diagnosis. No significant associations between GPSSZ or GPSBD with cognitive outcomes were found. Furthermore, these risk scores did not confound the effect of GPSEDU on cognitive outcomes. GPSEDU explains a small fraction of cognitive performance in adults with psychiatric disorders, specifically for domains related to linguistic learning and working memory. Investigating such a proxy-phenotype longitudinally, could give intriguing insight into the disease course, highlighting at what time genes play a more influential role on cognitive performance. Better understanding the origin of these deficits might help identify those patients at risk for lower levels of functioning and poor social outcomes. Polygenic estimates may in the future be part of predictive models for more personalized interventions.

Cognitive function of Brazilian elderly persons: longitudinal study with non-clinical community sample

Several biopsychosocial changes in individuals' life might happen, resulting in a decline of long-term cognitive abilities. In this way, the aim of this study was to compare cognition in non-clinical older adults in Brazil during a four-year period, as well as to examine which variables may explain cognitive function variations identified during this time. For this purpose, a longitudinal study was developed including 108 older Brazilians in phase I and 64 in phase II, from 2013 to 2017. Socio-demographic variables were assessed and the following instruments were administered: the Mini-Mental State Examination (MMSE), the Wechsler Adult Intelligence Scale (WAIS) - 3rd Edition - Digital Symbol-Coding subtests, the Verbal Fluency Test (animal category), the Rey Auditory-Verbal Learning Test, the Beck Anxiety Inventory (BAI), and the Geriatric Depression Scale 15-item version (GDS-15). In order to compare cognitive variables, the Wilcoxon signed-rank test for repeated measures was used. Temporal comparisons of nominal variables were carried out using McNemar’s chi-square tests for matched pairs. Finally, multiple linear regression and correlation analyses were applied, using the participants’ cognitive performance variation scores (Δ) as dependent variables. Global cognitive function delayed verbal episodic memory, and processing speed experienced a significant decline in four years. Symptoms of anxiety were the main predictor of cognitive performance variations in this sample.

Assessing the Efficacy and Mechanisms of Pycnogenol® on Cognitive Aging From In Vitro Animal and Human Studies.

Brain aging is a complex and multifactorial process broadly involving changes in the brain’s structure, neuronal activity, and biochemical profile. These changes in brain function have also been linked to age-associated variations in cognitive function. Recent research has suggested a role of increased oxidative stress and reduced cognition in older people. Therefore, studies that examine the effects of antioxidants on cognitive performance are important, particularly in the context of an increase in elderly populations in most Western countries. One such antioxidant, Pycnogenol, is a standardized plant-based extract obtained from the bark of the French maritime pine and has a long historical use to treat inflammation and improve health. More recently, Pycnogenol has been subjected to more than 100 research trials. In vitro and animal studies using the standardized extract have indicated a multimodal action of Pycnogenol, and several human studies have shown improvements in cognitive function after chronic administration. In this paper, we review these studies in the context of understanding both biological and cognitive changes due to Pycnogenol and evaluate possibilities of Pycnogenol to improve neurocognitive function.

A Critical Analysis of FDA Guidance for User Percentile Device Design Criteria Versus Currently Available Human Factors Engineering Data Sources and Industry Best Practices

A staggering report was recently released by the International Consortium of Investigative Journalists (ICIJ) indicating that 83,000 deaths and 1.7 million injuries were linked to medical device adverse events reported over the last decade (Diaz-Struck, 2018). Furthermore, a 2013 report by McKinsey & Company suggested that such adverse events and associated quality issues cost the medical device industry between $2.5 billion and $5 billion per year on average (Fuhr, George, & Pai, 2013). There is also indication that some aspects of both medical device human factors engineering (HFE) design and Food and Drug Administration (FDA) HFE validation criteria may not provide proper methodologies for selecting and testing patient populations. This may lead medical devices that pass FDA HFE validation to still exhibit significant use errors when utilized by actual patients in the real world. This paper explores the possible sources of HFE performance problems with medical devices and links potential problems to HFE validation methodologies within the FDA HFE guidance framework. The paper also examines device design teams’ failure to utilize HFE best practices in the design and testing of medical devices. Critical conclusions drawn from this analysis suggest that, currently, medical devices may not be designed and validated according to the full percentile range recommended by FDA guidance and HFE best practice. The analysis also indicates that both the FDA and medical device design teams have failed to understand that designing devices to meet a specific range of user needs includes not only physical attributes, but also a wide range of percentile-based cognitive and physiological HFE performance variables. This problem is potentially causing patients who reside at the extremes of percentile distributions (i.e., those with extreme, but acceptable degrees of functional and/or cognitive limitations) to not be able to use devices successfully, which may significantly impact clinical outcomes. The analysis additionally indicates that such failure to design for proper percentile extremes is related to respondent recruiting methods and, more generally, a lack of awareness regarding HFE theory and best practice. Furthermore, for certain categories of modern medical devices, including drug delivery devices, little to no validated HFE percentile-based device design data exists to facilitate medical device development. These issues are not limited to the design of medical devices, but also apply to the design of secondary components of the device system, including device packaging, labeling and instructions for use. To resolve such issues, the authors propose generation of an HFE medical device design criteria dataset for use by development teams during design and testing. The FDA may also reference the proposed dataset during HFE review and validation.