Cognitive Tests Research Articles

Delirium risk profiles in a population-based study of United States older adults undergoing common noncardiac surgeries.

Older adults often require surgical care and are at elevated risk of delirium. We explored delirium risk profiles across the population of U.S. older adults who underwent one of 10 common noncardiac surgeries. We analyzed Health and Retirement Study (HRS) participants linked with Medicare billing data who underwent the following 10 noncardiac surgeries from 2000 to 2018 at age 65 or more: total knee arthroplasty (TKA), total hip arthroplasty (THA), spine surgery, cholecystectomy, colorectal surgery, hernia repair (ventral, umbilical, or incisional), endarterectomy, prostatectomy, transurethral resection of the prostate (TURP), and hysterectomy. Demographic and health covariates were obtained from the HRS dataset. Latent cognitive ability was calculated from cognitive testing, proxy reports, and demographics at the preoperative HRS interview. We compared standardized differences for delirium risk factors across the 10 surgeries and qualitatively clustered them into phenotypical subgroups. We analyzed 7424 older adults (mean age 76 ± 6 years, 45% male). Endarterectomy patients presented with the highest burden of nearly all health and cognitive factors, implying higher delirium risk (e.g., stroke, 22%; depressive symptoms, 30%; high school or less education, 73%; frailty, 42%; lowest latent cognitive ability). A second "general surgery" phenotype, including cholecystectomy, colorectal, and hernia surgery patients, experienced more frailty (29%-32%) and depressive symptoms (24%-26%), with moderate comorbidity burden. A third "pain" phenotype, which included TKA, THA, and spine surgery patients, commonly reported moderate or severe pain (47%-53%) and impairment in activities of daily living (ADL, 23%-30%), but fewer comorbid medical conditions. The remaining surgery types (hysterectomy, prostatectomy, TURP) were not phenotypically grouped and generally had lower risk features for delirium. In an epidemiological cohort of US older adults, we identified clinically meaningful heterogeneity in delirium risk profiles across different surgical types, which may have implications for delirium risk stratification and delirium prevention or treatment.

Plasma neurofilament light chain in fibromyalgia: A case control study exploring correlation with clinical and cognitive features.

Plasma neurofilament light chain (NFL) has been measured as a biomarker of neuronal damage in various neurological disorders. Elevated tau and β-amyloid levels have been found in patients with fibromyalgia (FM). The aim of the present study was to compare plasma neurofilament levels in fibromyalgia patients with normal controls and to investigate the correlation with clinical features and cognitive tests. Plasma NFL levels were assessed in 33 FM patients and compared with 22 age-matched controls. All patients were also assessed with clinical scales examining fibromyalgia disability, sleep quality and duration, fatigue, anxiety, and depression, and a neuropsychological battery examining executive function, verbal short-term memory, and working memory, as well as attentional executive function and selective attention, interference sensitivity, and inhibition of automatic responses. NFL levels were higher in FM patients (controls 6.19± 1.92; FM 17.28± 15.94 pg/mL ANOVA p 0.002). Working memory was the most impaired cognitive function significantly correlated with high NFL scores (Pearson p 0.034). Short sleep times also correlated with higher NFL scores (Pearson p 0.02) and poorer working memory performance (Pearson p 0.02). No correlation was found with indices of disease severity and duration. Plasma NFL levels are elevated in fibromyalgia patients, suggesting neuronal damage and correlating with a slight decrease in working memory and short sleep duration. Plasma neurofilament levels are elevated in patients with fibromyalgia, regardless of disease severity and duration. Neurofilament levels are higher in patients with mild working memory impairment and sleep disorders. Subgroups of patients with primary neuronal damage phenomena could be individualized for prospective evaluation with regard to the possible development of cognitive decline and sleep disturbances, which would justify a tailored therapeutic approach.

Identifying Factors that Increase False-Positive Rates on Embedded Performance Validity Testing in ADHD Evaluations.

This study investigated why certain embedded performance validity indicators (EVIs) are prone to higher false-positive rates (FPRs) in attention-deficit/hyperactivity disorder (ADHD) evaluations. The first aim was to establish the relationship between FPRs and 15 EVIs derived from six cognitive tests when used independently and together among adults with ADHD who have valid test performance. The second aim was to determine which specific EVIs increase the FPRs in this population. Participants were 517 adult ADHD referrals with valid neurocognitive test performance as determined by multiple performance validity tests and established empirical criteria. FPRs were defined by the proportion of participants who scored below an empirically established EVI cutoff with ≥0.90 specificity. EVIs derived from two of the six tests exhibited unacceptably high FPRs (>10%) when used independently, but the total FPR decreased to 8.1% when the EVIs were aggregated. Several EVIs within a sustained attention test were associated with FPRs around 11%. EVIs that did not include demographically adjusted cutoffs, specifically for race, were associated with higher FPRs around 14%. Conversely, FPRs did not significantly differ based on whether EVIs included timed versus untimed, verbal versus nonverbal, or graphomotor versus non-graphomotor components, nor whether they had raw versus standardized cut scores. Findings suggest that practitioners should consider both the type of test from which an EVI is derived and the aggregate number of EVIs employed to minimize the FPRs in ADHD evaluations. Findings also indicate that more nuanced approaches to validity test selection and development are needed.

Rauvolfia vomitoria phenol extract relieves pentylenetetrazol-induced seizures in Swiss mice and protects some temporal lobe structures

BackgroundRauvolfia vomitoria (R. vomitoria) is a plant of economic importance due to its diverse ethnomedicinal properties, including the anticonvulsant effect. In this study, we studied the antiseizure and neuroprotective potentials of R. vomitoria extracts against pentylenetetrazol (PTZ)-induced kindling.MethodsTwenty-five adult Swiss mice (25–30 g) were assigned to five groups (n = 5): control group, PTZ treatment group, and PTZ treatment after receiving oral R. vomitoria crude extract (100 mg/kg), R. vomitoria phenol extract (50 mg/kg) or sodium valproate (15 mg/kg) every 48 h for 28 days. Seizure scores, cognitive behavioral tests including novel object test, Y-maze test, and the elevated plus maze test, as well as brain neurochemicals and histomorphology studies, were performed.ResultsCompared with the control group, the PTZ group showed comparable body weight and durations in closed and open arms (P > 0.05), but preference for familiar objects, significant (P < 0.05) spontaneous alternation, increased monoamine oxidase activity and nitric oxide level, and Nissl chromatolysis in the temporal lobe structures including the cortex, hippocampus, and amygdala. R. vomitoria phenol extract pretreatment significantly (P < 0.05) reduced seizures, prevented adverse cognitive behaviors, decreased the nitric oxide level, and reduced the temporal lobe Nissl chromatolysis compared with the R. vomitoria crude extract pretreatment group and the sodium valproate pretreatment groups.ConclusionsThus, R. vomitoria phenol extract showed promising results against seizures and potential for general brain protection, suggesting that the anticonvulsant property of R. vomitoria may be attributed to its phenol constituent. More studies are needed to delineate the mechanisms of its action.

Exploring the Relationship Between CAIDE Dementia Risk and EEG Signal Activity in a Healthy Population

Background: Accounting for dementia risk factors is essential in identifying people who would benefit most from intervention programs. The CAIDE dementia risk score is commonly applied, but its link to brain function remains unclear. This study aims to determine whether the variation in this score is associated with neurophysiological changes and cognitive measures in normative individuals. Methods: The sample comprised 38 participants aged between 54 and 79 (M = 67.05; SD = 6.02). Data were collected using paper-and-pencil tests and electroencephalogram (EEG) recordings in the resting state, channels FP1 and FP2. The EEG signals were analyzed using Power Spectral Density (PSD)-based features. Results: The CAIDE score is positively correlated with the relative power activation of the θ band and negatively correlated with the MMSE cognitive test score, and MMSE variations align with those found in distributions of EEG-extracted PSD-based features. Conclusions: The findings suggest that CAIDE scores can identify individuals without noticeable cognitive changes who already exhibit brain activity similar to that seen in people with dementia. They also contribute to the convergent validity between CAIDE and the risk of cognitive decline. This underscores the importance of early monitoring of these factors to reduce the incidence of dementia.

Sensitive written hedgehog PICture Naming and Immediate Recall (PICNIR) as a valid and brief test of semantic and short-term episodic memory for very mild cognitive impairment.

Semantic and short-term episodic memory are impaired in some brain disorders including Alzheimer's disease. Development and validation of an almost self-administered, but cognitively demanding four-minute test identifying very mild cognitive impairment (vMCI). The innovative hedgehog PICture Naming and Immediate Recall (PICNIR) consisted of two parts. The first task was to write down the names of 20 black-and-white pictures to evaluate long-term semantic memory and language. The second task involves immediate recall and writing the names of as many previously named pictures as possible in one minute. The PICNIR is assessed using the number of naming errors (NE) and correctly recalled picture names (PICR). The PICNIR and a neuropsychological battery were administered to 190 elderly individuals living independently in the community. They were divided into those with vMCI (n = 43 with Montreal Cognitive Assessment (MoCA) 24 ± 3 points) and sociodemographically matched cognitively normal (CN) individuals (n = 147 with MoCA 26 ± 3). Both subgroups had predicted mean Mini-Mental State Examination scores of 28-29 points. Compared to CN, vMCI participants made more NE (0.3 ± 0.6 versus 0.6 ± 0.9; p = 0.02) and recalled fewer PICR (8.9 ± 2.2 versus 6.8 ± 2.2; p < 0.000001). Discriminative validity was satisfactory using the area under the ROC curve (AUC): 0.76 for PICR, 0.74 for MoCA, 0.67 for MoCA-five-word recall, and 0.59 for NE. The AUCs of PICR and MoCA were comparable and larger than those of MoCA five-point recall or NE. Logical Memory scores, RAVLT scores, Digit symbol, and animal fluency correlated with PICR. The picture-based PICNIR is an ultra-brief, sensitive cognitive test valid for assessing very mild cognitive impairment. Its effectiveness should be validated for other languages and cultures.

Comparison of Cognitive Functions between Healthy Controls and Individuals with Chronic Low Back Pain with High and Low Pain Catastrophizing: A Cross-sectional Study.

Researchers suggested that the interruptive effects of chronic pain on cognitive functions may be modulated by the level of pain catastrophizing (PC). However, in individuals with chronic low back pain (CLBP), domains of cognitive function that may be affected by the level of PC remain largely unclear. Therefore, this study was aimed to compare cognitive functions between healthy controls and individuals with CLBP with high and low PC. This cross-sectional study examined cognitive functions of 42 individuals with CLBP and 21 healthy controls. The PC scale was used to stratify participants with CLBP into high and low PC. Participants performed 5 cognitive tests from the Cambridge Neuropsychological Test Automated Battery, namely five-choice reaction time, rapid visual processing, spatial working memory, attention switching task, and stop signal task. The statistical analyses revealed that compared to individuals with CLBP with low PC and healthy controls, individuals with high PC demonstrated greater values of the between errors (P=0.01), reaction latency (P<0.001), and stop signal reaction time variables (P=0.004, P=0.003, respectively) but lower values of probability of hit (P=0.02, P=0.01, respectively), A' (P=0.01, P<0.001, respectively), and percent correct trials variables (P=0.002, P<0.001, respectively). The results of the current study showed deficits in sustained attention, working memory, cognitive flexibility, and inhibitory control in individuals with CLBP with high PC. From a clinical perspective, therapeutic interventions targeting PC should be considered to decrease catastrophic thinking about pain in individuals with CLBP. Additional research is warranted to explore cognitive functioning as an outcome of these interventions in individuals with CLBP.

Digital detection of Alzheimer’s disease using smiles and conversations with a chatbot

In super-aged societies, dementia has become a critical issue, underscoring the urgent need for tools to assess cognitive status effectively in various sectors, including financial and business settings. Facial and speech features have been tried as cost-effective biomarkers of dementia including Alzheimer’s disease (AD). We aimed to establish an easy, automatic, and extensive screening tool for AD using a chatbot and artificial intelligence. Smile images and visual and auditory data of natural conversations with a chatbot from 99 healthy controls (HCs) and 93 individuals with AD or mild cognitive impairment due to AD (PwA) were analyzed using machine learning. A subset of 8 facial and 21 sound features successfully distinguished PwA from HCs, with a high area under the receiver operating characteristic curve of 0.94 ± 0.05. Another subset of 8 facial and 20 sound features predicted the cognitive test scores, with a mean absolute error as low as 5.78 ± 0.08. These results were superior to those obtained from face or auditory data alone or from conventional image depiction tasks. Thus, by combining spontaneous sound and facial data obtained through conversations with a chatbot, the proposed model can be put to practical use in real-life scenarios.

Empowering minds: An e-book blending contextual teaching learning with plant tissue exploration to boost argumentation and cognitive skills

This research was motivated by obstacles in implementing biology learning which resulted in the lack of training in argumentation skills and low cognitive learning outcomes. The current teaching materials does not yet support these skills optimally. The aim of this research is to develop an e-book blending contextual teaching learning that is feasible, practical and effective to boost high school student’s argumentation and cognitive skills. A research and development method was used using the ADDIE (Analyze, Design, Development, Implementation, Evaluation) development model. The subjects of this research were 34 high school students in Sleman, Yogyakarta in limited trials and 62 students in field trials. The type of research used in the field test was quasi-experimental with a pretest-post-test control group design. Class XI MIPA 1 was used as the control class and class XII MIPA 2 as the experimental class. Data collection instruments used included product assessment questionnaires by experts, biology teachers and students, argumentation skills and cognitive learning outcomes test instruments. Data analysis used the paired sample t-test, independent sample t-test and n-gain score test. The research results show that e-books is suitable for use in learning according to material experts and media experts, e-books is practical for use in learning according to teacher and student assessments, and e-books is effective for improving students' argumentation skills and learning outcomes. The conclusion in this research is that e-books blending contextual teaching and learning are feasible, practical and effective to use to boost students' argumentation and cognitive skills.

Mapping computational cognitive profiles of aging to dissociable brain and sociodemographic factors

Aging is associated with declines in cognition and brain structural integrity. However, there is equivocality over (1) the specificity of affected domains in different people, (2) the location of associated patterns of brain structural deterioration, and (3) the sociodemographic factors contributing to ‘unhealthy’ cognition. We aimed to identify cognitive profiles displayed by older adults and determine brain and sociodemographic features potentially shaping these profiles. A sample of Southeast-Asian older adults (N = 386) participated in a multi-session study comprising cognitive testing, neuroimaging, and a structured interview. We used computational models to extract latent mechanisms underlying cognitive flexibility and response inhibition. Data-driven methods were used to construct cognitive profiles based on standard performance measures and model parameters. We also investigated grey matter volume and machine-learning derived ‘brain-ages’. A profile associated with poor set-shifting and rigid focusing was associated with widespread grey matter reduction in cognitive control regions. A slow responding profile was associated with advanced brain-age. Both profiles were correlated with poor socioeconomic standing and cognitive reserve. We found that the impact of sociodemographic factors on cognitive profiles was partially mediated by total grey and white matter, and dorsolateral prefrontal and cerebellar volumes. This study furthers understanding of how distinct aging profiles of cognitive impairment uniquely correspond to specific vs. global brain deterioration and the significance of socioeconomic factors in informing cognitive performance in older age.

Design and methodology of the harmonized diagnostic assessment of dementia for the longitudinal aging study in India: Wave 2.

The rising burden of dementia calls for high-quality data on cognitive decline and dementia onset. The second wave of the Harmonized Diagnostic Assessment for the Longitudinal Aging Study in India (LASI-DAD) was designed to provide longitudinal assessments of cognition and dementia in India. All Wave 1 participants were recruited for a follow-up interview, and a refresher sample was drawn from the Longitudinal Aging Study in India, a nationally representative cohort of Indians aged 45 and older. Respondents underwent a battery of cognitive tests, geriatric assessments, and venous blood collection. Their health and cognitive status were also assessed through an interview with a close family member or friend. Clinical consensus diagnosis was made based on the Clinical Dementia Rating®, and comprehensive data on risk factors of dementia were collected, including neurodegenerative biomarkers, sensory function, and environmental exposures. A total of 4635 participants were recruited between 2022 and 2024 from 22 states and union territories of India, accounting for 97.9% of the population in India. The response rate was 84.0%, and 71.5% of the participants provided venous blood specimen. LASI-DAD provides rich new data to study cognition, dementia, and their risk factors longitudinally in a nationally representative sample of older adults in India. Longitudinal cognitive data, together with longitudinally assessed biomarker data and novel data on sensory function and environmental exposures, provide a unique opportunity to establish associations between risk factors and biologically defined cognitive aging phenotypes.

Plasma exchange with albumin replacement for Alzheimer's disease treatment induced changes in serum and cerebrospinal fluid inflammatory mediator levels.

There is extensive literature indicating that inflammatory pathways are affected in Alzheimer's disease (AD). We examined whether plasma exchange with albumin replacement (PE-Alb) can impact the inflammatory status of AD patients and alter the relationship between inflammatory mediators and cognitive measures. Serum and cerebrospinal fluid (CSF) samples from 142 AD patients participating in the AMBAR trial (14-month schedule of PE-Alb treatment vs. placebo [sham PE-Alb]) were analyzed for changes from baseline for 19 inflammatory mediators (6 inflammatory cytokines, 9 chemokines, and 4 vascular injury indicators) at representative time points across the AMBAR study (lasting effects) as well as in pre- versus post-PE-Alb procedure (acute effects). Association between mediator changes and clinical outcomes reported in the AMBAR study (cognitive, functional, behavioral function, and global change tests) was assessed. PE-Alb significantly reduced IFN-γ, eotaxin, MIP-1α and ICAM-1 levels in serum, and eotaxin-3 and MIP-1β levels in CSF, at various time points during treatment (p < 0.05; false discovery rate-corrected). Vascular injury indicators were the mediators mostly affected by post- versus pre-PE-Alb level reduction. Increased serum MIP-1α levels were associated with worsening in ADAS-Cog, CDR-sb, and ADCS-CGIC scores in the placebo group, but not in the PE-Alb-treated group. Peripheral intervention could affect AD by reducing inflammatory mediators in both peripheral and central compartments. Changes in MIP-1α due to PE-Alb were associated with changes in clinical outcomes.

Intellectual Differences Between Boys and Girls, 35 Years of Evolution in France from WISC-R to WISC-V

The French adaptation of the Wechsler Intelligence Scale of Children, 5th edition (WISC-V) was an opportunity to examine if some common representations of gender differences in intellectual abilities are supported by empirical evidence. The WISC-V standardization sample provided data on a wide range of cognitive tests in a large sample of 6- to 16-year-old children representative of the French population. This sample included 517 boys and 532 girls. The WISC-V data were compared to those of the French standardization samples of three previous versions of the WISC (WISC-R, WISC-III, and WISC-IV). These four standardization samples span a 35-year period. The data analysis of the WISC-V standardization sample and the three previous versions of this intelligence scale showed that the performance gaps on intellectual tests between girls and boys have gradually narrowed over time. Almost no gender differences were observed in the WISC-V standardization sample, not only in IQ but also in key facets of intelligence. Data do not support the stereotype that girls are better at verbal tasks and boys are better at visuospatial tasks. However, some statistically significant differences remain, but the magnitude was generally small with no practical implications. The only important difference is in favor of girls and concerns performance on processing speed tasks that require visual discrimination, attentional control, and writing.

Investigating the Potential Impact of LH on the Progression of Alzheimer’s Disease via Microglia Activation and C/EBPβ pathway

Background: Alzheimer’s disease (AD) is a neurodegenerative disease that causes irreversible cognitive decline and memory loss. The disproportionate effect of AD on postmenopausal women prompts investigation into the role of hormonal changes in disease pathogenesis. However, previous studies on estrogen replacement therapies have shown inconsistent results. Therefore, further confirmation is needed to ensure the independent effects of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) on AD pathology. Our study will 1) focus on microglial activation pathway 2) focus on the LH-C/EBPβ-AEP pathway and its potential influence on AD progression.Methods: Using cell lines to investigate whether microglial activation is present. HMC3 cells will be treated with LH or control phosphate buffered saline (PBS). Carry out Western Blot (WB) and qPCR to confirm presence of cytokines, which is the product of microglial activation. Using 3xTg-AD mice treated with LH or control PBS. To identify AD progression, immunofluorescent (IF) micrograph will be used to quantify amyloid-beta (Aβ) load. WB and qPCR will be used to identify cytokines. Morris water maze (MWM) will be carried out for cognitive testing. Using an ovariectomized mice model to investigate the LH-C/EBPβ-AEP pathway. Mice will be treated with LH antibodies or control IgG, followed by assessments using IVIS imaging and MWM test to measure spatial memory. IF, WB and qPCR will be used to quantify Aβ and Tau protein levels and gene expression changes. Furthermore, the study will explore the precise relationship between LH and C/EBPβ expression through inhibition experiments targeting AKT and ERK1/2 signaling pathways.Expected results: Our hypothesis is that LH activates microglia, with both pro-inflammatory and anti-inflammatory cytokine released. This change in microglia function suggests LH has an effect on microglia and hence removal of Aβ plaques. Another hypothesis is that LH antibody manages to cross the blood-brain barrier. The cognitive ability will be improved in LH-Ab treated mice with reduced Aβ and Tau protein levels and downregulation of the C/EBPβ–AEP/δ-secretase pathway. Simultaneously, we expect that there will be a positive correlation between LH levels and expression of C/EBPβ-related pathways, suggesting the involvement of AKT and ERK1/2 signaling pathways in AD progression.Conclusion: This study aims to provide evidence for the link between LH activation of the C/EBPβ pathway and AEP production, promoting our understanding of AD pathogenesis. The insights gained may implicate therapeutic strategies targeting LH mechanisms in postmenopausal women at risk of AD.

Pre- and Post-Operative Cognitive Assessment in Patients Undergoing Surgical Aortic Valve Replacement: Insights from the PEARL Project

Background: Aortic valve stenosis (AVS) is a common valvular heart disease affecting millions of people worldwide. It leads to significant neurocognitive and neuropsychological impairments, impacting patients’ quality of life. Objective: The objective of this article is to identify and discuss the potential neurocognitive effects on patients with aortic stenosis before and after undergoing surgical aortic valve replacement (SAVR). Method: Our study involved the assessment of 64 patients undergoing aortic valve replacement (SAVR) using a neurocognitive evaluation comprising a battery of 11 different cognitive tests. These tests were designed to analyze the patients’ overall cognitive functioning, executive abilities, short- and long-term memory, and attentional performance. The tests were administered to patients before the aortic valve surgery (T0) and after the surgery (T1). From a statistical perspective, numerical variables are presented as means (±standard deviation) and medians (IQR), while categorical variables are presented as counts and percentages. Normality was assessed using the Shapiro–Wilk test. T0 and T1 scores were compared with the Wilcoxon signed rank test, with p &lt; 0.05 considered significant. Analyses were performed using SAS version 9.4. Results: Conducted as part of a fully financed Italian Ministry of Health project (RF-2016-02361069), the study found that most patients showed normal cognitive functioning at baseline. Cognitive assessments showed that executive functions, attention, language, and semantic knowledge were within the normal range for the majority of participants. After SAVR, cognitive outcomes remained stable or improved, particularly in executive functions and language. Notably, verbal episodic memory demonstrated significant improvement, with the percentage of patients scoring within the normal range on the BSRT increasing from 73.4% at T0 to 92.2% at T1 (p &lt; 0.0001). However, visuospatial and visuoconstructive abilities showed stability or slight decline, while attentional skills remained relatively stable. The Clock Drawing Test indicated the maintenance of cognitive functions. Conclusions: The findings of our study indicate a global stability in cognitive status among patients after undergoing SAVR, with significant improvement noted in verbal episodic memory. While other cognitive domains did not demonstrate statistically significant changes, these insights are valuable for understanding the cognitive effects of SAVR and can guide future research and clinical practice in selecting the most effective surgical and rehabilitative options for patients. Monitoring cognitive outcomes in patients undergoing aortic valve replacement surgery remains crucial.

Patient-Reported Indicator Surveys (PaRIS): measuring patient reported experiences and outcomes across populations and health systems

Abstract We aimed to develop and test the performance of a questionnaire for adults (aged 45 or older) with one or more chronic conditions who use primary/ambulatory care across populations and health systems in multiple countries. Candidate scales and items were identified through a systematic process supported by international stakeholders (PaRIS Patient Advisory Panel, Technical Advisory Community and Working Party members of participating countries). Four instruments for each domain, covering patient reported outcome measures (PROMs), patient reported experience measures (PREMs), health behaviours, and health and health care capabilities, were shortlisted using predefined criteria and evaluated using the EMPRO method. A modified Delphi supported selecting a core instrument for each domain and additional relevant scales/items. Consultations took place with the stakeholders to confirm the suitability of the proposed questionnaire. The questionnaire was evaluated through cognitive testing and further modified accordingly. The survey was piloted in a Field Trial. Psychometric evaluation was conducted with data from a Field trial on an item level and scale level. Out of 217 instruments, the Delphi resulted in consensus on a core instrument for each main domain and additional questions to ensure comprehensiveness. The cognitive testing of the draft survey (17 languages, 20 countries) confirmed that most questions were interpreted as intended. The version of the survey developed for the field trial included 118 questions. The field trial psychometric evaluation was based on 10,145 patients, across 18 countries. The questionnaire performed well at item level and at scale level. Performance in terms of structure and validity was good overall. A revised version of the patient questionnaire was created with 115 items. A comprehensive questionnaire has been constructed based on the PaRIS survey framework for people living with chronic conditions and following an inclusive approach.

Silent cerebral microvascular disease and longitudinal risk of cognitive decline in atrial fibrillation

Abstract Background A relationship between silent stroke and cognitive disorder has recently been suggested in patients with nonvalvular atrial fibrillation (NVAF). This research is an exploratory research study to investigate the occurrence of asymptomatic cerebrovascular disorders with NVAF. Methods The SKAF (Silent cerebral microvascular disease and longitudinal risK of cognitive decline in Atrial Fibrillation) study is a prospective, investigator-initiated, multicenter, observational study of Japanese patients with NVAF aged 60 years or older. We had planned to enroll two hundred NVAF patients with no history of symptomatic stroke or dementia, and an anticoagulant therapy with edoxaban is being performed or an anticoagulant therapy is not being performed, and one hundred patients with sinus rhythm, for comparison. We collected patient characteristics, clinical course, the data of head MRI test and cognitive function test (Montreal Cognitive Assessment (MoCA)) at the baseline and the 24 months follow-up. The primary endpoint was the composite of silent ischemic stroke and micro-bleeding over a 24-month follow-up period. The secondary endpoint was cognitive decline over a 24-month follow-up period. Results The study was started in October 2016, with a planned 2-year recruitment period. As of January 31, 2018, a total of 326 patients were enrolled. Of those, 99 patients with sinus rhythm (SR group) and 214 patients with NVAF (NVAF group) were analyzed (male, 193 (62%) patients; age, 72.2±6.5 years). 156 of 195 (80%) patients with NVAF received the anticoagulant therapy with edoxaban. There was no significant difference of the primary composite for the endpoints between two groups (17.4% versus 17.4%; p=1.00). The incidences of silent ischemic stroke and micro-bleeding in SR and NVAF groups over a 24-month follow-up period were 9.3% and 10.8% (p= 0.833), and 8.1% and 9.2% (p=1.00), respectively. The NVAF group exhibited a significantly larger decline in cognition changes in MoCA score than SR group (-0.830 versus 0,000; p=0.0131). Notably, NVAF was found to be associated with cognitive decline. Conclusion The SKAF registry provided an equivalent risk of silent cerebral microvascular disease in patients with SR and NVAF. Clinically, NVAF had an impact on cognitive decline.

Phosphorylated tau protein serum levels increase over time in patients with chronic heart failure

Abstract Background/Introduction Amongst various potential biomarkers associated with cognitive deficits, phosphorylated Tau (pTau) appears to link brain and cardiac abnormalities through a systemic tauopathy pathway. Purpose A recent report on the potential importance of myocardial pTau in chronic heart failure (HF) prompted the here described longitudinal quantification of circulating pTau serum levels in patients with HF. We hypothesized that serum pTau accumulates in HF and is associated with markers of myocardial dysfunction. Methods Eligible patients within the prospective, investigator-initiated, monocentric follow-up study Cognition.Matters-HF were older than 18 years, suffered from stable chronic HF and were free from major neurological or psychiatric disorders. Beyond the cardiological assessment including transthoracic echocardiography and six minute walking distance (6-MWD), investigations at baseline, 1 year and 3 years comprised extensive, domain-specific psychological testing and volumetric brain magnetic resonance imaging. Serum pTau was measured using the pTau181 advantage kit. Results Serum samples were available from 78 patients. Mean age was 63±10 years and 87% were men. Serum pTau longitudinally increased from a median of 1.05 (quartiles 0.26, 1.21) pg/ml at baseline to 1.84 (1.36, 3.60) pg/ml after 3 years (p&amp;lt;0.001). During that time period, LVEF, NT-proBNP, 6-MWD and the hippocampal volume remained unaltered, whereas global brain volume and cortical thickness shrank age-appropriately. Cognitive testing revealed that domain-specific T-scores within 36 months remained stable for attentional intensity and executive functioning, and even improved for memory. When we entered baseline values of age and above-mentioned cardiac, brain-volumetric, and cognitive parameters into a multivariable regression model predicting log-transformed pTau, only age (β=0.34), NT-proBNP (β=0.24) and GBV (β=0.26) were independently associated with pTau serum levels (R2=0.18). Consistently, at 36 months, the same predictors were selected by the model (R2=0.29): age (β=0.41), NT-proBNP (β=0.43), and global brain volume (β=0.26). Moreover, higher baseline pTau (β=0.23) and lower 6-MWD (β=-0.39) independently predicted ΔpTau with an explained variance (R2) of 0.24. Conclusions We observed a prominent increase of serum pTau over time, which was predicted by prevalent myocardial dysfunction. Moreover, absolute NT-proBNP levels were independently associated with absolute pTau serum levels, along with age and global brain volume. Mechanistically, phosphorylation of cardiac tau is thought to destabilize its interaction with microtubules causing microtubule detyronisation and increased myocardial stiffness through enhancing the mechanical resistance of contracting cardiomyocytes. The etiological role of pTau in the development of HF and the potential of serum pTau as a novel biomarker of chronic HF warrants further studies.

Social Diversity in Focus: Assessing the Impact of Socioeconomic Backgrounds and Work Experience on Psychological Well-Being and Academic Confidence Among German First-Year Medical Students

This investigation pioneers an examination of the scarcely explored terrain of social diversity in medical education, assessing the complex impacts of socioeconomic status (SES), prior working experiences, and completed apprenticeships on a spectrum of psychological and academic facets among first-year medical students (n = 336) in an urban university setting. By utilizing a systematic and detailed approach, the study illuminates prior anatomical knowledge and various psychological constructs, marking a significant stride into a domain where knowledge remains profoundly limited. Analyses indicated that SES significantly affects financial anxiety (F(4, 331) = 17.391, p &lt; 0.001) and academic behavioral confidence (F(4, 331) = 4.323, p = 0.002). Students with prior working experience reported higher self-perceived clinical experience but lower A-level grades (t(279.459) = −6.690, p &lt; 0.001), competence in natural sciences (t(321.045) = −3.178, p = 0.002), and online competence (t(319.429) = −2.026, p = 0.044). Those who completed an apprenticeship showed higher resilience, academic confidence, self-efficacy, and greater concerns about balancing studies and work (t values ranging from 2.020 to 3.158, p &lt; 0.05). Correlation analysis revealed a positive relationship between resilience (RQS) and coping with academic stress (CAS) (r = 0.632, p &lt; 0.001), as well as between resilience and academic behavioral confidence (ABC) (r = 0.608, p &lt; 0.001). Negative correlations were observed between resilience, coping with academic stress, academic confidence, and cognitive test anxiety (CTA) (r values from −0.235 to −0.404, p &lt; 0.001). The findings emphasize the need for tailored support for students from diverse SES backgrounds and with varying experiences. The study highlights the value of a comprehensive approach in medical education, considering the diverse backgrounds and experiences of students. Future research should explore the long-term impact of these factors on professional competencies and patient care, leveraging the diversity of the student body for a holistic educational experience.

Cross-species translational paradigms for assessing positive valence system as defined by the RDoC matrix.

Functions associated with processing reward-related information are fundamental drivers of motivation, learning, and goal-directed behavior. Such functions have been classified as the positive valence system under the Research Domain and Criteria (RDoC) criteria and are negatively impacted across a range of psychiatric disorders and mental illnesses. The positive valence system is composed of three comprehensive categories containing related but dissociable functions that are organized into either Reward Responsiveness, Reward Learning, or Reward Valuation. The presence of overlapping behavioral dysfunction across diagnostic mental disorders is in-part what motivated the RDoC initiative, which emphasized that the study of mental illness focus on investigating relevant behavior and cognitive functions and their underlying mechanisms, rather than separating efforts on diagnostic categories (i.e., transdiagnostic). Moreover, the RDoC approach is well-suited for preclinical neuroscience research, as the rise in genetic toolboxes and associated neurotechnologies enables researchers to probe specific cellular targets with high specificity. Thus, there is an opportunity to dissect whether behaviors and cognitive functions are supported by shared or distinct neural mechanisms. For preclinical research to effectively inform our understandings of human behavior however, the cognitive and behavioral paradigms should have predictive, neurobiological, and pharmacological predictive validity to the human test. Touchscreen-based testing systems provide a further advantage for this endeavor enabling tasks to be presented to animals using the same media and task design as in humans. Here, we outline the primary categories of the positive valence system and review the work that has been done cross-species to investigate the neurobiology and neurochemistry underlying reward-related functioning. Additionally, we provide clinical tasks outlined by RDoC, along with validity and/or need for further validation for analogous rodent paradigms with a focus on implementing the touchscreen-based cognitive testing systems.