Cognitive Markers Research Articles

Evidence of elevated situational awareness for active duty soldiers during navigation of a virtual environment.

U.S. service members maintain constant situational awareness (SA) due to training and experience operating in dynamic and complex environments. Work examining how military experience impacts SA during visual search of a complex naturalistic environment, is limited. Here, we compare Active Duty service members and Civilians' physiological behavior during a navigational visual search task in an open-world virtual environment (VE) while cognitive load was manipulated. We measured eye-tracking and electroencephalogram (EEG) outcomes from Active Duty (N = 21) and Civilians (N = 15) while they navigated a desktop VE at a self-regulated pace. Participants searched and counted targets (N = 15) presented among distractors, while cognitive load was manipulated with an auditory Math Task. Results showed Active Duty participants reported significantly greater/closer to the correct number of targets compared to Civilians. Overall, Active Duty participants scanned the VE with faster peak saccade velocities and greater average saccade magnitudes compared to Civilians. Convolutional Neural Network (CNN) response (EEG P-300) was significantly weighted more to initial fixations for the Active Duty group, showing reduced attentional resources on object refixations compared to Civilians. There were no group differences in fixation outcomes or overall CNN response when comparing targets versus distractor objects. When cognitive load was manipulated, only Civilians significantly decreased their average dwell time on each object and the Active Duty group had significantly fewer numbers of correct answers on the Math Task. Overall, the Active Duty group explored the VE with increased scanning speed and distance and reduced cognitive re-processing on objects, employing a different, perhaps expert, visual search strategy indicative of increased SA. The Active Duty group maintained SA in the main visual search task and did not appear to shift focus to the secondary Math Task. Future work could compare how a stress inducing environment impacts these groups' physiological or cognitive markers and performance for these groups.

Diffusion Tensor Imaging Analysis Along the Perivascular Space in the UK Biobank

BackgroundThe recently discovered glymphatic system may support the removal of neurotoxic proteins, mainly during sleep, that are associated with neurodegenerative diseases such as Alzheimer’s and Parkinson’s Disease. Diffusion tensor image analysis along the perivascular space (DTI-ALPS) has been suggested as a method to index the health of glymphatic system (with higher values indicating a more intact glymphatic system). Indeed, in small-scale studies the DTI-ALPS index has been shown to correlate with age, cognitive health, and sleep, and is higher in females than males. ObjectiveTo determine whether these relationships are stable we replicated previous findings associating the DTI-ALPS index with demographic, sleep-related, and cognitive markers in a large sample of participants from the UK Biobank. MethodsWe calculated the DTI-ALPS index in UK Biobank participants (n = 17723). Using Bayesian and Frequentist analysis approaches, we replicate previously reported relationships between the DTI-ALPS index. ResultsWe found the predicted associations between the DTI-ALPS index and age, longest uninterrupted sleep window (LUSWT) on a typical night, cognitive performance, and sex. However, these effects were substantially smaller than those found in previous studies. Parameter estimates from this study may be used as priors in subsequent studies using a Bayesian approach. These results suggest that the DTI-ALPS index is consistently, and therefore predictably, associated with demographics, LUWST, and cognition. ConclusionWe propose that the metric, calculated for the first time in a large-scale, population-based cohort, is a stable measure, but one for which stronger links to glymphatic system function are needed before it can be used to understand the relationships between glymphatic system function and health outcomes reported in the UKBiobank.

A Strategy for Allowing Earlier Diagnosis and Rigorous Evaluation of BACE1 Inhibitors in Preclinical Alzheimer’s Disease

Given continued failure of BACE1 inhibitor programs at symptomatic and prodromal stages of Alzheimer’s disease (AD), clinical trials need to target the earlier preclinical stage. However, trial design is complex in this population with negative diagnosis of classical hippocampal amnesia on standard memory tests. Besides recent advances in brain imaging, electroencephalogram, and fluid-based biomarkers, new cognitive markers should be established for earlier diagnosis that can optimize recruitment to BACE1 inhibitor trials in presymptomatic AD. Notably, accelerated long-term forgetting (ALF) is emerging as a sensitive cognitive measure that can discriminate between asymptomatic individuals with high risks for developing AD and healthy controls. ALF is a form of declarative memory impairment characterized by increased forgetting rates over longer delays (days to months) despite normal storage within the standard delays of testing (20–60 min). Therefore, ALF may represent a harbinger of preclinical dementia and the impairment of systems memory consolidation, during which memory traces temporarily stored in the hippocampus become gradually integrated into cortical networks. This review provides an overview of the utility of ALF in a rational design of next-generation BACE1 inhibitor trials in preclinical AD. I explore potential mechanisms underlying ALF and relevant early-stage biomarkers useful for BACE1 inhibitor evaluation, including synaptic protein alterations, astrocytic dysregulation and neuron hyperactivity in the hippocampal-cortical network. Furthermore, given the physiological role of the isoform BACE2 as an AD-suppressor gene, I also discuss the possible association between the poor selectivity of BACE1 inhibitors and their side effects (e.g., cognitive worsening) in prior clinical trials.

Uremic toxins and the brain in chronic kidney disease.

Chronic kidney disease (CKD) patients have an increased risk for cognitive impairment compared to the general population. The risk is much higher in CKD patients who progress to end-stage kidney disease (ESKD) and require hemodialysis or peritoneal dialysis. Multiple factors maycontribute to cognitive impairment in CKD patients and in patients on chronic dialysis. However, the observation that, after kidney transplantation, there is an improvement in several cognitive performance markers and that some structural and functional brain abnormalities mayimprove suggests that cognitive deficits in patients on dialysis may be at least partially reversible. Recent evidence supports the hypothesis that uremic toxins may disrupt the blood brain barrier and damage the brain cells. Such brain toxicity should prompt efforts to lower the burden of uremic toxins through dialytic and non-dialytic strategies.

Feasibility and Preliminary Efficacy of American Elderberry Juice for Improving Cognition and Inflammation in Patients with Mild Cognitive Impairment.

Despite data showing that nutritional interventions high in antioxidant/anti-inflammatory properties (anthocyanin-rich foods, such as blueberries/elderberries) may decrease risk of memory loss and cognitive decline, evidence for such effects in mild cognitive impairment (MCI) is limited. This study examined preliminary effects of American elderberry (Sambucus nigra subsp. canadensis) juice on cognition and inflammatory markers in patients with MCI. In a randomized, double-blind, placebo-controlled trial, patients with MCI (n = 24, Mage = 76.33 ± 6.95) received American elderberry (n = 11) or placebo (n = 13) juice (5 mL orally 3 times a day) for 6 months. At baseline, 3 months, and 6 months, patients completed tasks measuring global cognition, verbal memory, language, visuospatial cognitive flexibility/problem solving, and memory. A subsample (n = 12, 7 elderberry/5 placebo) provided blood samples to measure serum inflammatory markers. Multilevel models examined effects of the condition (elderberry/placebo), time (baseline/3 months/6 months), and condition by time interactions on cognition/inflammation outcomes. Attrition rates for elderberry (18%) and placebo (15%) conditions were fairly low. The dosage compliance (elderberry-97%; placebo-97%) and completion of cognitive (elderberry-88%; placebo-87%) and blood-based (elderberry-100%; placebo-100%) assessments was high. Elderberry (not placebo) trended (p = 0.09) towards faster visuospatial problem solving performance from baseline to 6 months. For the elderberry condition, there were significant or significantly trending decreases over time across several markers of low-grade peripheral inflammation, including vasorin, prenylcysteine oxidase 1, and complement Factor D. Only one inflammatory marker showed an increase over time (alpha-2-macroglobin). In contrast, for the placebo, several inflammatory marker levels increased across time (L-lactate dehydrogenase B chain, complement Factor D), with one showing deceased levels over time (L-lactate dehydrogenase A chain). Daily elderberry juice consumption in patients with MCI is feasible and well tolerated and may provide some benefit to visuospatial cognitive flexibility. Preliminary findings suggest elderberry juice may reduce low-grade inflammation compared to a placebo-control. These promising findings support the need for larger, more definitive prospective studies with longer follow-ups to better understand mechanisms of action and the clinical utility of elderberries for potentially mitigating cognitive decline.

Temporal interplay between cognitive conflict and attentional markers in social collaboration.

Cognitive processes deal with contradictory demands in social contexts. On the one hand, social interactions imply a demand for cooperation, which requires processing social signals, and on the other, demands for selective attention require ignoring irrelevant signals, to avoid overload. We created a task with a humanoid robot displaying irrelevant social signals, imposing conflicting demands on selective attention. Participants interacted with the robot as a team (high social demand; n = 23) or a passive co-actor (low social demand; n = 19). We observed that theta oscillations indexed conflict processing of social signals. Subsequently, alpha oscillations were sensitive to the conflicting social signals and the mode of interaction. These findings suggest that brains have distinct mechanisms for dealing with the complexity of social interaction and that these mechanisms are activated differently depending on the mode of the interaction. Thus, how we process environmental stimuli depends on the beliefs held regarding our social context.

Secure patient-therapist attachment following therapy for personality disorder in a forensic mental health setting

ABSTRACT Therapy for personality disorder can be understood as a process of enhancing attachment security. This study tests the theory that individuals in a secure forensic mental health setting with a diagnosis of personality disorder who have undertaken psychological therapy will report secure patterns of attachment in their relationship with their therapist. It uses a novel pattern matching approach that assesses the behavioural, cognitive and affective markers of attachment security in a group of patients undergoing therapy. Eight behavioural, cognitive and affective characteristics of secure attachment were identified. Ten patients completed a semi-structured interview about their experiences in therapy and key relationships, and their responses were reviewed for evidence of these eight characteristics. Nine out of ten participants were judged to have demonstrated a pattern of six or more of the eight characteristics of secure attachment. This study supports the theory that treatment for this group of patients works by developing patient-therapist attachments. A focus on attachment issues should, therefore, be a core aspect of therapy.

"Therapeutic potential of licorice extract in a prenatal valproic acid model of autism spectrum disorder in Wistar rats: Neurobehavioral and neurobiochemical insights"

Neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD), impose significant burdens on society due to their genetic and clinical complexity. We explored the therapeutic potential of Glycyrrhiza glabra (licorice) extract in a prenatal valproic acid (VPA) model of ASD. Neurobehavioral parameters encompassing social interaction, locomotor activity, repetitive behaviour, anxiety-related behaviour, and learning and memory were assessed in Wistar rat offspring. Licorice extract administration at 150 mg/kg and 300 mg/kg was initiated from postnatal day 21, emulating the developmental stage of early childhood. The study incorporated a controlled group, a VPA-induced ASD group, and groups treated with two different doses of licorice extract and Risperidone.Results revealed that licorice extract, particularly at 300 mg/kg, exhibited remarkable potential in restoring social interaction deficits, enhancing locomotor activity, attenuating repetitive behaviour, and mitigating anxiety-related behaviour-like behaviours. Furthermore, licorice extract displayed cognitive benefits, as evidenced by the discrimination index enhancement in object recognition memory. Importantly, licorice extract demonstrated modulatory effects on neuroinflammation and oxidative stress, evident through suppressed interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) levels, as well as reduced thiobarbaturic acid reactive substances (TBARS) in the brain.These findings underscore the promising neuroprotective properties of Glycyrrhiza glabra extract against prenatal VPA-induced ASD-like behaviours. The elucidation of licorice's multifaceted impact on behaviour, cognition, and neurobiochemical markers offers a potential avenue for future therapeutic interventions for ASD, meriting further investigation in clinical contexts. This study contributes to the expanding knowledge of natural compounds in ameliorating complex neurodevelopmental disorders and highlights the necessity of multi-faceted approaches to address their intricate etiology and manifestation.

A biological characterization of patients with postmenopausal Parkinson's disease.

Menopause increases the risk for Parkinson's disease (PD), although the underlying biological mechanisms have not been established in patients. Here, we aimed to understand the basis of menopause-related vulnerability to PD. Main motor and non-motor scores, blood levels of estradiol, testosterone, follicle-stimulating hormone, and luteinizing hormone, CSF levels of total α-synuclein, amyloid-β-42, amyloid-β-40, total tau, and phosphorylated-181-tau were examined in 45 women with postmenopausal-onset PD and 40 age-matched controls. PD patients had higher testosterone and lower estradiol levels than controls, and the residual estradiol production was associated with milder motor disturbances and lower dopaminergic requirements. In PD but not in controls, follicle-stimulating hormone levels correlated with worse cognitive scores and CSF markers of amyloidopathy and neuronal loss. In conclusion, menopause-related hormonal changes might differentially contribute to clinical-pathological trajectories of PD, accounting for the peculiar vulnerability to the disease.

Modeling Effects of Rumination on Free Recall Using ACT-R.

Ruminative thinking, characterized by a recurrent focus on negative and self-related thought, is a key cognitive vulnerability marker of depression and, therefore, a key individual difference variable. This study aimed to develop a computational cognitive model of rumination focusing on the organization and retrieval of information in memory, and how these mechanisms differ in individuals prone to rumination and individuals less prone to rumination. Adaptive Control of Thought-Rational (ACT-R) was used to develop a rumination model by adding memory chunks with negative valence to the declarative memory. In addition, their strength of association was increased to simulate recurrent negative focus, thereby making it harder to disengage from. The ACT-R models were validated by comparing them against two empirical datasets containing data from control and depressed participants. Our general and ruminative models were able to recreate the benchmarks of free recall while matching the behavior exhibited by the control and the depressed participants, respectively. Our study shows that it is possible to build a computational theory of rumination that can accurately simulate the differences in free recall dynamics between control and depressed individuals. Such a model could enable a more fine-tuned investigation of underlying cognitive mechanisms of depression and potentially help to improve interventions by allowing them to more specifically target key mechanisms that instigate and maintain depression.

Allopurinol and blood pressure variability following ischemic stroke and transient ischemic attack: a secondary analysis of XILO-FIST.

Blood Pressure Variability (BPV) is associated with cardiovascular risk and serum uric acid level. We investigated whether BPV was lowered by allopurinol and whether it was related to neuroimaging markers of cerebral small vessel disease (CSVD) and cognition. We used data from a randomised, double-blind, placebo-controlled trial of two years allopurinol treatment after recent ischemic stroke or transient ischemic attack. Visit-to-visit BPV was assessed using brachial blood pressure (BP) recordings. Short-term BPV was assessed using ambulatory BP monitoring (ABPM) performed at 4 weeks and 2 years. Brain MRI was performed at baseline and 2 years. BPV measures were compared between the allopurinol and placebo groups, and with CSVD and cognition. 409 participants (205 allopurinol; 204 placebo) were included in the visit-to-visit BPV analyses. There were no significant differences found between placebo and allopurinol groups for any measure of visit-to-visit BPV. 196 participants were included in analyses of short-term BPV at week 4. Two measures were reduced by allopurinol: the standard deviation (SD) of systolic BP (by 1.30 mmHg (95% confidence interval (CI) 0.18-2.42, p = 0.023)); and the average real variability (ARV) of systolic BP (by 1.31 mmHg (95% CI 0.31-2.32, p = 0.011)). There were no differences in other measures at week 4 or in any measure at 2 years, and BPV was not associated with CSVD or cognition. Allopurinol treatment did not affect visit-to-visit BPV in people with recent ischemic stroke or TIA. Two BPV measures were reduced at week 4 by allopurinol but not at 2 years.

Association of Plasma YKL-40 With MRI, CSF, and Cognitive Markers of Brain Health and Dementia.

Higher YKL-40 levels in the CSF are a known biomarker of brain inflammation. We explored the utility of plasma YKL-40 as a biomarker for accelerated brain aging and dementia risk. We performed cross-sectional and prospective analyses of 4 community-based cohorts in the United States or Europe: the Age, Gene/Environment Susceptibility-Reykjavik Study, Atherosclerosis Risk in the Communities study, Coronary Artery Risk Development in Young Adults study, and Framingham Heart Study (FHS). YKL-40 was measured from stored plasma by a single laboratory using Mesoscale Discovery with levels log transformed and standardized within each cohort. Outcomes included MRI total brain volume, hippocampal volume, and white matter hyperintensity volume (WMHV) as a percentage of intracranial volume, a general cognitive composite derived from neuropsychological testing (SD units [SDU]), and the risk of incident dementia. We sought to replicate associations with dementia in the clinic-based ACE csf cohort, which also had YKL-40 measured from the CSF. Meta-analyses of MRI outcomes included 6,558 dementia-free participants, and for analysis of cognition, 6,670. The blood draw preceded MRI/cognitive assessment by up to 10.6 years across cohorts. The mean ages ranged from 50 to 76 years, with 39%-48% male individuals. In random-effects meta-analysis of study estimates, each SDU increase in log-transformed YKL-40 levels was associated with smaller total brain volume (β = -0.33; 95% CI -0.45 to -0.22; p < 0.0001) and poorer cognition (β = -0.04; 95% CI -0.07 to -0.02; p < 0.01), following adjustments for demographic variables. YKL-40 levels did not associate with hippocampal volume or WMHV. In the FHS, each SDU increase in log YKL-40 levels was associated with a 64% increase in incident dementia risk over a median of 5.8 years of follow-up, following adjustments for demographic variables (hazard ratio 1.64; 95% CI 1.25-2.16; p < 0.001). In the ACE csf cohort, plasma and CSF YKL-40 were correlated (r = 0.31), and both were associated with conversion from mild cognitive impairment to dementia, independent of amyloid, tau, and neurodegeneration status. Higher plasma YKL-40 levels were associated with lower brain volume, poorer cognition, and incident dementia. Plasma YKL-40 may be useful for studying the association of inflammation and its treatment on dementia risk.

Action and understanding in the semi-structured research interview: Using CA to analyse European research scientists’ attitudes to linguistic (dis)advantage

The semi-structured research interview is commonly used in EAP research to gain emic or insider perspectives. However, critics suggest that simplistic approaches to interview are pervasive, and that interview data is over-used and under-analysed by qualitative researchers. In this study, I consider the interactional nature of the EAP research interview by using the Conversation Analysis (CA) lens of action and understanding to enhance a more traditional qualitative analysis of interview data from semi-structured interviews with six European research scientists. I examine how the scientists position attitudes to the proposition that non-native English speakers are disadvantaged in writing for publication compared to their native speaker counterparts. The analysis focuses on how the scientists use pronominal subject + cognitive verb discourse markers (e.g., you know, I mean, I guess) to mark stance, shift focus, and renegotiate the linguistic (dis)advantage proposition. In doing so, they move beyond the native/non-native binary and introduce non-discursive factors as barriers to research publication success. The study highlights how an analysis of both the structure and the content of interview talk can enrich understanding of the worldviews of interview participants. It also illustrates how EAP researchers might address existing methodological critiques concerning the simplistic use of interview data.

Accelerated long-term forgetting: from subjective memory decline to a defined clinical entity

ABSTRACT Subjective memory decline (SMD) might represent the preclinical phase of Alzheimer’s disease (AD), and has been reported in epileptic amnesia associated with accelerated long-term forgetting (ALF). We investigated ALF in SMD subjects by means of RAVLT recall and recognition and ROCF recall after 1-week retention and compared with a control group. Two-way ANOVAs for RAVLT and ROCF were conducted, and stepwise regression analysis was administered considering EMQ and DASS-21 as factors. SMD subjects performed significantly worse than controls at 1-week delay on RAVLT recall and recognition, but not on ROCF, and not associated with depression or memory complaints. SMD patients showed ALF, which is usually associated with temporomesial dysfunctions, representing a cognitive marker to assess objectively memory problems in SMD, and to undisclose initial neurodegenerative disease involving temporal structures usually compromised in AD. Therefore, SMD might no longer be “subjective,” but rather a specific and defined clinical entity.

Physical Fitness and Cognitive Function in Persons with Dementia and their Caregiver

A cross-sectional design investigated the physical attributes of 15 dyads of people with dementia and their caregivers. Physical and cognitive markers determined deviations from clinical thresholds for loss of functional independence, where 100% of participants performed below criterion-referenced threshold values for aerobic endurance. Walking distance for people with dementia was associated with bath/shower activity (p = .007), transfers (p < .001), and mobility (p = .013). Less distance walked was associated with more assistance with self-care tasks. Physical deficits associated with low aerobic endurance and lower body strength compromised independence, placing dyads at risk for falls and mobility-related health issues.

Serum S100β Levels Are Linked with Cognitive Decline and Peripheral Inflammation in Spinocerebellar Ataxia Type 2.

Experimental and clinical studies have indicated a potential role of the protein S100β in the pathogenesis and phenotype of neurodegenerative diseases. However, its impact on spinocerebellar ataxia type 2 (SCA2) remains to be elucidated. The objective of the study is to determine the serum levels of S100β in SCA2 and its relationship with molecular, clinical, cognitive, and peripheral inflammatory markers of the disease. Serum concentrations of S100β were measured by enzyme-linked immunosorbent assay in 39 SCA2 subjects and 36 age- and gender-matched controls. Clinical scores of ataxia, non-ataxia symptoms, cognitive dysfunction, and some blood cell count-derived inflammatory indices were assessed. The SCA2 individuals manifested S100β levels similar to the control group, at low nanomolar concentrations. However, the S100β levels were directly associated with a better performance of cognitive evaluation within the SCA2 cohort. Moreover, the S100β levels were inversely correlated with most peripheral inflammatory indices. Indeed, the neutrophil-to-lymphocyte ratio significantly mediated the effect of serum S100β on cognitive performance, even after controlling for the ataxia severity in the causal mediation analysis. Our findings suggested that, within physiologic concentrations, the protein S100β exerts a neuroprotective role against cognitive dysfunction in SCA2, likely via the suppression of pro-inflammatory mechanisms.

Pragmalinguistic and cognitive markers of oral speech: correlation with the psychotype of the speaker

This article provides information on the important role of pragmalinguistic and cognitive features of oral speech in the formation of effective communication and the fact that pragmalinguistic features include various elements of language use under the influence of the context and the speaker's communicative goals

Neural and Cognitive Predictors of Stimulant Treatment Efficacy in Medication-Naïve ADHD Adults: A Pilot Diffusion Tensor Imaging Study

Objective: Stimulant medications are the main treatment for Attention Deficit Hyperactivity Disorder (ADHD), but overall treatment efficacy in adults has less than a 60% response rate. This study aimed to identify neural and cognitive markers predictive of longitudinal improvement in response to stimulant treatment in drug-naïve adults with ADHD. Method: We used diffusion tensor imaging (DTI) and executive function measures with 36 drug-naïve adult ADHD patients in a prospective study design. Results: Structural connectivity (measured by fractional anisotropy, FA) in striatal regions correlated with ADHD clinical symptom improvement following stimulant treatment (amphetamine or methylphenidate) in better medication responders. A significant positive correlation was also found between working memory performance and stimulant-related symptom improvement. Higher pre-treatment working memory scores correlated with greater response. Conclusion: These findings provide evidence of pre-treatment neural and behavioral markers predictive of longitudinal treatment response to stimulant medications in adults with ADHD.

From sleepiness to inattention: investigating the attentional impacts of hypersomnolence in children through electrophysiological and cognitive markers

From sleepiness to inattention: investigating the attentional impacts of hypersomnolence in children through electrophysiological and cognitive markers

Naturalistic assessment of reaction time variability in older adults at risk for Alzheimer's disease.

Maintaining attention underlies many aspects of cognition and becomes compromised early in neurodegenerative diseases like Alzheimer's disease (AD). The consistency of maintaining attention can be measured with reaction time (RT) variability. Previous work has focused on measuring such fluctuations during in-clinic testing, but recent developments in remote, smartphone-based cognitive assessments can allow one to test if these fluctuations in attention are evident in naturalistic settings and if they are sensitive to traditional clinical and cognitive markers of AD. Three hundred and seventy older adults (aged 75.8 +/- 5.8 years) completed a week of remote daily testing on the Ambulatory Research in Cognition (ARC) smartphone platform and also completed clinical, genetic, and conventional in-clinic cognitive assessments. RT variability was assessed in a brief (20-40 seconds) processing speed task using two different measures of variability, the Coefficient of Variation (CoV) and the Root Mean Squared Successive Difference (RMSSD) of RTs on correct trials. Symptomatic participants showed greater variability compared to cognitively normal participants. When restricted to cognitively normal participants, APOE ε4 carriers exhibited greater variability than noncarriers. Both CoV and RMSSD showed significant, and similar, correlations with several in-clinic cognitive composites. Finally, both RT variability measures significantly mediated the relationship between APOE ε4 status and several in-clinic cognition composites. Attentional fluctuations over 20-40 seconds assessed in daily life, are sensitive to clinical status and genetic risk for AD. RT variability appears to be an important predictor of cognitive deficits during the preclinical disease stage.