Continuous Performance Test Research Articles

A comparative study of cognitive function in young patients with bipolar disorder with and without non-suicidal self-injury

ObjectiveBipolar disorder (BD) is a chronic mental disorder characterized by alternating or mixed episodes of mania or hypomania and depression. Cognitive function impairment is a frequent associated feature of the disease. While many BD patients also engage in non-suicidal self-injury (NSSI), there is a lack of studies on the cognitive function of BD patients with NSSI. This study aimed to evaluate cognitive functioning of BD patients with NSSI and provide a clinical basis for the differential diagnosis and treatment of BD and NSSI. MethodsA total of 60 BD patients with NSSI, 60 BD patients without NSSI, and 60 healthy controls (HC) were selected for the study. All participants met the inclusion criteria and were not taking any medications, excluding the potential effects of medication on cognitive functions. The following neurocognitive tests were used to measure the cognitive functions in areas such as speed of processing, reasoning and problem solving, attention/vigilance, working memory, visual learning, and verbal learning: The Trail Making Test (TMT), Category Fluency, Digit Symbol Coding Test (DSCT), Brief Visuospatial Memory Test-Revised (BVMT-R), The Neuropsychological Assessment Battery Mazes (NABM), Wechsler Memory Scale Third Edition Spatial Span Test (WMS III-SST), Hopkins Verbal Learning Test-Revised (HVLTR) and Continuous Performance Test and Identical Prs (CPT-IP). ResultsThe findings indicated that BD patients with NSSI exhibited cognitive impairment in all measured cognitive domains. On the other hand, BD patients without NSSI showed less pronounced impairment in terms of speed of processing, but exhibited significant cognitive impairment in the remaining five areas compared to the HC group. ConclusionThe study underscores the presence of cognitive impairment in BD, and the cognitive impairment is more severe in BD patients with NSSI compared to those without NSSI. In conclusion, both individuals with NSSI and those without NSSI in BD exhibit cognitive impairment, which provides ideas and strategies for using cognitive-behavioral therapy to treat BD and NSSI.

Aberrant brain network topology in youth with a familial risk for bipolar disorder: a task-based fMRI connectome study.

Youth with a family history of bipolar disorder (BD) may be at increased risk for mood disorders and for developing side effects after antidepressant exposure. The neurobiological basis of these risks remains poorly understood. We aimed to identify biomarkers underlying risk by characterizing abnormalities in the brain connectome of symptomatic youth at familial risk for BD. Depressed and/or anxious youth (n = 119, age = 14.9 ± 1.6 years) with a family history of BD but no prior antidepressant exposure and typically developing controls (n = 57, age = 14.8 ± 1.7 years) received functional magnetic resonance imaging (fMRI) during an emotional continuous performance task. A generalized psychophysiological interaction (gPPI) analysis was performed to compare their brain connectome patterns, followed by machine learning of topological metrics. High-risk youth showed weaker connectivity patterns that were mainly located in the default mode network (DMN) (network weight = 50.1%) relative to controls, and connectivity patterns derived from the visual network (VN) constituted the largest proportion of aberrant stronger pairs (network weight = 54.9%). Global local efficiency (Elocal, p = .022) and clustering coefficient (Cp, p = .029) and nodal metrics of the right superior frontal gyrus (SFG) (Elocal: p < .001; Cp: p = .001) in the high-risk group were significantly higher than those in healthy subjects, and similar patterns were also found in the left insula (degree: p = .004; betweenness: p = .005; age-by-group interaction, p = .038) and right hippocampus (degree: p = .003; betweenness: p = .003). The case-control classifier achieved a cross-validation accuracy of 78.4%. Our findings of abnormal connectome organization in the DMN and VN may advance mechanistic understanding of risk for BD. Neuroimaging biomarkers of increased network segregation in the SFG and altered topological centrality in the insula and hippocampus in broader limbic systems may be used to target interventions tailored to mitigate the underlying risk of brain abnormalities in these at-risk youth.

Effects of Game-Related Tasks for the Diagnosis and Classification of Gaming Disorder.

Gaming disorder (GD) is an addictive behavior characterized by an insatiable need to play video games and shares similar symptoms with the failure of self-control due to a decline in cognitive function. Current GD diagnostic and screening tools rely on questionnaires and behavioral observations related to cognitive functions to assess an individual's capacity to maintain self-control in everyday life. However, current GD screening approaches rely on subjective symptoms, and a reliable diagnosis requires long-term clinical follow-up. Recent studies have measured biosignals along with cognitive functional tasks to provide objectivity to GD diagnosis and to acquire immediate results. However, people with GD are hypersensitive to game-related cues, so their responses may vary depending on the type of stimuli, and the difference in response to stimuli might manifest as a difference in the degree of change in the biosignal. Therefore, it is critical to choose the correct stimulus type when performing GD diagnostic tasks. In this study, we investigated the task dependence of cognitive decline in GD by comparing two cognitive functional tasks: a continuous performance task (CPT) and video game play. For this study, 69 young male adults were classified into either the gaming disorder group (GD, n = 39) or a healthy control group (HC, n = 30). CPT score, EEG signal (theta, alpha, and beta), and HRV-HF power were assessed. We observed differences in the left frontal region (LF) of the brain between the GD and HC groups during online video game play. The GD group also showed a significant difference in HF power of HRV between CPT and online video gaming. Furthermore, LF and HRV-HF significantly correlated with Young's Internet Addiction Test (Y-IAT) score, which is positively associated with impulsivity score. The amount of change in theta band activity in LF and HRV-HF-both biomarkers for changes in cognitive function-during online video game play suggests that people with GD express task-dependent cognitive decline compared with HC. Our results demonstrate the feasibility of quantifying individual self-regulation ability for gaming and underscore its importance for GD classification.

Limited usefulness of neurocognitive functioning indices as predictive markers for treatment response to methylphenidate or neurofeedback@home in children and adolescents with ADHD.

Earlier studies exploring the value of executive functioning (EF) indices for assessing treatment effectiveness and predicting treatment response in attention-deficit/hyperactivity disorder (ADHD) mainly focused on pharmacological treatment options and revealed rather heterogeneous results. Envisioning the long-term goal of personalized treatment selection and intervention planning, this study comparing methylphenidate treatment (MPH) and a home-based neurofeedback intervention (NF@Home) aimed to expand previous findings by assessing objective as well as subjectively reported EF indices and by analyzing their value as treatment and predictive markers. Children and adolescents (n = 146 in the per protocol sample) aged 7-13 years with a formal diagnosis of an inattentive or combined presentation of ADHD were examined. We explored the EF performance profile using the Conners Continuous Performance Task (CPT) and the BRIEF self-report questionnaire within our prospective, multicenter, randomized, reference drug-controlled NEWROFEED study with sites in five European countries (France, Spain, Switzerland, Germany, and Belgium). As primary outcome for treatment response, the clinician-rated ADHD Rating Scale-IV was used. Patients participating in this non-inferiority trial were randomized to either NF@home (34-40 sessions of TBR or SMR NF depending on the pre-assessed individual alpha peak frequency) or MPH treatment (ratio: 3:2). Within a mixed-effects model framework, analyses of change were calculated to explore the predictive value of neurocognitive indices for ADHD symptom-related treatment response. For a variety of neurocognitive indices, we found a significant pre-post change during treatment, mainly in the MPH group. However, the results of the current study reveal a rather limited prognostic value of neurocognitive indices for treatment response to either NF@Home or MPH treatment. Some significant effects emerged for parent-ratings only. Current findings indicate a potential value of self-report (BRIEF global score) and some objectively measured neurocognitive indices (CPT commission errors and hit reaction time variability) as treatment markers (of change) for MPH. However, we found a rather limited prognostic value with regard to predicting treatment response not (yet) allowing recommendation for clinical use. Baseline symptom severity was revealed as the most relevant predictor, replicating robust findings from previous studies.

Differentiating Performance on the Connors Continuous Performance Test (CPT-3) as a Function of Comorbid Internalizing Psychopathology.

Internalizing psychopathology commonly co-occurs with attention-deficit/hyperactivity disorder (ADHD). Attention concerns are present in both ADHD and internalizing disorders, yet the neuropsychological functioning of those with comorbid ADHD and internalizing psychopathology is underexamined. This study compared Conners' Continuous Performance Test-Third Edition (CPT-3) profiles across ADHD (n = 141), internalizing psychopathology (n = 78), and comorbid (ADHD/internalizing psychopathology; n = 240) groups. Compared to the internalizing psychopathology group, the comorbid group had higher mean T-scores on CPT-3 indices indicative of inattentiveness and impulsivity and more clinically elevated T-scores (T>60) on indices measuring inattentiveness and impaired sustained attention. Patients in the comorbid group were also more likely to have abnormal overall CPT-3 profiles (>2 elevated T-scores) than the ADHD and psychopathology only groups. Patients with comorbid ADHD/internalizing psychopathology may evidence a more impaired attentional performance on the CPT-3, which could aid in more tailored treatment planning.

Temporal Alpha Dissimilarity of ADHD Brain Network in Comparison With CPT and CATA.

Attention deficit hyperactivity disorder (ADHD) is a chronic neurological and psychiatric disorder that affects children during their development. To find neural patterns for ADHD and provide subjective features as decision references to assist specialists and physicians. Many studies have been devoted to investigating the neural dynamics of the brain through resting-state or continuous performance tests (CPT) with EEG or functional magnetic resonance imaging (fMRI). The present study used coherence, which is one of the functional connectivity (FC) methods, to analyze the neural patterns of children and adolescents (8-16 years old) under CPT and continuous auditory test of attention (CATA) task. In the meantime, electroencephalography (EEG) oscillations were recorded by a wireless brain-computer interface (BCI). 72 children were enrolled, of which 53 participants were diagnosed with ADHD and 19 presented to be typical developing (TD). The experimental results exhibited a higher difference in alpha and theta bands between the TD group and the ADHD group. While the differences between the TD group and the ADHD group in all four frequency domains were greater than under CPT conditions. Statistically significant differences ( [Formula: see text]) were observed between the ADHD and TD groups in the alpha rhythm during the CATA task in the short-range of coherence. For the temporal lobe FC during the CATA task, the TD group exhibited statistically significantly FC ( [Formula: see text]) in the alpha rhythm compared to the ADHD group. These findings offering new possibilities for more techniques and diagnostic methods in finding more ADHD features. The differences in alpha and beta frequencies were more pronounced in the ADHD group during the CPT task compared to the CATA task. Additionally, the disparities in brain activity were more evident across delta, theta, alpha and beta frequency domains when the task given was a CATA as opposed to a CPT. The findings presented the underlying mechanisms of the FC differences between children and adolescents with ADHD. Moreover, these findings should extend to use machine learning approaches to assist the ADHD classification and diagnosis.

Emotion Comprehension and Socio-cognitive Skills in Children with High Functioning Autism Spectrum Disorders.

This study aimed to compare socio-cognitive skills and emotion comprehension between children with Autism Spectrum Disorder (ASD) and children with neurotypical development. This quantitative, cross-sectional, controlled study involved 19 children in each group, matched by age (6-12 years) and sex. The assessments examined cognitive aspects (Intelligence Quotient was assessed using the Vocabulary and Matrix Reasoning subtests; working memory using the digit span and letter-number sequencing subtests; attention using the Continuous Performance Test - Identical Pairs; and executive functions using the Trail Making Test), social functions (Children's Social Skills, Behavior Problems, and Academic Competence Inventory), and emotion comprehension (language was assessed using the Strange Stories Test; emotional facial expressions using the digital emotion comprehension test; emotional/affective prosody using the Profiling Elements of Prosody in Speech-Communication - Brazilian Portuguese adapted version). The group with ASD exhibited better performance in executive functions (p=0.02). However, they lagged the control group in social skills (p=0.04), behavior problems (p=0.03), and emotion comprehension (language, facial expressions, and prosody) (all p<0.05). The findings indicate that children with ASD have diminished performance in social skills and emotion comprehension compared to children with neurotypical development. Therefore, the development of technologies and/or therapeutic interventions that address these deficits among children with ASD is recommended.

Comparison of the Impact of Body Percussion Exercises on Executive and Balance Performance in Intellectually Disabled and Healthy Girls of Ramhormoz City

Objective: The purpose of the present study was to compare the effects of body percussion exercises on the executive and balance performance of children with intellectual disabilities and their healthy counterparts. Methods and Materials: The statistical population included healthy children and those with intellectual disabilities from Ramhormoz city, from which 20 healthy children (10 experimental, 10 control) and 20 children with intellectual disabilities (10 experimental, 10 control) aged 9 to 11 years were selected to participate in this research through pre-test and post-test evaluations using the Continuous Performance Test (sustained attention), Stroop Color and Word Test (response inhibition), Stork Stand (static balance), and Heel-Toe Walking (dynamic balance). The experimental groups (both healthy and with disabilities) received the selected body percussion intervention program in 45-minute group sessions twice a week for 8 weeks; however, the control groups (both healthy and with disabilities) engaged in usual school activities. Data analysis was performed using covariance analysis at the significance level of p ≤ 0.05. Results: The results showed that the effect of body percussion exercises on sustained attention (p = 0.001), response inhibition (p = 0.001), and static and dynamic balance (p = 0.001) was significant, and participants in the experimental groups performed better than those in the control groups (p = 0.001). Conclusions: Based on the findings, it seems that body percussion exercises are a beneficial intervention for improving motor and cognitive skills in both healthy children and those with intellectual disabilities; therefore, it is recommended that these exercises be used in physical education programs in schools and rehabilitation centers.

Neuroanatomical mapping of inhibitory attention and working memory with functional magnetic resonance imaging in healthy children

The objective is to produce an average brain activation mapping template in healthy children using functional magnetic resonance imaging (fMRI), with specific paradigms for activating inhibitory attention and working memory functions. A nutritional and neuropsychological evaluation was performed on 87 right-handed children. The inclusion criteria were met by 30 children (15 boys and 15 girls) between 9 and 11 years old, who were studied with fMRI in two inhibitory attention tests (Go/No Go), with food cues, a working memory test (Continuous Performance Test Identical Pairs) and measurement of anatomical volumes. These data were subsequently processed with the FSL-v5 program, with a threshold of p < 0.05 (cluster-wise). The brain areas activated were located using a standard Montreal Neurological Institute brain template and the Harvard-Oxford structural cortical atlas. The inhibitory attention tests showed activation frontal areas predominantly on the right, and the cingulate, parietal and occipital areas, with preponderance in occipital areas in the food cues test. In the Continuous Performance Test-Identical Pairs test, activation was obtained predominantly in the occipital, frontal and parietal areas. Brain activity mapping templates are obtained in healthy children with tests for inhibitory attention, food cues and working memory. The activation areas are mostly those reported in the literature. This provides baseline brain activation patterns for studying pathologies related to inhibitory attention, impulsivity and working memory.

Impact of subjective sleep quality on objective measures of neurocognitive dysfunction in patients with major depressive disorder

Background: Sleep disturbances are prevalent in major depressive disorder (MDD). MDD and sleep disturbances are both linked to cognitive impairments. Studies exploring the mechanisms and impact of sleep disturbances on neurocognitive functioning in depressed patients are lacking and proper assessment and therapeutic interventions for sleep disturbances are not part of clinical management of MDD. Aim: We investigated the association between subjective sleep quality and neurocognitive dysfunction in patients with MDD. Materials and Methods: Patients with moderate MDD episode were matched and assigned to two groups with poor and good sleep quality. We used Pittsburgh Sleep Quality Index (PSQI) to assess sleep quality. To measure frontotemporally mediated cognitive functioning, following tests were administered: Wisconsin Card Sorting Test (WCST) and degraded continuous performance test (CPT-DS). Two-tailed independent samples t tests or Mann–Whitney U tests and Pearson’s correlation coefficient were performed for the statistical analysis of sleep latency, sleep duration, overall sleep quality, CPT d’ value, WCST correct answers, errors, and perseverative errors. Results: Participants with MDD and poor sleep quality performed worse on cognitive tests compared to patients with MDD and good sleep quality. Scores of subjective sleep on PSQI positively correlated with WCST errors (r (60) =0.8883 P = .001) and negatively correlated with WCST correct answers (r (60) = -.869 P = .001) and measures of CPT-DS d’ value (r (60) = -.9355 P = .001). Conclusions: Poor sleep quality, notably sleep duration and sleep latency, worsens the neurocognitive impairments of MDD patients. As these impairments are found to be associated with treatment outcomes, sleep disturbances should be additionally assessed and treated in MDD episode.

Driving impairment due to psychoactive substances and attention deficit disorder: A pilot study

ObjectiveAttention disorder and substance use disorder are linked to driving impairment and increased road crash involvement. This study explores attention deficits in a population of drivers found driving under the influence (DUI) of psychoactive substances. MethodsA case-control study was conducted comparing subjects with a previous DUI episode (cases) to subjects who were negative for DUI offenses (controls). Personal, socio-demographic, and DUI data were collected for both groups. All subjects were administered the Continuous Performance Test–third edition (CPT-3), which measures dimensions of attention, including inattentiveness, impulsivity, sustained attention, and vigilance. Possible associations with a previous DUI episode, the use of illicit substances or excessive alcohol use, and road crash involvement were analyzed statistically. ResultsOverall, the study included 147 subjects (100 cases, 47 controls). The parameter distributions of detectability, probability of ADHD, and inattentiveness indicated statistical differences between the two groups. No attention deficits predicted substance use disorder or excessive alcohol consumption. Inattentiveness was an independent risk factor for previous road collision involvement. ConclusionsThe results suggest that alterations exist in some attention dimensions in a population of DUI subjects who were users of alcohol or other psychoactive substances and involved in road traffic crashes. The CPT-3 had successfully distinguished between the two study groups, and after validation, it could be useful in the process of reinstating a driver's license. Future research should expand the study sample to better understand the relevance of the proposed methodological approach in terms of prevention, rehabilitation, and the monitoring of subjects evaluated for driving eligibility requirements.

Cognitive Mechanisms Underlying Sports Performance of Athletes Engaged in Strategic Team Sports

We examined the cognitive performance of athletes engaged in strategic team sports such as football and basketball with sixty participants including athletes with at least five years of experience at National/State level in football and basketball and non-athletes. Measures of vigilance (continuous performance task), selective attention (spatial cuing task), visual search (feature and conjunction search task), attention network task, working memory (n-back task) and motion perception (apparent motion task) were employed. Athletes outperformed non- athletes on measures of vigilance, visual search, selective attention, and motion perception as they need to process multiple stimuli and engage in coordinated actions. Compared to football players, basketball players performed better with respect to vigilance, attentional facilitation and shifting; and faster target detection in conjunction search task with higher set-size. This is explained in terms of the need to assess the diverse environment and dynamically respond to the requirements related to movement sequences. Basketball and football players were comparable to non-athletes on the working memory task. Football players showed better performance on motion perception task compared to basketball players by effectively varying the temporal distance between stimuli for a strong motion percept, which may account for their ability to judge the speed of motion helping them to accurately perceive other’s actions to prepare for their own action. Thus, different strategic team sports may involve different cognitive skills mediating sports performance. Future work needs to explore more about sport- specific cognitive-perceptual expertise in athletes engaged in team sports as a function of training and experience using a longitudinal design.

BOLD Activation During the Application of MOXO-CPT in School Patients With and Without Attention Deficit Hyperactivity Disorder

Introduction: Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder that affects 3% of children in the world. Objective: In this work, we seek to compare the different brain activations of pediatric patients with and without ADHD. Methods: A functional resonance examination with BOLD contrast was applied using the MOXO-CPT test (Continuous Performance test with single and double visual-auditory distractors). Results: Differences in BOLD activation were observed indicating that control children regularly presented negative BOLD activations that were not found in children with ADHD. Inhibitory activity in audiovisual association zones in control patients was greater than in patients with ADHD. The inhibition in the frontal and motor regions in the controls contrasted with the overactivation of the motor areas in patients with ADHD, this, together with the detection of cerebellar activation which attempted to modulate the responses of the different areas that lead to executive failure in patients with ADHD. Conclusions: In view of these results, it can be argued that the lack of inhibition of ADHD patients in their executive functions led to a disorganization of the different brain systems.

Aberrant Neurofunctional Responses During Emotional and Attentional Processing Differentiate ADHD Youth With and Without a Family History of Bipolar I Disorder

Objective: To compare neurofunctional responses in emotional and attentional networks of psychostimulant-free ADHD youth with and without familial risk for bipolar I disorder (BD). Methods: ADHD youth with (high-risk, HR, n = 48) and without (low-risk, LR, n = 50) a first-degree relative with BD and healthy controls (n = 46) underwent functional magnetic resonance imaging while performing a continuous performance task with emotional distracters. Region-of-interest analyses were performed for bilateral amygdala (AMY), ventrolateral (VLPFC) and dorsolateral (DLPFC) prefrontal cortex, and anterior (ACC) and posterior cingulate cortex (PCC). Results: Compared with HC, HR, but not LR, exhibited predominantly left-lateralized AMY, VLPFC, DLPFC, PCC, and rostral ACC hyperactivation to emotional distractors, whereas LR exhibited right VLPFC and bilateral dorsal ACC hypoactivation to attentional targets. Regional responses correlated with emotional and attention symptoms. Conclusion: Aberrant neurofunctional responses during emotional and attentional processing differentiate ADHD youth with and without a family history of BD and correlate with relevant symptoms ratings.

Abnormal wiring of the structural connectome in adults with ADHD.

Current knowledge of white matter changes in large-scale brain networks in adult attention-deficit/hyperactivity disorder (ADHD) is scarce. We collected diffusion-weighted magnetic resonance imaging data in 40 adults with ADHD and 36 neurotypical controls and used constrained spherical deconvolution-based tractography to reconstruct whole-brain structural connectivity networks. We used network-based statistic (NBS) and graph theoretical analysis to investigate differences in these networks between the ADHD and control groups, as well as associations between structural connectivity and ADHD symptoms assessed with the Adult ADHD Self-Report Scale or performance in the Conners Continuous Performance Test 2 (CPT-2). NBS revealed decreased connectivity in the ADHD group compared to the neurotypical controls in widespread unilateral networks, which included subcortical and corticocortical structures and encompassed dorsal and ventral attention networks and visual and somatomotor systems. Furthermore, hypoconnectivity in a predominantly left-frontal network was associated with higher amount of commission errors in CPT-2. Graph theoretical analysis did not reveal topological differences between the groups or associations between topological properties and ADHD symptoms or task performance. Our results suggest that abnormal structural wiring of the brain in adult ADHD is manifested as widespread intrahemispheric hypoconnectivity in networks previously associated with ADHD in functional neuroimaging studies.

Vigilance to Painful Laser Stimuli is Associated with Increased State Anxiety and Tense Arousal.

Pain is frequently accompanied by enhanced arousal and hypervigilance to painful sensations. Here, we describe our findings in an experimental vigilance task requiring healthy participants to indicate when randomly timed moderately painful stimuli occur in a long train of mildly painful stimuli. During a continuous performance task with painful laser stimuli (CPTpain), 18 participants rated pain intensity, unpleasantness, and salience. We tested for a vigilance decrement over time using classical metrics including correct targets (hits), incorrectly identified non-targets (false alarms), hit reaction time, and false alarm reaction time. We measured state anxiety and tense arousal before and after the task. We found a vigilance decrement across four 12.5-minute blocks of painful laser stimuli in hits [F3,51=2.91; p=0.043; time block 1>block 4 (t=2.77; p=0.035)]. Both self-report state anxiety (tpaired,17=3.34; p=0.0039) and tense arousal (tpaired,17=3.20; p=0.0053) increased after the task. We found a vigilance decrement during our laser pain vigilance task consistent with vigilance decrements found in other stimulus modalities. Furthermore, state anxiety positively correlated with tense arousal. CPTpain acutely increased tense arousal and state anxiety, consistent with previous results implicating the reciprocal interaction of state anxiety and acute painful sensations and the role of pain in augmenting tense arousal. These results may indicate a psychological process which predisposes the hypervigilant to developing greater acute pain, resulting in positive feedback, greater pain and anxiety.

Impact of overall task length, target frequency, and interstimulus interval on a continuous visual attention performance test

Impact of overall task length, target frequency, and interstimulus interval on a continuous visual attention performance test

Plasma Alzheimer’s disease biomarkers and intraindividual cognitive variability measured by ecological momentary assessment in adults with type 1 diabetes

AbstractBackgroundOlder adults with type 1 diabetes (T1D) have elevated risk of Alzheimer’s disease and related dementias (ADRD) compared to non‐diabetic controls. Because of oscillations in blood glucose, individuals with T1D are also prone to physiological and cognitive fluctuations. Intraindividual cognitive variability (IICV), or within‐person standard deviation across cognitive tests, has been proposed as an alternative marker of early dementia. The aim of this study was to characterize the relationships between ADRD plasma biomarkers and IICV in adults with T1D via ecological momentary assessment (EMA) of cognition during regular daily activities.MethodAdults with T1D (age range 19‐84 yrs, mean = 48.9) who participated in the Glycemic Variability and Fluctuations in Cognitive Status in Adults with Type 1 Diabetes (GluCog) study and had available data on plasma β‐amyloid42/40, ptau181, NfL and GFAP levels measured using Quanterix assays were included in these analyses (N = 114). Cognition was assessed three times per day for 15 days. Within‐person measures of IICV were computed for each cognitive test after accounting for practice effects using multilevel modeling: Digit Symbol Matching reaction time (DSM‐RT; processing speed), Gradual Onset Continuous Performance Test d‐prime (GradCPT; cognitive control, attention), and Multiple Object Tracking accuracy (MOT; visual working memory). Multilinear regression models estimated associations between IICV and blood biomarkers, controlling for age, sex, education, person‐level mean cognition, and glucose variability (measured via continuous glucose monitoring).ResultsPTau181 and NfL were associated with IICV‐DSM‐RT (p&lt;0.05). GFAP and β‐amyloid42/40 were not associated with any of the measures of cognitive variability investigated.ConclusionThese findings suggest that pTau181 and NfL are associated with cognitive variability measured via EMA in an adult sample at risk for ADRD. This is the first study to (i) investigate the association between plasma biomarkers of dementia and IICV measured via EMA and (ii) report plasma biomarker results in individuals with T1D. The results encourage future studies investigating diabetes‐related factors that may contribute to increased dementia risk.

Next generation humanized mice to investigate how Traumatic Brain Injury interacts with ApoE4 genetic risk factor to accelerate dementia

AbstractBackgroundTraumatic brain injury (TBI) is among the leading causes of disability and has been strongly linked to Alzheimer’s disease (AD), the most prevalent cause of dementia. Patients with a history of repeated TBI can present pathologies and symptoms similar to AD: Tau protein neurofibrillary tangles, Amyloid Beta Plaques, and chronic inflammation. We propose that TBI triggers pathological processes that underlie AD development and thereby accelerates AD’s development and severity.Apolipoprotein E4 (ApoE4) protein has been thought to play a central role in several processes underlying AD development. ApoE4 is one of the biggest genetic risk factors for AD, which is also linked to worse short‐term and long‐term outcomes after TBI. However, how ApoE4 mechanistically affects the development of AD‐pathology after TBI has yet to be understoodMethodTo explore this gap, we will use mice with humanized genes which develop AD like pathology with age (Late‐onset AD). The humanized genes include amyloid precursor protein (hAPP) and microtubule‐associated protein tau (hMAPT) ‐ precursors to amyloid beta plaques and neurofibrillary tangles, respectively ‐ in addition to two copies of apolipoprotein E4 (ApoE4) or the control ApoE3 allele. Half of these mice will experience three mild TBIs modeled after human concussions, while the other half will only be anesthetized. All mice will undergo behavioral testing to measure cognitive deficits and molecular analyses to characterize the timing and severity of AD pathology. Cognitive testing will be carried out using the rodent touchscreen Continuous Performance Test (rCPT), which are widely used with AD patients to test attentional processes.ResultPreliminary results from rCPT before TBI, reveal no significant differences between genotypes and sex at 6‐month of age.ConclusionWe aim to uncover how TBI interacts with ApoE4 protein to accelerate AD pathology at the molecular and behavioral levels. To maximize the clinical relevance of this project, we use mice with human genes implicated in AD, a clinically relevant noninvasive model of concussion, and touchscreen cognitive testing identical to touchscreen testing in humans. We aim to bridge the gap between animal models and clinical settings to identify future therapeutic targets for TBI and AD.

Sustained attention in mild cognitive impairment with Lewy bodies and Alzheimer's disease.

Attentional impairments are common in dementia with Lewy bodies and its prodromal stage of mild cognitive impairment (MCI) with Lewy bodies (MCI-LB). People with MCI may be capable of compensating for subtle attentional deficits in most circumstances, and so these may present as occasional lapses of attention. We aimed to assess the utility of a continuous performance task (CPT), which requires sustained attention for several minutes, for measuring attentional performance in MCI-LB in comparison to Alzheimer's disease (MCI-AD), and any performance deficits which emerged with sustained effort. We included longitudinal data on a CPT sustained attention task for 89 participants with MCI-LB or MCI-AD and 31 healthy controls, estimating ex-Gaussian response time parameters, omission and commission errors. Performance trajectories were estimated both cross-sectionally (intra-task progress from start to end) and longitudinally (change in performance over years). While response times in successful trials were broadly similar, with slight slowing associated with clinical parkinsonism, those with MCI-LB made considerably more errors. Omission errors were more common throughout the task in MCI-LB than MCI-AD (OR 2.3, 95% CI: 1.1-4.7), while commission errors became more common after several minutes of sustained attention. Within MCI-LB, omission errors were more common in those with clinical parkinsonism (OR 1.9, 95% CI: 1.3-2.9) or cognitive fluctuations (OR 4.3, 95% CI: 2.2-8.8). Sustained attention deficits in MCI-LB may emerge in the form of attentional lapses leading to omissions, and a breakdown in inhibitory control leading to commission errors.