Neurocognitive Abilities Research Articles

Childhood maltreatment and adult aggression: The moderating role of neurocognitive ability and substance use

BackgroundAchieving positive intervention outcomes for aggressive behaviour in adulthood is challenging. This difficulty is enhanced by the complex presentations of those engaging in such behaviours and the impact this has on their engagement with interventions. ObjectiveThis study assessed the cumulative impact of childhood maltreatment, substance use, and neurocognitive ability (working memory, cognitive flexibility, decision making, response inhibition, and cognitive control) on aggressive behaviour in adulthood. Participants and settingAdult participants (N = 179; 69 % female) recruited from the community, and clinical and forensic services, aged 18 to 81 (M = 40.5, SD = 15.9). MethodsParticipants completed an online Qualtrics survey and remote neurocognitive testing via Inquisit. ResultsWe implemented an a priori approach, assessing three-way interactions between childhood maltreatment, substance use, neurocognitive ability, and aggression. No three-way interactions were significant. We then utilised a data-driven modelling approach, using automatic linear forward stepwise modelling to identify the most important variables for predicting aggression. Four were significant: physical maltreatment (b = 0.053, p < .001), drug use risk level (b = 0.015, p < .001), poorer response inhibition (b = 0.001, p = .016), and the interaction between poorer response inhibition and physical maltreatment (b = 0.205, p = .017). ConclusionsPhysical maltreatment in childhood, drug use risk level, and response inhibition impact significantly on adult aggression, indicating a need for early intervention for children who have experienced maltreatment. Consideration should be given to how maltreatment in childhood may impact on ability to engage with interventions as an adult, particularly response inhibition difficulties that may hinder skill implementation.

The impact of maturation level, not chronological age, on attentional control: implications for sports injury prevention in female adolescents

BackgroundNon-contact injuries are highly prevalent among young athletes and occur particularly in situations that require fast decision making and divided attention. Administering relevant neurocognitive tests could help identify deficiencies in these cognitive abilities and thus potentially mitigate injury risk. However, processes such as selective attention and response inhibition might depend to some extent on the athlete’s maturation stage. We aimed to examine the effect of maturation on selective visual attention and response inhibition among adolescent volleyball players.MethodsIn this cross-sectional study, 52 female adolescents (age 12.3 ± 2.1 years) performed an Eriksen Flankers task. Participants were divided into subgroups based on their estimated adult stature, using the Khamis & Roche method: Pre-pubertal (PRE; n = 13, age: 9.9 ± 1.3), early-puberty (EPUB; n = 7, age: 10.5 ± 0.6), mid-puberty (MPUB; n = 8, age: 12.6 ± 0.8) and late puberty (LPUB; n = 24, age: 14.1 ± 0.9). Analyses of covariance (ANCOVA) were performed on congruent and incongruent reaction times (RT), with corresponding success rates (% correct responses) as covariate. Flanker interference effect was tested using ANOVA. Correlations were further examined between the dependent variables and participants’ chronological age.ResultsThere was a significant group effect, with PRE demonstrating longer RT compared with LPUB (P < 0.001) for both congruent and incongruent RT. Moderate negative correlations were observed between age and RT (Rp = -0.695, Rp = -0.614 for congruent and incongruent RT, respectively) and low positive correlations between age and incongruent success rate (Rs = 0.318). Low to moderate correlations were also observed within the LPUB group for RT (Rp = -0.431–-0.532) and success rate (negative Rs = -574 for congruent and positive Rs = 0.417 for incongruent). There were no group differences nor age associations with interference effect.ConclusionsOur findings indicate that information processing and selective visual attention are superior at late maturation compared with early maturation among female adolescents. The same cannot be said for response inhibition, which did not differ between maturation groups. Similar tendencies were observed with regards to chronological age, but not entirely explained by it. Maturation level, rather than chronological age, should guide practitioners during sport participation and injury prevention programs for young athletes, whose neurocognitive abilities are not yet fully developed, placing them at risk for non-contact injuries.

Blood metabolites, neurocognition and psychiatric disorders: a Mendelian randomization analysis to investigate causal pathways

BackgroundNeurocognitive dysfunction is observationally associated with the risk of psychiatric disorders. Blood metabolites, which are readily accessible, may become highly promising biomarkers for brain disorders. However, the causal role of blood metabolites in neurocognitive function, and the biological pathways underlying their association with psychiatric disorders remain unclear.MethodsTo explore their putative causalities, we conducted bidirectional two-sample Mendelian randomization (MR) using genetic variants associated with 317 human blood metabolites (nmax = 215,551), g-Factor (an integrated index of multiple neurocognitive tests with nmax = 332,050), and 10 different psychiatric disorders (n = 9,725 to 807,553) from the large-scale genome-wide association studies of European ancestry. Mediation analysis was used to assess the potential causal pathway among the candidate metabolite, neurocognitive trait and corresponding psychiatric disorder.ResultsMR evidence indicated that genetically predicted acetylornithine was positively associated with g-Factor (0.035 standard deviation units increase in g-Factor per one standard deviation increase in acetylornithine level; 95% confidence interval, 0.021 to 0.049; P = 1.15 × 10−6). Genetically predicted butyrylcarnitine was negatively associated with g-Factor (0.028 standard deviation units decrease in g-Factor per one standard deviation increase in genetically proxied butyrylcarnitine; 95% confidence interval, −0.041 to −0.015; P = 1.31 × 10−5). There was no evidence of associations between genetically proxied g-Factor and metabolites. Furthermore, the mediation analysis via two-step MR revealed that the causal pathway from acetylornithine to bipolar disorder was partly mediated by g-Factor, with a mediated proportion of 37.1%. Besides, g-Factor mediated the causal pathway from butyrylcarnitine to schizophrenia, with a mediated proportion of 37.5%. Other neurocognitive traits from different sources provided consistent findings.ConclusionOur results provide genetic evidence that acetylornithine protects against bipolar disorder through neurocognitive abilities, while butyrylcarnitine has an adverse effect on schizophrenia through neurocognition. These findings may provide insight into interventions at the metabolic level for risk of neurocognitive and related disorders.

Eight brain structures mediate the age-related alterations of the working memory: forward and backward digit span tasks.

Working memory (WM) as one of the executive functions is an essential neurocognitive ability for daily life. Findings have suggested that aging is often associated with working memory and neural decline, but the brain structures and resting-state brain networks that mediate age-related differences in WM remain unclear. A sample consisting of 252 healthy participants in the age range of 20 to 70years was used. Several cognitive tasks, including the n-back task and the forward and backward digit span tests were used. Also, resting-state functional imaging, as well as structural imaging using a 3T MRI scanner, were performed, resulting in 85 gray matter volumes and five resting-state networks, namely the anterior and posterior default mode, the right and left executive control, and the salience networks. Also, mediation analyses were used to investigate the role of gray matter volumes and resting-state networks in the relationship between age and WM. Behaviorally, aging was associated with decreased performance in the digit span task. Also, aging was associated with a decreased gray matter volume in 80 brain regions, and with a decreased activity in the anterior default mode network, executive control, and salience networks. Importantly, the path analysis showed that the GMV of the medial orbitofrontal, precentral, parieto-occipital, amygdala, middle occipital, posterior cingulate, and thalamus areas mediated the age-related differences in the forward digit span task, and the GMV of superior temporal gyrus mediated the age-related differences in the backward digit span task. This study identified the brain structures mediating the relationship between age and working memory, and we hope that our research provides an opportunity for early detection of individuals at risk of age-related memory decline.

Microembolizations in the arterial cerebral circulation during atrial fibrillation ablation: cryoballoon technique advantages and neurocognitive safety-results of a prospective observational study.

The significance of micro-embolic signals (MESs) during atrial fibrillation (AF) ablation is unclear. Previous studies had limitations, and cryoballoon (CB) ablation patients were under-represented. Minimizing MESs is recommended due to their uncertain neurocognitive impact. This prospective observational study included AF patients from a German centre between February 2021 and August 2022. Patients were equally divided into paroxysmal (Group A) and persistent (Group B) AF. Group A received cryoballoon-pulmonary vein isolation only, while Group B also had left atrial roof ablation. MESs were detected using transcranial Doppler ultrasonography during ablation. Neurocognitive status was assessed pre- and post-procedure and at 3 months using the CERAD Plus battery. The study analyzed 100 patients with a median age of 65.5 years. A total of 19 698 MESs were observed, with 80% being gaseous and 20% solid in origin, primarily occurring during pulmonary vein angiography and the balloon freeze and thawing phase. The median MES per patient was 130 (IQR: 92-256) in total, 298 (IQR: 177-413) in bilateral (36%), and 110 (IQR: 71-130) in unilateral (64%) recordings. No significant difference in total MES counts was found between the groups. None of the 11 neuropsychological tests showed cognitive decline post-procedure or at 3 months. Our observations confirm that neurocognitive abilities are not affected either 24 h or 3 months after AF ablation using the CB technique. However, despite the low MES burden associated with the CB, more work is needed to reduce small embolic events during AF ablation.

Relationship between maternal biological features, environmental factors, and newborn neuromotor development associated with visual fixation abilities

Newborn visual fixation abilities predict future cognitive, perceptive, and motor skills. However, little is known about the factors associated with the newborn visual fixation, which is an indicator of neurocognitive abilities. We analyzed maternal biological and environmental characteristics associated with fine motor skills (visual tracking) in 1 month old infants. Fifty-one infants were tested on visual tracking tasks (Infant Visuomotor Behavior Assessment Scale/ Guide for the Assessment of Visual Ability in Infants) and classified according to visual conducts scores. Differences between groups were compared considering motor development (Alberta Infant Motor Scale) maternal mental health (Edinburgh Postnatal Depression Scale and Hamilton Anxiety Scale); home environment (Affordances in the Home Environment for Development Scale); maternal care (Coding Interactive Behavior); breastmilk composition (total fatty acids, proteins, and cortisol); and maternal metabolic profile (serum hormones and interleukins). Mothers of infants with lower visual fixation scores had higher levels of protein in breastmilk at 3 months. Mothers of infants with better visual conduct scores had higher serum levels of T4 (at 1 month) and prolactin (at 3 months). There were no associations between visual ability and motor development, home environment, or maternal care. Early newborn neuromotor development, especially visual and fine motor skills, is associated with maternal biological characteristics (metabolic factors and breastmilk composition), highlighting the importance of early detection of maternal metabolic changes for the healthy neurodevelopment of newborns.

Neuroprotective Effect of Colocasia esculenta Var. Mentawai Corm Flour High-Fat Diet Fed Mice

The transformation of our era, resulting in a change in dietary habits towards a higher intake of fatty foods, presents a worldwide health issue. Among these challenges is neurodegeneration, which leads to cognitive impairment. It is imperative to seek alternative solutions rooted in nature to address the limitations associated with non-natural treatment methods. This entails harnessing the properties of secondary metabolite compounds found in plants, such as Colocasia esculenta Var. Mentawai. This research aims to assess the efficacy of C. esculenta Var. Mentawai corm as neuroprotective agents in mitigating CNS damage and preventing cognitive decline associated with neurodegeneration. Daily administration of a high-fat diet and a mixture of taro flour is conducted on young adult male mice for a duration of 60 days. Furthermore, analysis of the neurocognitive ability of mice, determination of malondialdehyde levels, and observation of histopathological structures on brain tissue were carried out. The results showed that the group of mice fed with taro flour mixture effectively showed a positive impact on maintaining neurocognitive abilities and histopathological structure of brain tissue against neurodegeneration (p

Discernible interindividual patterns of global efficiency decline during theoretical brain surgery

The concept of functional localization within the brain and the associated risk of resecting these areas during removal of infiltrating tumors, such as diffuse gliomas, are well established in neurosurgery. Global efficiency (GE) is a graph theory concept that can be used to simulate connectome disruption following tumor resection. Structural connectivity graphs were created from diffusion tractography obtained from the brains of 80 healthy adults. These graphs were then used to simulate parcellation resection in every gross anatomical region of the cerebrum by identifying every possible combination of adjacent nodes in a graph and then measuring the drop in GE following nodal deletion. Progressive removal of brain parcellations led to patterns of GE decline that were reasonably predictable but had inter-subject differences. Additionally, as expected, there were deletion of some nodes that were worse than others. However, in each lobe examined in every subject, some deletion combinations were worse for GE than removing a greater number of nodes in a different region of the brain. Among certain patients, patterns of common nodes which exhibited worst GE upon removal were identified as “connectotypes”. Given some evidence in the literature linking GE to certain aspects of neuro-cognitive abilities, investigating these connectotypes could potentially mitigate the impact of brain surgery on cognition.

Neurocognitive markers during maximum alcohol use in late adolescence as predictors of change in later drinking behaviors

AbstractThe influence of alcohol use on later neurocognitive functioning is well researched, yet few studies have investigated whether neurocognition post‐drinking initiation in adolescence predicts changes in later alcohol use. The objective of this study was to investigate neurocognitive task performance during maximum alcohol use in late adolescence as predictors of drinking behaviors 3–7 years later. Analyses (n = 105) were conducted on a longitudinal data set involving adolescents (12–13 years old) who were followed for 16 years. Time 1 (T1) was defined as the individuals' maximum drinking year within the first 10 study years and Time 2 (T2) was the first available data entry 3–7 years after T1. Four hierarchical linear regression models predicting follow‐up alcohol use were estimated: drinking days, average drinks per drinking day, peak drinks, and binge episodes. All models included inhibition/cognitive flexibility, visuospatial ability, verbal memory, working memory, and their interactions with sex, while covarying for age at T1, follow‐up duration, and controlling for T1 drinking. Better visuospatial ability at T1 predicted decreases in later binge episodes at T2 (β = −0.19, p = 0.048, partial r2 = 0.039). While better inhibition/cognitive flexibility at T1 predicted increases in follow‐up drinks per drinking day at T2 (β = 0.18, p = 0.016, partial r2 = 0.057). Findings suggest specific neurocognitive abilities during maximum drinking in late adolescence are useful as predictors of change in later drinking quantity per occasion and could potentially inform intervention research targeting this age group.

“Why am I still suffering?”: Experience of long-term fatigue and neurocognitive changes in oropharyngeal cancer survivors following (chemo)radiotherapy

BackgroundLate effects of cancer treatment, such as neurocognitive deficits and fatigue, can be debilitating. Other than head and neck–specific functional deficits such as impairments in swallowing and speech, little is known about survivorship after oropharyngeal cancer. This study examines the lived experience of fatigue and neurocognitive deficits in survivors of oropharyngeal squamous cell cancer and impact on their daily lives. MethodsThis work is part of the multicentre mixed method ROC-oN study (Radiotherapy for Oropharyngeal Cancer and impact on Neurocognition), evaluating fatigue and neurocognitive function in patients following radiotherapy +/- chemotherapy for oropharyngeal cancer and impact on quality of life. Semi-structured interviews were conducted in adults treated with radiotherapy (+/-chemotherapy) for oropharyngeal squamous cell carcinoma >/=24 months from completing treatment. Reflexive thematic analysis performed. Results21 interviews (11 men and 10 women; median age 58 years and median time post-treatment 5 years) were conducted and analysed, yielding six themes: (1) unexpected burden of fatigue, (2) noticing changes in neurocognitive function, (3) the new normal, (4) navigating changes, (5)insufficient awareness and (6)required support. Participants described fatigue that persisted beyond the acute post-treatment period and changes in neurocognitive abilities across several domains. Paid and unpaid work, emotions and mood were impacted. Participants described navigating the new normal by adopting self-management strategies and accepting external support. They reported lack of recognition of these late effects, being poorly informed and being unprepared. Follow-up services were thought to be inadequate. ConclusionsFatigue and neurocognitive impairment were frequently experienced by survivors of oropharyngeal cancer, at least two years after treatment. Patients felt ill-prepared for these late sequelae, highlighting opportunities for improvement of patient information and support services.

NUTRITIONAL AND SOCIOECONOMIC DETERMINANTS OF COGNITIVE STATUS AND SELF-ESTEEM AMONG SCHOOLCHILDREN IN THE URBAN AREA OF KENITRA (MOROCCO)

Low cognitive performance and low self-esteem can be influenced by nutritional factors, such as dietary deficiencies, as well as socio-economic aspects including the level of education and economic status. These elements can interact in complex ways, contributing to variations in cognitive performance and self-es- teem. It is important to consider all aspects of mental and physical health to fully understand this relationship.A sample of 174 urban schoolchildren, aged between 15 and 19, and hailing from modest socio-economic backgrounds, participated in the study. They underwent a cognitive test (the Raven test) to evaluate their intellectual induction abilities. Additionally, a questionnaire was administered to gauge their socio-economic status. Nutritional status was assessed through various indices, including weight, height, and indicators such as weight-for-age, height-for-age, and emaciation. Self-esteem was measured using the French translation of Pelham and Swann’s self-assessment questionnaire, completed by the students.Neurocognitive abilities exhibited significant correlations with gender, mathematical performance, nutritional status, and the educational level of mothers. Conversely, self-esteem demonstrated correlations with parental education levels and the presence of emaciation.The results of this study highlight a significant relation between malnutrition and neurocognitive abilities, as well as self-esteem in schoolgirls. These findings suggest that nutritional management could play an essential role in preventing self-esteem problems and cognitive difficulties among schoolchildren.

Trauma Memory Characteristics and Neurocognitive Performance in Youth Exposed to Single-Event Trauma

Cognitive models of posttraumatic stress disorder (PTSD) highlight characteristics of trauma memories, such as disorganisation, as key mechanisms in the aetiology of the disorder. However, studies investigating trauma memory in youth have provided inconsistent findings. Research has highlighted that PTSD in youth may be accompanied by difficulties in neurocognitive functioning, potentially impacting ability to recall the trauma memory. The present study sought to investigate both trauma memory characteristics and neurocognitive functioning in youth aged 8–17 years. Youths exposed to single-event trauma, with (N = 29, Mage = 13.6, 21 female) and without (N = 40, Mage = 13.3, 21 female) a diagnosis of PTSD, completed self-report measures of trauma memory, a narrative memory task and a set of neurocognitive tests two to six months post-trauma. A group of non trauma-exposed youths (N = 36, Mage = 13.9, 27 female) were compared on narrative and neurocognitive tasks. Results indicated that trauma memories in youth with, versus without, PTSD were more sensory-laden, temporally disrupted, difficult to verbally access, and formed a more ‘central’ part of their identity. Greater differences were observed for self-reported memory characteristics compared to narrative characteristics. No between group differences in neurocognitive function were observed. Self-reported trauma memory characteristics highlight an important factor in the aetiology of PTSD. The observed lack of significant differences in neurocognitive ability potentially suggests that cognitive factors represent a more relevant treatment target than neurocognitive factors in single-event PTSD. Further research to understand the cognitive factors represented by self-reported trauma memory characteristics is recommended.

Neuropsychological assessment fails to predict relapse among cigarette smokers: A prospective study of neurocognitive abilities

ObjectivesUnderstanding the factors that lead to relapse is a major challenge for the clinical support of smoking cessation. Neurocognitive abilities such as attention, executive functioning and working memory, are possible predictors of relapse and can be easily assessed in everyday clinical practice. In this prospective longitudinal study, we investigated the relationship between pre-smoking cessation neurocognitive performance and relapse at six months in a sample of patients being treated for their tobacco dependence. Methods130 tobacco consumers were included in the study. They completed a comprehensive neuropsychological and clinical assessment before smoking cessation. The targeted abilities were intelligence, inhibition, shifting, working memory updating, verbal fluency and decision-making. ResultsThe rate of tobacco relapse at 6 months was 58%. Logistic regressions were used to assess which variables best explained relapse. None of the neuropsychological tests was a significant predictor of relapse at either 1, 3 or 6 months, either alone, or controlling for other covariates acting as significant predictors of relapse. ConclusionsCommon neuropsychological tests, even those specifically targeting executive functioning such as inhibition, are not useful predictors of the success of a smoking cessation program in a clinical setting. Other variables, such as motivation to quit smoking or the presence of comorbid depression or anxiety disorders, appear to be more useful predictors of relapse.

Fusion of dual modalities of non-invasive sensory feedback for object profiling with prosthetic hands.

Either non-invasive somatotopic or substitute sensory feedback is capable of conveying a single modality of sensory information from prosthetic hands to amputees. However, the neurocognitive ability of amputees to integrate multi-modality sensory information for functional discrimination is unclear. The purpose of this study was to assess the fusion of non-invasive somatotopic tactile and substitute aperture feedbacks for profile perception of multiple physical features during grasping objects. Two left transradial amputees with somatotopic evoked tactile sensation (ETS) of five fingers participated in the study. The tactile information of prosthetic hand was provided to amputees by the ETS feedback elicited on the stump projected finger map. Hand aperture information was conveyed to amputees with substitute electrotactile stimulation on the forearm or upper arm. Two types of sensory feedback were integrated to a commercial prosthetic hand. The efficacy of somatotopic ETS feedback on object length identification task was assessed with or without substitute aperture stimulation. The object size identification task was utilized to assess how ETS stimulation at the stump may affect aperture perception with stimulation on the ipsilateral upper arm or forearm. Finally, the task of identifying combined length and size was conducted to evaluate the ability of amputees to integrate the dual modalities of sensory feedback for perceiving profile features. The study revealed that amputee subjects can effectively integrate the ETS feedback with electrotactile substitutive feedback for object profile discrimination. Specifically, ETS was robust to provide object length information with electrotactile stimulation at either the forearm or upper arm. However, electrotactile stimulation at the upper arm for aperture perception was less susceptible to the interference of ETS stimulation than at the forearm. Amputee subjects are able to combine somatotopic ETS and aperture feedbacks for identifying multi-dimensional features in object profiling. The two sensory streams of information can be fused effectively without mutual interference for functional discrimination.

A 10‐minute Digitally Administered and Scored Neuropsychological Protocol Assessing Executive Control and Episodic Memory

AbstractBackgroundDigital assessment technology provides rapid and reliable assessment of neurocognitive abilities associated with Alzheimer’s Disease and Related Dementia (ADRD) and Mild Cognitive Impairment (MCI). Dysexecutive and amnestic impairment typify many ADRD and MCI disorders. Here, we evaluate a 10‐minute digitally administered protocol assessing these neurocognitive constructs.Method229 community dwelling participants were assessed (age = 68.32+9.85; education = 15.01+2.58, MMSE = 26.84+2.78; 144 females). Executive abilities were assessed with three trials of 5‐digits backward digit span test (BDST) and the ‘animal’ fluency test. Episodic memory was assessed with a 6‐word Philadelphia (repeatable) Verbal Learning Test (PrVLT) consisting of 2 immediate free recall (IFR) trials, delayed free recall (DFR), and delayed recognition. Traditional pencil and paper testing was not used. Data were obtained with an iPad processed using automatic speech recognition.ResultA K‐means cluster analysis (k = 3) classified participants with possible dementia (pDem = 31), MCI (n = 96), and cognitively normal (CN, n = 100; Table 1). Groups differed from each other on all three P(r)VLT parameters (p = 0.001). CN participants outperformed other groups on executive measures (p = 0.001). All between‐group analyses yielded large effect sizes (η2 = 0.277–0.642). Logistic regression analysis using P(r)VLT‐DFR, P(r)VLT‐recognition, BDST, and ‘animal’ fluency parameters classify MCI and pDem participants into their respective groups compared to CN participants (p = 0.003). For the pDem group, within‐group t‐tests found rapid forgetting (PrVLT‐DFT&lt;PrVLT‐IFR trial 2, p = 0.013; PrVLT‐recognition&lt;PrVLT‐DFR (p = 0.013). Additional, within‐group pDem group comparisons found no differences between P(r)VLT‐recognition and either executive tests. Within group comparisons for the MCI group found P(r)VLT delayed recognition improved compared to P(r)VLT delayed free recall (p&lt;0.001), and worse performance on both executive measures compared to P(r)VLT‐ recognition (p = .001). All of these comparisons are consistent with a mild dysexecutive syndrome.ConclusionThe protocol described above is efficient, reliable, removes any inter‐rater reliability issues, and is able to operationally‐define dysexecutive and amnestic cognitive impairment ‐ key neurocognitive constructs related to ADRD and MCI. This 10‐minute digitally administered and automatically scored neuropsychological protocol assessing executive abilities and episodic memory could easily be deployed in clinical trials and in primary‐ and specialty‐care settings to screen for emergent cases of MCI and ADRD by efficient assessment of episodic memory and executive abilities.

A 10‐minute Digitally Administered and Scored Neuropsychological Protocol Assessing Executive Control and Episodic Memory

AbstractBackgroundDigital assessment technology provides rapid and reliable assessment of neurocognitive abilities associated with Alzheimer’s Disease and Related Dementia (ADRD) and Mild Cognitive Impairment (MCI). Dysexecutive and amnestic impairment typify many ADRD and MCI disorders. Here, we evaluate a 10‐minute digitally administered protocol assessing these neurocognitive constructs.Method229 community dwelling participants were assessed (age = 68.32+9.85; education = 15.01+2.58, MMSE = 26.84+2.78; 144 females). Executive abilities were assessed with three trials of 5‐digits backward digit span test (BDST) and the ‘animal’ fluency test. Episodic memory was assessed with a 6‐word Philadelphia (repeatable) Verbal Learning Test (PrVLT) consisting of 2 immediate free recall (IFR) trials, delayed free recall (DFR), and delayed recognition. Traditional pencil and paper testing was not used. Data were obtained with an iPad processed using automatic speech recognition.ResultA K‐means cluster analysis (k = 3) classified participants with possible dementia (pDem = 31), MCI (n = 96), and cognitively normal (CN, n = 100; Table 1). Groups differed from each other on all three P(r)VLT parameters (p = 0.001). CN participants outperformed other groups on executive measures (p = 0.001). All between‐group analyses yielded large effect sizes (η2 = 0.277–0.642). Logistic regression analysis using P(r)VLT‐DFR, P(r)VLT‐recognition, BDST, and ‘animal’ fluency parameters classify MCI and pDem participants into their respective groups compared to CN participants (p = 0.003). For the pDem group, within‐group t‐tests found rapid forgetting (PrVLT‐DFT&lt;PrVLT‐IFR trial 2, p = 0.013; PrVLT‐recognition&lt;PrVLT‐DFR (p = 0.013). Additional, within‐group pDem group comparisons found no differences between P(r)VLT‐recognition and either executive tests. Within group comparisons for the MCI group found P(r)VLT delayed recognition improved compared to P(r)VLT delayed free recall (p&lt;0.001), and worse performance on both executive measures compared to P(r)VLT‐ recognition (p = .001). All of these comparisons are consistent with a mild dysexecutive syndrome.ConclusionThe protocol described above is efficient, reliable, removes any inter‐rater reliability issues, and is able to operationally‐define dysexecutive and amnestic cognitive impairment ‐ key neurocognitive constructs related to ADRD and MCI. This 10‐minute digitally administered and automatically scored neuropsychological protocol assessing executive abilities and episodic memory could easily be deployed in clinical trials and in primary‐ and specialty‐care settings to screen for emergent cases of MCI and ADRD by efficient assessment of episodic memory and executive abilities.

Catechol-O-methyltransferase gene (COMT) is associated with neurocognitive functioning in patients with sickle cell disease

PurposeNeurocognitive impairment is a common and debilitating complication of sickle cell disease (SCD) resulting from a combination of biological and environmental factors. The catechol-O-methyltransferase (COMT) gene modulates levels of dopamine availability in the prefrontal cortex. COMT has repeatedly been implicated in the perception of pain stimuli and frequency of pain crises in patients with SCD and is known to be associated with neurocognitive functioning in the general population. The current study aimed to examine the associations of genetic variants in COMT and neurocognitive functioning in patients with SCD. Patients and MethodsThe Sickle Cell Clinical Research and Intervention Program (SCCRIP) longitudinal cohort was used as a discovery cohort (n = 166). The genotypes for 5 SNPs (rs6269, rs4633, rs4818, rs4680, and rs165599) in COMT were extracted from whole genome sequencing data and analyzed using a dominant model. A polygenic score for COMT (PGSCOMT) integrating these 5 SNPs was analyzed as a continuous variable. The Cooperative Study of Sickle Cell Disease (CSSCD, n = 156) and the Silent Cerebral Infarction Transfusion (SIT, n = 114) Trial were used as 2 independent replication cohorts. Due to previously reported sex differences, all analyses were conducted separately in males and females. The Benjamini and Hochberg approach was used to calculate false discovery rate adjusted p-value (q-value). ResultsIn SCCRIP, 1 out of 5 SNPs (rs165599) was associated with IQ at q<0.05 in males but not females, and 2 other SNPs (rs4633 and rs4680) were marginally associated with sustained attention at p<0.05 in males only but did not maintain at q<0.05. PGSCOMT was negatively associated with IQ and sustained attention at p<0.05 in males only. Using 3 cohorts’ data, 4 out of 5 SNPs (rs6269, rs4633, rs4680, rs165599) were associated with IQ (minimum q-value = 0.0036) at q<0.05 among male participants but not female participants. The PGSCOMT was negatively associated with IQ performance among males but not females across all cohorts. ConclusionSelect COMT SNPs are associated with neurocognitive abilities in males with SCD. By identifying genetic predictors of neurocognitive performance in SCD, it may be possible to risk-stratify patients from a young age to guide implementation of early interventions.

Neurocognitive Improvement with Hydroxyurea Therapy in Children with Sickle Cell Anemia in Uganda: Interim Analysis at Month 18

Introduction: Cerebrovascular injury can lead to neurocognitive impairment in children with sickle cell anemia (SCA). The prospective impact of hydroxyurea therapy on neurocognitive function has not been previously reported in a large sample of children with SCA in sub-Saharan Africa. We assessed the impact of hydroxyurea therapy at the trial's18-month midpoint on neurocognitive function compared to baseline assessments and to non-SCA controls. Methods: A sample of267 children with SCA, ages 3 to 9 years, were randomly selected for screening and enrollment from eligible patients who attended the Mulago Hospital Sickle Cell Clinic (MHSCC). BRAIN SAFE II is an open label hydroxyurea treatment trial with escalation to maximal tolerated dose. Primary outcomes are stroke, stroke risk and neurocognitive assessment. Controls were aged 3 to 12 years and siblings/relatives of participants with SCA.Attention, cognition and executive function were assessed for all participants by age-appropriate neurocognitive testing. Controlsestablished test z-scores for each age. Baseline (month 0) SCA group z-scores were compared to the controls and to the SCA sample at trial month 18. Results: At trial baseline, SCA trial participants (n=267) were younger than the control group (mean age 5.1±1.7 vs. 7.1± 3.9 years, p&amp;lt;0.001), had lower weight-for-age ( p=0.03) and had similar socio-economic score and caregiver age and educational attainment. Participants had lower z-scores in attention (p&amp;lt;0.001) and neurocognitive ability (p&amp;lt;0.001), and in executive function ( p=0.001) in a total of 15 of 17 subtests. After 18 months of hydroxyurea therapy (mean dose 25.4mg/kg) for all active SCA participants (95.1%) (n=254), significant improvements in z-scores were seen at 18 months in attention ( p&amp;lt;0.001), all 4 subtests for cognitive ability ( p&amp;lt;0.001) and in 3 of 6 subtests of executive function ( p=0.003 to &amp;lt;0.001). Conclusion: After 18 months of hydroxyurea therapy reaching MTD dosing, children showed significant improvements in attention and cognition, with more modest improvements in executive function. Their scores moved closer to those from non-SCA controls in most subtests. These findings suggest that hydroxyurea therapy may play an important role in enhancing overall neurocognitive function in children with SCA. Trial procedures are ongoing to assess the effects from longer-term therapy.

6 Subjective Sleep Measures and Neurocognitive Outcomes in Pediatric Sickle Cell Disease

Objective:Youth with sickle cell disease (SCD) are at increased risk of neurocognitive difficulties with and without neurological complications. Research has identified disease-related, socioeconomic, and sociodemographic risk factors as independently having significant associations with brain physiology for youth with SCD. Notably, sleep has a profound effect on youth’s neurocognitive abilities including learning, executive function, memory, attention, and processing speed. Furthermore, youth with SCD are at an increased risk for poor sleep measured by self-report questionnaires and by polysomnography (PSG). Within the SCD literature, only a few studies have examined the relationship between sleep and cognition. Of these, the majority examined individuals with SCD and comorbid sleep disorder diagnoses. The aim of this study is to identify associations between subjective sleep measures and neurocognitive outcomes in youth with SCD.Participants and Methods:This study investigated a cohort of 24 youth with SCD (ages 9-16, 11 males, 13 females; HbSS [63%], HbSB+ [8%], HbSC [21%], HbSB0 [8%]) who received sleep questionnaires and a neuropsychological evaluation. Exclusion criteria included a history of neurological disorder (e.g., overt stroke, seizures, or moyamoya disease) or prescribed psychotropic medication. Sleep questionnaires measuring sleep disturbance (e.g., sleep onset, sleep continuity, and sleep quality) and sleep-related impairments (e.g., daytime sleepiness, sleepiness interference with concentration, and difficulty with activities of daily living skills) were collected. Executive function, working memory, processing speed, and verbal comprehension measures were assessed. Demographics and disease-related risk factors were analyzed individually from medical records.Results:All analyses were controlled for age, the time between neuropsychological testing and sleep questionnaires, SCD genotype, and sex. Partial correlations were conducted to explore associations with neurocognitive outcomes. Verbal comprehension was significantly correlated with sleep disturbance (r= -.673, p=.001). Multiple linear regressions revealed that sleep disturbance significantly predicts verbal comprehension (ß= -.572, p=.003). Specifically, verbal comprehension decreased by 4.4 standard points for every one-point increase in sleep disturbance. Additionally, total sleep problems significantly predicted working memory (ß=-.414, p=.044) and processing speed (ß= -.411, p= .046). Specifically, working memory decreased by 3.5 standard points while processing speed decreased by 3.3 standard points for every one-point increase in total sleep problems reported. Sleep parameters did not significantly predict executive function.Conclusions:Results support the association between poor sleep and neurocognitive difficulty in youth with SCD. Three of the participants in this study received a PSG, which further demonstrates the importance of the current findings. This study serves to identify potential risk factors for neurocognitive deficits and provides potential methods for identifying youth with SCD who may need to be referred for a PSG assessment. Research should replicate these findings with increased sample sizes including utilizing PSG and investigating neurobiological effects. Findings may inform future screening tools, treatment approaches, and advanced cognitive initiatives and resources for this population.

92 Validation of Coin-in-Hand Procedure in a Veteran Population

Objective:Performance validity tests (PVTs) provide a methodological approach to detecting credible neurocognitive performances. This proves invaluable to the diagnostic process, as it allows neuropsychologists to objectively determine if an evaluation reflects a patient’s true neurocognitive abilities or if external factors are impacting the results. However, their addition to a testing battery can increase an already lengthy evaluation. As such, there is a need for sensitive but less time intensive PVTs. The purpose of this study is to validate the Coin-in-Hand (CIH) procedure as a quick and effective PVT within a veteran population.Participants and Methods:68 English-speaking patients were identified from an outpatient neuropsychological assessment dataset. Performances were correlated to the well- validated Reliable Digit Span (RDS), and several other soft indicators of task engagement including expanded COWAT, BVMT-False Alarms (FA), WCST Failure to Maintain Set (FTM), TOMM, and the RBANS Effort Index (EI). All participants attempted CIH and RDS, testing was discontinued if 2 or more PVTs were invalid. An AUC analysis was conducted to determine how well the CIH discriminated between valid and invalid performance and determine the tests optimal cut-off score (sensitivity &gt; 0.90 while maintaining the highest possible specificity). Logistic Regression was conducted to determine how well the CIH predicted performance validity.Results:Subject mean(SD) age and education were 55.25 (16.06) and 13.41 (2.55) years, respectively. 17% female, 60% Caucasian, and 32% Black. Descriptive statistics for each of the other performance validity tests were gathered. The CIH demonstrated low diagnostic accuracy (AUC = .66; p &gt;.05; CI = .51 -.81); a cut score of &lt;8 resulted in a sensitivity of .96 and a specificty of .64. Logistic Regression showed that CIH performance significantly predicted performance validity (X2 = -0.93; df = 1; N = 68; p &lt; .05), accounting for 18-28% of the variance in performance classification (Cox &amp; Snell R2 = .18; Nagelkerke R2 = .28). It correctly classified 96% of valid performers, but only correctly classified 35% of invalid performers, with an overall correct prediction rate of 83%. A predicted chase in log odds (B= -.93) and odd ratio [Exp (B) =.40] indicated that every unit increase in CIH score was associated with a decrease probability of performance invalidity. Logistic regression was also used to calculate the probability of performance invalidity at each possible CIH score (Table 1).Conclusions:Results suggests that poor performance on CIH does not necessarily equate to invalid performances, but instead, should act as a screener to cue neuropsychologists working with Veterans that additional PVTs should be considered. Overall, it was determined that CIH was able to correctly predict 35% of invalid performers and 96% of valid performers, with an overall correct prediction rate of 83%, suggesting the procedure may be too simple to be an effective standalone PVT for clinical use. These results also highlight that every correct response on the CIH was associated with a decreased probability of performance invalidity. Additionally, an AUC analysis determined the tests optimal cut off score to be &lt;8, suggesting that shortening the procedure may be as effective as giving the full 10 trials.