Although remote neuropsychological assessments have become increasingly common, current research on the reliability and validity of scores obtained from remote at-home assessments are sparse. No studies have examined remote at-home administration of the National Alzheimer’s Coordinating Center (NACC) Uniform Data Set (UDS) even though this battery is being used to track over 45,000 participants over time. This study aimed to determine whether remote UDS scores can be combined with in-person data by assessing whether rates of score changes over time (i.e., reliability) differed by modality and whether remote and in-person scores converge (i.e., validity).

Data for UDS visits conducted from 09/2005 to 12/2021 from 43 Alzheimer’s Disease Research Centers were examined. We identified 311 participants (254 cognitively unimpaired, 7 impaired - not mild cognitive impairment, 25 mild cognitive impairment, 25 dementia) who completed 2 remote UDS visits 0.868 years apart (SD = 0.200 years). First, initial remote scores were correlated with most recent in-person scores. Second, we examined whether rates of change differed between remote and in-person assessments. Repeated-measure one-way ANOVA were used to compare rates calculated from the same individual from remote versus inperson assessments. We additionally identified a demographically- and visit-number-matched group of 311 participants with in-person UDS visits given that all remote visits occurred after in-person visits; one-way ANOVAs were used to compare remote rates to rates from in-person assessments from the matched in-person group. Finally, accuracy of remote scores were assessed by quantifying the difference between the actual remote scores and predicted scores based on repeated in-person assessments. These residual values were then divided by the maximum score to form error rates.

Remote UDS score on MoCA-blind, Craft story immediate and delayed recall, digits forward, digits backward, phonemic fluency (F, L, F + L), and semantic fluency (animals, vegetables, animals + vegetables) were all highly correlated (all ps < 0.001) with scores obtained from preceding in-person assessments. At the group level, within-subject comparisons between remote and in-person rates of change were not significantly different for 7/11 tests; between-subject comparisons were not significantly different for 10/11 tests. Vegetable fluency had slightly reduced rates of change with remote assessment compared to inperson assessments. Critically, remote scores were consistent with predicted scores based on the trajectory of each subject’s in-person assessments with group mean error rates ranging from 0.7% (Craft Delayed Recall) to 3.9% (Phonemic fluency - F).

Our results demonstrate adequate reliability and convergent validity for remotely administered verbally based tests from the NACC UDS battery. Importantly, our findings provide some support for combining remote and in-person scores for studies that transitioned to remote testing due to COVID-19. However, future research is needed for tests with visual stimuli that assess visual memory, visuospatial function, and aspects of executive function.

Measures of clinical significance are critical for meaningful interpretation of treatment outcome research on Alzheimer’s disease. A common method of quantifying clinical significance is to calculate a minimal clinically important difference (MCID), which represents the smallest numerical change on an outcome measure that corresponds to an added benefit in a patient’s life. Often the MCID is calculated based on an anchor response. Individuals who report a meaningful change serve as the “anchors”, and the mean level of change for this group serves as the MCID. In research on Alzheimer’s disease, there are several possible raters to provide anchors, including patients, family observers, and clinicians, who may or may not agree on whether there has been a meaningful change in outcome. The goal of this study was to examine the extent to which agreement among anchors impacts MCID estimation and whether this relationship is moderated by cognitive severity status.

Analyses were completed on a longitudinal sample of 2,247 adults, age 50-103, from the Uniform Data Set 3.0. Outcome measures included the Clinical Dementia Rating - Sum of Boxes (CDR-SB), Functional Activities Questionnaire, and Montreal Cognitive Assessment.

For all of the outcomes, the MCID estimate was significantly higher when meaningful decline was endorsed by all of the raters compared to situations in which there was disagreement among the raters. For example, on the CDR-SB, agreement significantly impacted MCID estimates (F(1, 2241)=168.80, p<0.001; partial h2 = 0.07), such that the agreement group had greater CDR-SB change score (mean=1.29, SD1.98) than the no agreement group (mean=0.37, SD=1.38; Tukey HSD: p<0.001). In addition, the MCID estimate increased with increasing levels of cognitive impairment. For instance, on the CDR-SB, MCID estimates were significantly different across the severity groups (F(2, 2241)=138.27, p<0.001; partial h2 = 0.11), such that increase in CDR-SB was highest for the mild dementia group (mean=1.84, SD=2.42), moderate in the MCI group (mean=0.71, SD=1.30), and lowest for the cognitively normal group (mean=0.07, SD=0.55; Tukey HSD; all p’s < 0.001). Finally, cognitive severity status moderated the influence of agreement among raters on MCID estimation for the CDR-SB and FAQ, such that rater agreement demonstrated less influence on the MCID as disease severity increased. For example, on the CDR-SB, post-hoc tests revealed that there was a significant difference across agreement groups in the cognitively normal (p<0.001; Cohen’s d = 0.96) and MCI groups (p<0.001; Cohen’s d = 0.49), but agreement did not impact MCID estimates for the mild dementia group (p=0.065).

MCID estimates based on one anchor may underestimate meaningful change, and researchers should consider the viewpoints of multiple raters in constructing MCIDs. Consideration of agreement appears most important in the early stages of cognitive decline, which are the focus of most modern clinical trials.

Spontaneous speech involves tight coordination of a constellation of cognitive mechanisms (including planning, lexical selection, grammatical encoding, internal & external monitoring). Recent years brought a flurry of interest in detailed analysis of spontaneous speech in search of markers of prodromal Alzheimer’s disease. This work dates back to the nun studies by Snowdon et al (1996) and reveals promise for early detection through identification of subtle but significant changes in the nature of speech output years prior to diagnosis of dementia. A major challenge for neuropsychology is to develop methods to harness the potential sensitivity of language to subtle cognitive changes when testing individuals in clinical settings. In this talk I will present two lines of research that illustrate how reading aloud can be used to engage the cognitive mechanisms of spontaneous speech production in a manner that provides an easily accessible measure of Alzheimer’s disease/risk.

In the first study, Spanish-English bilinguals with mild-to-moderate Alzheimer’s disease (n=20) and proficiency matched controls (n=29) read aloud mixed-language paragraphs with a small number of language-switched words, and we recorded the number of times they automatically translated switch words by accident (e.g., saying pero instead of but; effectively autocorrecting language switches to avoid producing switches overtly). In the second study, cognitively normal monolinguals at risk for AD based on CSF biomarkers (n=14) and controls (n=50) read aloud short paragraphs in which ten critical target words were replaced with autocorrect targets (e.g., The player who scored that final [paint] for the local team reported [him] experience). Participants were instructed to avoid autocorrecting (e.g., avoid saying point instead of paint or his instead of him), and we recorded the number of times they autocorrected by accident.

Bilinguals with AD translated switch words more often than controls, and ROC curves revealed good-to-excellent discrimination between patients and controls based solely on the number of errors produced during reading aloud (AUC or Area Under the Curve values ranged from .71-.92). In the second study, cognitively normal monolinguals with high CSF Tau/Aß42 (i.e., an AD-like biomarker profile) produced more autocorrect errors (e.g., saying point instead of paint)than those below the biomarker threshold, and autocorrection errors showed potential for discriminating individuals with higher AD risk from controls (AUC=.76; 95%CI .62-.90).

Difficulty stopping automatic translation of language switch words and autocorrection during reading aloud reveals promise as a diagnostic tool. Reading aloud elicits rapid production of hundreds of words while maintaining tight experimental control over the content of speech and harnessing the power and complexity of language to enable detection of very subtle cognitive changes through simple analysis of critical targets. I will discuss the theoretical implications of this work for understanding how bilinguals choose a single language for production, the nature of cognitive impairments in early AD and areas of need for further research to maximize the potential utility of reading aloud for detection of cognitive impairment.

Alzheimer’s disease (AD) clinical trials lack diverse representation, limiting their generalizability. In addition, the clinical meaningfulness of observed changes during treatment may vary as a function of participant characteristics. Defining meaningful change in AD within diverse ethnoracial groups is therefore greatly needed. Meaningful change in AD trials can be assessed by three different anchors: participants, informants, or clinicians. Previous research has suggested that estimations of the minimal clinically important difference (MCID) vary by disease severity, choice of anchor, and anchor agreement. These relationships have been studied primarily within non-Hispanic white (NHW) samples. This project evaluates anchor-based MCID within and across the three most prevalent ethnoracial groups in the United States, non-Hispanic White (NHW), Hispanic/Latino (H/L), and Black/African-American (B/AA).

Data from the National Alzheimer’s Coordinating Center Uniform Dataset (NACC UDS) were used to investigate MCID within older adults (ages 50+) diagnosed as cognitively normal or cognitively impaired due to suspected AD. Data were taken from all versions of the UDS and consisted of all available participants with two consecutive annual visits. The identified sample (N=22,043) is approximately 83.6% NHW, 4.7% H/L, and 11.7% B/AA. Participant, informant, and clinician anchor variables were utilized to compare proportions of anchor agreement within and across ethnoracial groups. MCID on the Mini-Mental State Exam (MMSE) was estimated within each ethnoracial group and compared across the independent variables of anchor agreement and disease severity (cognitively normal (CN), mild cognitive impairment (MCI), and dementia) in 2x3 ANOVAs.

Participant age (M = 71.56, SD = 9.03) did not significantly differ across ethnoracial groups; years of education significantly differed across groups, p < .001, with NHW (M=15.83 SD=3.05), H/L (M=12.49, SD=5.01), and B/AA (M=14.42, SD=3.22). Across all three anchors (participant, informant, clinician), unanimous agreement about the presence or absence of a decline in functioning was present in about 75.1% of the full sample. To further explore agreement differences across groups, anchor agreement was classified into a 3-level variable: 1) agreement that the participant remained stable over time, 2) agreement that the participant declined, and 3) disagreement. The proportion of each level within each ethnoracial group was significantly different, (x2(4, n = 22,043) = 179.16, p < .001, phi = .09, NHW (34.5% agreement-stable, 41.4% agreement-declined, 24.1% disagreement), H/L (30.5%, 42.6%, 26.9%, respectively), and B/AA (42.2%, 28.1%, 29.7%, respectively). MCID estimates on the MMSE followed similar trends within each ethnoracial group. There was a significant main effect of disease severity, such that MCID estimates increased in magnitude with increasing disease severity. There were no significant main effects of anchor agreement for any ethnoracial group. Within the NHW sample only, an interaction effect between diagnostic severity and anchor agreement was significant (p = .007).

Across ethnoracial groups, MCID estimates on the MMSE are reliably influenced by the severity of disease. However, the benefit of anchor-based MCID estimates may vary by ethnoracial group with respect to both anchor choice and use of anchor agreement. The origins of anchor disagreement and perceived stability in functioning warrant further exploration.

Inequity in Alzheimer’s disease and related dementias (ADRD) clinical research is severely hindering our progress towards a cure for all, while inflating national costs. ADRD alone is currently costing United States 321 billion dollars in 2022, projected to increase to 1 trillion by 2050. Alzheimer’s disease disproportionately impacts Black, Hispanic, Asian or Native Americans. Yet, ADRD clinical research to date has not included equitable number of participants from communities of color to be representative of the U.S. population. Hispanic/Latinos currently represent 1% of ADRD clinical trials’ samples despite representing 18% of the US population.

In our previous outreach and recruitment study with the Human Connectome Project - Aging, we attained a 11.35% recruitment success rate of Hispanics/Latinos living in Los Angeles County Districts. We implemented a comprehensive Spanish-English bilingual, multi-method, multi-setting community-academic engagement, outreach, and recruitment protocol with a focus on brain health literary and ADRD biomarker research literacy.

Whereas community educational engagement and outreach was the most efficient and highest interest turn-out recruitment strategy, 61% of engaged and interested Hispanic/Latinos (50 years old and older) were automatically excluded during the telephone screening due to English-language proficiency/fluency. Highest enrollment success rate was from UCLA mailing list, clinical registries, and referrals. Hispanics/Latinos successfully recruited were bilingual or multilingual, 83% identified white as their racial background, 85% attained higher education, and 70% resided in middle-to-high income levels areas.

Our results captured institutional barriers leading to a recruitment bias towards affluent Hispanics/Latinos with access to healthcare systems. Our applied science of recruitment and retention requires significant improvements in study design and methodology, tailored and targeted to communities’ socio-ecological context. It also requires the extrapolation of generalizable theoretically informed mechanisms of successful engagement, recruitment, and retention strategies for replication and/or modification in other settings/locations, and countries.

With participant recruitment being a top barrier to AD research progress, the rate of screen failure in Alzheimer’s disease (AD) clinical trials is unsustainable. Although steps have been undertaken to consider solutions to the continued recruitment shortage, there is unfortunately minimal emphasis on reducing screen failure rates based on study inclusion criteria. Here we present information attempting to understand the cognitive, emotional, and functional features of individuals who failed screening measures for AD trials.

The current study is a retrospective, cross-sectional analysis. Thirty-eight participants (aged 50-83) having (1) previously received a clinical diagnostic workup at a transdisciplinary cognitive specialty clinic and (2) previously screened for a specific industry-sponsored clinical trial of MCI/early AD (EMERGE) met inclusion criteria. Previously collected clinical data were analyzed to identify predictors of AD trial screen pass/fail status.

Of the 38 participants in the current study, 14 screen passed into this AD clinical trial, and 24 screen failed. Higher screen failure rates were significantly related to gender, with 83% of female participants screen failing this AD trial versus 45% of male participants. There was no difference in age or education between screen pass/fail groups, nor were differences present for performance on visual or verbal memory tasks, or the MOCA. Conversely, those participants screen failing this AD clinical trial performed significantly worse on nonmemory cognitive domains pertaining to general fund of knowledge, working memory, and executive functioning. Additionally, the screen fail group reported greater levels of anxiety, but not depression nor endorsements on a measure of functional status.

Worse performance on non-memory neuropsychological domains was related to screen failure status for the EMERGE AD clinical trial. This finding may be explained by the traditional recruitment pathway from clinic to trials, which beyond the diagnosis of interest is up to the opinion of the physician to determine “fit” for a trial. Higher screen failure rates may result from physicians erroneously viewing more globally-impaired patients as being more appropriate for an AD clinical trial, resulting in greater tendencies towards recruiting patients who are too severe to meet inclusion criteria for a trial. Recruiting patients into clinical trials earlier in their disease course - when disease severity is less - may result in reduced screen failure rates in AD trials. That we could not detect a relationship between memory-related tasks and screen fail/pass status may be explained by either (1) the measures used in the EMERGE trial were not as sensitive to subtle changes in memory, or (2) that memory dysfunction is necessary for a diagnosis of AD but not sufficient to distinguish who will be successfully screened into an AD clinical trial. Overall, these findings have the potential to advance the field by reducing screen failure rates in AD clinical trials by using information already available to clinical trial teams, which will enhance trial-recruitment infrastructure and encourage greater engagement of older adults in AD research.

Traumatic brain injury (TBI) is a prevalent cause of long-term morbidity in children and adolescents and can lead to persistent difficulties with social and behavioral function. TBI may impact brain structures that support social cognition, social perception, and day-to-day social interactions—termed the social brain network (SBN). We examined differences in links among the SBN and regions of interest from other neural networks thought to support social outcomes, i.e., the default mode network (DMN) and salience network (SN). Furthermore, we examined how differences in co-activation among the SBN and these other key networks were associated with ratings of social and day-to-day adaptive outcomes.

Participants included children and adolescents with moderate to severe TBI (msTBI; n=11, Mage=11.78, 6 male), complicated-mild TBI (cmTBI; n=12, Mage=12.59, 9 male), and orthopedic injury (OI; n=22, Mage=11.69, 15 male). Participants underwent resting-state functional MRI on a 3Tesla Siemens Prisma scanner. Parents rated their child’s social and adaptive function on the Child Behavior Checklist (CBCL) and Adaptive Behavior Assessment System-Third Edition (ABAS-3). Resting-state connectivity was assessed using the CONN Toolbox, including preprocessing, denoising, and alignment to the participants’ processed T1 MPRAGE sequence followed by seed-to-voxel analysis using a SBN mask and targeted regions of interest within the DMN and SN. Individual-level r-to-z correlations were extracted from resulting clusters of co-activation with the SBN mask and exported into SPSSv28.0 for integration with behavioral data.

One-way ANOVAs used to examine group differences in social and adaptive outcome revealed significant group differences in CBCL Social Competence (F=4.49, p=.019) and all composite scores on the ABAS-3 (Fs=3.78 to 5.17, ps=.031 to .010). In each domain, children with msTBI were rated as having elevated difficulties relative to cmTBI or OI, whereas cmTBI and OI groups did not differ. Connectivity also differed significantly between groups, with children with OI demonstrating greater connectivity between the SBN and the anterior cingulate cortex of the SN (t=5.19, p(FDR)<.0001) and posterior cingulate cortex of the DMN (f=4.30, p(FDR)<.001) than children with msTBI. Children with cmTBI also showed greater connectivity between the SBN and left temporal pole of the DMN (t=7.45, p(FDR)<.000001) than children with msTBI. Degree of connectivity between the SBN and posterior cingulate was significantly positively correlated across all domains of adaptive function (rs=.451 to .504, ps=.010 to .003), whereas degree of connectivity between the SBN and left temporal pole was strongly positively related to Social Competence (a=.633, p=.006) and conceptual adaptive skills on the ABAS (A=.437, p=.037).

Our findings provide insights into the neural substrates of social and adaptive morbidity after pediatric TBI, particularly msTBI, by linking alterations in connectivity among the SBN, DMN, and SN with measures of social and adaptive outcome. While the posterior cingulate was broadly associated with adaptive outcome, the temporal pole was particularly strongly associated with social competence. This may reflect the diverse functions and high degree of interconnectivity of the posterior cingulate, which contributes to various cognitive and attentional processes, relative to the strong amygdala/limbic connections of the temporal pole.

Imitation has pervasive associations with social and communicative development. However, few methods have been developed to measure this construct in typically developing infants, and even less is available for at-risk populations, such as infants born preterm. Autism spectrum disorder (ASD), a particular risk of premature birth, is associated with atypical imitation and social communication. Although imitation emerges in infancy, most current screening and diagnostic tools for ASD cannot be utilized prior to 12 months. The present study aimed to develop and validate a caregiver-report measure of infant imitation, characterize imitation profiles at 4, 6, and 9 months in term and preterm infants, and explore the relationship between imitation and scores on an ASD screening questionnaire at 18 months.

Participants (N = 571) were recruited from a larger multi-site study of PediaTrac™ v3.0, a web-based tool for monitoring and tracking infant development, and were surveyed longitudinally at birth, 2, 4, 6, 9, 12, 15, and 18 months. Participants completed the online PediaTrac™ survey and several reliable and validated questionnaires via pen-and-paper format. For the purposes of this study, only the Ages and Stages Questionnaire (3rd ed.; ASQ-3), Communication and Symbolic Behavior Scales-Developmental Profile (CSBS-DP), Brief Infant Sleep Questionnaire (BISQ), and the Modified Checklist for Autism in Toddlers - Revised with Follow-Up (M-CHAT-R/F) were examined. The following hypotheses were tested: (1) proposed imitation items will represent a unitary latent construct, for which convergent and discriminant validity will be demonstrated, (2) there will be measurement invariance between term status groups at each assessment period, (3) preterm infants will obtain lower caregiver-reported imitation scores compared to term infants, and (4) imitation abilities at the assessment period with the most robust imitation factor will predict M-CHAT-R/F scores at 18 months.

Distinct imitation factors at 4, 6, and 9 months were modeled with confirmatory and exploratory factor analyses. Relationships between the factors and established measures of infant communication (CSBS; ASQ) and sleep (BISQ) revealed convergent and discriminant validity, respectively. Strict measurement invariance was demonstrated for the 4- and 9-month factors, and metric invariance for the 6-month measure. Full term infants scored higher on imitation at 9 months, though variance in this outcome was related to term status differences in sensorimotor skills. Lastly, the 9-month imitation factor, coupled with 6-month sensorimotor skills, predicted 18-month ASD risk over and above gestational age.

This study provides support for the assessment of infant imitation, utilizing imitation to detect risk in preterm infants, and extending the age of identification for ASD risk into the first year. PediaTrac™ imitation, in combination with the PediaTrac™ sensorimotor domain, may be useful in detecting developmental risk, and specifically risk for ASD, within the first year, leading to earlier initiation of intervention. Further, with its minimal completion time and ease of dissemination through digital platforms, this measure can expand access to care and improve long-term outcomes for children and families.

Survivors of childhood ALL treated with CNS-directed chemotherapy are at risk for neurocognitive deficits that emerge during treatment and impact functional and quality of life outcomes throughout survivorship. Neurocognitive monitoring is the recommended standard of care for this population; however, information on assessment timing and recommendations for assessment measures are limited. We examined the role of serial neurocognitive monitoring completed during protocol-directed therapy in predicting parent-reported neurocognitive late effects during survivorship.

Parents of 61 survivors of childhood ALL completed a semi-structured survey focused on parent perspective of neurocognitive late effects as part of a quality improvement project. Survivors completed protocol-directed treatment for newly diagnosed ALL on two consecutive clinical trials (St. Jude Total Therapy Study 15, 47.5%; Total Therapy 16, 52.5%). The majority of survivors were White (86.9%), 52.5% were male, and 49% were treated for low risk disease. Mean age at diagnosis was 7.77 years (standard deviation [SD] = 5.31). Mean age at survey completion was 15.25 years (SD = 6.29). Survivors completed neurocognitive monitoring at two prospectively determined time points during and at the end of protocol-directed therapy for childhood ALL.

During survivorship, parents reported that 73.8% of survivors experienced neurocognitive late effects, with no difference in frequency of endorsement by protocol (p = .349), age at diagnosis (p = .939), patient sex (p = .417), or treatment risk arm (p = .095). In survivors with late effects, 44.3% sought intervention in the form of educational programming (i.e., 504 or Individualized Education Program). Among the group with late effects, compared to those without educational programming, those with educational programming had worse verbal learning (CVLT Trials 1-5 Total, Mean[SD]; T = 56.36 [11.19], 47.00 [10.12], p = .047) and verbal memory (CVLT Short Delay Free Recall, Z = 0.86 [0.67], -0.21 [1.01], p = .007); Long Delay Free Recall, Z = 0.91 [0.92], -0.25 [1.25], p = .020) during therapy. Compared to those without educational programming, survivors with educational programming had lower estimated IQ (SS = 109.25 [13.48], 98.07 [15.74], p = .045) and greater inattention [CPT Beta T = 56.80 [13.95], 75.70 [22.93], p = .017) at the end of therapy.

Parents report that nearly three quarters of children treated for ALL with chemotherapy only experience neurocognitive late effects during early survivorship, with no difference in frequency by established risk factors. Of those with late effects, nearly half required educational programming implemented after diagnosis, suggesting a significant impact on school performance. Results from neurocognitive monitoring beginning during therapy has utility for predicting educational need in survivors experiencing late effects. Our findings provide direction on the timing and content of neurocognitive monitoring, which is the recommended standard of care for childhood cancer patients treated with CNS-directed therapy.

A common assumption to maximise cognitive training outcomes is that training tasks should be adaptive, with difficulty adjusted to the individual’s performance. This has only been tested once in adults (von Bastian & Eschen, 2016). We aimed to examine children’s outcomes of working memory training using adaptive, self-select and stepwise approaches to setting the difficulty of training tasks compared to an active control condition.

In a randomised controlled trial (ACTRN 12621000990820), children in Grades 2-5 (7 to 11 years) were allocated to one of four conditions: adaptive working memory training, self-select working memory training, stepwise working memory training, or active control. An experimental intervention embedded in Minecraft was developed for teachers to deliver in the classroom over two weeks (10 x 20-minute sessions). The working memory training comprised two training tasks with processing demands similar to daily activities: backward span with digits and following instructions with objects. The control condition comprised creative building tasks. As part of a larger protocol, children completed at baseline and immediately post-intervention working memory measures similar to the training activities (primary outcome): backward span digits and letters versions, following instructions objects and letters versions. Primary analyses were intention-to-treat. Secondary analyses included only children who completed 10 sessions.

Of 204 children recruited into the study, 203 were randomised, with 95% retention at post-intervention. 76% of children completed all 10 training sessions. Comparisons between each working memory training condition and the active control on working memory measures were non-significant (f 2 = 0.00), with one exception. Children in the self-select condition on average performed 1-point better than the controls on the following instructions objects measure (p = .02, f2 = 0.03). A pattern emerged that the self-select condition performed better on most measures.

We found little evidence that an adaptive approach to setting the difficulty of training tasks maximises training outcomes for children. Findings suggest that working memory outcomes following training are limited and are not modulated by the approach to setting the difficulty of training tasks. This is consistent with findings from von Bastian & Eschen (2016), who also observed that the self-select condition (and not the adaptive condition) showed a slightly larger change in working memory performance following training than the control. It is helpful for clinicians to be aware that adaptive working memory training programs might not be superior in improving children’s working memory, and the benefits of programs are limited.

Hemispherectomy (HE) is a surgical intervention to treat intractable epilepsy. It involves disconnecting or removing the right or left cerebral hemisphere, depending on the location of the pathological substrate or epileptogenic activity. HE impacts neural functions related to social cognition (Fournier et al., 2008). This study investigates the effects of childhood HE on social deception and sarcasm using the Thames Awareness of Social Inferences Task (TASIT; McDonald, Flanagan, & Rollins, 2010) to explore emotion identification and social inference appraisal as adults.

Fifteen adults with hemispherectomy and 16 neurotypical controls completed the TASIT. All HE patients underwent hemispherectomy (right-HE = 10) during childhood (age of surgery = 3 months to 16 years) and had FSIQ > 70 at the time of study. HE and control groups were matched for age (HE M = 25.7, SD = 5.4; control M = 27.1, SD = 10.7) and education (HE M = 14.0, SD = 1.88; control M = 13.3, SD = 1.8). FSIQ was significantly lower in the HE group than control group (HE M= 90.8, SD = 9.4; control (M = 100.4, SD = 7.1). TASIT uses videotaped vignettes to assess aspects of social perception: emotion recognition (Part 1), social inference regarding sincerity, simple sarcasm, and paradoxical sarcasm (Part 2) and social inference regarding sincerity of speech (lie vs sarcasm) in the presence of additional text or visual cues (Part 3).

For Part 1, MANCOVA (covarying FSIQ) found no group difference in emotion identification. Analysis of data from Part 2 was conducted using repeated measures ANCOVA accounting for 2 groups x 3 conditions (sincere, simple sarcasm, and paradoxical sarcasm) and revealed only a significant overall group effect, F (1, 28) = 5.72, p = .024, np2 = .170. Likewise, analysis of Part 3 using repeated measures ANCOVA accounting for 2 groups x 2 cue types (visual, text) and 2 actor intentions (lie, sarcasm) revealed only a significant overall group effect, F (1,28) = 11.35, p = .002, np2 = .288, with no interaction of group by condition.

HE patients exhibited no difficulty identifying basic emotional expressions. Performance was significantly impaired when additional social information was added to the context (i.e., detecting sarcasm or deception). HE patients begin to struggle with the complexity of new social information or how it changes the meaning of a conversation. Even simple sarcastic exchanges are difficult to interpret. When a visual or textual cue was introduced to reveal the true state of affairs, HE patients could not could integrate the information into their interpretations of the scenario. There are unique contributions of the left and right hemispheres to cognitive processes for complex social behavior, and absence of an entire hemisphere results in deficits in social language comprehension. Future research should investigate performance differences in left vs. right HE patients.

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.

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.

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.

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.

Attention-Deficit/Hyperactivity Disorder (ADHD) is associated with impaired executive functioning and anxiety/depressive symptoms, which may contribute to reduced quality of life. We tested the hypotheses that (1) a childhood diagnosis of ADHD is related to reduced quality of life in emerging adulthood and that (2) this relationship is mediated by impaired executive functioning and anxiety/depressive symptoms.

We assessed 85 children and adolescents with ADHD and 50 typically developing peers at baseline (Mean age = 11.6 years, 58% males), two-year follow-up, and 10-year follow-up with neuropsychological tests of executive functioning, the Behavioral Rating Inventory of Executive Function (BRIEF), the Short Moods and Feelings Questionnaire (SMFQ), and the Revised Children’s Manifest Anxiety Scale, second edition (RCMAS-2), as well as the Perceived Quality of Life scale (PQoL) at the 10-year follow-up. Four neuropsychological tests of executive functioning, the Letter-Number Sequencing test (working memory), the Color-Word Interference test condition 3 (response inhibition), the Color-Word Interference test condition 4 (shifting), and the trail making test condition 4 (cognitive flexibility) were combined into a neuropsychological executive functioning composite score based on high factor loadings (> .73). the parent-reported BRIEF indexes, the behavioral regulation index, and the metacognition index were used as measures of everyday executive functioning. We conducted independent samples t-tests to compare the groups and simple and parallel mediation analyses with full information maximum likelihood estimation to examine whether the different executive functioning measures and anxiety/depressive symptoms at two-year follow-up mediated the relationship between baseline ADHD and self-reported quality of life at 10-year follow-up.

Baseline ADHD was associated with more difficulties with executive functioning on a composite measure of neuropsychological tests (p < .001, Hedges g = .79) and parent-reported everyday metacognitive (p < .001, Hedges g = 2.37) and behavioral regulation executive functioning (p < .001, Hedges g = 1.55), as well as self-reported anxiety (p < .001, Hedges g = 1.05) and depressive symptoms (p < .001, Hedges g = 1.00) at two-year follow-up. Baseline ADHD was associated with lower self-reported quality of life (p = .001, Hedges g = -.67) at 10-year follow-up. The mediation analysis showed that everyday metacognitive executive functioning (p = .011, ß = -.497) and an anxiety/depressive symptoms composite (p < .001, ß = -.404) parallelly mediated the relationship between ADHD and quality of life.

Impaired everyday executive functioning and anxiety/depressive symptoms may represent two distinct pathways to reduced quality of life in emerging adults with a childhood diagnosis of ADHD. These findings stress the importance of targeting both cognitive and emotional aspects in interventions for children and adolescents with ADHD to improve later quality of life.