Inhibitory control impairment is highly prevalent following traumatic brain injury (TBI). There have not been any empirical investigations into whether this could explain social disinhibition following severe TBI, i.e. socially inappropriate behaviour of verbal, physical or sexual nature. Further, social context has proven to be important in studying social disinhibition and using a social version of an established task for the assessment of inhibitory control may provide a new perspective. Therefore, the objectives of this research study were to investigate the role of inhibitory control impairment in social disinhibition following severe TBI, using a social and a non-social task. We hypothesized that people with TBI and clinical levels of social disinhibition would perform worse on both task versions, when compared to those with low disinhibition levels. Further, we hypothesized that participants high on social disinhibition would perform worse on the social, when compared to the non-social version.

We conducted a between-group comparative study. Twenty-six adult participants with severe TBI were matched with 27 adult, healthy controls based on gender, age and education. Frontal Systems Behavior Scale and Social Disinhibition Interview were used to assess social disinhibition. A computerized task based on the cued go/no-go paradigm was used to assess inhibitory control. We included two versions of this task – a coloured (non-social) Go/No-Go with different colored rectangles, and an emotional (social) Go/No-Go with emotional faces serving as ‘go‘ and ‘no-go‘ cues. Two-way mixed ANCOVAs were used to test between-group differences in errors of commission and response speed.

Unexpectedly, the TBI and the control group did not significantly differ on their levels of depression, anxiety, stress, or their level of social disinhibition. Overall, participants were slower (F(1,47) = 15.212, p<.001, ηp2 = .245) and made more errors of commission on no-go trials (F(1,44) = 11.560, p = .001, ηp2 = .208) on the social Go/No-Go task. There was no main effect of participants‘ brain injury status on errors of commission on no-go trials or mean reaction times. When categorized based on disinhibition level (high vs low), participants in the highdisinhibition group made more errors on the social task (F(1,41) = 4.095, p = .050, ηp2 = .091) than those in the low-disinhibition group, and more errors on the social, compared to the non-social task (task-group interaction (F(1,41) = 7.233, p = .010, ηp2 = .150)).

Based on these initial results, social disinhibition is associated with inhibitory control impairment, although this is only evident when a social inhibitory control task is used for assessment. We did not find any relationship between social disinhibition and the speed with which people react to stimuli. The results of this study add to the conceptualization of social disinhibition that is commonly present after severe TBI.

Memory impairment is a common comorbidity in individuals with temporal lobe epilepsy (TLE). Further, in medication-resistant epilepsy the frontline option, neurosurgical epileptogenic zone destruction, places memory at significant risk. Research has highlighted that TLE causes whole-brain network efficiency disruption, but it is not established how this may explain pre- and post-surgical cognition. Here we examine whether white matter structural network organization predicts pre-operative memory function and/or risk for post-operative memory decline.

Patients with drug-resistant TLE were recruited from two epilepsy centers in a prospective longitudinal study. The pre-operative sample included 51 individuals with left TLE (L-TLE), 52 with right TLE (R-TLE), and 57 healthy controls who underwent T1- and diffusion-weighted MRI (dMRI), and neuropsychological tests of verbal and visual memory. Forty-four patients (n=21 L-TLE) subsequently underwent temporal lobe surgery (36 anterior temporal lobectomy; 7 stereotactic laser amygdalohippocampectomy; 1 amygdalohippocampectomy) and completed post-operative memory testing. Whole-brain connectomes were generated via diffusion tractography and analyzed using graph theory, focusing on network integration (path length) and specialization (transitivity). In the preoperative dataset, first we compared TLE versus controls with analysis of covariance (ANCOVAs) controlling for age. Next, linear regressions examined the association between memory scores and network efficiency between L-TLE, R-TLE and controls. In the post-operative sample, bivariate correlations examined the association between pre- to post-operative memory change and 1) global network efficiency and 2) asymmetry of mesial temporal efficiency (i.e., local efficiency of the hippocampal, parahippocampal, and entorhinal nodes). Finally, efficiency metrics were entered into stepwise regressions along with established predictors of memory decline.

Compared to controls, TLE showed longer path length (p < .05; ηp2 = .03) and lower transitivity (p = .01; ηp2 = .04). Pre-operatively, better verbal learning and memory were associated with both shorter path length (β = -0.23 to -0.32; psadjusted < .05) and increased transitivity (β = 0.20 to 0.31; psadjusted < .05). These associations were greater in L-TLE than R-TLE (i.e., a significant interaction; β = -0.29 to 0.25; psadjusted <.05). Post-operatively, global metrics predicted decline on list learning for LTLEs (rs = -.57 to .58; ps < .01), and were marginal on list recall (rs = -.42 to .40; ps < .10). Leftward asymmetry of mesial temporal local efficiency predicted greater decline across most verbal memory measures for L-TLE (rs -.47 to -59; psadjusted <.05), but not R-TLE. Asymmetry of mesial network efficiency uniquely explained at least 20 to 43% of the variance in list learning, recall, and story learning for L-TLE, outperforming hippocampal asymmetry and preoperative score (psadjusted <.05).

Our findings suggest that global white matter network abnormalities contribute to verbal memory impairment pre-operatively and vulnerability to decline post-operatively in L-TLE. Asymmetry of a predefined mesial temporal sub-network may help predict post-operative memory function following left temporal lobe surgery, such that greater efficiency in the to-beresected mesial temporal network may be an important risk factor for decline. Our findings extend the importance of network approaches in TLE to include the relationships between neurobiological networks and memory function.

To apply the new IC-CoDE cognitive diagnostic taxonomy (Norman et al., 2020) to a large cohort of people with temporal lobe epilepsy (TLE) in India. The IC-CoDE taxonomy of cognitive diagnoses for 1,409 Englishspeaking adults with TLE from seven epilepsy centres in the U.S. has been published (McDonald et al., 2022). Initial results suggest that the IC-CoDE produces stable cognitive phenotypes across centres; however, its international applicability, including the suggested impairment cut-off needs to be considered across cultures and languages to avoid misclassification. The aim of this study was to apply the IC-CoDE to a population, outside of the U.S., diverse in language representation (i.e., bi/multi-lingual), assessment tools, normative data, and educational and cultural backgrounds to determine whether the same cognitive phenotypes and their relative frequencies would emerge.

Data from 549 adults with TLE (mean age=27.14 (8.04), 60.47% males) from a tertiary referral hospital in Mumbai, India who had undergone a comprehensive neuropsychological evaluation (minimum two tests in at least 4 of the 5 cognitive domains: memory, language, executive function, attention/processing speed and visuospatial) were analysed using the ICCoDE criteria. The base rate of impairment for individual tests was calculated using a cutoff of 1.5 standard deviations (S.D.) below the normative mean. The cognitive diagnostic criteria were applied, and the distribution and base rate of cognitive phenotypes was compared to the published taxonomy data from the U.S. (McDonald et al., 2022).

In comparison to the U.S. cohort, the India group was relatively younger, lower in the education level, had a younger age at seizure onset and a shorter duration of the epilepsy. Application of the IC-CoDE taxonomy using a 1.5 S.D. cutoff revealed an Intact cognitive profile in 48% of patients, Single Domain impairment in 32%, Bi Domain impairment in 15% and Generalised impairment in 5%. These findings were mostly comparable to percentages reported in the U.S. cohorts with Intact profile (47%; c2= 0.158, p=0.690), Single Domain (29%; c2= 46.26, p<0.01), Bi Domain (16%; c2= 0.298, p=0.585) and Generalised (8%; c2= 5.347, p=0.021) impairment. However, the most common impairment in the Single Domain group for the bi/multilingual India population was Memory (38%) followed by Attention (20%) and then Language (13%), diverging from the distribution in the U.S. data with maximum impairment in Language (49%) followed by Memory (32%) in the Single Domain Group.

These findings demonstrate that the IC-CoDE can be applied internationally, and the broad taxonomy of cognitive diagnosis holds even in a culturally, linguistically diverse population. Differences in rates of impairments across specific domains emerged with language relatively preserved in the India bi/multilingual population, and memory more frequently impaired than observed in the multi-centre U.S. sample. These findings may reflect differences in demographics, rates of bi/multilingualism, normative data, language tools, or underlying neuropathology, which should be further explored to determine their impact on cognitive profiles.

The Pediatric Epilepsy Research Consortium (PERC) Epilepsy Surgery Database Project is a multisite collaborative that includes neuropsychological evaluations of children presenting for epilepsy surgery. There is some evidence for specific neuropsychological phenotypes within epilepsy (Hermann et al, 2016); however, this is less clear in pediatric patients. As a first step, we applied an empirically-based subtyping approach to determine if there were specific profiles using indices from the Wechsler scales [Verbal IQ (VIQ), Nonverbal IQ (NVIQ), Processing Speed Index (PSI), Working Memory Index (WMI)]. We hypothesized that there would be at least four profiles that are distinguished by slow processing speed and poor working memory as well as profiles with significant differences between verbal and nonverbal reasoning abilities.

Our study included 372 children (M=12.1 years SD=4.1; 77.4% White; 48% male) who completed an age-appropriate Wechsler measure, enough to render at least two index scores. Epilepsy characteristics included 84.4% with focal epilepsy (evenly distributed between left and right focus) and 13.5% with generalized or mixed seizure types; mean age of onset = 6.7 years, SD = 4.5; seizure frequency ranged from daily to less than monthly; 53% had structural etiology; 71% had an abnormal MRI; and mean number of antiseizure medications was two. Latent profile analysis was used to identify discrete underlying cognitive profiles based on intellectual functioning. Demographic and epilepsy characteristics were compared among profiles.

Based on class enumeration procedures, a 3-cluster solution provided the best fit for the data, with profiles characterized by generally Average, Low Average, or Below Average functioning. 32.8% were in the Average profile with mean index scores ranging from 91.7-103.2; 47.6% were in the Low Average profile with mean index ranging from 80.7 to 84.5; and 19.6% were in the Below Average profile with mean index scores ranging from 55.0-63.1. Across all profiles, the lowest mean score was the PSI, followed by WMI. VIQ and NVIQ represented relatively higher scores for all three profiles. Mean discrepancy between indices within a profile was as large as 11.5 IQ points. No demographics or epilepsy characteristics were significantly different across cognitive phenotypes.

Latent cognitive phenotypes in a pediatric presurgical cohort were differentiated by general level of functioning; however, across profiles, processing speed was consistently the lowest index followed by working memory. These findings across phenotypes suggest a common relative weakness which may result from a global effect of antiseizure medications and/or the widespread impact of seizures on neural networks even in a largely focal epilepsy cohort; similar to adult studies with temporal lobe epilepsy (Hermann et al, 2007). Future work will use latent profile analysis to examine phenotypes across other domains relevant to pediatric epilepsy including attention, naming, motor, and memory functioning. These findings are in line with collaborative efforts towards cognitive phenotyping which is the aim of our PERC Epilepsy Surgery Database Project that has already established one of the largest pediatric epilepsy surgery cohorts.

The International Classification of Cognitive Disorder in Epilepsy (IC-CoDE) is a new consensus-based taxonomy that classifies patients into one of four cognitive phenotypes (i.e., cognitively intact, single-domain impairment, bi-domain impairment, generalized impairment). The IC-CoDE has been effectively applied to patients with temporal lobe epilepsy (TLE), but little is known about the relationship between pre-operative cognitive phenotype and post-operative cognitive outcome following epilepsy surgery. The purpose of this study was to examine whether the IC-CoDE classifications are related to memory decline following surgery for TLE.

347 patients (ages 16-66; 57% female) with pharmacoresistant TLE completed comprehensive pre- and post-surgical neuropsychological assessments. Patients were classified into IC-CoDE phenotypes based on pre-surgical pattern of cognitive impairment using a threshold of >1.5 standard deviations (SD) below the normative mean. Change scores were calculated from delay trial scores of the following memory tests: Rey Auditory Verbal Learning Test (RAVLT), and Logical Memory (LM) and Verbal Paired Associates (VPA) subtests from the Wechsler Memory Scale - Third Edition (WMS-III). Cutoffs were applied using epilepsy-specific reliable change indices and patients were classified within the ‘decline’ group if they experienced significant decline on any of the three memory measures.

The distribution of IC-CoDE phenotypes in our sample were as follows: 57% intact, 29% single-domain, 10% bi-domain, and 5% generalized impairment. 108 patients (31%) demonstrated post-surgical memory decline. Patients who underwent dominant temporal lobectomy were more likely to show post-surgical memory decline compared to non-dominant temporal lobectomy. However, there was no significant difference in phenotype distribution between patients who underwent left versus right-sided resections; thus, analyses were conducted on the entire sample to increase power. Chi-square analyses revealed unique patterns of post-surgical memory decline across phenotypes, X2 = 8.79, p = .032. There was a significantly higher proportion of patients with memory decline in the single-domain phenotype (39%) and this was followed by the bi-domain phenotype (33%) and the intact phenotype (29%). In contrast, patients with generalized impairment were unlikely to show memory decline (.06%). Within the single domain impaired phenotype, there were no differences between the specific domains impaired and memory decline. Logistic regression model was also significant; after controlling for surgery side, the IC-CoDE phenotypes significantly predicted the likelihood of a patient experiencing post-surgical memory decline; X2 = 8.18, p = .043.

In addition to the IC-CoDE providing a useful cognitive classification scheme in epilepsy, the IC-CoDE phenotypes appear helpful in identifying those at risk for post-operative memory decline. Previous literature has suggested that those with better pre-surgical cognition are generally at highest risk for cognitive decline. Our results generally follow this trend, but interestingly, patients with single domain impairment were at the highest risk of memory decline, even above those in the cognitively intact group. Future studies are important to confirm this pattern in other samples and examine additional contributing factors and underlying mechanisms that may influence risk of memory decline across these cognitive phenotypes.

Cannabis is classified as a class B drug in the UK with penalties for possession of up to 5 years in prison, an unlimited fine or both. Nevertheless it is widely available and is the most commonly used drug in the UK with approximately 2.6 million (7.6%) of adults reporting that they sometimes or regularly use it. It is not uncommon for people who present in our epilepsy clinic to report regular use of cannabis; some use it recreationally whilst others report ‘self-medicating’ based on the belief that it has a beneficial impact on their seizures. The aim of this study was to establish the prevalence of cannabis use in people with epilepsy referred for a neuropsychological assessment and to examine the impact of cannabis use on cognitive function in this group.

All patients who attend for a neuropsychological assessment are routinely asked about illegal drug use in their clinical interview. This information is also captured in the medical and neuropsychiatric assessments they undergo when assessed by the multidisciplinary team. The electronic medical records of 800 consecutive patients who had undergone a neuropsychological assessment between 2019 and 2022 were searched for references to cannabis use. The neuropsychological profiles of patients reporting cannabis use were compared to those seen in the larger series across multiple cognitive domains.

Seventy (8.75%) of the patients in the series reported past or present cannabis use. Cannabis users were more likely to be male (p<0.01) and were younger (p<0.01) than those who did not report use. Reading IQ was significantly lower in the cannabis group (p<0.001). Patients who were regularly using cannabis at the time of the neuropsychological assessment did not differ from the rest of the cohort on tests of processing speed, working memory, naming or verbal fluency. There were no differences between the groups in their performance on an embedded measure of performance validity. However the patients who were regularly using cannabis at the time of their neuropsychological assessments scored significantly lower on tests of verbal learning (p<0.05) and reported significantly greater subjective memory problems in everyday life (p=0.02) than the non-cannabis group. The group using cannabis also scored significantly more highly on the depression (p<0.01) and anxiety scales (p=0.02) on the Hospital Anxiety and Depression Scale.

The prevalence and patterns of cannabis use in the epilepsy population mirror those seen in the wider population. The impact on regular cannabis use on neuropsychological function appears to be most evident on measures of new learning and subjective measures of memory disturbance. Cannabis use is significantly associated with lower levels of cognitive reserve and elevated levels of anxiety and low mood. Whilst caution must be employed with respect to any direct attribution in these complex clinical presentations, these findings may be helpful in the interpretation of neuropsychological test scores and the planning of interventions, particularly with respect to subjective memory complaints in this group.

Treatment of childhood central nervous system (CNS) tumors can lead to sensorineural hearing loss (SNHL), with prior research indicating associations between SNHL and cognitive difficulties. Infants (0-3 years) treated for CNS tumors are at particular risk for neurocognitive deficits due to increased vulnerability of the developing brain and missed developmental opportunities secondary to prolonged treatment. This study expands upon existing research by examining the association between treatment-related SNHL and later neurocognitive outcomes among infants.

Serial audiology and neurocognitive assessments were conducted as part of a prospective, multisite, longitudinal trial (SJYC07). Children with newly diagnosed CNS tumors were treated with chemotherapy, with or without focal proton or photon radiation therapy (RT). SNHL was dichotomized based on hearing in the better ear as present versus not present (Chang grade ≥1a vs. <1a). Neurocognitive assessments included intellectual functioning (IQ), and parent ratings of executive functioning and behavioral functioning. Demographic and clinical variables investigated included: sex, age at diagnosis (years), treatment type (chemotherapy only vs. chemotherapy + RT), risk group (low vs. intermediate vs. high), and socioeconomic status (SES, continuous). Logistic regression models were used to identify factors associated with SNHL. Change point longitudinal models were used to examine the effect of each covariate individually and the potential impact of SNHL on trajectories of neurocognitive outcomes.

Of 135 patients (median age at diagnosis= 1.5 years), 67% had mild-to-severe SNHL as defined by Chang grade ≥1a at last follow-up. SNHL occurred early after treatment with a 1-year cumulative incidence 63.0% ±4.3%. SNHL was associated with age at diagnosis (p <.001) but not sex, treatment exposure or study risk arm (p >.10). At pretreatment baseline, IQ was associated with age at diagnosis (older age= higher IQ) and SES (higher SES= higher IQ) with a change in the trajectory of IQ after SNHL (stable prior to SNHL and declined 1.46 points/year after SNHL), which was impacted by tumor location (patients with supratentorial tumors stable prior to SNHL and declined 2.84 points/year after SNHL; whereas, patients with infratentorial tumors increased 1.93 points/year prior to SNHL and were stable after SNHL). At pre-treatment baseline, adaptive functioning was associated with age at diagnosis (older age= higher skills) with a change in adaptive functioning after SNHL that varied by age. There was a change in trajectory of attention problems (stable before SNHL and worsening 1.39 points/year after SNHL). SNHL was not associated with parent report of emerging executive functioning.

Children with brain tumors experience SNHL and cognitive difficulties early in treatment that can worsen over time. Younger age at diagnosis is associated with greater risk for SNHL and cognitive difficulties. Analyses of the time course between the emergence of SNHL and cognitive late effects suggests even mild SNHL is associated with a clinically signficant decline in IQ and attention problems. These findings have notable implications with respect to refining monitoring guidelines, informing modifications to treatment, advocating for interventions, and helping educate parents, teachers, and providers about the significant impact of mild SNHL.

Radiotherapy for pediatric brain tumor is associated with reduced white matter structural integrity and neurocognitive decline. Superior cognitive outcomes have been reported following proton radiotherapy (PRT) compared to conventional photon radiotherapy (XRT), presumably due to sparing of healthy brain tissue. This study examined long-term white matter change and neuropsychological performance in pediatric brain tumor survivors treated with XRT vs. PRT.

Pediatric brain tumor survivors treated with either XRT (n = 10) or PRT (n = 12) underwent neuropsychological testing and diffusion weighted imaging > 7 years following radiotherapy. A healthy control group (n = 23) was also recruited. Groups had similar demographic characteristics, except for handedness (p = .01), mean years of age at testing (XRT = 21.7, PRT = 16.9, Control = 15.5; p = .01), and mean years since radiation (XRT =14.7, PRT = 8.9, p < .001). Age and handedness were selected as covariates; analyses were not adjusted for time since radiation due to redundancy with treatment group (i.e., standard of care transitioned from XRT to PRT in 2007). Participants completed age-appropriate versions of the Weschler Intelligence Scales (WAISIV/WISC-IV/WISC-V) and the Beery-Buktenica Developmental Test of Visual-Motor Integration (VMI and Motor Coordination subtests). Tractography was conducted using automated fiber quantification (AFQ), and fractional anisotropy (FA) was extracted from 12 tracts of interest. Linear mixed models were used to summarize group differences in FA, with tracts nested within subjects. Neuropsychological performance and tract-level FA were compared between groups using analysis of covariance (ANCOVA). Pearson correlation was used to examine associations between cognitive functioning and tract-level FA.

Across all tracts, FA was significantly lower in the XRT group than the PRT group (t(514) = -2.58, p = .01), but did not differ between PRT and Control groups (t(514) = .65, p = .51). For individual tracts, FA differed significantly between treatment groups (XRT < PRT) in the left inferior fronto-occipital fasciculus (IFOF), right IFOF, left inferior longitudinal fasciculus (ILF) and right uncinate (all t < -2.05, all p < .05). No significant differences in FA were found between PRT and Control participants for any tract. All neuropsychological scores were significantly lower for XRT than PRT patients (all p < .03), while PRT and Control groups performed similarly on these measures (all p >.19). Cognitive functioning was most consistently associated with FA of the corpus callosum major forceps (4/7 domains; all r > .33, all p < .04) and the left ILF (4/7 domains; all r > .37, all p <.02).

Both white matter integrity and neuropsychological performance were generally reduced in patients with a history of XRT, but not in those who received PRT. The PRT group was similar to healthy control participants with respect to both FA and cognitive scores, suggesting improved long-term outcomes compared to patients receiving XRT. This exploratory study is the first to provide direct support for white matter integrity as a mechanism of cognitive sparing in PRT. Future work with larger samples is necessary to replicate these findings.

Pediatric brain tumor survivors (PBTS) represent a growing group of childhood cancer survivors vulnerable to adverse neuropsychological outcomes following treatment. Although the identification of risk factors has motivated the efforts to reduce the incidence of neuropsychological late effects in PBTS, most of the prior research on late effects has examined these risk factors on an individually selective basis. Given that tumordirected treatments generally involve a multimodal approach, consisting of a combination of surgical resection, chemotherapy, and/or radiation, and that each patient may have varying degrees of neurological complications, research is needed that focuses on neurocognitive risk factors holistically. The Neurological Predictor Scale (NPS) measures neurological complications associated with neurocognitive risks (e.g., hydrocephalus) and the use of various tumordirected treatment modalities (e.g., craniospinal radiation). The Pediatric Neuro-Oncology Rating of Treatment Intensity (PNORTI) measures the intensity of pediatric brain tumor treatments, but its association with neuropsychological late effects has not been well-established. The present study aims to 1) evaluate treatment intensity as a risk factor for the development of neuropsychological late effects; and 2) expand upon the validity and clinical utility of the NPS and PNORTI as predictive measures for the development of neuropsychological late effects in PBTS.

A retrospective chart review was completed of PBTS (n = 167, Mage = 13.47, SD = 2.80) who were at least 2 years from the end of tumor-directed treatment (surgery, chemotherapy, and/or radiation therapy) and without a multi-system genetic disorder or severe developmental delay prior to brain tumor diagnosis. Neuropsychological outcomes of interest (IQ, processing speed, working memory, verbal comprehension, and perceptual reasoning) were analyzed in relation to the NPS and PNORTI.

NPS scores ranged from 1 to 11 (M = 5.58, SD = 2.28) and PNORTI scores ranged from 1 (n = 101; 62.7%) to 3 (n = 18; 11.2%). Survivors were on average approximately 6 years post-treatment (M = 6.13, SD = 3.39). Pearson bivariate correlations revealed that NPS scores were significantly correlated with IQ (r = -.20, p = .015) and processing speed (r = -.27, p = .015). Models examining the predictive utility of the NPS on neuropsychological outcomes showed that, when controlling for age at diagnosis and sex, NPS scores significantly predicted IQ [F(3, 147) = 10.83, p < .001, R2 = .18, R2adjusted = .16] and processing speed [F(3,88) = 5.62, p = .001, R2 = .16, R2adjusted = .13]. A one-way ANOVA showed no significant differences on neuropsychological outcomes based on PNORTI scores.

The findings suggest that the NPS has value in predicting IQ and processing speed above and beyond demographic variables. However, treatment intensity (PNORTI) was not associated with neuropsychological domains in our sample. Future longitudinal research should examine which specific neurological risk factors within the NPS account for the most variance in neuropsychological outcomes.

Survivors of pediatric brain tumor (BT) experience impaired executive function (EF) and adaptive behavior (i.e. the ability to complete daily living tasks independently). The literature hypothesizes that executive dysfunction contributes to suboptimal adaptive behavior outcomes in BT survivors; however, the aspects of EF that drive this relationship remain unexplored. Task-switching is an EF component that involves switching between concurrently presented tasks. This skill is critical for many day-to-day activities and may therefore contribute to observed adaptive functioning difficulties. This study investigates relationships between performance on two task-switching measures and adaptive behavior outcomes in BT survivors compared to healthy controls.

86 survivors of pediatric BT (Mage(SD)= 23.42(4.24), 44 females) and 86 age- and sex-matched controls (Mage(SD) = 23.09(4.40), 44 females) from the Atlanta area completed the Delis-Kaplan Executive Function System Trail Making Test (TMT) and Verbal Fluency Test (VFT). Respectively, the Letter-Number Sequencing (LNS) and Category Switching (CS) conditions were isolated as measures of task-switching. Baseline conditions, representing the foundational skills needed to perform these timed task-switching measures rapidly (TMT: Letter Sequencing, Number Sequencing; VFT: Category Fluency), were included as covariates in all regressions. Informants familiar with the participants’ daily living were interviewed with the Scales of Independent Behavior-Revised (SIB-R) to measure adaptive behavior in four domains (Motor Skills, Social Communication, Personal Living, Community Living). Linear regressions and t-tests confirmed group differences on task-switching performance and on adaptive functioning outcomes, respectively. Then, linear regressions investigated relationships between performance on each task-switching measure (LNS, CS) and SIB-R scores for survivors. A group by task-switching interaction was added to directly explore group differences in these relationships. α=.0125 was used due to Bonferroni correction for the four SIB-R comparisons within each task-switching measure.

BT survivors were more impaired than controls on LNS, CS, and SIB-R scores (p<.05, except Personal Living p=.058). For TMT, decreased performance on LNS predicted lower SIB-R scores in Social Communication (p=.001, r2semipartial=.14), Personal Living (p=.002, r2semipartial=.13), and Community Living (p=.003, r2semipartial =.11), but not Motor Skills (p=.184) in BT survivors. Strength of significant relationships was greater for survivors than controls (all p<.002). For VFT, decreased performance on CS predicted lower SIB-R scores in Personal Living (p=.036, r2semipartial =.06) and Community Living (p=.04, r2semipartial =.05), but not in Motor Skills (p=.716) or Social Communication (p=.14) in BT survivors. Positive relationships between CS and SIB-R scores for all 4 domains were greater in survivors than controls (p<.0125).

These findings reveal a robust, positive relationship between task-switching performance and independent, daily behaviors that is specific to BT survivors. The relationship between LNS and Motor Skills may have been weakened by covariates involving baseline motor abilities; however, CS results suggest that task-switching is important for motor skills in survivors relative to controls. Community living skills were impaired in survivors and consistently related to task-switching performance. This work may inform interventions to target task-switching abilities and consequently, promote everyday living skills. Interventions aimed at vulnerabilities in adaptive behavior may help increase independence and quality-of-life as survivors transition to adulthood.

Sexual dimorphism in human brain structure and behavior is influenced by exposure to sex hormones during critical developmental periods. In children, cancer and cancer treatments may alter hormone activity and brain development, impacting neurocognitive functions.

Five-year survivors of childhood cancer (N=15,560) diagnosed at <21 years from 1970 to 1999, and 3,206 siblings from the Childhood Cancer Survivor Study completed the Neurocognitive Questionnaire (NCQ), a measure of self-reported task efficiency (TE), emotion regulation (ER), Organization, and working memory (WM). We compared rates of cognitive impairment (i.e., NCQ scores >90th percentile) in survivors and same-sex siblings, and sex differences in risk factors for cognitive impairment (i.e., treatment exposures, chronic health conditions (CHCs), cancer diagnosis, age at diagnosis) using modified Poisson regressions.

Survivors were more likely to report cognitive impairment than same-sex siblings (Males: TE OR=2.3, p<.001; ER OR=1.7, p=.008; Organization OR=1.5, p=.04; WM OR=2.3, p<.001. Females: TE OR=2.6, p<.001; ER OR=1.9, p<.001; Organization OR=1.5, p=.02; WM OR=2.6, p<.001). Within survivors, females were more likely than males to report impairment in TE (OR=1.2, p=.001), ER (OR=1.5, p<.001), and WM (OR=1.2, p<.001). There were no sex differences in symptom severity in siblings (all ps>.05). Risk factors for cognitive impairment in survivors included cranial radiation dose (TE <20Gy OR=1.5, p=.008, ≥20Gy OR=2.5, p<.001; ER OR=1.5, p<.001; Organization <20 Gy OR=1.4, p<.001; < WM 20 Gy OR=1.8, p<.001, ≥20Gy OR=2.7, p<.001), presence of moderate to severe CHCs (TE 1 CHC OR=1.9, p<.001, >1 CHC OR=3.6, p<.001; ER 1 CHC OR=1.7, p<.001, >1 CHC OR=2.2, p<.001; Organization 1 CHC OR=1.5, p=.001, >1 CHC OR=2.5, p<.001; WM 1 CHC OR=1.8, p<.001, >1 CHC OR=4.1, p<.001). There were sex differences in cognitive impairment risk factors in survivors. In females, cranial radiation dose (<20 Gy TE OR=1.6, p=.02; ≥20Gy TE OR=1.4, p=.01), leukemia diagnosis (TE OR=1.4, p=.02), or diagnosis age between 3-5 years (WM OR=1.4, p=.02) conferred higher risk for cognitive impairment compared to males with the same history. Females diagnosed with Hodgkin’s lymphoma (Organization OR=0.61, p=.05) or non-Hodgkin’s lymphoma (Organization OR=0.55, p=.03) were at lower risk for cognitive impairment compared to males.

We found sex-specific differences in rates of, and risk factors for, neurocognitive impairment, suggesting a sex vulnerability. Future studies examining interactions between sex hormones and treatment exposures during brain development will enable tailoring treatments follow-up interventions to ensure that quality of life is maximized.

Adolescent and young adult survivors of pediatric brain tumors often live with long-term neuropsychological deficits, which have been found to be related to functional and structural brain changes related to the presence of the tumor itself as well as treatments such as radiation therapy. The importance of brain networks has become a central focus of research over recent decades across neurological populations. Graph theory is one way of analyzing network properties that can describe the integration, segregation, and other aspects of network organization. The existing literature using graph theory with survivors of brain tumor is small and inconsistent; therefore, more work is needed, particularly in survivors of pediatric brain tumors. The present study used graph theory to determine whether functional network properties in this population differ from healthy controls; whether graph metrics relate to core cognitive skills: attention, working memory, and processing speed; and whether they relate to a cumulative measure of neurological risk.

31 survivors and 31 matched controls completed neuropsychological testing including measures of attention, working memory, and processing speed. They also underwent resting state functional magnetic resonance imaging. Resting state data were preprocessed and spatially constrained independent component analysis was completed to construct connectivity matrices. Finally, graph metrics were calculated utilizing an area under the curve method, including global efficiency, clustering coefficient, betweenness centrality, and small-worldness. Group differences and associations between graph metrics, cognitive outcomes, and neurological risk were analyzed using SPSS version 28.0.

Results revealed a significant difference such that brain tumor survivors exhibited less small-world properties in their functional brain networks. This was found to be related to working memory, such that less smallworldness in the network was related to poorer performance. There were no significant relationships with neurological risk, but there were nonsignificant correlations of small-moderate effect size such that lower global efficiency and clustering coefficient were associated with greater neurological risk. Comparisons to structural network analysis from a similar sample and additional post-hoc analyses are also discussed.

These findings reveal that survivors of pediatric brain tumor indeed display significant differences in functional brain networks that are quantifiable by graph theory. It is also possible that, with further work, we might better understand how metrics such as smallworldness can be used to predict long-term cognitive outcomes and functional independence in adulthood.

Hispanic/Latino (H/L) older adults are at greater risk of developing Alzheimer’s disease and related dementias compared to non-Hispanic whites (NHW), and there is an urgent need to identify important factors that may help prevent and/or reduce age-related cognitive health disparities. Positive psychosocial factors, such as social support, may protect against cognitive impairment and decline. However, recent research has highlighted that the effect of social support on cognitive outcomes may differ across racial/ethnic groups. Given the emphasis placed on family relationships and support in H/L culture, the current study sought to clarify whether H/L ethnicity moderated the association between social support and cognitive functioning in a well-characterized sample of community-dwelling older adults residing in Texas.

Participants included 766 NHW and 817 H/L (predominantly Mexican American) older adults (Mage = 66.25 ±8.64) without dementia enrolled in the Health and Aging Brain Study-Health Disparities. Participants completed study questionnaires and a comprehensive neuropsychological battery. Perceived social support was measured using the total sum score from the 12-item abbreviated version of the Interpersonal Support Evaluation List. Episodic memory performance was operationalized as the z-score composite of the immediate and delayed recall totals from the Spanish English Verbal Learning Test and the Weschler Memory Scale (WMS)-III Logical Memory 1 and 2. Executive functioning was operationalized as the z-score composite of scores from the WMS-III Digit Span, Verbal Fluency (FAS), and Trails B. Analyses of covariance were used to explore racial/ethnic group differences in self-reported levels of social support. Multiple linear regression models examined (1) ethnicity x social support interactions on cognition, and (2) ethnicity-stratified social support and cognition associations. Covariates included age, education, sex, yearly income, and depressive symptoms.

H/L older adults reported less perceived social support compared to NHWs (F = 41.16, p < .001). There were no significant ethnicity x social support interactions on episodic memory (ß = 0.04, p = .53) or executive functioning (ß = 0.004, p = .95). However, stratified models revealed that more social support was associated with better memory performance in H/Ls (ß = 0.08, p = .01), but not in NHWs (ß = 0.0004, p = .99). No significant associations between social support and executive functioning were observed amongst H/Ls (ß = -0.01, p = .60) or NHWs (ß = 0.04, p = .29).

Although H/Ls reported lower levels of social support relative to NHWs, we observed that social support was linked to better memory performance within the H/L group only. Results suggest that culturally tailored interventions which encourage strong interpersonal relationships and caring for family could enhance social support in H/Ls and thus help to prevent memory decline. Future work should focus on the development of assessment measures that better characterize unique cultural elements of social support within H/Ls, such as multigenerational households, and explore the direct effects of social support on brain metrics.

In the United States, Alzheimer’s disease (AD) is the most common cause of dementia and the seventh leading cause of death. Exercise has demonstrated health benefits in older adults and reduces the risk of developing AD. Exploring underlying biological mechanisms of exercise could aid in identifying therapeutic targets to prevent AD progression, especially for high-risk individuals such as those with Mild Cognitive Impairment (MCI). Many studies of dementia focus on memory; however, executive function and processing speed are also vulnerable to the neuropathology that causes AD. This exploratory study aimed to identify potential mechanisms by which physical activity can facilitate change in cognitive functioning in older adults. This was accomplished by investigating correlations between changes in neurology-related plasma proteins and changes in measures of executive function and processing speed after participation in a water-based exercise intervention.

The sample included 20 older adults with amnestic MCI, ages 55-82 years (mean 68.15 ±7.75). Participants were predominately male (90%), White (70%), and non-Hispanic (85%), with more than high school education (95%). Participants engaged in supervised high-intensity water-based exercise three times per week for six months. Neuropsychological assessments and blood samples were assessed at baseline and after completion of the exercise intervention. Cognitive measures included: the Digit Span subtests from the Wechsler Adult Intelligence Scale, 4th Edition, Trail-Making Test (TMT), Stroop Color Word Test (SCWT), and the Symbol Digit Modalities Test (SDMT). Plasma protein levels were analyzed using the Olink Target 96 Neurology assay (Uppsala, Sweden), selected a priori for the established markers linked to neurobiological processes and diseases. Changes in cognitive measures and protein levels were assessed using paired-sample t-tests, and Pearson’s correlations were calculated for significant findings.

Participants’ cognitive performance significantly improved on the SCWT color trial (t = -2.19, p = 0.042) and SDMT (t = -2.17, p = .043). Significant decreases in plasma proteins levels were found for GDNF family receptor alpha-1 ([GFRA1]: t =2.05, p = 0.055), neuroblastoma suppressor tumorigenicity-1 ([NBL1]: t = 2.13, p= .046), and neuropilin-2 ([NRP2]: t = 2.61 p= 0.017). Correlational analyses showed reductions in NBL1 were significantly associated with changes in both SDMT (r = -.61, p = 0.006) and the color trial of SCWT (r = .48, p = .038), and NRP2 was significantly associated with improvement on the SDMT (r = -.46, p = 0.045). GFRA1 was not significantly associated with change on any cognitive measure.

In a sample of older adults with MCI, participation in high-intensity water-based exercise led to significant improvements in cognitive function as well as changes in neurological plasma proteome. Improved outcomes in processing speed, attention, visuospatial scanning, and working memory were associated with changes in specific plasma protein concentrations. This highlights potential activity-dependent neurobiological mechanisms that may underlie the cognitive benefits derived from physical activity. Future studies should explore these findings in Randomized Control Trials with a comparative condition and larger sample size.

Gait speed is associated with poorer executive functioning performance in older adults such that individuals with slower gait speed have shown declines in cognitive flexibility and set-shifting. Body mass index (BMI) is associated with sedentary lifestyles and slower gait speed, and has demonstrated negative effects on executive set-shifting in this population. However, the interaction between gait speed, BMI, and executive functioning has yet to be examined. The purpose of this study is to investigate the potential mediating effect of BMI on the negative relationship between gait speed and executive functioning in older adults.

The sample included 154 community-dwelling older adults drawn from two clinical trials. Participants were recruited from the VA Palo Alto Health Care System and Stanford/VA Alzheimer’s Disease Research Center. Gait speed was measured using the six-minute walk test, with longer distances representing faster gait speeds. Weight and height were used to calculate BMI. Each participant completed the Trail Making Test Part B (TMTB), which was used to measure executive functioning. A simple mediation analysis was performed using SPSS PROCESS Macro version 3.5. The outcome variable for the analysis was TMTB completion times. The predictor variable was gait speed, and the mediator variable was BMI. Age was entered as a covariate. We hypothesized that gait speed will negatively predict time to completion on the executive functioning task. We also hypothesized that BMI will mediate this relationship.

The analysis found that gait speed negatively predicted executive functioning scores (b = -.12, p = .02). The overall mediation model was statistically significant (F(3,150) =9.17, p < .001). Gait speed and age negatively predicted BMI (p < .001). BMI was a significant predictor of executive functioning (p = .001). The direct effect of gait speed on executive functioning remained significant after including BMI in the model (p < .001), which suggests that BMI partially mediated the relationship between gait speed and executive functioning. The indirect effect of the model when including BMI was tested using the bootstrap estimation approach with 5,000 samples, and was found to be significant (95% CI [.03,.11]), indicating that mediation did occur in the analysis.

BMI partially mediated the relationship between gait speed and executive set-shifting. Thus, the path by which gait speed predicted executive functioning abilities was partially attributable to BMI, one measure of obesity. This finding suggests that older adults with slower gait speeds may have poorer executive function partially due to greater BMI. Given the importance of executive functions on independence and well-being in older adulthood, management of BMI could lead to improved functioning and quality of life. Interventions to decrease weight in older adults is likely to result in several positive health outcomes, and these results suggest that they may also promote important cognitive processes.

Although relationships between Fried frailty criteria (i.e., weakness, slowness, weight loss, exhaustion and low physical activity), cognitive decline, and adverse childhood experiences (ACEs) have been examined (Brigalo et al., 2015, Brown et al., 2022, Fabricio et al., 2020, & Tani et al., 2021), the moderating effect of age on the relationship between ACEs and frailty has yet to be explored. The present study examined whether age moderates the relationship between total number of ACEs and number of frailty criteria in older age.

137 older adults were recruited from University of Miami clinics and surrounding community care centers. Collected data included demographic information, number of frailty criteria met, and number of ACEs endorsed. Participants were primarily Hispanic-White (64.2%) and female (56.9%), with a mean age of 73.62 years (SD=6.252). Data were initially analyzed using descriptive statistics. A hierarchical linear regression was run to test the effect of ACE score on number of frailty criteria met. A simple moderation analysis using the PROCESS macro was then performed with total number of medical conditions included as a covariate to address any potentially confounding effects. To avoid multicollinearity issues, number of ACEs endorsed and age were mean centered and an interaction term between the two was produced.

Scores on the ACE did substantially effect the total number of frailty criteria met by participants in this study (f=2.37, p=0.028, ΔR2=0.023), independent of number of medical conditions. The overall moderation model was significant (f=2.99, p=0.022, R2=0.103), and the addition of the interaction effect resulted in a statistically significant change to the model (f=4.08, p=0.045, ΔR2=0.035). Taken together, support for a moderating effect was found, specifically within the lower age group (65 - 71years), but not older (greater than 72 years) with ACE score positively predicting the number of frailty criteria met (b =0.230, t=2.62, p=0.010).

Results largely support the positive effect of ACE endorsement on the number of frailty criteria met in later life. Age acted as a moderating effect, for the younger old population, such that as number of ACEs endorsed increased, so too did the number of frailty criteria met. This finding highlights the importance of early intervention among those in younger late life who have experienced trauma. Given the positive relationship between frailty and cognitive decline in late life (Brigalo et al., 2015 & Fabricio et al., 2020), these findings also support the need for a better understanding of how childhood adversity impacts physical well-being over the life course.

Hypertension is a common disorder that has been inconsistently associated with worse cognition in older adults. Antihypertensive medications offer treatment for high blood pressure but previous studies on the association between blood pressure, antihypertensive use, and cognitive performance in older adults have yielded inconsistent findings. Individuals without high blood pressure may also take antihypertensive medications for other medical conditions, including migraines. It is unclear whether antihypertensive medications have any effect on cognitive performance in older adults, and whether the differences, if any, are similar in hypertensives and normotensives.

4,969 participants from the National Alzheimer Coordinating Center (NACC) database were included in this study (Mage=72.4 years, SD=7.3 years). Cognitive assessment included Letter Fluency, Category Fluency (animals and vegetables), Trail Making Test A & B, Digit Ordering (forward and backward), and MoCA total score. Participants were included if they had a clinician diagnosis of hypertension or normotension and recorded history of whether they take any antihypertensive medication. Participants with a history of stroke were excluded. Cognitive differences between medication groups were investigated in hypertensive participants and normotensive participants using Bayesian Mann-Whitney tests.

Bayesian Mann-Whitney tests in hypertensive individuals showed no cognitive differences between those taking antihypertensive medications and those not taking antihypertensives (all BF10s < 3). Bayesian Mann-Whitney tests in normotensive individuals showed individuals taking antihypertensive medications performed worse on Trail Making Test B compared to individuals not taking antihypertensives (123.6 seconds vs 108.8 seconds; BF10 = 35.1), with a small effect size (d=-.156).

These results suggest that antihypertensive use in older adults with normal blood pressure may be associated with worse executive functioning. Antihypertensive use in normotensive older adults may lower blood pressure and reduce cerebral perfusion, resulting in worse cognitive functioning. Future studies should investigate long-term antihypertensive use and associated cognitive changes in both hypertensive and normotensive individuals.

When deciding between now and later, the tendency to devalue later outcomes is known as temporal discounting. The degree of devaluing is known as one’s discounting rate. Steeper temporal discounting rates indicate preferences for immediate gains and delayed losses, reflecting a desire for instant gratification and greater loss aversion, respectfully. Considering that decrements in decision-making abilities may precipitate cognitive dysfunction and decline, a better understanding of decision-making preferences among older adults represents an important endeavor. Thus, the current study aimed to investigate whether differences among temporal discounting rates for gains and losses exist when outcomes are monetary or interpersonal in nature.

One hundred and forty community-dwelling older adults aged 50 to 90 (75% female, Mage=71.6) completed a hypothetical discounting task in which they chose between smaller immediate outcomes and larger delayed outcomes presented at various delay periods of one week, one month, six months, and one year. An iterative algorithm determined the indifference point for each delay period. Indifference points were fit to hyperbolic models using nonlinear regressions to determine discounting rates within each condition. Nonparametric Wilcoxon Signed-Rank tests compared discounting rates.

Older adults more steeply discounted monetary gains as compared to monetary losses (Z=-6.88, p<.001), as well as for social gains compared to social losses (Z=-4.81, p<.001). They also discounted social gains more steeply than monetary gains (Z=-5.44, p<.001), and social losses more steeply than monetary losses (Z=-4.44, p<.001).

Preliminary findings suggest older adults displayed a greater desire for instant gratification of rewards, particularly social rewards, yet also displayed lower loss aversion, particularly for monetary losses. Stronger preferences for instant gratification of gains in certain contexts may inform ways in which healthier lifestyle choices or changes could be framed to appeal to older adults.

COVID-19 misinformation proliferating online has led to adverse health and societal consequences. Older adults are a particularly vulnerable population due to increased risk for both COVID-19 related complications and susceptibility to, as well as sharing of, misinformation on social networking sites. The present study aimed to: 1) investigate differences in COVID-19 headline accuracy discernment and online sharing of COVID-19 misinformation in older and younger adults; and 2) examine individual differences in global cognition, health literacy and verbal IQ in online sharing of COVID-19 misinformation.

Fifty-two younger (age 18 to 35 years) and fifty older adults (age 50 and older) completed a telephone neurocognitive battery, health literacy and numeracy measures and self-report questionnaires. Participants also completed a social media headline-sharing experiment (Pennycook et al.,2020) in which they were presented true and false COVID-19 headlines and asked to indicate: 1) the likelihood that they would share the story on social media; and 2) the factual accuracy of the story.

A repeated measures multivariate analysis of variance controlling for gender and race/ethnicity showed no effects of age (p=.099), but a significant interaction between actual COVID-19 headline accuracy and likelihood of sharing (p<.001), such that accuracy is more strongly related to sharing false headlines (r=-.64) versus true headlines (r=-.43). Moreover, higher likelihood of sharing false COVID-19 headlines was associated with lower verbal IQ and numeracy skills in older adults (rs=-.51--.40; ps<.01) and with lower verbal IQ, numeracy, and global cognition in younger adults (rs=-.66--.60; ps<.01).

Findings indicate that headline accuracy judgements are an important predictor of sharing COVID-19 misinformation in both older and younger adults. Further, individual differences in cognition, IQ, and numeracy may predict the likelihood of misinformation sharing in younger adults, while IQ and numeracy skills may act as important antecedents of misinformation sharing in older adults. Future work might leverage modern, neuropsychologically-based psychoeducation approaches to improving health and science literacy related to COVID-19.

The world population is rapidly aging, and consequently, cognitive decline is becoming a larger public health crisis. There is no cure for dementia, but exercise has been consistently shown to improve cognitive function and slow cognitive decline in older adults. Given the many barriers to starting an exercise routine, walking is a particularly appealing intervention because it is safe, low-impact, and highly accessible (i.e., no upfront costs, no necessary equipment, and can be done almost anywhere and by anyone, given they are ambulatory). This abstract describes a systematic review and meta-analysis on peer-reviewed studies that examined randomized walking interventions for cognitive function in older adults.

The analyses included 1,286 older adults aged 55 and older (mean age = 73.1 years) across 19 studies that met inclusion criteria. All studies were randomized controlled trials (RCTs) of walking interventions with pre-post cognitive outcome data. A total of eight cognitive domains were identified: global cognition, attention, processing speed, working memory, language, visuospatial skills, declarative memory, and executive function. Effect sizes, measured as net treatment gain, were extracted and converted to Hedges’ g. Three-level meta-analysis was used to account for dependency of effect sizes. Meta-regression analyses were used to examine whether the following variables moderated effect sizes: (a) cognitive status, (b) baseline activity level, (c) age, (d) walking intervention duration, and (e) duration of individual walking sessions.

Participation in walking interventions significantly benefitted broad cognitive functioning (Hedges’ g = 0.19). The cognitive domains that specifically benefitted from walking were global cognition (g = 0.60), processing speed (g = 0.15), working memory (g = 0.22), declarative memory (g = 0.18), and executive functioning (g = 0.15). Cognitive status moderated this relationship, so that cognitively impaired older adults showed greater cognitive benefit from walking interventions. Baseline activity level did not moderate the effect; being sedentary at baseline yielded an effect size significantly greater than zero. The remaining moderator analyses were nonsignificant.

This systematic review and meta-analysis shows that walking interventions are associated with broad improvement in cognitive function in older adults. Walking benefits global cognition, processing speed, working memory, declarative memory, and executive function— the same cognitive domains that decline with normal cognitive aging. These findings are particularly important because walking is among the safest and most universally accessible forms of exercise. This will help healthcare providers make better lifestyle recommendations to their older patients. Future research should more rigorously examine potential moderating variables, such as walking intensity.