Recent work has shown that dysfunctional brain EEG responses to anesthetic drugs can be an indicator of both preoperative cognitive impairment and postoperative delirium risk. However, since excessive anesthetic dosage can also cause abnormal EEG brain responses, it is unclear how to tell to what extent such abnormal brain EEG responses reflect latent neurocognitive impairment versus excessive anesthetic dosage. Further, it is unclear what underlying mechanisms might underlie the link between phenotypes (such as delirium and cognitive impairment) and these abnormal neurophysiologic responses to anesthetic drugs.

Dual center prospective cohort design. 139 total older surgical patients from two academic centers underwent intraoperative EEG monitoring with the bispectral index (BIS) EEG monitor during anesthesia and surgery, and postoperative delirium screening by geriatrician interview (Duke cohort) or by trained research staff (Mt Sinai cohort). We developed the Duke Anesthesia Resistance Scale (DARS), defined as the average BIS EEG values divided by the quantity 2.5 minus the age adjusted end tidal anesthetic gas concentration). We then examined the relationship between the DARS and postoperative delirium risk using the Youden index to identify an optimal low DARS threshold for delirium risk, and we used multivariable logistic regression to control for potential confounders.

Neither BIS scores nor inhaled anesthetic dosage differed significantly between patients with vs without postoperative delirium. Yet, patients with delirium had lower DARS scores than those who did not develop delirium (27.92 vs 32.88, p=0.015). A DARS threshold of 28.7 maximized the Youden index for the association between the DARS and delirium. In multivariable models adjusting for site (Duke vs Mt Sinai) and individual patient risk factors, DARS values <28.7 were associated with a 3.79 fold increased odds ratio (95% CI 1.63-9.10; p=0.03) for postoperative delirium. These results remained unchanged after adjusting for intraoperative medications including opioids, benzodiazepines, propofol, phenylephrine and ketamine. Patients with structural/functional MRI or CSF biomarker evidence of preclinical/prodromal Alzheimer's disease and/or neurovascular pathology were more likely to show altered anesthetic-induced EEG activity patterns.

Lower scores on a processed EEG-based scale of neurophysiologic resistance to anesthetic induced brain activity changes were independently associated with a nearly 4 fold increased delirium risk. The altered anesthetic-induced brain EEG patterns in patients who go on to develop postoperative delirium may reflect latent pre-clinical/pro-dromal Alzheimer's disease and/or neurovascular pathology.

Older adults represent 50% of surgical patients and are disproportionately at risk of poor cognitive outcomes after surgery including delirium, accelerated cognitive decline, and dementia. Delirium alone is estimated to occur in up to 50% of older adults postoperatively, while research indicates it is preventable in 30-40% of cases. Individuals with pre-existing cognitive impairments or neurodegenerative diseases are at the highest risk of such outcomes, but (1) cognitive diagnoses are grossly underrepresented in patients' medical records, and (2) routine preoperative cognitive clearance remains rare. The purpose of this presentation is to demonstrate the extent and nature of cognitive vulnerability in older adults preparing for elective surgery within a tertiary care hospital. A case series is also reviewed to illustrate varying surgical outcomes with and without consideration of preoperative cognitive risk.

This presentation incorporated IRB-approved and data honest broker management to assess diagnoses and cognitive profiles of adults age 65 and older electing surgery with anesthesia between January 2018 and December 2019. Data were assessed across two phases of the Perioperative Cognitive Anesthesia Network (PeCAN) program within the University of Florida and UF Health. First, data from the preoperative anesthesia clinic were reviewed for the percentage of patients with cognitive difficulties within the patient problem list. Second, based on neuropsychological domains, the cognitive profiles of patients assessed by neuropsychologists within the preoperative anesthesia clinic were divided into primary attention, primary memory, or combined memory attention. From these patients, the presenter highlight cases to demonstrate how individuals with cognitive difficulties can be provided care by a multidisciplinary team to mitigate the presence of postoperative complications.

Of 14,794 older adults entering the tertiary care medical center for surgical procedures, 4% (n=591) of the sample had ICD cognitive or neurodegenerative codes in the record. When a comprehensive neurobehavioral assessments were conducted on 1,363 of these presurgical patients, 70% had confirmed cognitive deficits on neuropsychological testing. These deficits included primary attention and executive deficits (12%), primary memory impairment (27%), or both attention and memory impairment (31%). Cases from these patients are reviewed and highlight how preoperative cognitive risk status can inform conservative perioperative practices including opioid-sparing analgesia, depth of anesthesia monitoring, and postoperative inpatient geriatric medicine consultation.

Medical records listed cognitive diagnoses in 4% of hospital preoperative medical records, yet neuropsychological assessment of a subset of cases revealed a markedly higher rate of impairment. Patients with preoperative cognitive assessment show cognitive symptoms consistent with known neurological disorders of aging including Alzheimer's disease and cerebrovascular disease. Appreciation of pre-existing neurocognitive disorders can alter perioperative practices to prevent or reduce the risk of delirium and other postoperative neurocognitive changes. These data and cases reviewed will highlight how neuropsychology can be involved in perioperative care and champion perioperative interventions for perioperative "rescues".

Post-stroke depression (PSD) and anxiety disorders are the most common psychiatric issues that occur after cerebrovascular accident (CVA), with prevalence rates of up to 50%. Less studied, post-stroke apathy and pseudobulbar affect (PBA) also occur in a subset of individuals after CVA leading to reduced quality of life. Cognitive impairments also persist, especially memory, language, and executive difficulties. Residual cognitive and emotional sequelae after CVA limit return-to-work with between 20-60% becoming disabled or retiring early. This study examined the frequency and relative contribution of cognitive, behavioral and emotional factors for not returning-to-work after CVA.

Participants included 242 stroke survivors (54% women, average age of 59.2 years) who underwent an outpatient neuropsychological evaluation approximately 13 months after unilateral focal CVA. Exclusion criteria were a diagnosis of dementia, comprehension issues identified during assessment, multifocal or bilateral CVA, and inpatients. Predictors of return-to-work included in logistic regression analyses were psychological (depressive and anxiety disorders, apathy, PBA, history of psychiatric treatment before stroke) and neuropsychological (memory, executive functioning) variables. Depression and anxiety were diagnosed using DSM-IV-TR or -5 criteria. Apathy was operationalized as diminished goal-directed behavior, reduced initiation and decreased interest that impacted daily life more than expected from physical issues after stroke (including self- and family-report using the Frontal Systems Behavior Scale [FrSBe]). PBA was defined by the Center for Neurologic Study-Lability Scale and clinical judgment based on chart review.

Post-stroke apathy persisted in 27.3% of patients 13 months after stroke, PBA persisted in 28.2% of patients (i.e., uncontrollable crying spellings not simply attributable to depression alone, uncontrollable laughing spells), anxiety disorders persisted in 18.6% of patients (mainly panic attacks), and PSD persisted in 29.8% of patients. Memory loss persisted in 67.4% of patients and executive difficulties persisted in 74.4% of patients. Thirteen months after stroke, 34.7% of individuals had returned-to-work and 47.1% had not returned-to-work. The other 18.2% were not working either at the time of their stroke or after the stroke. Logistic regression indicated that post-stroke apathy, PBA, and memory loss were significant predictors of not returning-to-work (odds ratio p < 0.001). Patients who experienced post-stroke apathy were 7.1 times more likely to not return-to-work after stroke (p=0.008), those who suffered from PBA were 4.8 times more likely to not return-to-work (p=0.028), and those with memory loss were 6.6 times more likely to not return-to-work (p=0.005). PSD, history of treatment for psychiatric issues before the stroke, presence of an anxiety disorder after stroke, and executive difficulties were not significant predictors (p’s>0.05).

Results replicate the finding that return-to-work is hindered by residual cognitive deficits after stroke and extends previous research by clarifying the multifactorial emotional and behavioral barriers to not returning-to-work. Results highlight the importance of quantifying post-stroke apathy and pseudobulbar affect in a standard neuropsychological work-up after stroke to identify candidates for services to facilitate efforts in returning to work (e.g., vocational rehabilitation services, psychotherapy, interventions for decreased initiation).

Traumatic brain injury and cardiovascular disease (CVD) are modifiable risk factors for cognitive decline and dementia. Greater concussion history can potentially increase risk for cerebrovascular changes associated with cognitive decline and may compound effects of CVD. We investigated the independent and dynamic effects of CVD/risk factor burden and concussion history on cognitive function and odds of mild cognitive impairment (MCI) diagnoses in older former National Football League (NFL) players.

Former NFL players, ages 50-70 (N=289; mean age=61.02±5.33 years), reported medical history and completed the Brief Test of Adult Cognition by Telephone (BTACT). CVD/risk factor burden was characterized as ordinal (0-3+) based on the sum of the following conditions: coronary artery disease/myocardial infarction, chronic obstructive pulmonary disease, hypertension, hyperlipidemia, sleep apnea, type-I and II diabetes. Cognitive outcomes included BTACT Executive Function and Episodic Memory Composite Z-scores (standardized on age- and education-based normative data), and the presence of physician diagnosed (self-reported) MCI. Concussion history was discretized into five groups: 0, 1-2, 3-5, 6-9, 10+. Linear and logistic regression models were fit to test independent and joint effects of concussion history and CVD burden on cognitive outcomes and odds of MCI. Race (dichotomized as White and Non-white due to sample distribution) was included in models as a covariate.

Greater CVD burden (unstandardized beta [standard error]; B=-0.10[0.42], p=.013, and race (B=0.622[0.09], p<.001), were associated with lower executive functioning. Compared to those with 0 prior concussions, no significant differences were observed for those with 1-2, 3-5, 6-9, or 10+ prior concussions (ps >.05). Race (B=0.61[.13], p<.001), but not concussion history or CVD burden, was associated with episodic memory. There was a trend for lower episodic memory scores among those with 10+ prior concussion compared to those with no prior concussions (B=-0.49[.25], p=.052). There were no significant differences in episodic memory among those with 1-2, 3-5, or 6-9 prior concussions compared to those with 0 prior concussions (ps>.05). CVD burden (B=0.35[.13], p=.008), race (greater odds in Non-white group; B=0.82[.29], p=.005), and greater concussion history (higher odds of diagnosis in 10+ group compared to those with 0 prior concussions; B=2.19[0.78], p<.005) were associated with higher odds of MCI diagnosis. Significant interaction effects between concussion history and CVD burden were not observed for any outcome (ps >.05).

Lower executive functioning and higher odds of MCI diagnosis were associated with higher CVD burden and race. Very high concussion history (10+) was selectively associated with higher odds of MCI diagnosis. Reduction of these modifiable factors may mitigate adverse outcomes in older contact sport athletes. In former athletes, consideration of CVD burden is particularly pertinent when assessing executive dysfunction, considered to be a common cognitive feature of traumatic encephalopathy syndrome, as designated by the recent diagnostic criteria. Further research should investigate the social and structural determinants contributing to racial disparities in long-term health outcomes within former NFL players.

Abusive head trauma (AHT) is a form of inflicted brain injury that is associated with significant neurological impairment. Given that injuries occur during infancy, cognitive deficits may not become fully apparent for years. It is useful to understand injury factors related to outcomes. A recent study by Eismann et al. (2020) used length of PICU stay as a measure of injury severity and found that it is predictive of short-term and long-term outcomes in AHT. The current study aimed to examine injury severity factors related to acute outcomes (<3 months since injury) within a population of infants admitted to an inpatient rehabilitation unit (IRU).

The sample consisted of 45 infants (32 male, 13 female) hospitalized with suspected AHT. Age at injury was 0-21 months (MED= 4.89 months, SD = 5.48). The majority of patients (93%) had moderate to severe injury based on length of PICU stay (4+ days) [3]. Patients were administered the Mullen Scales of Early Learning (MSEL) during IRU admission, within 3 months of injury (range: 13-68 days; MED: 31 days). Pearson bivariate correlations were used to examine the relationship between MSEL subscales (ELC: Early Learning Composite; VR: Visual Reception; RL: Receptive Language; EL: Expressive Language; FM: Fine Motor; GM: Gross Motor) and the following factors: days since injury and hospitalization time (days in PICU, PICU/General Pediatrics, IRU, total hospitalization). P-values less than .05 were considered significant.

Scores on the MSEL Early Learning Composite ranged from exceptionally low to high average (Standard Score Range: <49-111; MED: 82; SD = 18.79). Unlike prior studies, time in PICU and time in PICU/General Pediatrics were not associated with any MSEL subscales. MSEL was moderately correlated with days in IRU (ELC: r = -.44; VR: r = -.37; RL: r = -.32; EL: r = -.36; GM: r = -.29) and total hospitalization time (ELC: r = -.46; VR: r = -.42; RL: r = -.36; EL: r = -.37; GM: r = -.31), such that longer hospitalization was associated with lower scores. Greater days since injury was also associated with lower MSEL scores (ELC: r = -.45; VR: r = -.42; RL: r = -.40; EL: r = -.36; FM: r = -.33; GM: r = -.35).

These results suggest that within an inpatient rehabilitation setting, longer total hospitalization time (including time on IRU) is moderately associated with worse acute neurobehavioral outcomes. While length of PICU stay has been associated with short-term outcomes in the outpatient setting (Eismann et al., 2020), this was not found in the current inpatient sample which had more severe injuries (longer PICU stay, inpatient rehabilitation admission). Interestingly, children assessed further out from injury had worse scores on the MSEL, which has previously been noted. Though this seems counterintuitive, it may reflect that participants with more severe injuries had a longer delay before they were capable of engaging in a neurodevelopmental assessment. These findings have implications for prognosticating early outcomes of AHT in an inpatient rehabilitation setting.

To explore the use of Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) and Heart Rate Variability (HRV) tests in the follow-up of concussions among college athletes. To provide a foundation for interpreting changes following a concussion by exploring the effects of self reported biological sex at birth on ImPACT and HRV values at baseline and after a concussion.

Data was prospectively collected within a pre-existing concussion management program. Baseline assessment (T1) included psychological questionnaires, the ImPACT test, and six minutes of HRV recording (standing, sitting, following a pacer). When a concussion occurred, the athlete was re-tested within 72 hours (T2) and tested again before returning to play (T3). 169 (55 females) athletes aged 16 to 22 years old completed the baseline testing and 30 (8 females) concussion cases were followed.

At baseline, females had higher Total Symptom scores, Sleep-Arousal Symptoms scores and Affective Symptoms scores (p ≤ 0.001). They also displayed significantly higher relative power of the very low-frequency bands (%VLF) (p < 0.05) in sitting position compared to males. There were no significant sex-related differences for any of the five ImPACT Index scores (Verbal Memory, Visual Memory, Impulse Control, Visual Motor, Reaction Time).

Mixed model repeated measure ANOVAs were performed within the concussed group. Significant differences were found between T1 and T2 as well as between T2 and T3 for Vestibular-Somatic Symptoms scores (p < 0.05); as expected, athletes displayed higher scores at T2 and scores were similar at T1 and T3. Total Symptoms scores and Cognitive-Sensory Symptoms scores were only found significantly higher at T2 compared to T3. Affective Symptoms scores were significantly higher at T1 and T2 compared to T3. < 0.05). There was no significant influence of sex on symptom scores. Of the ImPACT scores, the Visual Memory Index score showed a significant increase after concussion (T2 vs T1) (p < 0.05), with no significant difference between T2 and T3. For HRV, concussion showed a significant effect on %High Frequency (HF) HRV value sitting (p < 0.05) where T2 was significantly lower than T3.There was also a significant effect of sex on %HF when time and position were considered, with males having higher %HF values at T1 and lower %HF at T2 and T3 than females.

At baseline, females displayed higher symptoms scores than males but after a concussion there were no significant differences in symptoms scores. No sex-related differences were found for any of the ImPACT scores at baseline nor after a concussion. Before concussion, female athletes had higher HRV %VLF while sitting, suggesting more activation of their sympathetic nervous system and stress. For concussed athletes, Vestibular-Somatic Symptoms seemed to be the most stable and reliable when assessing symptoms at baseline and before returning to play. For ImPACT, Visual Memory Index was decreased significantly after a concussion. HRV %HF values showed significant variations according to sex after a concussion. HF values are thought to reflect parasympathetic nervous system activation. Our results support the idea that the activity of the autonomic nervous system can be disturbed in the days/weeks following a concussion.

Traumatic brain injury is one of several recognized risk factors for cognitive decline and neurodegenerative disease. Currently, risk scores involving modifiable risk/protective factors for dementia have not incorporated head injury history as part of their overall weighted risk calculation. We investigated the association between the LIfestyle for BRAin Health (LIBRA) risk score with odds of mild cognitive impairment (MCI) diagnosis and cognitive function in older former National Football League (NFL) players, both with and without the influence of concussion history.

Former NFL players, ages ≥ 50 (N=1050; mean age=61.1±5.4-years), completed a general health survey including self-reported medical history and ratings of function across several domains. LIBRA factors (weighted value) included cardiovascular disease (+1.0), hypertension (+1.6), hyperlipidemia (+1.4), diabetes (+1.3), kidney disease (+1.1), cigarette use history (+1.5), obesity (+1.6), depression (+2.1), social/cognitive activity (-3.2), physical inactivity (+1.1), low/moderate alcohol use (-1.0), healthy diet (-1.7). Within Group 1 (n=761), logistic regression models assessed the association of LIBRA scores and independent contribution of concussion history with the odds of MCI diagnosis. A modified-LIBRA score incorporated concussion history at the level planned contrasts showed significant associations across concussion history groups (0, 1-2, 3-5, 6-9, 10+). The weighted value for concussion history (+1.9) within the modified-LIBRA score was based on its proportional contribution to dementia relative to other LIBRA risk factors, as proposed by the 2020 Lancet Commission Report on Dementia Prevention. Associations of the modified-LIBRA score with odds of MCI and cognitive function were assessed via logistic and linear regression, respectively, in a subset of the sample (Group 2; n=289) who also completed the Brief Test of Adult Cognition by Telephone (BTACT). Race was included as a covariate in all models.

The median LIBRA score in the Group 1 was 1.6(IQR= -1, 3.6). Standard and modified-LIBRA median scores were 1.1(IQR= -1.3, 3.3) and 2(IQR= -0.4, 4.6), respectively, within Group 2. In Group 1, LIBRA score was significantly associated with odds of MCI diagnosis (odds ratio[95% confidence interval]=1.27[1.19, 1.28], p <.001). Concussion history provided additional information beyond LIBRA scores and was independently associated with odds of MCI; specifically, odds of MCI were higher among those with 6-9 (Odds Ratio[95% confidence interval]; OR=2.54[1.21, 5.32], p<.001), and 10+ (OR=4.55;[2.21, 9.36], p<.001) concussions, compared with those with no prior concussions. Within Group 2, the modified-LIBRA score was associated with higher odds of MCI (OR=1.61[1.15, 2.25]), and incrementally improved model information (0.04 increase in Nagelkerke R2) above standard LIBRA scores in the same model. Modified-LIBRA scores were inversely associated with BTACT Executive Function (B=-0.53[0.08], p=.002) and Episodic Memory scores (B=-0.53[0.08], p=.002).

Numerous modifiable risk/protective factors for dementia are reported in former professional football players, but incorporating concussion history may aid the multifactorial appraisal of cognitive decline risk and identification of areas for prevention and intervention. Integration of multi-modal biomarkers will advance this person-centered, holistic approach toward dementia reduction, detection, and intervention.

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.