Women have a greater lifetime risk of developing Alzheimer’s disease (AD) dementia than men, a sex/gender disparity that cannot be explained by female longevity alone. There is substantial evidence for sex differences in the effects of APOE £4 on risk for AD. While APOE e4 increases AD risk in both sexes, women who carry APOE e4 are disproportionately vulnerable to cognitive impairment and AD compared to their counterpart men. In contrast to APOE e4, APOE £2 is associated with slower cognitive decline and a lower risk of AD. Although a less robust literature, APOE e2 may also have sex-specific effects. Because APOE e2 is the rarest major APOE allele, well-powered studies are needed to examine sex-specific effects. The objective of the present study was to examine sex-specific associations of APOE e2 carriage with longitudinal cognitive decline in a large cohort of clinically unimpaired adults.

We used observational data from two sources: the National Alzheimer’s Coordinating Center (NACC) and the Rush Alzheimer’s Disease Center (ROS/MAP/MARS) studies. We included data from clinically unimpaired adults who were >50 years old at baseline who self-identified as non-Hispanic White (NHW) or non-Hispanic Black (NHB). Participants were categorized as APOE £2, £4, or £3/e3 carriers. APOE e2/e4 carriers were excluded. The same battery of neuropsychological tests was used to assess global cognition in participants from both data sources. Linear mixed models examined interactive associations of genotype (£2 or £4 vs. £3/£3), sex, and time on longitudinal cognition in NHW and NHB participants separately. Analyses were first performed in a pooled sample of NACC and ROS/MAP/MARS participants and if significant they were repeated separately in each data source.

Across both data sources, 9,766 NHW (mean (SD) age=73.0(9.00) years, mean (SD) education=16.3(2.83) years, n(%) women=6,344(65.0)) and 2,010 NHB participants (mean(SD) age=71.3(7.59) years, mean(SD) education=14.9(3.10) years, n(%) women=1,583(78.8)) met inclusion criteria. Sex modified the association between APOE £2 and cognitive decline in NHW (ß=0.097, 95% CI: 0.023-0.172, pint=.01) but not NHB participants (ß=-0.011, 95% CI: -0.153-0.131, pint=.9). In sex-stratified analyses of NHW participants, APOE £2 (vs. £3/£3) carriage was associated with attenuated cognitive decline in men (ß=0.096, 95% CI: 0.037-0.155, p=.001), but not women (ß=-0.001, 95% CI: -0.044-0.043, p=.97). In analyses comparing men and women APOE £2 carriers, men exhibited slower cognitive decline than women (ß=0.120, 95% CI: 0.051-0.190, p=.001). Analyses performed separately in NACC and ROS/MAP revealed the same pattern of male-specific APOE £2 protection in NHW participants in both data sources.

In light of the longstanding view that APOE £2 protects against AD and dementia, our results provide evidence that APOE £2 is associated with attenuated cognitive decline in men but not women among NHW adults. This male-specific protection may contribute to sex differences in AD-related cognitive decline. Our findings have important implications for understanding the biological drivers of sex differences in AD risk, which is crucial for developing sex-specific strategies to prevent and treat AD dementia.

To examine patterns of cognitive function among a clinical sample of patients seeking treatment for Post-Acute Sequelae of COVID-19 (PASC).

One hundred nineteen patients each completed a baseline neuropsychological evaluation, including clinical diagnostic interview, cognitive assessments, and a comprehensive battery of self-report questionnaires. Patients had a mean age of 50 years (range:18 to 74, SD=10.1) and a mean of 15.5 years (SD=2.54) of formal education. Patients were primarily female (74%) and of White/Caucasian race (75%). Hierarchical agglomerative clustering was used to partition the data into groups based on cognitive performance. Euclidean distance was used as the similarity measure for the continuous variables and within-cluster variance was minimized using Ward’s method. The optimal number of clusters was determined empirically by fitting models with 1 to 15 clusters, with the best number of clusters selected using the silhouette index. All analyses were conducted using the NbClust package, an R package for determining the relevant number of clusters in a data set.

Clustering yielded two distinct clusters of cognitive performance. Group 1 (n=57) performed worse than Group 2 (n=62) on most cognitive variables (including a brief cognitive screener and tests of attention/working memory, executive function, processing speed, learning and delayed recall). Of note, there were no significant differences between groups on an infection severity scale, hospitalizations/ICU admissions, initial or current COVID-19 symptoms, or prior comorbidities. Groups did not differ in age or gender, but Group 1 had a lower education level than Group 2 (M=14.7, SD=2.45 vs. M=16.2, SD=2.42; p=.001). Group 1 also had significantly more minorities than Group 2 (40% vs. 8%; p<.001). No other demographic differences (income, living arrangement, or marital status) were observed. In comparison to Group 2 patients, Group 1 patients self-reported significantly higher levels of anxiety and depression and functional impairment (Functional Activities Questionnaire: M=11.3, SD=8.33 vs. M=7.65, SD=7.97), perceived stress (Perceived Stress Scale: M=24.7, SD=7.90 vs. M=20.3, SD=7.89), insomnia (Insomnia Severity Index: M=16.0, SD=6.50 vs. M=13.1, SD=6.76), and subjective cognitive functioning (Cognitive Failures Questionnaire: M=58.8, SD=16.9 vs. M=50.3, SD=18.6; p’s<.05).

Findings indicate two predominant subtypes of patients seeking treatment for PASC, with one group presenting as more cognitively impaired and reporting greater levels of anxiety, depression, insomnia, perceived stress, functional limitations, and subjective cognitive impairment. Future directions include follow-up assessments with these patients to determine cognitive trajectories over time and tailoring treatment adjuncts to address mood symptoms, insomnia, functional ability, and lifestyle variables. Understanding mechanisms of differences in cognitive and affective symptoms is needed in future work. Limitations to the study were that patients were referred for evaluation based on the complaint of “brain fog” and the sample was a homogenous, highly educated, younger group of individuals who experienced generally mild COVID-19 course.

Associative memory is impacted early in Alzheimer’s disease (AD). Poorer performance on associative memory tests has been related to greater amyloid and regional tau burden in preclinical AD. Our group previously examined the association of brain pathology and performance on the Free and Cued Selective Reminding Test (FCSRT) in Autosomal Dominant Alzheimer’s Disease (ADAD), finding that associative memory summary scores distinguished non-demented mutation carriers from non-carriers several years before clinical onset of cognitive impairment. In the current study, we examined whether FCSRT learning slopes were associated with brain pathology in a sample of ADAD carriers and non-carriers.

There were 119 participants including 57 non-demented carriers of the Colombian kindred with the Presenilin1 E280A mutation and 62 non-carrier family members (mean age= 36.3, 60% female). Participants were administered the Mini-Mental State Examination (MMSE), a measure of global cognitive status, and the FCSRT, which consists of three trials in which participants are asked to freely recall the same list of 16 items. It is a well-established measure known to be sensitive to early changes in AD. A subsample of 69 participants (32 carriers and 37 non-carriers) underwent positron emission tomography (PET) to measure in vivo cortical amyloid-beta (Pittsburgh compound B, PiB), and regional tau (Flortaucipir, FTP) burden in entorhinal and precuneus regions, which are among the earliest sites of tau accumulation in this ADAD population. Mann Whitney U tests, Spearman correlations, and chi-square tests were used to examine group differences and relations among variables of interest. Learning slope was calculated by subtracting the number of items freely recalled in FCSRT Trial 1 from the number of items freely recalled in Trial 3.

Compared to non-carriers, carriers had greater cortical amyloid-ß and regional tau burden, lower MMSE scores (mean [SD]: carriers= 27.5 [2.7]; non-carriers= 28.8 [1.0]), and lower scores on total immediate/ delayed free/ cued recall scores on the FCSRT (all p<.01). The groups did not differ on age, sex, or education level (all p> 0.05). In the whole sample and in carriers only, we found that higher MMSE scores were associated with higher learning slope, meaning faster learning (whole group p= 0.25, p= 0.006; carriers p= 0.30, p=0.029). In the whole sample, we found that lower learning slope was associated with higher levels of amyloid (p=-.34, p=.006) and tau in the left, right, and bilateral precuneus region (p=-.43, p<.001; p=-.46, p<.001; p=-.45, p<.001). In carriers only, lower learning slope was associated with higher tau burden in the left, right, and bilateral precuneus specifically (p=-.43, p=.017; p=-.48, p=.008; p=-.46, p=.010, respectively). No significant associations were found in non-carriers.

These findings suggest that learning curves on an associative memory test may be sensitive to preclinical pathological changes in AD, specifically within the precuneus, a brain region known to be involved in cue reactivity, episodic memory retrieval, and mental imagery strategies. Future studies with larger samples are warranted to further examine associations between the FCSRT learning curves and regional tau accumulation in individuals with ADAD.

The COVID-19 pandemic significantly disrupted schools and learning formats. Children with epilepsy are at-risk for generalized academic difficulties. We investigated the potential impact of COVID-19 on learning in those with epilepsy by comparing achievement on well-established academic measures among school-age children with epilepsy referred prior to the COVID-19 pandemic and those referred during the COVID-19 pandemic.

This study included 466 children [52% male, predominately White (76%), MAge=10.75 years] enrolled in the Pediatric Epilepsy Research Consortium Epilepsy (PERC) Surgery database project who were referred for surgery and seen for neuropsychological testing. Patients were divided into two groups based on a proxy measure of pandemic timing completed by PERC research staff at each site (i.e., “were there any changes to typical in-person administration [of the evaluation] due to COVID?”). 31% of the sample (N = 144) were identified as having testing during the pandemic (i.e., “yes” response), while 69% were identified as having testing done pre-pandemic (i.e., “no” response). Of the 31% who answered yes, 99% of administration changes pertained to in-person testing or other changes, with 1% indicating remote testing. Academic achievement was assessed by performance measures (i.e., word reading, reading comprehension, spelling, math calculations, and math word problems) across several different tests. T-tests compared the two groups on each academic domain. Subsequent analyses examined potential differences in academic achievement among age cohorts that approximately matched grade level [i.e., grade school (ages 5-10), middle school (ages 11-14), and high school (ages 15-18)].

No significant differences were found between children who underwent an evaluation before the pandemic compared to those assessed during the pandemic based on age norms across academic achievement subtests (all p’s > .34). Similarly, there were no significant differences among age cohorts. The average performance for each age cohort generally fell in the low average range across academic skills. Performance inconsistently varied between age cohorts. The youngest cohort (ages 5-10) scored lower than the other cohorts for sight-word reading, whereas this cohort scored higher than the middle cohort (ages 11-14) for math word problems and reading comprehension. There were no significant differences between the two pandemic groups on demographic variables, intellectual functioning, or epilepsy variables (i.e., age of onset, number of seizure medications, seizure frequency).

Academic functioning was generally equivalent between children with epilepsy who underwent academic testing as part of a pre-surgical evaluation prior to the pandemic compared to those who received testing during the pandemic. Additionally, academic functioning did not significantly differ between age cohorts. Children with epilepsy may have entered the pandemic with effective academic supports and/or were accustomed to school disruptions given their seizure history. Replication is needed as findings are based on a proxy measure of pandemic timing and the extent to which children experienced in-person, remote, and hybrid learning is unknown. Children tested a year into the pandemic, after receiving instruction through varying educational methods, may score differently than those tested earlier. Future research can address these gaps. Although it is encouraging that academic functioning was not disproportionately impacted during the pandemic in this sample, children with epilepsy are at-risk for generalized academic difficulties and continued monitoring of academic functioning is necessary.

COVID-19 caused a worldwide restructuring of daily life, necessitating a sharp increase in social distancing, telecommunication, and adherence to rapidly changing public health recommendations. Coping, a response to stressors, is a protective mechanism to increase resiliency against uncertainty and decreased social connectedness. This disruption of daily life has prompted unanticipated and unique research opportunities and allowed researchers to consider whether individuals' primary coping style with the pandemic is associated with cognition. Previous research has found that problem coping, or action-oriented approaches to a stressor, is the most adaptive coping strategy. Emotion-based coping, like venting or humor, varies and depends on the stressor. Avoidant coping, like denial or ignoring the stressor, is generally considered maladaptive (Carver, 1977), which may lead to increased psychosocial disturbance. Executive functioning, responsible for planning, organizing, inhibition, and self-management are theorized to be most impacted by the social and psychological effects of COVID-19 (Pollizi et al., 2021). While some research has examined this question in working parent and older adult populations, we seek to understand this relationship in emerging adults, whose frontal lobes, responsible for executive functioning, are still developing. The present study seeks to examine the association between coping with the COVID-19 pandemic and executive functioning.

College students (N=440; M=19.30 years old, SD=1.42, 76% female) across seven US universities completed self-report questionnaires on SONA, which included Barkley's Deficits in Executive Functioning, Short Form (BDEFS-SF; Barkley, 2011) and the Brief Coping Orientation to Problems Experienced Inventory adapted for coping with the COVID-19 pandemic (Brief COPE; Carver 1989). Items on the BDEFS-SF were summed to create a global executive functioning score. Items on the Brief COPE were combined to create three factors: emotional,, avoidant,, and problem-focused (Dias et al., 2011).

Stepwise linear regression was used to assess whether coping style predicted executive functioning. Results indicate that the use of emotional coping (ß =0.19, p< .001) and avoidant coping (ß =0.33, p< .001) predicted higher scores on the BDEFS (greater deficits in executive functioning). Additionally, the use of problem coping (ß =-0.27, p< .001) predicted lower BDEFS scores (better executive functioning), with this overall model explaining 16.37% of the variance.

Results from this study confirm that COVID-19 coping styles are associated with decreased executive functioning. Specifically, emotional coping and avoidant coping predicted decreased executive functioning, which has been supported in non-pandemic samples. The use of problem-focused coping predicted increased executive functioning, indicating that this may be a protective form of coping with the pandemic. Because tasks necessary for daily life, such as planning, organizing, and judgment, rely on executive functioning, maladaptive coping with COVID-19 may impede college students' daily functioning necessary for successful engagement in schoolwork, emotion regulation, and activities of daily living. This research begins to address the gap in knowledge regarding the relationship between coping with the COVID-19 pandemic and executive functioning. This knowledge can be used in future crises in order to promote the use of problem-focused coping and mitigate the self-observed deficits in executive functioning demonstrated in this population.

The Biber Figure Learning Test (BFLT) is a serial figure learning assessment previously been shown to be sensitive to various biomarkers of the aging brain. BFLT is an extensive assessment requiring about 30 minutes for administration. In this study, we investigated BFLT’s associations with subjective cognitive decline (SCD), an early marker for preclinical Alzheimer’s Disease (AD), and examined whether alternative BFLT indices could be utilized to considerably shorten the length of assessment without decreasing its sensitivity to SCD.

Participants were 50 cognitively normal older adults (8% Hispanic, 92% Non-Hispanic; 78% White, 16% Black; 64% female; mean age =72.7 (SD =6.2); mean education =17.05 (SD =2.09)). SCD was measured using a 20-item age-anchored dichotomous questionnaire that assessed complaints of cognitive functioning, and the BFLT was administered in full. Pearson correlations were conducted between SCD and BFLT scores including: Trial 1 Learning (T1), Trials 1 to 2 Total Learning (T1T2), Trials 1 to 3 Total Learning (T1T3), Trials 1 to 5 Total Learning (Total Learning), Immediate Recall, Delayed Recall, Proactive Interference (Trial B – Trial 1), Retroactive Interference (Immediate Recall – Trial 5), and Total Discrimination (calculated as [Recognition Total Correct + 0.5]/16) − ([Total False Alarms + 0.5]/31]). A Fishers Exact Test was utilized to compare the correlational strength between SCD and each of the BFLT scores. Lastly, demographically adjusted (age, gender, and education) regression models were conducted to examine SCD as an individual predictor for the various BFLT scores.

SCD was negatively associated with BFLT T1 (r =-0.406, p =0.003), T1T2 (r =-0.331, p =0.019), T1T3 (r =-0.323, p =0.022), Total Learning (r =-0.283, p =0.046), Immediate Recall (r =-0.322, p =0.023), Delayed Recall (r =-0.318, p =0.025), and Retroactive Interference (r =-0.388, p =0.005) and positively associated with Proactive Interference (r =0.308, p =0.029). There was no significant difference in correlational strength between any of these BFLT scores and SCD. Adjusting for demographics, SCD predicted Immediate Recall (B =-0.273, p =0.029), Total Learning (B =- 0.253, p =0.040), T1 (B =-0.412, p =0.002), T1T2 (B =-0.326, p =0.010), T1T3 (B =-0.299, p =0.017), Proactive Interference (B =0.292, p =0.050), and Retroactive Interference (B =- 0.330, p =0.025).

Eight of the nine assessed BFLT scores were strongly correlated with age-anchored SCD and age-anchored SCD predicted seven of the nine assessed BFLT indices when adjusted for demographics. Although additional work is needed, these findings suggest SCD’s sensitivity to changes in visuospatial learning and memory, supporting its use as an early marker for preclinical AD. Likewise, our results suggest that an abbreviated version of the BFLT could be utilized that shortens testing time and reduces participant fatigue without a decrease in clinical relevance. Through ongoing longitudinal work, we hope to further disentangle the relationship between SCD and visuospatial learning and memory as measured through the BFTL and to examine how associations between SCD and the BFLT assessment change over time.

The Dunning-Krueger effect is a cognitive bias where individuals tend to overestimate their abilities in areas where they are less competent. The Cordoba Naming Test (CNT) is a 30-item confrontation naming task. Hardy and Wright (2018) conditionally validated a measure of perceived mental workload called the NASA Task Load Index (NASA-TLX). Researchers reported that workload ratings on the NASA-TLX increased with increased task demands on a cognitive task. Anxiety is known as an emotion that can make an individual more susceptible to develop a mental health condition. We examine if the Dunning-Krueger effect occurs in a Mexican population with and without current symptoms of anxiety and possible factors driving individuals to overestimate their abilities on the CNT. We predicted the abnormal symptoms of anxiety (ASA) group would report better CNT performance, report higher perceived workloads on the CNT, and underperform on the CNT compared to the normal symptoms of anxiety (NSA) group. We also predicted the low-performance group would report better CNT performance, report higher perceived workloads on the CNT, and underperform on the CNT compared to the high-performance group.

The sample consisted of 192 Mexican participants with NSA (79 low-performance & 113 high-performance) and 74 Mexican participants with ASA (44 low-performance & 30 high-performance). Participants completed the CNT, NASA-TLX, and the Hospital Anxiety and Depression Scale (HADS) in Spanish. The NASA-TLX was used to evaluate perceived workloads after the completion of the CNT. Meanwhile, the HADS was used to create our anxiety groups. Finally, CNT raw scores were converted into T-scores, which then were averaged to create the following two groups: low-performance (CNT T-Score <50) and high-performance (CNT T-Score 50+). A series of 2x2 ANCOVAs, controlling for gender were used to evaluate CNT performance and perceived workloads.

We found a significant interaction where the low-performance ASA and the high-performance NSA groups demonstrated better CNT performance and reported higher perceived workloads (i.e., performance, temporal demand) on the CNT compared to their respective counterparts (i.e., low-performance NSA & high-performance ASA groups), p's<.05, ηp's2=.02. We found a main effect where the high-performance group outperformed the low-performance group on the CNT and reported lower perceived workloads on the CNT, p's<.05, ηp's2 =.04-.46.

The Dunning-Krueger effect did not occur in our sample. Participants that demonstrated better CNT performance also reported higher perceived workloads regardless of their current symptoms of anxiety. A possible explanation can be our sample's cultural norms of what would be considered as abnormal symptoms of anxiety, is a normal part of life, decreasing the possibilities to experience self-efficacy distoritions. Future studies should investigate whether the Dunning-Kruger effect may be influencing other aspects of cognitive functioning subjectively in Mexicans residing in Mexico and the United States with and without current symptoms of anxiety.

To determine the effects of the non-classic psychedelic, ibogaine, on cognitive functioning. Ibogaine is an indole alkaloid derived from the Tabernanthe Iboga plant family, indigenous to Africa, and traditionally used in spiritual and healing ceremonies. Ibogaine has primarily been studied with respect to its clinical efficacy in reducing substance addiction. There are, however, indications that it also may enhance recovery from traumatic experiences. Ibogaine is a Schedule 1 substance in the USA.

Participants were U.S. Special Operations Veterans who had independently and voluntarily referred themselves for an ibogaine retreat at a specialized clinic outside the USA prior to learning about this observational study. After meeting rigorous screening requirements, 30 participants were enrolled, all endorsing histories of combat and repeated blast exposure, as well as traumatic brain injury. Participants were seen in person pre-treatment, post-treatment, and one-month post-treatment for neuropsychological testing, neuroimaging, and collection of clinical outcome measures. All 30 participants were seen pre- and post-treatment, of whom 27 were also able to return one-month post-treatment.

The neuropsychological battery included the the Hopkins Verbal Learning Test (HVLT), the Brief Visuospatial Memory Test - Revised (BVMT-R), the Wechsler Adult Intelligence Scale - Fourth Edition (WAIS-IV) Working Memory Index (Digit Span and Arithmetic) and Processing Speed Index (Symbol Search and Coding), and the Delis-Kaplan Executive Function System (D-KEFS) tests of Verbal Fluency (VF), Trail Making (TMT), Color Word (CW), and Tower Test (TT). For repeated measures, alternate forms were used whenever possible.

Repeated-measures ANOVA revealed significant effects of time, with post-treatment improvements across multiple measures including processing speed (WAIS-IV PSI; F(2,25) = 26.957, p < .001), executive functions (CW Conditions 3 and 4: F(1.445,25) = 11.383, p < .001 and F(1.381,25) = 7.687, p = .004, respectively), verbal fluency (VF Condition 3 correct and accuracy: F(2,25) = 6.419, p = .003 and F(2,25) = 153.076, p < .001, respectively), and verbal learning (HVLT Total Recall (alternate forms used at each time point): F(1.563,23) = 6.958, p = .004). Score progression graphs are presented. Performance on all other cognitive measures did not significantly change following treatment.

To our knowledge, this is the first prospective study examining neuropsychological test performance following ibogaine use at post-treatment and one-month post-treatment time points. Our results indicated that several cognitive domains improved either post-treatment or one-month post-ibogaine treatment, suggesting ibogaine’s therapeutic potential for cognition in the context of traumatic brain injury and mood disorders. Potential explanations include neuroplastic changes, reduction of PTSD and mood-related effects on cognitive functioning, and practice effects. While we found no evidence of negative cognitive consequences for up to one-month post-single-ibogaine treatment, further study of this substance is necessary to clarify its clinical utility and safety parameters.

The prevalence of ADHD diagnoses more than doubled in VA settings between 2009 and 2016 (Hale et al., 2020). However, attentional difficulties are not exclusive to ADHD and can also be seen in non-neurodevelopmental disorders, including depression, anxiety, substance use, and PTSD (Marshall et al., 2018, Suhr et al., 2008). Further, patients can easily feign symptoms of ADHD with few available instruments for accurate detection (Robinson & Rogers, 2018). Given the significant symptom overlap and rising rates of reported ADHD among Veterans, accurate detection of feigned ADHD is essential.

This study examined the utility of the experimental Dissimulation ADHD scale (Ds-ADHD; Robinson & Rogers, 2018) on the MMPI-2, in detecting feigned ADHD presentation within a mixed sample of Veterans.

In this retrospective study, 173 Veterans (Mage = 36.18, SDage = 11.10, Medu = 14.01, SDedu = 2.11, 88% male, 81% White, and 17% Black) were referred for neuropsychological evaluation of ADHD that included the MMPI-2 and up to 10 PVTs. Participants were assigned to a credible group (n=146) if they passed all PVTs or a non-credible group (n=27) if they failed two or more PVTs. Group assignment was also clinically confirmed. The Ds-ADHD was used to differentiate groups who either had credible or non-credible performance on cognitive measures. Consistent with Robinson and Rogers’ study, “true” answers (i.e., erroneous stereotypes) were coded as 1 and “false” answers were coded as 2, creating a 10- to 20-point scale. Lower scores were associated with a higher likelihood of a feigned ADHD presentation.

Preliminary analyses revealed no significant group differences in age, education, race, or gender (ps > .05). An ANOVA indicated a significant difference between groups (F[1, 171] = 10.44, p = .001; Cohen’s d = .68) for Ds-ADHD raw scores; Veterans in the non-credible group reported more “erroneous stereotypes” of ADHD (M raw score = 13.33, SD = 2.20) than those in the credible group (M = 14.82, SD = 2.20). A ROC analysis indicated AUC of .691 (95% CI = .58 to .80). In addition, a cut score of <12 resulted in specificity of 91.8% and sensitivity of 18.5%, whereas a cut score of <13 resulted in specificity of 83.6% and sensitivity of 44.4%.

The Ds-ADHD scale demonstrated significant differences between credible and non-credible respondents in a real-world setting. Previously, this scale has primarily been studied within laboratory settings. Further, results indicate a cut score of <12 could be used in order to achieve adequate specificity (i.e., >90%), which were similar findings to a study examining SVT-based groups (Winiarski et al., 2023). These results differ slightly from prior research by Robinson and Rogers (2018), who indicated a cut score of <13 based on the initial simulation-based study. In similar clinical settings, where there are high rates of psychiatric comorbidity, a cut score of <12 may prove clinically useful. However, this cut-score was associated with low sensitivity within this mixed Veteran sample. Further research should focus on replicating findings within other clinical settings, including ones with larger non-credible samples.

Digitized cognitive assessment captures rich behavioral information that remains unmeasured using conventional methods. Data capture tools recently accessible only in specialized laboratories are now feasible at scale using off-the-shelf tablet devices. This study aims to share data from a digitized cognitive assessment embedded in an open-science research program collecting extensive neuroimaging, health, behavioral, neuropsychological, and psychiatric characterizations to advance translational cognitive neuroscience. In this research we present normative performance metrics from a digital version of the Trail Making Test.

The NKI-Rockland Sample (NKI-RS) has provided a model for openly-shared lifespan normative neuroimaging resources contributed by a community-ascertained sample (n=1,500, aged 6-85) and generating over 400 publications across diverse research areas. The next generation NKI-RS study (recruitment target= 600, aged 9-75) aims to enrich these resources for brain-behavioral research, normative reference, and biomarker discovery. One focus of innovation is the inclusion of digitized cognitive assessments (DCAs) utilizing an open-resource task development and data collection platform (Mindlogger, Child Mind Institute). We present preliminary data from a digitized version of the Trail Making Tests and report early descriptive metrics. The TMTs was administered via an iPad Pro using an Apple pen as part of a laboratory-based EEG procedure. The TMTs follows standard administration instructions, including a practice sample before each test condition. Error feedback is included in the task implementation such that an incorrect connection is marked with an “x” and the participant is directed to the last correct circle to continue. Feedback is automated within the task. Pixel-level spatial resolution and millisecond timing is captured across all drawing tasks. Task design, implementation, and preliminary performance metrics including speed, accuracy, and variability are reported.

Preliminary data include 12 participants from the NKI-RS2 study ranging in age from 11-75 years (M= 52.83, SD= 19.97); 67% female. Overall participants took longer to complete condition B (Mb = 51.71 secs) compared to condition A (Ma = 23.07 secs), p= 0.0005. Connections were made more slowly (Ma = 37.47 secs vs. Mb = 24.50 secs, p< 0.001) and connection speed was more variable (CVa = 0.90 vs. CVb = 1.22, p< 0.01) on condition B versus A. Connection speed decreased and speed variability increased with age (t[11 ]= -3.25, p= 0.05, t[11]= -3.63, p< 0.01, respectively). Time spent within circles (dwell time) was significantly greater in B versus A (t[11]= 6.81, p< 0.001). Number of errors were limited (MA = .89 and MB = 1.0, range 0-2 in both tests) with no difference between tests or effects of age (both ps >0.05).

These preliminary data from the NKI-RS2 normative neuroimaging study demonstrate that a digitized version of a classic neuropsychological test is feasible across a diverse range of community participants, and replicates known age effects. The advantages of growing access to these DCA tools and the shared data resources they will produce has the potential to revolutionize neuropsychological research and clinical practice.

Neuroimaging is commonly used in medicine to identify neuropathology and is widely considered to be a reliable and valid diagnostic modality. Personality testing is commonly used to identify psychopathology but is generally perceived to have less clinical efficacy than neuroimaging. The purpose of the current study was to compare the clinical efficacy of personality tests to neuroimaging using meta-analysis.

Multiple databases were searched for original research utilizing either personality tests or neuroimaging. The search interval covered articles published within the last 10 years. Studies were selected based on the criteria of having a clinical group and a healthy control sample with a reported diagnostic outcome. For this meta-analysis, neuroimaging studies focusing on diagnostic utility for Alzheimer’s dementia were included. Personality testing studies were included if they broadly reported a clinical outcome, due to fewer studies in this area. Studies were coded using a complex multi-comparison, outcome, and subgroup schema, and were analyzed under random-effects modeling.

Out of the 240 studies identified for the personality domain, 13 were selected for the meta-analysis. Out of 6522 studies identified for the neuroimaging domain, 21 studies were selected for the meta-analysis. Results indicated a significant difference between the neuroimaging and personality testing effect sizes. Specifically, neuroimaging [Hedge’s g = -1.623, 95% CI = -1.973 to -1.273, p<.001] yielded a greater effect size in comparison to the personality tests effect size [Hedge’s g = -0.658, 95% CI = -0.751 to -0.565, p<.001]. The effect size for clinical utility of neuroimaging was close to double that of the effect for personality tests diagnostic utility.

Findings from this meta-analysis showed a significant difference in the effect sizes obtained from neuroimaging studies compared to the studies of personality tests. While both neuroimaging and personality testing demonstrated meaningful clinical utility, neuroimaging studied had a larger effect size.

Cognitive training is a non-pharmacological intervention aimed at improving cognitive function across a single or multiple domains. Although the underlying mechanisms of cognitive training and transfer effects are not well-characterized, cognitive training has been thought to facilitate neural plasticity to enhance cognitive performance. Indeed, the Scaffolding Theory of Aging and Cognition (STAC) proposes that cognitive training may enhance the ability to engage in compensatory scaffolding to meet task demands and maintain cognitive performance. We therefore evaluated the effects of cognitive training on working memory performance in older adults without dementia. This study will help begin to elucidate non-pharmacological intervention effects on compensatory scaffolding in older adults.

48 participants were recruited for a Phase III randomized clinical trial (Augmenting Cognitive Training in Older Adults [ACT]; NIH R01AG054077) conducted at the University of Florida and University of Arizona. Participants across sites were randomly assigned to complete cognitive training (n=25) or an education training control condition (n=23). Cognitive training and the education training control condition were each completed during 60 sessions over 12 weeks for 40 hours total. The education training control condition involved viewing educational videos produced by the National Geographic Channel. Cognitive training was completed using the Posit Science Brain HQ training program, which included 8 cognitive training paradigms targeting attention/processing speed and working memory. All participants also completed demographic questionnaires, cognitive testing, and an fMRI 2-back task at baseline and at 12-weeks following cognitive training.

Repeated measures analysis of covariance (ANCOVA), adjusted for training adherence, transcranial direct current stimulation (tDCS) condition, age, sex, years of education, and Wechsler Test of Adult Reading (WTAR) raw score, revealed a significant 2-back by training group interaction (F[1,40]=6.201, p=.017, η2=.134). Examination of simple main effects revealed baseline differences in 2-back performance (F[1,40]=.568, p=.455, η2=.014). After controlling for baseline performance, training group differences in 2-back performance was no longer statistically significant (F[1,40]=1.382, p=.247, η2=.034).

After adjusting for baseline performance differences, there were no significant training group differences in 2-back performance, suggesting that the randomization was not sufficient to ensure adequate distribution of participants across groups. Results may indicate that cognitive training alone is not sufficient for significant improvement in working memory performance on a near transfer task. Additional improvement may occur with the next phase of this clinical trial, such that tDCS augments the effects of cognitive training and results in enhanced compensatory scaffolding even within this high performing cohort. Limitations of the study include a highly educated sample with higher literacy levels and the small sample size was not powered for transfer effects analysis. Future analyses will include evaluation of the combined intervention effects of a cognitive training and tDCS on nback performance in a larger sample of older adults without dementia.

Approximately half of all children and adults newly diagnosed with epilepsy also show behavioral and/or cognitive difficulties upon evaluation. While neuropsychological screening is recommended as a routine part of care at seizure onset, in reality, access to care is often restricted by many factors. In order to better define the extent of the problem, we developed a survey to understand how frequently youth with new onset epilepsy currently undergo neuropsychological evaluation or screening and whether virtual assessment tools are used to extend access to care.

We created an online survey to better understand new onset epilepsy care provided within neuropsychological practice settings in the United States and Canada. The survey was disseminated via multiple listservs (e.g., AACN listservs, APPCN, PERF neuropsychologists) and respondents included 45 neuropsychologists. Survey questions were grouped by the following domains: 1) location characteristics (e.g., urban versus rural location, type of practice, affiliation with comprehensive epilepsy center); 2) volume of new onset epilepsy patient cases (e.g., number of neuropsychologists within practice who see new onset patients, percentage of new onset cases who received neuropsychological evaluations/screeners, wait time), and 3) tele-neuropsychology procedures (e.g., use of virtual testing, frequency of virtual testing, frequency of virtual intakes/feedbacks).

Practice locations of the 45 respondents included academic medical center (n=34, 75.6%), community medical center (n=10, 22.2%), and private practice (n=1, 2.2%). All but one respondent practiced in an urban setting. Respondents were generally affiliated with Comprehensive Epilepsy Centers (level 3 or 4) (n=39, 86.7%). Practice settings typically included < 3 epilepsy neuropsychologists (n=29, 65.9%). Of interest, neuropsychological evaluation of new onset pediatric epilepsy patients generally ranged from 0-25% of cases (n=32, 71%; mode=11-25%). Reported barriers included: insurance, poor access to rural populations, interdisciplinary communication, departmental referral patterns, limited number of providers, and need to prioritize pre-surgical patients. In terms of access, neuropsychology waitlist times for patients with nonsurgical epilepsy ranged from <1 to 6 months (n=34, 75%) with an equal proportion of patients waiting 1-3 months (33%) and 4-6 months (33%). Telehealth was not frequently utilized in non-surgical epilepsy test administration (Do not use, n=39; 86.7%), but frequently incorporated for non-testing purposes (i.e., intakes, feedbacks) (n=40, 88.9%).

Results of this provider survey indicate that children with new-onset epilepsy do not routinely undergo neuropsychological evaluation (< 25%). Barriers included prioritizing presurgical workups, referral patterns, access to care, and limited provider bandwidth. Clearly, there is a need to improve access to care. Possible solutions include developing more time efficient screening batteries with measures most sensitive to early cognitive and psychosocial deficits, and incorporating the use of virtual technology all in the service of improving the lives of children with epilepsy.

Apathy, or loss of motivation and interest, is a common sequela of moderate to severe traumatic brain injury (msTBI) and has been associated with frontal lesions and with executive dysfunction in a sample an average of one year post injury (Andersson & Bergdalen, 2002). In older adults sustaining msTBI in particular, the appearance of apathy is more likely to be comorbid with depression when compared to injury in younger adults (Kant et al., 1998). However, studies have consistently shown an important dissociation between apathy and depression, despite overlapping symptoms, with apathy in particular associated with frontal lobe damage (Worthington & Wood, 2018). The present study holds two primary goals. First, to examine the relationship between current apathy ratings and cognition after controlling for ratings of depression and perceived changes in apathy, to account for the unique relationship of injury-related apathy on cognition. Second, to examine the potential variable role of APOE4 carrier status on depression and apathy ratings.

110 older adults with a lifetime history of msTBI (M=9.5 years post-injury) were included as part of a cross-sectional study. Apathy was measured using the Frontal Systems and Behaviors Scale (FrSBe) for both current apathy ratings and perceived change in apathy from pre- to post-injury. Depression was measured using the depression subscale of the Brief Symptom Inventory (BSI). Outcome measures included normed scores for learning (HVLT-R total recall), retention (HVLT-R percent retention), processing speed (Trails A), set-shifting and working memory (Trails B, Digit Span Backwards), and phonemic and category fluency (D-KEFS letter and category fluency). The main independent variable of interest was current apathy ratings. Depression and perceived apathy change were included as control variables for all analyses. Vif scores were calculated for all analyses to ensure that variables were not multicollinear. Finally, we ran an ANOVA to examine the relationship between apathy, depression, and APOE4 carrier status.

When controlling for depression and perceived changes in apathy, current apathy ratings were associated with poorer performance on learning (p=.04, n2=.04), processing speed (p=.001, n2=.10), set-shifting (p=.02, n2=.05), attention (p=.04, n2=.04), phonemic fluency (p=.001, n2=.09), category fluency (p=.001, n2=.10). Current apathy ratings were not associated with retention or working memory. Apathy was significantly associated with depression (p <.001), but was not associated with APOE4 carrier status or the interaction between depression and carrier status.

Despite overlap between depressive symptoms and apathy questionnaires (i.e., loss of interest/pleasure), by controlling for depressive symptoms and perceived changes following injury, we demonstrate the significant independent association of apathy and cognition in an older sample with chronic msTBI. Further, although previous work has shown strong associations between depression and APOE4 carrier status in chronic msTBI samples (Vervoordt et al., 2021), there was no significant relation with apathy directly in our sample, providing further evidence that these are neurobiologically distinct syndromes.

Memory is a critical piece of the human experience and impairments in neural memory networks can have devastating consequences for the affected person. A subtype of memory, episodic memory generates context for the present based on past experience and allows us to make predictions about the future. Episodic memories become stable fixtures through long-term memory consolidation. It is believed that consolidation of episodic memory requires a dynamic interplay between connected hippocampal-cortical networks, mainly during sleep. Sleep oscillations, slow oscillations and thalamocortical spindles, coupled with hippocampal sharp wave ripples (SWR) is proposed to be mechanistically involved in establishing the crucial cortical-subcortical dialog. The current study aimed to determine alterations in typical sleep oscillations and oscillation coupling in patients with and without structural hippocampal damage and correlate them with neuropsychological measures believed to be sensitive to hippocampal dysfunction, i.e., Rey Auditory Verbal Learning Task (RAVLT) and Verbal Paired Associates (VPA-II).

We used intracranial electroencephalography (iEEG) in 14 patients with epilepsy to directly record hippocampal and neocortical oscillations and neuropsychological measures obtained prior to implantation. Half of the participants were diagnosed with mesial temporal sclerosis (MTS) in the left hippocampus and healthy tissue in the right hippocampus. The other half did not have MTS and had either mesial temporal epilepsy without MTS or extra-temporal seizures. We analyzed hippocampal SWR output from both hippocampi and characterized neocortical slow oscillations and spindles and their coupling for each participant. We correlated electrophysiological data with behavioral results of neuropsychological testing in order to characterize the clinical relevance.

SWR analysis revealed significant differences in the frequency, t(7639) = 15.52, p>.001, p > .001), amplitude, t(7664) = -23.93, p > .001, and waveforms (p > .001) of SWR in the sclerotic versus healthy hippocampi. Patients with a sclerotic hippocampus but relatively preserved verbal memory scores (RAVLT, VPA-II) showed increased SWR amplitudes in the contralateral hippocampus compared to patients with low verbal memory scores. Additionally, we found differences between hemispheres in phase amplitude coupling of SWRs to spindles and SOs (p > 0.001). Results of our correlational analysis were variable and dependent upon additional factors, such as age of onset and diagnosis duration.

Results from this work will aid in establishing a criterion for characterizing a relationship between subcortical and cortical oscillations as they relate to memory performance. Besides aiding our understanding of the neural mechanisms underpinning memory consolidation this will ideally help with developing neurophysiological biomarkers that may predict possible memory decline in resective or ablative neurosurgery absent of structural lesion. In addition, this work may potentially provide first evidence of a neurophysiological biomarker directly recorded from the human hippocampus to support possible reorganization of memory functioning in the non-sclerotic hippocampus.

Given the lack of comprehensive neuropsychological tools and neuropsychological services in Sub-Saharan Africa (SSA), cognitive screeners for dementia can be useful tools to screen for suspected dementia at the population level. However, most available screeners have not been developed or validated in SSA populations. The Community Screening Instrument for Dementia (CSID) was developed for cross-cultural use, and it has a cognitive testing component and informant interview. We have previously demonstrated that lower years of education and female sex are associated with lower scores on the CSID. Here, we examine the utility of demographically adjusted CSID scores in a community sample of Congolese older adults.

354 participants (mean age=73.6±6.7, mean education (years) =7.3±4.7; 50% female) were randomly recruited in Kinshasa, Democratic Republic of the Congo, and completed the CSID and the Alzheimer's Questionnaire (AQ) to examine functional abilities. Raw scores were demographically adjusted for education and sex by adding 1 point for <12 years of education and 1 point for female. Cognitive impairment was classified as a total score below 25.5. Rates of impairment were compared between raw scores and demographically-adjusted scores. Demographic profiles were examined between both classifications

Average raw CSID scores were 25.23 (SD=4.19) and average demographically-adjusted scores were 26.59 (SD= 4.09). Approximately 43.1% of the sample was impaired based on the raw CSID scores compared to 30.4% with the demographically-adjusted scores (x2= 12.334, p<.001). There was a higher proportion of females (n=95; 26.8%) classified as impaired with the raw SCID scores compared to the demographically-adjusted scores (n=62; 17.5%; x2= 8.87, p=0.003). Approximately 27.4% (n=97) of the participants classified as impaired with the raw SCID scores had primary education or less (i.e., 1-6 years) compared to 18.9% with the demographically-adjusted scores (n=67; (x2= 107.77, p<.001). Forty-five participants were re-classified as not impaired with the demographically-adjusted scores with the majority of these participants being female (73.3%), having primary education (66.7%), and being functionally unimpaired on the AQ (91.1% unimpaired).

We demonstrate that raw scores on the CSID can lead to misclassification of impairment in females and in individuals with lower years of education. Demographically-adjusted scores on the CSID can help properly capture those with suspected dementia while reducing false positives. Given the effects of education and sex on performance, future studies should examine if demographically adjusted scores improve the sensitivity and specificity of the CSID in Congolese populations and compare its performance to other screening tools to determine the most appropriate screener for this population.

Transcutaneous vagus nerve stimulation (tVNS) is a promising potential intervention for Alzheimer's disease (AD) due to its influence on brain functions and mechanisms important in disease progression. Regions of interest include projection to the nucleus of the solitary tract, locus coeruleus, and hippocampus. Deterioration of the hippocampus is one of the most prominent early characteristics of AD, particularly during the mild cognitive impairment (MCI) stage. tVNS could modify function of the hippocampus. We examined resting state functional connectivity from the bilateral hippocampus in response to tVNS in patients with MCI.

Fifty older adults (28 women, 60-89 years of age) diagnosed with MCI were assessed. MCI was confirmed via diagnostic consensus conference with a neurologist and neuropsychologist (sources of information: Montreal Cognitive Assessment Test [MoCA], Clinical Dementia Rating scale [CDR], Functional Activities Questionnaire (FAQ), Hopkins Verbal Learning Test - Revised [HVLT-R] and medical record review). Resting state functional magnetic resonance imaging (fMRI) was collected on a 3T Siemens Prisma scanner while participants received either unilateral tVNS (left tragus, n = 25) or sham stimulation (left ear lobe, n = 25). fMRI data were processed using CONN toolbox v18b and hippocampal seed to voxel (whole brain) analyses were conducted with voxel and cluster level multiple comparison correction.

Contrasting tVNS and sham stimulation, whole-brain seed-to-voxel analysis demonstrated significant changes in connectivity from the left hippocampus to several cortical and subcortical regions bilaterally. Specifically, there was increased connectivity to prefrontal regions and cingulate gyri, and decreased connectivity to anterior and medial temporal lobes. A seed-to-voxel analysis from the right hippocampus indicated significant decrease in connectivity to a single cluster of regions in the left anterior temporal lobe in response to tVNS.

In conclusion, tVNS modified connectivity from the hippocampus to multiple brain regions implicated in semantic and salience functions, in which disruption correlates with deterioration in AD. These findings indicate afferent target engagement of tVNS. Future work is needed to investigate the long-term effects of tVNS in patients with MCI and whether it could contribute to meaningful cognitive change and subsequent improvements in quality of life.

Pediatric cancer and cancer-related treatments may disrupt brain development and place survivors at risk for long term problems with cognitive functions. Processing efficiency has been operationalized as a nuanced cognitive skill that reflects both processing speed (PS) and working memory (WM) abilities and is sensitive to neurobiological disruption. Pediatric cancer survivors are at risk for processing efficiency deficits; however, a thorough characterization of processing efficiency skills across pediatric primary central nervous system (CNS) tumor and non-CNS cancer survivors has not yet been reported.

Participants were selected from a mixed retrospective clinical database of pediatric cancer survivors (Total n=160; primary CNS tumor n=33; Non-CNS n=127). Univariate analyses were conducted to examine differences in processing efficiency mean scores (t-tests) and percent impairment (scores >1 SD below mean; chi-squared tests) between the total sample and normative sample, and across groups (CNS vs. Non-CNS). Multiple linear regressions were utilized to evaluate the relationships between additional risk factors, including biological sex, age at diagnosis, time since treatment, and socioeconomic status, and processing efficiency outcomes.

The total sample obtained lower scores on WM (M=90.83, SD=13.35) and PS (M=88.86, SD=14.38) measures than normative samples (M=100, SD=15), p < 0.001. Greater percentage of pediatric cancer survivors demonstrated impairment across all processing efficiency measures (24.8-38.1%) than normative samples (15.9%), p < 0.001. Regarding group differences, the CNS group obtained lower mean WM (M=84.85, SD =11.77) and PS (M=80, SD=14.18) scores than the Non-CNS group (WM M=92.39, SD=13.32; PS M=91.16, SD=13.56), p < 0.001. Rates of impairment between groups only differed for PS scores, with 63.6% of the CNS group and 31.5% of the non-CNS group demonstrating impairment, p < 0.001. Primary CNS tumor cancer type and male biological sex emerged as the only significant risk factors that predicted processing efficiency skills, with male sex predicting lower scores on PS (ß=8.91 p<.001) and semantic fluency (ß=7.59, p=.007).

These findings indicate that both pediatric primary CNS tumor and non-CNS cancer survivors exhibit substantial weaknesses in processing efficiency skills after treatment. While both groups demonstrated deficits compared to normative samples, the CNS group was more susceptible to PS impairments than non-CNS group. A basic initial study of the relationships between risk factors and processing efficiency skills revealed that primary CNS cancer was a predictor of lower performance on working memory and processing speed measures, while male biological sex was a significant risk factor for worse performance on processing speed and semantic fluency measures. Continued focus on the construct of processing efficiency in pediatric cancer survivors is warranted. Applying a standardized approach to assessing and communicating this nuanced cognitive skill could contribute to advancing both clinical practice and outcomes research of pediatric cancer survivors.