US forces used Agent Orange (AO) during the Vietnam War and continued to store/test it at other locations after the war. AO is a powerful herbicide including dioxin, a highly toxic ingredient classified as a human carcinogen. The National Academies of Sciences, Engineering, and Medicine periodically review the literature on the health effects of AO exposure (AOE) and concluded in 2018 that there is sufficient evidence linking AO with a wide range of adverse health outcomes, including neurologic disorders (e.g., Parkinson’s disease). The VA has a list of medical disorders considered presumptive conditions related to AOE. More recently, AOE has been linked to a nearly double risk compared to those without AOE for receiving a dementia diagnosis. To our knowledge, no one has investigated the association of AOE to mild cognitive impairment (MCI), a condition thought to precede dementia.

We examined men in three waves of the Vietnam Era Twin Study of Aging (VETSA). In wave 3, participants self-reported yes/no to the question of whether they ever had prolonged or serious AOE. MCI was diagnosed by the Jak-Bondi approach. Impairment was defined as 2+ tests within a cognitive domain that were more than 1.5 standard deviations below normative means after adjusting for premorbid cognitive ability. In mixed effects models, we tested the effect of AOE on MCI status. Models were adjusted for age, ethnicity, and non-independence within twin pairs.

In wave 3, 12.6% (230) of 1167 participants reported AOE. Those with AOE data had mean ages of 51.1 (wave 1), 56.0 (wave 2), and 61.4 (wave 3). Those with data on both AOE and MCI numbered 861 (wave 1), 900 (wave 2), 1121 (wave 3), and 766 had AOE and MCI at all waves. AOE was significantly related to wave 2 MCI (p < .001), but not to waves 1 and 3 MCI. AOE was significantly associated with the number of time points at which someone met criteria for MCI (p = .011). Analyses were conducted on six cognitive domains used to diagnose MCI, using available participants per wave. At all 3 waves, AOE was significantly associated with lower scores in processing speed (p = .003, p = .004, p = .005, respectively), working memory (p < .001, p = .002, p = .008) and nearly significant at all waves for executive dysfunction (p < .001, p < .001, p = .050). There were two other significant associations [wave 2 memory (p = .038), wave 3 fluency (p = .024)]. The semantic fluency cognitive domain was unrelated to AOE in all waves.

AOE was consistently associated with lower processing speed, working memory, and executive dysfunction in males ages 51-61. It was also associated with the number of time points at which one met criteria for MCI in that age range, and with MCI in the mid-fifties. Findings support the idea of a risk for greater cognitive decline in those exposed to AO earlier in their lives, and with a risk for developing MCI.

Ecological momentary assessment (EMA) allows for tracking participant responses across multiple timepoints within the context of typical daily experiences. This study used EMA delivered via smartwatches to investigate dynamic associations between older adults’ fluctuations in cognitive performance as measured by an n-back test and self-reports of current internal (i.e., mental sharpness, fatigue, stress) and external (i.e., environmental distractions, time of day) contextual states over seven days. We hypothesized that 1) cognitive test fluctuations throughout the week would be meaningful beyond average cognitive test scores and 2) cognitive test scores would fluctuate in response to internal and external contexts.

Participants were 28 community-dwelling older adults recruited for a larger clinical trial assessing the influence of lifestyle factors and compensatory strategy use on cognitive health. During week one of the trial, participants received a smartwatch which sent prompts four times a day for seven consecutive days. The prompts included a 45-second one-back shape test, along with Likert-style questions about their current experience. Questions assessing participants’ internal contexts asked about participants’ experience “right now” of mental sharpness, physical fatigue, and stress. External context was assessed via the EMA prompt, “Right now my environment is distracting,” and time of day of the response.

Data was screened such that all data points outside the 7-day prompt window were removed, one participant who did not respond to any prompts was removed, and participants who responded to less than 60% of the shape test prompts were removed (n = 10). The sample used for this preliminary analysis included 17 participants (Age, M = 71.94 years; Education, M = 14 years; 88% Female; 88% White) with an average compliance of 75% (Range = 17 - 26 shape test responses) and an average shape test accuracy of > 92%. Hypothesis 1 was supported by the large fluctuations of the average cognitive test scores across timepoints (M = 24.35, Min = 16, Max = 27, SD = 2.54) and by repeated-measures ANOVA of average cognitive test scores by day (F(1,7) = 5.24, p < 0.01). Hypothesis 2: Cross-correlation lags 0 to 4 were assessed. For internal contexts, cross-correlation showed a medium correlation between mental sharpness and cognition for lags 0 (r = 0.46) and 1 (r = 0.4); a small to medium correlation between physical fatigue and cognition for lags 0 (r = -0.51) and 1 (r = -0.31); and no correlation between stress and cognition (r < 0.2). For external contexts, cross-correlation revealed no correlation between environmental distraction and cognition (r < 0.3), and repeated measures ANOVA revealed no effect of time of day on cognition scores (p > 0.05).

Older adults’ cognitive performance on an n-back shape test varied over time with internal contextual states. Cognitive performance was positively associated with feelings of mental sharpness and negatively associated with physical fatigue. Current external environmental distractions and time of day were less influential on cognitive performance. As more data is collected, influences of individual fluctuations in cognitive performance will be investigated.

The Brief Visuospatial Memory Test-Revised (BVMT-R) Recognition Discrimination (RD) index has emerged as an embedded performance validity test (PVT). However, there do not appear to be any studies that have examined its utility in Spanish-speaking samples. This pilot study examined the classification accuracy of the BVMT-R RD for detecting performance invalidity in a Spanish-speaking forensic sample.

This cross-sectional study utilized a sample of 89 Spanish speakers that were administered the BVMT-R during an outpatient neuropsychological evaluation. Out of the 89 Spanish speakers, 43 were subjects in litigation, 32 were neurological patients evaluated for clinical purposes, and 14 were healthy controls. The sample was 67% male/33% female, 53% South American, 33% Caribbean (Dominican, Puerto Rican, Cuban), 10% Central American, 3% North American (Mexican), and 1% Spanish, with a mean age of 44.2 years (SD = 14.2; range = 20-78) and mean education of 11 years (SD = 3.7; range = 0-20). Test administration for each patient was completed in Spanish by a fluent, Spanish-speaking examiner. In total, 64/89 (72%) were classified as valid and 25/89 (28%) as invalid based on performance across the Test of Memory Malingering (TOMM), at least one additional PVT (Rey-15 item memory test; Rey Dot Counting Test; Reliable Digit Span; WHO-AVLT recognition trial) and objective diagnostic criteria identifying invalid performance. Analyses included three univariate analyses of variance (ANOVA), with the groups (healthy vs neurological vs litigation) as independent variables and performance on BVMT-RD as the dependent variable.

Statistically significant differences among the groups were found F(2,86)=8.32, p < .001). Post-hoc analysis (Scheffe test) showed the mean of the litigation group to be significantly lower than the means of the other two groups (healthy and neurological), which showed no difference between them. An ANOVA with validity groups as the fixed factor and BVMT-R RD index as the dependent variable was significant F(1,85)= 21.02, p <.001). Results of a ROC curve analysis yielded statistically significant AUC (.794). The optimal cut-score was BVMT-R RD < 5 (48% sensitivity/88% specificity).

Results of the BVMT-R RD index in this Spanish-speaking population differed by subgroup, with worse performance seen in individuals involved in litigation, compared to those who were not (healthy and neurological). Notably, the BVMT-R RD index significantly differentiated validity groups, maintaining adequate sensitivity and good specificity. Overall, results demonstrate promise for BVMT-RD as a PVT for Spanish-speaking populations.

Following a traumatic brain injury (TBI), the majority of patients report difficulties with prospective memory (PM). However, there is not always a significant relationship between subjective and objective PM measures. Several variables may influence the degree of severity of perceived difficulties, including the severity of the injury and psychoemotional status. The aim of this study was to determine whether the severity of the TBI and anxiety and depressive symptoms were related to objective and subjective difficulties of PM.

50 patients (mean age = 31,3 years old) with a TBI (20 mild and 30 moderate/severe) in the post-acute phase of recovery and 15 matched healthy control participants (mean age = 32,3 years old) were recruited. They completed inventories assessing the presence of anxiety (BAI) and depressive (BDI) symptoms and performed the Ecological test of prospective memory (TEMP), an objective measure of PM. The Comprehensive Assessment of PM (CAPM), a subjective measure of PM, was also filled out by participants and their relatives.

In patients with moderate/severe TBI, significant correlations were found between the CAPM and the BDI (r =.601, p<.001) and the BAI (r =.507, p=.004). A negative correlation was also observed between the relatives’ CAPM scores and the performance of the patients on the TEMP (r= -.374, p=.042). In patients with mild TBI, there was only a strong significant correlation between the CAPM and the BAI scores (r =.574, p=.008). However, no other correlation was significant between this group of patients and their relatives. Additionally, results on the TEMP were not significantly correlated with the CAMP completed by healthy control participants or their relatives. A linear regression conducted in the group of participants with TBI showed that BAI and BDI scores are the only significant predictors of the results on the CAPM (31% of the variance), while TBI severity is the only significant predictor of the results on the TEMP (37% of the variance).

The perception of PM difficulties in patients with a TBI does not seem to be related to their objective performance. Anxiety and depressive symptoms appear to influence their perception more than their objective performance. As suggested by their relatives, a decrease in self-awareness could explain the lack of relationship between subjective PM difficulties of patients with moderate/severe TBI and their objective performance. On the other hand, TBI severity is more strongly related to objective performance on PM tests. These results highlight the importance of using different measures to accurately assess PM and the various factors influencing this construct.

Performance validity tests (PVTs) provide a methodological approach to detecting credible neurocognitive performances. This proves invaluable to the diagnostic process, as it allows neuropsychologists to objectively determine if an evaluation reflects a patient’s true neurocognitive abilities or if external factors are impacting the results. However, their addition to a testing battery can increase an already lengthy evaluation. As such, there is a need for sensitive but less time intensive PVTs. The purpose of this study is to validate the Coin-in-Hand (CIH) procedure as a quick and effective PVT within a veteran population.

68 English-speaking patients were identified from an outpatient neuropsychological assessment dataset. Performances were correlated to the well- validated Reliable Digit Span (RDS), and several other soft indicators of task engagement including expanded COWAT, BVMT-False Alarms (FA), WCST Failure to Maintain Set (FTM), TOMM, and the RBANS Effort Index (EI). All participants attempted CIH and RDS, testing was discontinued if 2 or more PVTs were invalid. An AUC analysis was conducted to determine how well the CIH discriminated between valid and invalid performance and determine the tests optimal cut-off score (sensitivity > 0.90 while maintaining the highest possible specificity). Logistic Regression was conducted to determine how well the CIH predicted performance validity.

Subject mean(SD) age and education were 55.25 (16.06) and 13.41 (2.55) years, respectively. 17% female, 60% Caucasian, and 32% Black. Descriptive statistics for each of the other performance validity tests were gathered. The CIH demonstrated low diagnostic accuracy (AUC = .66; p >.05; CI = .51 -.81); a cut score of <8 resulted in a sensitivity of .96 and a specificty of .64. Logistic Regression showed that CIH performance significantly predicted performance validity (X2 = -0.93; df = 1; N = 68; p < .05), accounting for 18-28% of the variance in performance classification (Cox & Snell R2 = .18; Nagelkerke R2 = .28). It correctly classified 96% of valid performers, but only correctly classified 35% of invalid performers, with an overall correct prediction rate of 83%. A predicted chase in log odds (B= -.93) and odd ratio [Exp (B) =.40] indicated that every unit increase in CIH score was associated with a decrease probability of performance invalidity. Logistic regression was also used to calculate the probability of performance invalidity at each possible CIH score (Table 1).

Results suggests that poor performance on CIH does not necessarily equate to invalid performances, but instead, should act as a screener to cue neuropsychologists working with Veterans that additional PVTs should be considered. Overall, it was determined that CIH was able to correctly predict 35% of invalid performers and 96% of valid performers, with an overall correct prediction rate of 83%, suggesting the procedure may be too simple to be an effective standalone PVT for clinical use. These results also highlight that every correct response on the CIH was associated with a decreased probability of performance invalidity. Additionally, an AUC analysis determined the tests optimal cut off score to be <8, suggesting that shortening the procedure may be as effective as giving the full 10 trials.

Higher cardiovascular burden and peripheral inflammation are associated with small vessel vascular disease, a predominantly dysexecutive cognitive profile, and a higher likelihood of conversion to vascular dementia. The digital clock drawing test, a digitized version of a standard neuropsychological tool, is useful in identifying cognitive dysfunction related to vascular etiology. However, little is known about the specific cognitive implications of vascular risk, peripheral inflammation, and varying levels of overall brain integrity. The current study aimed to examine the role of cardiovascular burden, peripheral inflammation, and brain integrity on digitally acquired clock drawing latency and graphomotor metrics in non-demented older adults.

The final prospectively recruited IRB-consented participant sample included 184 non-demented older adults (age: 69±6 years, education: 16±3 years, 46% female, 94% white) who completed digital clock drawing, vascular assessment, blood draw, and brain MRI. Digital clock drawing variables of interest included: total completion time (TCT), pre-first hand latency (PFHL), digit misplacement, hour hand distance from center, and clock face area (CFA). Cardiovascular burden was calculated using the revised version of the Framingham Stroke Risk Profile (FSRP-10). Peripheral inflammation was operationalized using interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor alpha (TNF-a), and high sensitivity C-reactive protein (hsCRP). The brain integrity composite was comprised of bilateral entorhinal cortex volume, bilateral ventricular volume, and whole brain leukoaraiosis.

Over and above age and cognitive reserve, hierarchical regressions showed FSRP-10, inflammatory markers, and brain integrity explained an additional 13.3% of the variance in command TCT (p< 0.001), with FSRP-10 (p=0.001), IL-10 (p= 0.019), and hsCRP (p= 0.019) as the main predictors in the model. FSRP-10, inflammatory markers, and brain integrity explained an additional 11.7% of the variance in command digit misplacement (p= 0.009), with findings largely driven by FSRP-10 (p< 0.001).

Overall, in non-demented older adults, subtle behavioral nuances seen in digital clock drawing metrics (i.e., total completion time and digit misplacement) are partly explained by cardiovascular burden, peripheral inflammation, and brain integrity over and above age and cognitive reserve. These nuanced behaviors on digitally acquired clock drawing may associate with an emergent disease process or overall vulnerability.

Funding sources: Barber Fellowship; K07AG066813; R01 AG055337; R01 NR014810; American Psychological Foundation Dissertation Award; APA Dissertation Research Award

Accumulating evidence from case-control and population studies suggests attention-deficit/hyperactivity disorder (ADHD) confers a 2- to 5-fold risk of all-cause dementia later in life. Here, we investigate vascular burden as a potential mediator of this relationship, because vascular integrity is well known to be compromised in ADHD (due to chronic obesity, diabetes, and hypertension) and is also a robust risk factor for neurodegeneration (due to reduced cerebral blood flow). We use brain white matter hyperintensities (WMH) as a measure of vascular burden.

Thirty-nine adults aged 48-81 years with clinical ADHD, and 37 matched controls, completed neuropsychological testing and 1.5 T structural neuroimaging. None had stroke. Cognitive tests were demographically-adjusted to Z scores using regression-based norms generated from the control group, and averaged across tests within domains of short- and long-term verbal memory (forward digit span, California Verbal Learning Test, Logical Memory), visual memory (Visual Recognition, Rey Complex Figure), processing speed (coding, trails A, Stroop word-reading and color-naming), language (Boston Naming Test, semantic fluency), visuoconstruction (clock drawing, Rey Complex Figure copy), and executive function (backward digit span, trails B, phonemic fluency, Stroop inhibition, Wisconsin Card Sorting Test). Total WMH volumes (i.e., combined periventricular and deep) within subcortical, temporal, frontal, parietal, and occipital regions were individually divided by regional volumes to produce a proportion of each region representing WMH, then log-transformed to correct for skew. Age-corrected linear regression quantified total effects of ADHD on cognition; when these were significant, mediation models quantified the direct effects of ADHD on WMH volumes and the direct effect of WMH volumes on cognition. Sobel’s test estimated indirect effects of ADHD on cognition via WMH.

Group had a significant total effect on Processing Speed (ß=-1.154, p<.001) and on Executive Functioning (ß=-0.587, p=.004), where ADHD participants had lower composite scores (M=-1.10, SD=1.76 and M=-0.54, SD=1.14 respectively) than controls (M=0.02, SD=0.74; M=0.00, SD=0.49). Only frontal-lobe WMH had direct effects on Processing Speed (ß=-0.315, p=.012) and Executive Functioning (ß=-0.273, p<.001). The direct effect of ADHD on frontal WMH was significant (ß=-0.734, p=.016), and Sobel’s tests supported an indirect effect of ADHD on Executive Functioning (z=2.079, p=.038) but not Processing Speed (z=1.785, p=.074) via WMH. Because the effect of ADHD on WMH was negative (i.e., fewer WMH in ADHD) despite worse cognition than controls, we tested the a posteriori hypothesis that WMH burden may be relatively more deleterious for ADHD than controls. We found considerably stronger negative correlations between total WMH volumes and Processing Speed (r=-.423, p=.009) and Executive Functioning (r=-.528, p<.001) in the ADHD group than in controls (r=-.231, p=.175 and r=-.162, p=.346, respectively), even though total whole-brain proportion of WMH (M=0.15%, SD=0.27; Mann-Whitney l/=430.0, p=.002) and frontal-lobe proportion of WMH volumes (M=0.33%, SD=0.51; Mann-Whitney U=464.0, p=.007) were lower in ADHD than in controls (M=0.29%, SD=0.42 and M=0.66%, SD=0.88, respectively).

WMH burden contributes significantly to the relationship between ADHD and cognition, but ADHD remains an independent contributor to worse processing speed and executive functioning in older adults. Vascular burden may have relatively more deleterious effects on cognition in ADHD, potentially due to decades of accumulated allostatic load, whereas healthy controls can accumulate greater amounts of WMH before cognition is impacted.

Historically, numerous studies have supported a male advantage in math. While more recent literature has shown that the gender gap is either decreasing or non-significant, a gender difference remains for higher level math (high school and college) (Hyde et. al. 1990; Casey et. al. 1995). It is known that both cognitive and non-cognitive factors influence math performance. There is little evidence for gender differences in working memory (Miller & Bichsel, 2004), which is a key predictor for mathematics. There is, however, evidence for gender differences in the non-cognitive domain, including math anxiety, with females having higher levels (Miller & Bichsel, 2004; Goetz, et. al. 2013). This study evaluates gender differences in both standardized and everyday math performances, and the way that cognitive and non-cognitive factors impact math. The study is focused on a very understudied group with high levels of math difficulty, namely community college students. We expected to find gender differences in math, and expect these to be in part accounted for by gender differences in strong mathematical predictors, particularly non-cognitive factors.

Participants included 94 community college students enrolled in their first math class (60 female; 34 male). Participants were administered the Kaufman Test of Educational Achievement - 3rd edition (KTEA3): Math Computation (MC) and Math Concepts Application (MCA) subtests, as well as an original Everyday Math (EM) measure which assessed their math ability in the context of common uses for math (e.g., financial and health numeracy). Additional measures included math anxiety, self-efficacy, and confidence. Finally, complex span working memory tasks were administered to assess verbal and spatial working memory. Analyses were performed using correlation and regression to examine relationships between the cognitive and non-cognitive variables and standardized and everyday math measures.

Correlations showed that all cognitive and non-cognitive variables are significantly correlated with all three math measures (all p < .05). There were no significant gender differences for any of the math measures, nor the working memory, or non-cognitive measures. Regression showed that across all three math outcomes, math anxiety and verbal working memory are significantly predictive of math performance. Overall R2 values were significant (range 27% to 37%, all p < .001). Working memory and math anxiety were unique predictors in all three regressions (all p < .05), but other non-cognitive variables such as self-efficacy did not show unique prediction (all p >.05).

There was no evidence for gender differences on any studied variable. This stands in contrast to prior studies, although few studies have included community college students. On the other hand, both cognitive and non-cognitive factors were complimentary in the prediction of math outcomes, which is consistent with prior work. Among non-cognitive predictors, math anxiety was particularly prominent. This study clarifies prior conflicting work regarding gender differences, and highlights the role of both math anxiety and working memory as relevant for multiple math outcomes.

Executive function is known to decline in later life, largely attributed to structural and functional changes in the prefrontal cortex. However, other regions of the brain are integral to executive functioning, including the hippocampus. The hippocampus plays a large role in memory but its intricate connections to limbic regions including the prefrontal cortex likely underlies associations between the hippocampus and executive functions. Due to the hippocampus’ complex structure, hippocampal subregions may be differentially associated with executive function, but this possibility remains largely unexplored. Therefore, we examined the association between volume of the hippocampus and its subregions with executive function to understand these relationships across the adult lifespan.

The study included 32 healthy, community-dwelling participants (age range = 18-81, mean age = 51.06 ± 20.98, 91% white, 72% female) who received a 3-Tesla magnetic resonance imaging (MRI) scan and completed a cognitive battery. We calculated an executive composite based on Trail Making Test Part B and the interference score from the Stroop Color and Word Test. Freesurfer (version 5.3) as used to quantify total hippocampal volume and subfield volumes for CA1, CA2-3, CA4-dentate gyrus, subiculum, and presubiculum. We conducted mixed-effects regression analyses with total hippocampal and subfield volume, age group (young, middle-aged, and older), and their interaction predicting the executive function composite, controlling for total intracranial volume.

Larger hippocampal subregion volumes in CA1 (p = 0.03), the subiculum (p = 0.01), and the CA4-dentate gyrus (p = 0.04) predicted better executive function. Total hippocampal volume and the presubiculum were not significantly associated with the executive function composite. The age group interaction was not significant for any of the models. Follow-up analyses by hemisphere showed that the effects were right lateralized in CA1and CA4-dentate gyrus, and bilateral in the subiculum.

These data support the literature demonstrating the involvement of the hippocampus in executive function and demonstrates variation across hippocampal subfields. The lack of significant age interactions suggests these relationships may not differ across the lifespan, although this finding would need to be replicated in larger samples. These findings support previous literature showing CA4-dentate gyrus’ association with neurogenesis may facilitate better executive function by increasing connection strength among CA1, CA2-3, and the frontal cortex. This study contributes to our understanding of how specific hippocampal subregions relate to executive function, which has both clinical and research implications.

Driving is a cognitively demanding activity commonly affected by brain injury and illness. Accurate driving assessment is essential for reducing risk, optimizing independence, and informing driving-related interventions. Virtual reality driving simulation (VRDS) enables safe, sensitive, objective, and standardized measurement of driving abilities. VRDS has been validated in relation to self-reports and driver records. However, self-reports are subjective, and driver records include only major events (collisions, violations). Video telematics platforms can measure naturalistic driving in a more objective and sensitive manner. The present study used video telematics to examine relationships between VRDS performance and directly observed naturalistic driving.

20 healthy adult drivers (ages 23-61, mean age=36; 75% women) completed a VRDS assessment that included 1) driving on a straight road, 2) following a truck on a highway, and 3) reacting to a child running into a street to retrieve a ball. Primary VRDS measures were 1) speed and lane management on the straight road; 2) speed and following distance management in the truck-following task; and 3) reaction time, stopping, and distance from the child in the child-ball task. Participants also completed 28 days of naturalistic driving with a video telematics platform in their vehicle. Driving events were detected automatically using accelerometer, GPS, and video data, and driving behaviors were coded by driving risk analysts. The primary naturalistic measure was the number of unsafe driving behaviors per hour driven; specific driving behaviors served as exploratory variables. We examined correlations between VRDS and naturalistic driving variables. Given limited statistical power, we reported correlations that were small-to-medium or greater (r>.2) in primary analyses and medium-to-large or greater (r>.4) in exploratory analyses.

On average, drivers exhibited approximately one unsafe driving behavior per hour (M=0.9, SD=0.9, range=0.1-2.7). Common behaviors were failing to stop, unsafe following distance, speeding, and cell phone use. No collisions occurred. Average lane position in VRDS (specifically, leftward deviation from the center of the lane) was correlated with more real-world unsafe driving behaviors per hour (r=.35, p=.13), as were higher average straight road speed (r=.26, p=.27), greater straight road speed variability (r=.28, p=.24), and failing to stop for the child in the child-ball task (r=.22, p=.36). In exploratory analyses, failing to stop for the child was associated with real-world distracted driving (r=.45, p=.047), greater lane position variability in VRDS was associated with real-world unsafe following distance (r=.57, p=.009), and greater speed variability in VRDS was associated with real-world seat belt non-use/misuse (r=.49, p=.03).

The present findings provide preliminary evidence that VRDS variables are related to directly observed naturalistic driving, supporting the potential utility of VRDS as a sensitive, ecologically valid driving evaluation tool. As the present study used a small sample of healthy drivers, further research will explore this topic in larger samples and in clinical populations, such as acquired brain injury. Future work will also investigate whether incorporating VRDS with conventional driving evaluation tools (e.g., neuropsychological tests, behind-the-wheel assessments) can enhance the ability of clinical driving evaluations to predict real-world risky driving.

Integration of neuropsychological services into multidisciplinary clinics for pediatric patients requiring neurocritical care has previously been shown to improve access to care and promote connection to vital services for children recovering from traumatic brain injuries or other serious insults or infections impacting the brain. As such, the objective of this study is two-fold. First, to explore the unique model of care provided by a neuropsychological inpatient service at the Medical College of Wisconsin/Children’s Wisconsin. Secondly, to describe the benefit of neuropsychology in the Brain Recovery Assessment and Interdisciplinary Needs Clinic (BRAIN) a neurocritical care outpatient follow-up multidisciplinary clinic.

Participants include N =298 pediatric inpatients from a Level 1 Pediatric Trauma center referred to the neuropsychological inpatient consultation service from February 2020 to July 2022. Qualitative methods were used to describe the flow and number of patients initially referred to the neuropsychological inpatient service and then those who followed up in outpatient neuropsychological care prior to and after the implementation of a multi-disciplinary clinic for children admitted to the Neurocritical Care Unit. Rates of follow-up with neuropsychological care were compared pre- and post-establishment of the multidisciplinary clinic. Additional analyses were conducted to explore factors known to impact follow-up with care post-hospitalization (e.g., socioeconomic status, race, ethnicity).

Prior to the establishment of the BRAIN clinic, approximately 60 to 70% of patients were referred for outpatient neuropsychological follow-up. Approximately 30% of patients referred to the inpatient neuropsychological service following the establishment of the BRAIN clinic were referred for multidisciplinary care, while 20% did not require additional intervention and 50% were referred for outpatient neuropsychological follow-up. Analyses indicated increased follow-up rates with neuropsychological care following the establishment of the BRAIN clinic.

Integration of neuropsychology into inpatient care and subsequent multidisciplinary settings for pediatric patients with traumatic brain injuries or other serious insults and CNS infections increased access to neuropsychological care. Additional clinical implications will be discussed.

Education is known to impact neuropsychological test performance, and self-reported years of education is often used in stratifying normative data. However, this variable does not always reflect education quality, particularly among underrepresented populations, and may overestimate cognitive impairment in individuals with low education quality. This cross-sectional study evaluated relative contributions of years of education and reading level to several verbally mediated assessments to improve interpretation of neuropsychological performance.

Data was obtained from the Vanderbilt Memory and Aging Project. Cognitively-unimpaired participants (n=175, 72±7 years, 59% male, 87% Non-Hispanic White, 16±2 years of education) completed a comprehensive neuropsychological protocol. Stepwise linear regressions were calculated using education and Wide Range Achievement Test (WRAT)-3 Reading subtest scores as predictors and letter fluency (FAS, CFL), category fluency (Vegetable and Animal Naming), the Boston Naming Test (BNT), and California Verbal Learning Test (CVLT)-II as outcomes to assess increase in variance explained by educational quality. Models covaried for age and sex. The False Discovery Rate (FDR) based on the Benjamini-Hochberg procedure (Benjamini & Hochberg, 1995) was used to correct for multiple comparisons.

The mean WRAT-3 score was 51±4 (range:37-57), indicating post-high school reading level. Education and WRAT-3 scores were moderately correlated (r=0.36, p<0.01). Both WRAT-3 and years of education independently predicted letter fluency (WRAT-3 p<0.001; education p<0.02), category fluency (WRAT-3 p<0.001; education p<0.05), and CVLT-II performance (WRAT-3 p-values<0.005; education p-values<0.02) in single predictor models. On BNT, WRAT-3 (p<0.001), but not education (p=0.06), predicted performance in single predictor models. In combined models with both WRAT-3 and education, WRAT-3 scores remained a significant predictor of FAS (WRAT-3 b=1.21, p<0.001; education b=0.006, p=0.99) and CFL performance (WRAT-3 b=1.02, p<0.001; education b=0.51, p=0.14). Both WRAT-3 (b=0.21, p=0.01) and years of education (b=0.35, p=0.03) predicted Animal Naming, while WRAT-3 (b=0.16,p=0.008), but not years of education (p=0.37), predicted Vegetable Naming. WRAT-3 was a significant predictor of BNT performance (b=0.21, p<0.001) but not years of education (p=0.65). WRAT-3 predicted CVLT-II learning (b=0.32, p=0.04), immediate recall (b=0.16, p=0.005), and delayed recall performances (b=0.15, p=0.005), while education did not (p-values>0.14). All significant results persisted after FDR correction. WRAT-3 scores explained an additional level of variance beyond the covariates and education alone for FAS (AR=18%), CFL (AR=13%), Animal Naming and Vegetable Naming (AR= 3%), BNT (AR=18%), and CVLT-II learning (AR=2%), immediate recall (AR=4%), and delayed recall (AR=3%).

Reading level more strongly associated with performance on several verbally mediated neuropsychological measures than years of education. For all measures, the addition of reading level significantly increased the amount of variance explained by the model compared to covariates and education alone, which aligns with existing research. However, most of this past work looks at individuals with lower levels of educational quality. Because our cohort was highly educated and at the upper end of the reading spectrum, our results suggest that reading level is important to consider even for more highly educated individuals. Therefore, reading level is a critical variable to consider when interpreting verbally mediated neuropsychological measures for individuals across the educational spectrum.

Neurobiological and cognitive theories implicate deficits in executive function (EF) as a core facet of both depressive disorders and attention-deficit/hyperactivity disorder (ADHD), but empirical investigations inconsistently support this conclusion. Despite recognition of the likely bi-directional relationship of EF deficits to depression and ADHD, respectively, the extent to which comorbid depression might impact EF in adults remains unclear, considering more of the literature has examined children and adolescents. This study examined performance differences on EF measures in clinically-referred adults diagnosed with ADHD or a non-ADHD primary psychopathological condition in the presence/absence of comorbid depression.

This cross-sectional study included data from 404 adults referred for neuropsychological evaluation at a Midwestern academic medical center. In total, 343 met DSM-5 diagnostic criteria for ADHD (ADHD-all group:164 Predominantly Inattentive presentation [ADHD-I] and 179 Combined presentation [ADHD-C]) and 61 met criteria for a non-ADHD primary psychopathological condition (psychopathology group: 31 mood disorder, 17 anxiety disorder, and 13 posttraumatic stress disorder) when assessed via semi-structured clinical interview. All patients completed the Beck Depression Inventory-Second Edition (BDI-II) and five EF tests: Letter Fluency, Trail Making Test-Part B (Trails-B), Stroop Color and Word Test Color-Word trial (SCWT CW); and WAIS-IV Working Memory Index (WMI). Oneway MANOVAs assessed for significant EF differences between groups with high (BDI-II greater than or equal to 20) or low (BDI-II less than or equal to 19) depressive symptoms.

When group diagnosis (ADHD-all vs. psychopathology) was examined in the context of high or low depression, a significant difference in EF performance emerged between groups, F(12, 1042.72)=2.44, p<.01, Wilk's A=.93, partial n2=.02, with univariate analyses indicating a significant difference in FAS-T between at least two of the groups (F(3, 397)=3.92 , p< .01, partial n2=.03). Tukey's HSD Test for multiple comparisons found that the mean value of FAS-T was significantly different between the ADHD-high depression and ADHD-low depression groups (p=.046 , 95% CI = [5.81, -.04]) as well as between the ADHD-low depression and psychopathology-high depression groups (p=.05, 95% CI = [-8.89, .00]). A one-way MANOVA examining differences between groups when distinguishing ADHD by subtype revealed a statistically significant difference in EF performance between groups, F(20, 1301)=1.85, p<.05, Wilk's A=.91, partial n2=.02, with univariate analyses indicating a statistically significant difference in FAS-T between at least two of the groups (F(5, 395) = 2.39 , p<.05, partial n2 = .03). However, Tukey's HSD Test for multiple comparisons found that the mean value of FAS-T was not significantly different between any of the groups.

Overall, results indicate that clinically-referred patients with ADHD perform comparably on tests of EF regardless of the presence or absence of comorbid depression. These findings have implications for conceptualizing EF weaknesses in neuropsychological profiles for individuals with ADHD and suggest examining factors beyond comorbid depression.

Using a humanized APOE3/4 (Alzheimer’s disease genetic risk allele) mouse model we investigated the potential modulating effects of exercise on systemic risk factors and the ability of this mouse model to translate to active or sedentary, midlife, human participants. We present preliminary results of an ongoing, translational pilot study.

26 Midlife individuals, ages 40-65, were recruited from the community and dichotomized into active or sedentary groups following health screening and cognitive assessment. Blood samples were drawn from human participants for lipid assessment and other general health measures as well as peripheral growth factors concentrations (VEGF, BDNF and FGF21). Traditional, transgenic mouse models have helped the scientific community to understand biological mechanisms of Alzheimer’s disease (AD), but they do not develop significant neuronal loss, a hallmark of AD pathology. The MODEL-AD consortium has created a new “humanized” APOE4 model that has the human APOE4 allelic sequence in place of the mouse APOE gene; the model has shown known human phenotypes including deficits in cholesterol trafficking, amyloid clearance and BBB integrity. Of upmost importance, this model does not develop a full AD phenotype indicating that additional genetics and/or environmental factors are required as would be seen in human populations. We used males and females of this model to complete identical sedentary and active measures of each APOE genotype.

Lipid and general health marker assessment between mouse and human were similar and reproduced published literature. In both humans and mice we saw increased total cholesterol and HDL in active females and decreased total cholesterol and HDL in active males. We also saw similar relationships between APOE genotype, sex, and activity with regards to triglycerides. Although total cholesterol, HDL and LDL measures are the primary lipids needed to confirm or deny translation, other lipid measurements were not equivalent between the two models. Growth factor assessment in both species are also similar and reproduce published literature with regards to VEGF and BDNF as we see trending elevated levels in the active group. Less published on is the finding seen between active females and these elevated growth factors levels; our results indicates that although elevated as a result of exercise, this increase may be more prominent in females.

Based on the results found here we conclude that The Jackson Laboratory’s humanized APOE3/4 mouse model is a translatable model of vascular dysfunction, dementia and Alzheimer’s disease. We also conclude that exercise modulates these aspects by growth factor activation and increases resulting in downstream effects that reduce peripheral vascular risk factors and therefore reduce the risk of Alzheimer’s disease as a result of neuroinflammation. Complete, APOE genotype results from human participants are still ongoing. Descriptive analysis is limited by human samples size.

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.