Historically, psychiatric conditions and neurodegenerative diseases have been considered differential diagnoses in older adults with cognitive impairment. However, recent evidence has shown that neuropsychiatric symptoms may be prodromal for neurodegenerative disease. Subjective Cognitive Decline (SCD) is a potential marker for pre-clinical Alzheimer’s Disease (AD) that is frequently related to mood disturbances. Delineating the relationship between neuropsychiatric symptoms, SCD, and cognitive impairment will help to define both the independent and combined utility of SCD and neuropsychiatric symptoms as markers of preclinical AD. This abstract uses the DSM-5 Cross-Cutting Measure (DSM-5 CC), a novel comprehensive screening tool for psychiatric symptoms, to examine the relationship between objective and subjective measures of cognition as they relate to neuropsychiatric symptoms.

27 community dwelling, cognitively diverse older adults (78% female, mean age 71.9 ± 7) were enrolled in the Concerns about Memory Problems (CAMP) study. Inclusion criteria included the expressed concern about memory functioning by participants on a 5-item screener, while exclusion criteria were defined as previous diagnosis of neurodegenerative diseases and/or major stroke. All participants completed neuropsychological testing and study surveys including the DSM-5 CC. Participants completed Level 1 and all Level 2 (L2) forms of the DSM-5 CC. Spearman two-tailed non-parametric correlations and independent samples t-tests were conducted to examine the relationship between the DSM-5 CC and the 5-item subjective cognition screener, as well as the DSM-5 CC and objective cognition results.

Subjective measures of cognition, as measured by answers to the 5-item screening measure, were significantly associated with DSM-5 CC measures. Question 1 on the SCD screener which asks, “Compared to others your age, do you have difficulty with memory or thinking abilities?” was associated with anger (p=.033) and depression (p=.018) L2 forms. Question 3, “Do any difficulties with memory or thinking abilities make it difficult for you to do things in daily life?)” was associated with the L2 forms for somatic symptoms (p=.016) and repetitive thoughts and behaviors (p<.001). Objective measures of cognition from neuropsychological testing also correlated with DSM-5 CC sub-scores. Digits Backwards Length (DBL) correlated with DSM-5 CC Level 1 Sum (r= -.57, p=.002). DBL (r=-.59 p=.001) and Digits Backwards Total Correct (DBTC) (r=-.47, p=.013) associated with somatic symptoms L2 and sleep L2 (DBL: r=,-.45 p=.019; DBTC: r=-.39, p=.044). Category Naming (animals) was also associated with anxiety L2 (r=-.42, p=.030).

Subjective and objective measures of cognition were each related to sub-scores of the DSM-5 CC. Interestingly, the associations were largely non-overlapping. These results highlight the importance of considering a wide range of neuropsychiatric symptoms in the assessment of SCD and cognitive impairment. Findings contribute to the growing body of literature suggesting that neuropsychiatric symptoms should be studied in conjunction with cognitive symptoms among older adults as co-occurring phenomena. Future directions will need to include longitudinal studies that can examine the prodromal nature of SCD and neuropsychiatric symptoms for Alzheimer’s and other neurodegenerative disorders.

Childhood obesity is a serious health epidemic affecting the world today. Children who are obese earlier in life are more likely to stay obese and have an increased risk of poorer health outcomes later in life, such as diabetes and cardiovascular diseases. Obesity is also associated with deficits in executive function. Executive function (EF) is comprised of several distinct but interrelated abilities including working memory, planning, inhibition, and flexibility. Prior research suggests that obesity drives brain changes which implicate executive function structures. Our aim is to examine the relationship between childhood obesity and executive function in children with neurodevelopmental disorders.

These data are from an ongoing study on neural and behavioral phenotypes of executive functioning in children with developmental disabilities, primarily Attention-Deficit/Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD). Only study participants with complete BMI and BRIEF data were included in these analyses (n = 184). 134 representing (72.8%) of the participants were Male, 49 representing (26.6%) were Female, and 1 representing (.5%) were Gender nonconforming. 50 representing (27.2%) of the participants were between 8-9 years, 55 representing (29.9%) were between 10-11 years, and 80 representing (43.0%) were between 12-13 years. Average age was 11 years. 11 representing (6.0%) of the participants were underweight, 115 representing (62.5%) were healthy, 29 representing (15.8%) were overweight, and 29 representing (15.8%) were obese. Average BMI was 19.0, ranging from 13.2 to 36.3. 106 representing (57.6%) of the participants identified as White, 65 representing (35.3%) identified as BIPOC (2 Asian, 31 Hispanic/Latinx, 32 Black) and 13 representing (4.4%) identified as other/unspecified. 114 representing (61.9%) of the participants had a diagnosis of ADHD, ASD, or comorbid ASD and ADHD, 70 representing (38.1%) had a diagnosis of other. Average FSIQ-2 score was 106.98. Parents were asked to complete the Behavior Rating Inventory of Executive Function (BRIEF-2) and the Inhibit, Shift, Working Memory (WM), Planning, and Global Executive Composite (GEC) scales were used as the dependent measure in analyses. BMI (kg/mA2) was calculated based on CDC 2000 growth charts and classified into 4 mutually exclusive categories—underweight, healthy, overweight, and obese. There was a prediction that higher BMI would be associated with lower executive function.

A one-way ANOVA revealed a statistically significant difference between groups (F(3,180) = 3.649, p = .014). A Tukey post hoc test revealed more Shift problems in the obese group (74.55 ± 11.7) compared to the overweight group (65.79 ± 11.6, p = .026). There was no statistically significant difference between the underweight/healthy and obese groups (p = .999/p = .054). There was no statistically significant difference in mean T-scores for the Inhibit, WM, Planning, or GEC scales.

Childhood obesity and executive function deficits are significant risk factors for adult health outcomes. Obesity and elevated executive function T-scores for flexibility are related in a group of children with neurodevelopmental disorders. Future investigation will explore the role of cortical thickness and medication in these data.

Poststroke depression is common in those with stroke and is associated with worse functional outcomes, recurrence of stroke, and increased mortality. Poststroke depression has been most commonly associated with lesions of the frontal lobe and anterior regions of the brain, in addition to lesions in subcortical structures. Yet, there is also evidence that indicates the presence of depressive symptoms in those with infratentorial (including brainstem, pontine, and cerebellar) stroke, which may be mediated by alternative pathophysiologic mechanisms. Patients undergoing acute inpatient stroke rehabilitation may present with depressive symptoms that go unassessed or untreated throughout their recovery, including those with infratentorial stroke. The current objective was to evaluate the degree of depressive symptoms in patients with infratentorial stroke compared to those with supratentorial stroke.

Participants were admitted to an acute inpatient rehabilitation unit for stroke rehabilitation. Participants were enrolled in an ongoing clinical trial. Participants with recent infratentorial stroke (N = 7; 4 female; Median age = 69 years; Median education = 16 years) were administered the Patient Health Questionnaire-9 (PHQ-9) to assess symptoms of depression. Severity of depressive symptoms (PHQ-9 total score) in participants with infratentorial stroke was compared to those with supratentorial stroke (N = 19; 10 female; Median age = 69 years; Median education = 15 years) through Mann-Whitney U tests.

Participants with infratentorial stroke endorsed similar levels of depression to those with supratentorial stroke. Participants with infratentorial stroke endorsed overall mild depressive symptoms (Mean PHQ-9 score = 7.29; Median = 7), similar to those with supratentorial stroke (Mean PHQ-9 score = 7.11; Median = 6). Significant differences in depressive symptoms were not observed between participants with infratentorial and supratentorial stroke (p = .785).

Patients with infratentorial and supratentorial stroke may experience a similar degree of poststroke depression. Despite differences in suspected pathophysiologic mechanisms, infratentorial and supratentorial stroke appear to influence depressive symptoms to a similar extent. While future analyses with larger sample sizes are indicated, the current study indicates that patients with infratentorial and supratentorial stroke should be evaluated for depressive symptoms during the acute phases of recovery to inform treatment and potentially improve outcomes.

It has been posited that alcohol use may confound the association between greater concussion history and poorer neurobehavioral functioning. However, while greater alcohol use is positively correlated with neurobehavioral difficulties, the association between alcohol use and concussion history is not well understood. Therefore, this study investigated the cross-sectional and longitudinal associations between cumulative concussion history, years of contact sport participation, and health-related/psychological factors with alcohol use in former professional football players across multiple decades.

Former professional American football players completed general health questionnaires in 2001 and 2019, including demographic information, football history, concussion/medical history, and health-related/psychological functioning. Alcohol use frequency and amount was reported for three timepoints: during professional career (collected retrospectively in 2001), 2001, and 2019. During professional career and 2001 alcohol use frequency included none, 1-2, 3-4, 5-7 days/week, while amount included none, 12, 3-5, 6-7, 8+ drinks/occasion. For 2019, frequency included never, monthly or less, 2-4 times/month, 2-3 times/week, >4 times/week, while amount included none, 1-2, 3-4, 5-6, 7-9, 10+ drinks/occasion. Scores on a screening measure for Alcohol Use Disorder (CAGE) were also available at during professional career and 2001 timepoints. Concussion history was recorded in 2001 and binned into five groups: 0, 1-2, 3-5, 6-9, 10+. Depression and pain interference were assessed via PROMIS measures at all timepoints. Sleep disturbance was assessed in 2001 via separate instrument and with PROMIS Sleep Disturbance in 2019. Spearman’s rho correlations tested associations between concussion history and years of sport participation with alcohol use across timepoints, and whether poor health functioning (depression, pain interference, sleep disturbance) in 2001 and 2019 were associated with alcohol use both within and between timepoints.

Among the 351 participants (Mage=47.86[SD=10.18] in 2001), there were no significant associations between concussion history or years of contact sport participation with CAGE scores or alcohol use frequency/amount during professional career, 2001, or 2019 (rhos=-.072-.067, ps>.05). In 2001, greater depressive symptomology and sleep disturbance were related to higher CAGE scores (rho=.209, p<.001; rho=.176, p<.001, respectively), while greater depressive symptomology, pain interference, and sleep disturbance were related to higher alcohol use frequency (rho=.176, p=.002; rho=.109, p=.045; rho=.132, p=.013, respectively) and amount/occasion (rho=.215, p<.001; rho=.127, p=.020; rho=.153, p=.004, respectively). In 2019, depressive symptomology, pain interference, and sleep disturbance were not related to alcohol use (rhos=-.047-.087, ps>.05). Between timepoints, more sleep disturbance in 2001 was associated with higher alcohol amount/occasion in 2019 (rho=.115, p=.036).

Increased alcohol intake has been theorized to be a consequence of greater concussion history, and as such, thought to confound associations between concussion history and neurobehavioral function later in life. Our findings indicate concussion history and years of contact sport participation were not significantly associated with alcohol use cross-sectionally or longitudinally, regardless of alcohol use characterization. While higher levels of depression, pain interference, and sleep disturbance in 2001 were related to greater alcohol use in 2001, they were not associated cross-sectionally in 2019. Results support the need to concurrently address health-related and psychological factors in the implementation of alcohol use interventions for former NFL players, particularly earlier in the sport discontinuation timeline.

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

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

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

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

This study aimed to determine how modifiable risk factors, such as physical exercise and social support, and non-modifiable risk factors, such as genetic risk may affect cognitive function over time in older adults. As well, the study explored how changes in modifiable risk factors (i.e., increase in exercise) may affect cognitive function over time. This research question was shaped with the help of a patient partner team.

The study used UK Biobank data, and patient partners were involved in shaping research questions/goals. The UK Biobank study had participants complete comprehensive baseline assessments (2006-2010), with subgroups also completing repeat assessments (2012-2013), imaging assessments (2014-ongoing) and/or repeat imaging assessments (2019-ongoing; i.e., 2-4 data points per participant). Age, sex, education, ethnicity, and apolipoprotein E (APOE) e4 status (at least one e4 allele present) data were collected at baseline. Employment, physical activity, social support, and recent depressive symptom data were collected across timepoints. A Fluid intelligence score was obtained at each timepoint via a series of thirteen 1-pt. reasoning tasks (range: 0-13). Participants who did not complete cognitive testing at baseline and at least one other time point, and those with neurological conditions or events (e.g., stroke, epilepsy, dementia) were excluded (final N=17,409).

Multi-Level Modeling (with Maximum Likelihood) was utilized, with fluid intelligence as the primary outcome measure. We ran Model 1: fully unconditioned, Model 2: with time predictor in years (baseline= 0), and Model 3: with baseline physical activity, social support and APOE e-4 predictors and covariates (mean-centered as appropriate), time-varying physical activity and social support predictors, and interaction terms. Nonsignificant interaction terms were trimmed from Model 3 to facilitate interpretation.

Model 1 was significant (p<.001) with an intraclass correlation (ICC) of 0.64, suggesting that 64% of the total variance in fluid intelligence in this sample is due to interindividual differences. Model 2 revealed that the average fluid intelligence score at baseline mean age (55.85) was 6.79 and significantly decreased with each year increase since baseline. Results from Model 3 (trimmed) revealed that being male, white, and having at least a university degree were associated with higher score at baseline, while being older and having more recent depressive symptoms were associated with lower scores. Higher social support quality was associated with higher scores while higher social support quantity was associated with lower scores at baseline; however, higher social support quantity at baseline was associated with less decline in scores over time. Surprisingly, having at least one e4 allele was associated with higher scores. Engaging in more moderate physical activity was associated with lower scores at baseline, however, individuals who increased the length of their moderate physical activity sessions over time showed higher timepoint-specific fluid intelligence scores. Additional significant interactions will be elaborated.

Results suggest that increases in the length of moderate physical activity exercise sessions were associated with better cognitive function over time. Having better social support quality was also associated with better cognitive function, while higher social support quantity was associated with less cognitive decline over time. These findings suggest that positive lifestyle changes in older adulthood may slow cognitive decline.

Fetal alcohol spectrum disorder (FASD) is a life-long condition, and few interventions have been developed to improve the neurodevelopmental course in this population. Early interventions targeting core neurocognitive deficits have the potential to confer long-term neurodevelopmental benefits. Time-targeted choline supplementation is one such intervention that has been shown to provide neurodevelopmental benefits that emerge with age during childhood. We present a long-term follow-up study evaluating the neurodevelopmental effects of early choline supplementation in children with FASD approximately 7 years on average after an initial efficacy trial. In this study, we examine treatment group differences in executive function (EF) outcomes and diffusion MRI of the corpus callosum using the Neurite Orientation Dispersion and Density Index (NODDI) biophysical model.

The initial study was a randomized, double-blind, placebo-controlled trial of choline vs. placebo in 2.5- to 5-year-olds with FASD. Participants in this long-term follow-up study included 18 children (9 placebo; 9 choline) seen 7 years on average following initial trial completion. The mean age at follow-up was 11 years old. Diagnoses were 28% fetal alcohol syndrome (FAS), 28% partial FAS, and 44% alcohol-related neurodevelopmental disorder. The follow-up evaluation included measures of executive functioning (WISC-V Picture Span and Digit Span; DKEFS subtests) and diffusion MRI (NODDI).

Children who received choline early in development outperformed those in the placebo group across a majority of EF tasks at long-term follow-up (effect sizes ranged from -0.09 to 1.27). Children in the choline group demonstrated significantly better performance on several tasks of lower-order executive function skills (i.e., DKEFS Color Naming [Cohen's d = 1.27], DKEFS Word Reading [Cohen's d = 1.13]) and showed potentially better white matter microstructure organization (as indicated by lower orientation dispersion; Cohen's d = -1.26) in the splenium of the corpus callosum compared to the placebo group. In addition, when collapsing across treatment groups, higher white matter microstructural organization was associated with better performance on several EF tasks (WISC-V Digit Span; DKEFS Number Sequencing and DKEFS Word Reading).

These findings highlight long-term benefits of choline as a neurodevelopmental intervention for FASD and suggest that changes in white matter organization may represent an important target of choline in this population. Unique to this study is the use of contemporary biophysical modeling of diffusion MRI data in youth with FASD. Findings suggest this neuroimaging approach may be particularly useful for identifying subtle white matter differences in FASD as well as neurobiological responses to early intervention associated with important cognitive functions.

Cognitive deficits in first-episode psychosis (FEP) are well documented, particularly aspects of cognitive control, which is one of the primary hypothesized functions of the frontoparietal network (FPN). The clinical features of psychotic disorders are known to differ between men and women, but little work has systematically studied neurobiological differences between the sexes, particularly in FEP. The current study aimed to examine sexual dimorphisms in structural integrity of the frontoparietal network (FPN) and its role in cognitive control in FEP.

A total of 111 FEP patients (68 male, 43 female) and 55 healthy control participants (35 male, 20 female) from the Human Connectome Project for Early Psychosis underwent T1-weighted magnetic resonance imaging and neuropsychological testing were included in the study. Regions of interest (ROIs) included: left and right superior frontal gyrus, left and right middle frontal gyrus, left inferior frontal gyrus, left and right inferior parietal gyrus, right caudate and left thalamus. Using high-dimensional brain mapping procedures, surface shape of the caudate and thalamus was characterized using Large Deformation Diffeomorphic Metric Mapping, and cortical thickness of frontal and parietal regions was estimated using the FreeSurfer toolkit. Cognitive control was assessed using the Fluid Cognition Composite score from the NIH Toolbox Cognition Battery. Multivariate ANOVA models tested group differences, separated by sex, in cortical thickness ROIs, in addition to a whole-brain vertex-wise analysis. Vertex-wise statistical surface t-maps evaluated differences in subcortical surface shape, and Pearson correlations tested relationships between brain regions and Fluid Cognition performance.

Results of deep brain region comparisons between schizophrenia males (SCZM) and schizophrenia females (SCZF) groups revealed significant outward deformation at the tail of the right caudate and significant inward deformation along the dorsal aspects of the right caudate. Additionally, significant inward deformation in multiple nuclei of the left thalamus were revealed. Significant negative relationships between Fluid Cognition and the left superior/middle frontal gyrus (r = -0.24, p = 0.05) in the male FEP group were observed. Additionally, significant positive relationships between Fluid Cognition and left inferior frontal gyrus (r = 0.35, p = 0.02) and left inferior parietal gyrus (r = 0.35, p = 0.02) in the female FEP group were found.

Overall, findings revealed significant brain differences of the FPN in deep-brain structures only, including abnormal caudal and thalamic shape, in male FEP compared to female FEP, providing evidence of the importance to examine sex differences in deep-brain regions at the first episode. Differential brain relationships with cognitive control also highlight sex-specific presentations that may aid in clinical management and further characterization of the illness in early stages.

Recent studies have begun to explore the role of psychological resilience in pediatric mTBI recovery, with findings associating higher levels of resilience with shorter recovery and lower levels of resilience mediated by pre-injury anxiety and depression associated with persistent symptoms. The purpose of this study is to extend the current literature by further exploring the relationship between resilience, post-injury emotional changes, and length of recovery from pediatric mTBI. Based upon previous literature, we predicted that resilience would explain a unique portion of the variance in length of recovery above and beyond acute post-injury emotional symptoms in adolescents recovering from mTBI compared with orthopedic injured (OI) controls.

The current study pulled data from a larger project utilizing a prospective cohort design in two cohorts of high school student-athletes aged 14-18 (N = 32). Participants with mTBI (n = 17) or OI (n = 15) sustained during sport were recruited within 10 days of injury from a quaternary care setting. Participants completed a neuropsychological screening evaluation within one week of enrollment, including self-report rating scales of resilience (Connor-Davidson Resilience Scale-10; CD-RISC) and self- and parent-reported post-concussion symptoms (Post-Concussion Symptom Inventory, Second Edition; PCSI-2). Hierarchical regression analysis was performed with days from injury to recovery as the dependent variable. Predictors were entered in three steps: (1) group (mTBI/OI) and sex, (2) PCSI self- and parent-reported post-injury change in emotional symptoms, and (3) CD-RISC raw score. Bonferroni correction was utilized to control for multiple comparisons.

Group and sex did not provide significant prediction when entered into the first block of the model (p= .61). Introducing PCSI emotional ratings in the second block showed statistically significant improvement, F (2,26) = 5.12, p< .01), accounting for 31% of the variance in recovery length. Addition of the CD-RISC in the third block was not statistically significant (p=.59). Post hoc testing indicated parent ratings on the PCSI were significantly associated with recovery length t(32) = 3.16, p < .01, while self-reported ratings were not (p=.54).

Findings indicated that psychological resilience did not explain a unique portion of the variance in length of recovery above and beyond acute parent report of postinjury emotional symptoms in adolescents recovering from mTBI compared with orthopedic injured (OI) controls. Interestingly, sex, group (mTBI vs. OI), and self-reported acute postinjury emotional symptoms were not significant predictors of recovery length in this sample. Results highlight the significant role of acute changes in emotional symptoms in adolescents recovering from mTBI and OI in predicting length of recovery, as well as the importance of obtaining separate caregiver report. A more robust understanding of factors contributing to recovery from injury can help inform and improve preventive measures and treatment plants for those at risk or impacted; however, psychological resilience may not uniquely contribute to predicting length of recovery in acutely injured adolescents, limiting value added to the clinical exam. Future studies should explore the relationship between type of injury and recovery time in larger samples.

The association between adverse childhood experiences (ACEs) and adult depression and anxiety has been well described (Aafjes-van Doorn et al., 2020; Dolbier et al., 2021; Herzog & Schmahl, 2018). However, cognitive flexibility, as a potential moderating factor of this relationship, has been underreported (Kalia et al., 2021). We hypothesize that increased ACEs will be associated with increased symptoms of depression and anxiety, and cognitive flexibility will exhert a moderating role in this relationship.

Participants from the Evelyn F. McKnight University of Miami Frailty Registry were included in the study. 224 adults (Mage= 66.30, SD = 11.63; 59.4% female; 62.1% Hispanic/Latinx) without primary neurological disorders were recruited from University of Miami clinics and community centers. Participants completed a demographic questionnaire and neuropsychological evaluation including the Adverse Childhood Experiences inventory, Beck Depression Inventory, Beck Anxiety Inventory, and the Wisconsin Card Sorting Test (WCST). Current data were initially analyzed using descriptive statistics and correlations among variables. A series of hierarchical multiple linear regressions (HLR) were conducted to examine the effect that age has on cognitive flexibility (measured by number of perseverative errors on the WCST), as well as the association between number of ACEs endorsed on symptoms of depression and anxiety in late life.

Correlation analyses revealed a negative correlation between total ACE score and cognitive flexibility (r=-.16, p=0.03); a positive correlation between age and cognitive flexibility (r=0.19, p=0.01); and positive relationships between ACE score and both BDI (r=0.35, p<0.001) and BAI (r=0.28, p<0.001) scores. Correlations further revealed a negative correlation between cognitive flexibility and both BDI (r=-0.18, p=0.014) and BAI (r=-0.14, p=0.048) scores. A series of hierarchical multiple linear regressions revealed that total number of ACEs had a statistically significant effect on both depression (f=7.24, p<.001, ΔR2=0.072) and anxiety (f=4.57, p<.001, ΔR2=0.044) symptoms, in models adjusted for demographic correlates (i.e., age, sex, race, ethnicity). While the overall moderation model examining the effect of cognitive flexibility on the relationship between ACEs and psychopathology was significant (f=6.04, p<.001, ΔR2=0.191), the interaction was not significant (p=.4199). However, HLRs further revealed a statistically significant effect of age on cognitive flexibility (f=6.77, p=0.01, ΔR2=0.034).

Current findings support past research showing higher number of ACEs are associated with more symptoms of depression and anxiety in later life. However, cognitive flexibility did not moderate the relationship between ACEs and symptoms of depression and anxiery. This suggests cognitive flexibility might not play a significant role in the association between childhood trauma and symptoms of depression and anxiety in later life. Alternatively present results could be attributed to a small sample size, or the specific measure of cognitive flexibility used. This study expands on prior research highlighting the role of cognitive flexibility on age, with age serving as a prominent feature in the association between ACEs and adult depression and anxiety. Further research examining the role of cognitive flexibility in younger and middle years and its association with ACEs and psychopathology may provide unique insights on how to intervene earlier in the life course before cognitive flexibility begins to decline.

Even though the severity of HIV-associated neurocognitive disorders (HAND) has decreased with the introduction of combination antiretroviral therapy, mild forms of HAND remain prevalent. Many HIV-infected individuals live alone, so mild cognitive impairments are easily missed. It is important to check their neurocognitive and everyday functions during hospital visits; however, it is challenging for Japanese clinicians because many hospitals do not have enough clinical psychologists or neuropsychologists. Additionally, neuropsychological (NP) test results may not detect those mild cognitive impairments. A micro error has been given more attention as a new behavioral sign of the early stages of cognitive decline, especially among people with Mild Cognitive Impairment (MCI). The current study aimed to 1) develop a touch-panel HAND screening battery and 2) evaluate if the micro errors could differentiate individuals with HAND from their counterpart healthy individuals.

Forty HIV-infected men (age: 49.0±8.51 years old, education: 18.5±2.17 years) and 44 healthy men (age: 45.4±8.49 years old, education: 14.4±2.27 years) completed the touch-panel HAND screening battery which assessed six NP domains by seven subtests, everyday functions, and depression. A micro error is defined as a subtle action disruption or hesitation occurring immediately before making final actions. We evaluated the micro errors in short-term memory (STM) and long-term memory (LTM) of verbal learning tests (VLT).

Mann Whitney U tests revealed that the HIV+ group made significantly more micro errors on both STM (HIV+: 1.45±0.90 times, Healthy: 0.52±0.84 times) and LTM (HIV+: 1.85±0.73 times, Healthy: 1.29±0.71 times) than the healthy group (STM: W=1362, p< .001, Effect Size (EF)= .548; LTM: W=1199.5, p= .002, EF= .363). An independent samples T-test showed that the HAND group made significantly more micro errors than the non-HAND group (t=1.822, p= .038, ES= .595) on STM; moreover, the Asymptomatic Neurocognitive Impairment (ANI) group made significantly more micro errors than the healthy group (W=446, p< .001, ES= .689). On LTM, no significant micro error differences between HAND and non-HAND (W=184.5, p= .539, ES= -.189) nor between ANI and healthy group (W=327.5, p= .103, ES= .241) were found.

The present study suggests that a novel behavioral measure, micro errors, may be able to help detect even the mildest form of HAND, ANI. Given that the touch-panel HAND screening battery consists of NP and IADL tests, it is important to evaluate micro errors on these various measures. Additionally, the touch-panel screening battery requires minimal administrative staff involvement, which could be beneficial for busy HIV clinicians.

An accurate accounting of prior sport-related concussion (SRC) is critical to optimizing the clinical care of athletes with SRC. Yet, obtaining such a history via medical records or lifetime monitoring is often not feasible necessitating the use of self-report histories. The primary objective of the current project is to determine the degree to which athletes consistently report their SRC history on serial assessments throughout their collegiate athletic career.

Data were obtained from the NCAA-DoD CARE Consortium and included 1621 athletes (914 male) from a single Division 1 university who participated in athletics during the 2014-2017 academic years. From this initial cohort, 752 athletes completed a second-year assessment and 332 completed a third-year assessment. Yearly assessments included a brief self-report survey that queried SRC history of the previous year. Consistency of self-reported SRC history was defined as reporting the same number of SRC on subsequent yearly evaluation as had been reported the previous year.

For every year of participation, the number of SRC reported on the baseline exam (Reported) and the number of SRC recorded by athletes and medical staff during the ensuing season (Recorded) were tabulated. In a subsequent year, the expected number of SRC (Expected) was computed as the sum of Reported and Recorded. For participation years in which Expected could be computed, the reporting deviation (RepDev) gives the difference between the number of SRCs which were expected to be reported at a baseline exam based on previous participation year data and the number of SRCs which was actually reported by the athlete or medical record during the baseline exam. The reporting deviation was computed only for those SRC that occurred while the participant was enrolled in the current study (RepDevSO). Oneway intraclass correlations (ICC) were computed between the expected and reported numbers of SRC.

341 athletes had a history of at least one SRC and 206 of those (60.4%) had a RepDev of 0. The overall ICC for RepDev was 0.761 (95% CI 0.73-0.79). The presence of depression (ICC 0.87, 95% CI 0.79-0.92) and loss of consciousness (ICC 0.80, 95% CI 0.720.86) were associated with higher ICCs compared to athletes without these variables. Female athletes demonstrated higher self-report consistency (ICC 0.82, 95% CI 0.79-0.85) compared to male athletes (ICC 0.72, 95% CI 0.68-0.76). Differences in the classification of RepDev according to sex and sport were found to be significant (x2=77.6, df=56, p=0.03). The sports with the highest consistency were Women’s Tennis, Men’s Diving, and Men’s Tennis with 100% consistency between academic years. Sports with the lowest consistency were Women’s Gymnastics (69%), Men’s Lacrosse (70%), and Football (72%). 96 athletes had at least one study-only SRC in the previous year and 69 of those (71.9%) had a RepDevSO of 0 (ICC 0.673, 95% CI 0.64-0.71).

Approximately 40% of athletes do not consistently report their SRC history, potentially further complicating the clinical management of SRC. These findings encourage clinicians to be aware of factors which could influence the reliability of self-reported SRC history.

Non-motor symptoms, such as mild cognitive impairment and dementia, are an overwhelming cause of disability in Parkinson’s disease (PD). While subthalamic nucleus deep brain stimulation (STN DBS) is safe and effective for motor symptoms, declines in verbal fluency after bilateral DBS surgery have been widely replicated. However, little is known about cognitive outcomes following unilateral surgeries.

We enrolled 31 PD patients who underwent unilateral STN-DBS in a randomized, cross-over, double-blind study (SUNDIAL Trial). Targets were chosen based on treatment of the most symptomatic side (n = 17 left hemisphere and 14 right hemisphere). All participants completed a neuropsychological battery (FAS/CFL, AVLT, DKEFS Color-Word Test) at baseline, then 2, 4, and 6 months post-surgery. Outcomes include raw scores for verbal fluency, immediate and delayed recall, and DKEFS Color-Word Inhibition trial (Trial 3) completion time. At 2, 4, and 6 months, the neurostimulation type (directional versus ring mode) was randomized for each participant. We compared baseline scores for all cognitive outcome measures using Welch’s two-sample t-tests and used linear mixed effects models to examine longitudinal effects of hemisphere and stimulation on cognition. This test battery was converted to a teleneuropsychology administration because of COVID-19 mid-study, and this was included as a covariate in all statistical models, along with years of education, baseline cognitive scores, and levodopa equivalent medication dose at each time point.

At baseline, patients who underwent left hemisphere implants scored lower on verbal fluency than right implants (t(20.66) = -2.49, p = 0.02). There were not significant differences between hemispheres in immediate recall (p = 0.57), delayed recall (p = 0.22), or response inhibition (p = 0.51). Post-operatively, left STN DBS patients experienced significant declines in verbal fluency over the study period (p = 0.02), while patients with right-sided stimulation demonstrated improvements (p < .001). There was no main effect of stimulation parameters (directional versus ring) on verbal fluency, memory, or inhibition, but there was a three-way interaction between time, stimulation parameters, and hemisphere on inhibition, such that left STN DBS patients receiving ring stimulation completed the inhibition trial faster (p = 0.035). After surgery, right STN DBS patients displayed faster inhibition times than patients with left implants (p = 0.015).

Declines in verbal fluency after bilateral stimulation are the most commonly reported cognitive sequalae of DBS for movement disorders. Here we found group level declines in verbal fluency after unilateral left STN implants, but not right STN DBS up to 6 months after surgery. Patients with right hemisphere implants displayed improvements in verbal fluency. Compared to bilateral DBS, unilateral DBS surgery, particularly in the right hemisphere, is likely a modifiable risk factor for verbal fluency declines in patients with Parkinson’s disease.

Patients and their families often ask clinicians to estimate when full-time care (FTC) will be needed after Alzheimer's Disease (AD) is diagnosed. Although a few algorithms predictive algorithms for duration to FTC have been created, these have not been widely adopted for clinical use due to questions regarding precision from limited sample sizes and lack of an easy, user friendly prediction model. Our objective was to develop a clinically relevant, data-driven predictive model using machine learning to estimate time to FTC in AD based on information gathered from a) clinical interview alone, and b) clinical interview plus neuropsychological data.

The National Alzheimer's Coordinating Center dataset was used to examine 3,809 participants (M age at AD diagnosis = 76.05, SD = 9.76; 47.10% male; 87.20% Caucasian) with AD dementia who were aged >50 years, had no history of stroke, and not dependent on others for basic activities of daily living at time of diagnosis based on qualitative self or informant report. To develop a predictive model for time until FTC, supervised machine learning algorithms (e.g., gradient descent, gradient boosting) were implemented. In Model 1, 29 variables captured at the time of AD diagnosis and often gathered in a clinical interview, including sociodemographic factors, psychiatric conditions, medical history, and MMSE, were included. In Model 2, additional neuropsychological variables assessing episodic memory, language, attention, executive function, and processing speed were added. To train and test the algorithm(s), data were split into a 70:30 ratio. Prediction optimization was examined via cross validation using 1000 bootstrapped samples. Model evaluation included assessment of confusion matrices and calculation of accuracy and precision.

The average time to requiring FTC after AD diagnosis was 3.32 years (Range = 0.53-14.57 years). For the clinical interview only model (Model 1), younger age of onset, use of cholinesterase inhibitor medication, incontinence, and apathy were among the clinical variables that significantly predicted duration to FTC, with the largest effects shown for living alone, a positive family history of dementia, and lower MMSE score. In Model 2, the clinical predictors remained significant, and lower Boston Naming Test and Digit-Symbol Coding scores showed the largest effects in predicting duration to FTC among the neuropsychological measures. Final prediction models were further tested using five randomly selected cases. The average estimated time to FTC using the clinical interview model was within an average of 5.2 months of the recorded event and within an average of 5.8 months for the model with neuropsychological data.

Predicting when individuals diagnosed with AD will need FTC is important as the transition often carries significant financial costs related to caregiving. Duration to FTC was predicted by clinical and neuropsychological variables that are easily obtained during standard dementia evaluations. Implementation of the model for prediction of FTC in cases showed encouraging prognostic accuracy. The two models show promise as a first step towards creation of a user friendly prediction calculator that could help clinicians better counsel patients on when FTC after AD diagnosis may occur, though the development of separate models for use in more diverse populations will be essential.

Among people with HIV (PWH), the apolipoprotein e4 (APOE-e4) allele, a genetic marker associated with Alzheimer’s disease (AD), and self-reported family history of dementia (FHD), considered a proxy for higher AD genetic risk, are independently associated with worse neurocognition. However, research has not addressed the potential additive effect of FHD and APOE-e4 on global and domain-specific neurocognition among PWH. Thus, the aim of the current investigation is to examine the associations between FHD, APOE-e4, and neurocognition among PWH.

283 PWH (Mage=50.9; SDage=5.6) from the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) study completed comprehensive neuropsychological and neuromedical evaluations and underwent APOE genotyping. APOE status was dichotomized into APOE-e4+ and APOE-e4-. APOE-e4+ status included heterozygous and homozygous carriers. Participants completed a free-response question capturing FHD of a first- or second-degree relative (i.e., biologic parent, sibling, children, grandparent, grandchild, uncle, aunt, nephew, niece, half-sibling). A dichotomized (yes/no), FHD variable was used in analyses. Neurocognition was measured using global and domain-specific demographically corrected (i.e., age, education, sex, race/ethnicity) T-scores. t-tests were used to compare global and domain-specific demographically-corrected T-scores by FHD status and APOE-e4 status. A 2x2 factorial analysis of variance (ANOVA) was used to model the interactive effects of FHD and APOE-e4 status. Tukey’s HSD test was used to follow-up on significant ANOVAs.

Results revealed significant differences by FHD status in executive functioning (t(281)=-2.3, p=0.03) and motor skills (t(278)=-2.0, p=0.03) such that FHD+ performed worse compared to FHD-. Differences in global neurocognition by FHD status approached significance (t(281)=-1.8, p=.069). Global and domain-specific neurocognitive performance were comparable among APOE-e4 carriers and noncarriers (ps>0.05). Results evaluating the interactive effects of FHD and APOE-e4 showed significant differences in motor skills (F(3)=2.7, p=0.04) between the FHD-/APOE-e4+ and FHD+/APOE-e4- groups such that the FHD+/APOE-e4- performed worse than the FHD-/APOE-e4+ group (p=0.02).

PWH with FHD exhibited worse neurocognitive performance within the domains of executive functioning and motor skills, however, there were no significant differences in neurocognition between APOE-e4 carriers and noncarriers. Furthermore, global neurocognitive performance was comparable across FHD/APOE-e4 groups. Differences between the FHD-/APOE-e4+ and FHD+/APOE-e4- groups in motor skills were likely driven by FHD status, considering there were no independent effects of APOE-e4 status. This suggests that FHD may be a predispositional risk factor for poor neurocognitive performance among PWH. Considering FHD is easily captured through self-report, compared to blood based APOE-e4 status, PWH with FHD should be more closely monitored. Future research is warranted to address the potential additive effect of FHD and APOE-e4 on rates of global and domain-specific neurocognitive decline and impairment over time among in an older cohort of PWH, where APOE-e4 status may have stronger effects.

This study seeks to describe the context and contents of YouTube videos featuring non-evidence-based practices (NEBPs) for autism spectrum disorder, including recent fad usage of transcranial magnetic stimulation.

A sample search of autism intervention-related YouTube videos was conducted to reflect the experience of caregivers researching autism intervention information on the internet. Exclusion criteria was applied to create a preliminary dataset. The videos were categorized into general evidence-based practice (EBP), non-evidence-based practice (NEBP), and both EBP and NEBP. The NEBP-related videos were then qualitatively described using a priori codes based on the literature regarding signs of pseudoscience, as well as an iteratively developed codebook through a constant comparative method between two independent coders.

Total videos from the YouTube search using the query "Autism Treatment" were capped at 150 videos. Total videos in English were 138. Total discrete videos (non-repeated) were 134. Total NEBP-related discrete videos were 62 (46% of final dataset); Total EBP-related videos were 38 (28.3% of final dataset); and total videos containing both EBP and NEBP as subject matter were 25 (18.6% of final dataset). Of the NEBP-related in the final dataset, the most frequent NEBP which occurred was stem cell therapy (n=26), followed by the Son-Rise program (n=13), Cannabis/marijuana (n=5), transcranial magnetic stimulation/magnetic e-resonance therapy (n=5), neurofeedback (n=1), brain rehabilitation (n=1), suramin (n=2), fecal transplants (n=2), Hyperbaric Oxygen therapy (n=1), Ayurvedic medicine (n=1), virtual reality (n=1), and others. The constant comparative method of coding yielded results specific to videos about NEBPs in autism, including: statements declaring a treatment will be effective, a banner on the YouTube page indicating if the channel is from a reputable source, a parent testimonial, a parent or caregiver display of emotion with respect to treatment efficacy, statements regarding pre-intervention repetitive or challenging behaviors, statements regarding demonstrated effects of the treatment, statements of a definitive cause of autism, statements regarding the severity of the autism in the treatment subject, specific words in reference to autism, including "disease", "toxin", or "inflammation", discussion of the financial aspect of the treatment, and videos with both high and low production values.

The likelihood of a caregiver encountering and watching videos containing NEBP-related material when using a general query to search the internet for information on autism intervention is high. Additionally, videos regarding NEBPs have more engagements (e.g., likes, comments, shares) than videos regarding EBPs, oftentimes by multitudes. The information contained within videos in which an NEBP is the subject aligns with pre-established warning signs for pseudoscience for autism interventions, however this study also contributes new warning signs through the construction of the iterative codebook. Specifically, statements about treatment efficacy in the absence of cited research, an emotional parent testimony about the individual with autism's experience with the NEBP therapy, statements regarding behavioral improvements linked to participation in the therapy oftentimes in the context of inflated claims, and clear and confident statements regarding the cause of autism with no cited research.

Self-regulation is typically operationalized in neuropsychological assessment through self-report scales and measures of attention and executive functioning. However, there have been mixed findings on the relationships between self-report measures and physiological and performance-based measures believed to represent self-regulation. Poorer self-regulation is related to an array of negative behavioral and health-related outcomes. Therefore, it is critical to understand the process of self-regulation and the relationships between measures neuropsychologists use to assess it. The current study aims to investigate the relationships between four purported measures of self-regulation: resting-state high-frequency heart rate variability (HRV; a stable individual difference variable that reflects parasympathetic capacity for adapting to changing environmental demands), behavioral performance on the Delis-Kaplan Executive Function System (D-KEFS) and the Conners Continuous Performance Test - 3rd Edition (CPT-3), and trait self-control on the Brief Self-Control Scale (BSCS). It was hypothesized that physiological and behavioral self-regulation variables would predict the BSCS, such that higher resting HRV and better performance on the cognitive measures would predict higher self-reported self-control.

Thirty-five healthy adults (Age M = 29.80, SD =8.52, 45.7% female) recruited from the community completed the BSCS, CPT-3, and D-KEFS as part of a larger battery. Participants also completed a 10-minute eyes-open resting condition during electrocardiogram recording. High-frequency power (0.15 - 0.4 Hz) was extracted and used to operationalize resting HRV. Linear regression was used to test the predictive relationships between the BSCS total score, resting HRV, CPT-3 scores, and a residualized executive functioning score from the D-KEFS that controls for non-executive lower-order cognitive processes.

Regression analyses indicated that neither the D-KEFS composite, the CPT-3 indices, nor resting HRV were related to the BSCS. Resting HRV predicted the CPT-3 Hit Reaction Time (HRT; B = -2.97, p < .05) and HRT Standard Deviation (HRT SD; B = -4.55, p < .05). Resting HRV was unrelated to the D-KEFS executive composite score. CPT-3 performance variables and D-KEFS composite score were also unrelated to one another.

Results showed that the BSCS was unrelated to resting HRV, CPT-3, and D-KEFS performance. However, higher resting HRV was related to faster and more consistent responding on the CPT-3. These findings contradict previous research showing associations between the BSCS and performance on executive functioning measures. The relationship between resting HRV and reaction time on the CPT-3 is generally consistent with literature that suggests that higher resting HRV is associated with better cognitive performance. Although the association between resting HRV and executive functioning was not significant in this modest sample, it was comparable to that reported in a recent meta-analysis. Overall, despite limitations related to the small sample size, the results raise questions regarding the construct validity of common neuropsychological indices of self-regulation. Further research is needed to clarify the nature of the self-regulation construct and the relation of neuropsychological measures of behavioral self-regulation to physiological and self-report indices.

Definitive diagnosis of Alzheimer’s disease (AD) is often unavailable, so clinical diagnoses with some degree of inaccuracy are often used in research instead. When researchers test methods that may improve clinical accuracy, the error in initial diagnosis can penalize predictions that are more accurate to true diagnoses but differ from clinical diagnoses. To address this challenge, the current study investigated the use of a simple bias adjustment for use in logistic regression that accounts for known inaccuracy in initial diagnoses.

A Bayesian logistic regression model was developed to predict unobserved/true diagnostic status given the sensitivity and specificity of an imperfect reference. This model considers cases as a mixture of true (with rate = sensitivity) and false positives (rate = 1 - specificity) while controls are mixtures of true (rate = specificity) and false negatives (rate = 1 - sensitivity). This bias adjustment was tested using Monte Carlo simulations over four conditions that varied the accuracy of clinical diagnoses. Conditions utilized 1000 iterations each generating a random dataset of n = 1000 based on a true logistic model with an intercept and three arbitrary predictors. Coefficients for parameters were randomly selected in each iteration and used to produce a set of two diagnoses: true diagnoses and observed diagnoses with imperfect accuracy. Sensitivity and specificity of the simulated clinical diagnosis varied with each of the four conditions (C): C1 = (0.77, 0.60), C2 = (0.87, 0.44), C3 = (0.71, 0.71), and C4 = (0.83, 0.55), which are derived from published values for clinical AD diagnoses against autopsy-confirmed pathology. Unadjusted and bias-adjusted logistic regressions were then fit to the simulated data to determine the models’ accuracy in estimating regression parameters and prediction of true diagnosis.

Under all conditions, the bias-adjusted logistic regression model outperformed its unadjusted counterpart. Root mean square error (the variability of estimated coefficients around their true parameter values) ranged from 0.23 to 0.79 for the unadjusted model versus 0.24 to 0.29 for the bias-adjusted model. The empirical coverage rate (the proportion of 95% credible intervals that include their true parameter) ranged from 0.00 to 0.47 for the unadjusted model versus 0.95 to 0.96 for the bias-adjusted model. Finally, the bias-adjusted model produced the best overall diagnostic accuracy with correct classification of true diagnostic values about 78% of the time versus 62-72% without adjustment.

Results of this simulation study, which used published AD sensitivity and specificity statistics, provide evidence that bias-adjustments to logistic regression models are needed when research involves diagnoses from an imperfect standard. Results showed that unadjusted methods rarely identified true effects with credible intervals for coefficients including the true value anywhere from never to less than half of the time. Additional simulations are needed to examine the bias-adjusted model’s performance under additional conditions. Future research is needed to extend the bias adjustment to multinomial logistic regressions and to scenarios where the rate of misdiagnosis is unknown. Such methods may be valuable for improving detection of other neurological disorders with greater diagnostic error as well.

Although performance validity is critical in determining the quality and accuracy of test data, research suggests not all neuropsychologists incorporate performance validity tests (PVTs) in dementia evaluations (McGuire et al., 2019). Furthermore, well-validated embedded measures, such as Reliable Digit Span (RDS) from the Wechsler Adult Intelligence Scale - Fourth Edition (WAIS-IV), have evidenced an unusually high number of failures in a dementia population when utilizing typical clinical cut-offs (Zenisek et al., 2016). The objective of this study is to explore performance on embedded PVTs among older adults who have a major neurocognitive disorder (MND), specifically among Alzheimer disease (AD) and non-AD patients.

Archival data from outpatient neuropsychological evaluations were analyzed. All participants were at least 65 years of age, diagnosed with a MND, and completed Digit Span from the WAIS-IV, Brief Visuospatial Memory Test- Revised (BVMT-R), and Hopkins Verbal Learning Test-Revised (HVLT-R). In total, 84 participants, aged 67-96 (M=78.44, SD=6.11) with 6-20 years of education (M=13.47, SD=3.30), were included. The sample predominantly identified as female (n=60) and White (n=61). More individuals were diagnosed with AD (n=50) than non-AD dementia (n=34). Common non-AD diagnoses included Vascular (n=44), Lewy bodies (n=8), and Parkinson’s (n=2) dementias. Fisher’s Exact Test of Independence was used to account for the smaller sample to determine if there was a nonrandom association between diagnosis (AD vs non-AD) and embedded PVT performance: RDS< 7, BVMT-R Hits<4, BVMT-R Recognition Discrimination (RD) < 4, and HVLT-R RD < 5 (Bailey et al., 2018).

The Fisher’s Exact Test of Independence revealed a statistically significant association between neurocognitive diagnosis and RDS (p= .008), BVMT-R RD (p<.001), and HVLT-R RD (p<.001). BVMT-R Hits were not significantly associated with diagnosis (p = 0.10). These measures evidenced opposite patterns with RDS demonstrating a higher percentage of fails for the non-AD (63%) versus AD (20%) group. The AD group had a higher percentage of fails for BVMT-R RD (58% for AD and 13% for non-AD groups) and HLVT-R RD (66% for AD and 29% for non-AD group).

The current study suggests performance on embedded PVTs vary across MND diagnoses. Individuals with a non-AD diagnosis were more likely to fail RDS than those with AD. This is likely secondary to attention and working memory demands that are mediated by the frontal-subcortical networks, which are less impacted by AD pathology (Bonelli & Cummings, 2022; Loring et al., 2016). In contrast, AD patients were more likely to fail embedded PVTs within memory measures, which are largely mediated by the mesial temporal cortex associated with AD (Pluta, 2022). These results suggest embedded measures operate differently based on diagnosis and neuroanatomical systems affected. The clinical relevance of these findings includes potentially using alternative PVTs or different cut-offs based on diagnosis. Future research should attempt to better delineate more appropriate, as well as time efficient, PVTs among the dementia population.

Cognitive difficulties are amongst the most frequently reported sequelae following COVID-19 infection, even in those experiencing mild to moderate illness (Matos et al., 2021). Recent research has identified patterns of diminished cognitive performance on tests of memory and executive functioning in COVID-19 cases; however, the etiology of neurocognitive difficulties remains unclear (Delgado-Alonso et al., 2022). Emerging evidence has identified moderate associations between decreased performance on neuropsychological tests of memory and elevated anxiety and depression symptom reporting in COVID-19 patients. Similar associations are well-established in the literature in persons with anxiety and depression disorders, warranting further investigation as to whether mental health variables such as internalizing symptom severity may moderate the association between COVID-19 illness and cognitive difficulties. This study examined how internalizing symptoms as indexed by depression and anxiety symptom scales may differentially influence performance on neuropsychological tests of memory between persons who have and have not had COVID-19.

In this cross-sectional study, 104 adults aged 19-80, were recruited in Ontario and British Columbia, Canada; 84 adults met inclusion criteria and participated in neuropsychological testing. There were 40 participants who tested positive for COVID-19 infection (N=44 with no suspected exposures or confirmed diagnosis of COVID-19). Participants had no history of dementia, mild cognitive impairment, or other known neurological disorder. Anxiety and depression symptoms were measured using the Generalized Anxiety Disorder-7 (GAD-7) and Center for Epidemiologic Studies Depression Scale (CES-D) via self-report on Qualtrics. Memory encoding and delayed recognition performance were assessed using the Hopkins Verbal Learning Test Revised (HVLT-R) and the Neuropsychological Assessment Battery Shape Learning subtest (NAB-SL). To test for potential moderating effects of anxiety and depression symptoms on the association between COVID-19 infection status and memory performance, a series of multiple linear regressions were conducted. Age and sex were included as covariates in all analyses.

Moderation analyses revealed that the interaction between COVID-19 infection and anxiety symptoms accounted for a significant portion of variance in both HVLT-R recognition (B= -0.78, SE= 0.34, p<0.05) and NAB-SL delayed recognition scores (B= -0.83, SE= 0.35, p<0.05). Simple slopes analyses revealed that among participants who tested positive for COVID-19 infection, higher GAD-7 scores were associated with lower verbal and visual recognition scores. A similar interaction was observed between COVID-19 and depressive symptoms in accounting for variance in NAB-SL delayed recognition scores, however, for that model the threshold of p=0.05 was not met in our small sample (p=0.07).

Findings demonstrate that anxiety symptom severity had a moderating effect on the impact of COVID-19 on delayed retrieval of verbal and visual information from memory. Future work in a larger sample is needed to further elucidate the potential moderating role of depression on memory in COVID-19 positive persons, as the current work suggests that depression symptoms could have a similar impact as anxiety. Further identifying the relationships between key modifiable psychological factors such as anxiety and memory following COVID-19 infection will provide insight into potential interventions to minimize the negative effects of internalizing symptoms on long-term cognitive outcomes.