Symptoms and cognition are both utilized as indicators of recovery following pediatric concussion, yet their interrelationship is not well understood. This study aimed to investigate: 1) the association of post-concussion symptom burden and cognitive outcomes (processing speed and executive functioning [EF]) at 4 and 12 weeks after pediatric concussion, and 2) the moderating effect of sex on this association.

This prospective, multicenter cohort study included participants aged 5.00–17.99 years with acute concussion presenting to four Emergency Departments of the Pediatric Emergency Research Canada network. Five processing speed and EF tasks and the Post-Concussion Symptom Inventory (PCSI; symptom burden, defined as the difference between post-injury and retrospective [pre-injury] scores) were administered at 4 and 12 weeks post-concussion. Generalized least squares models were conducted with task performances as dependent variables and PCSI and PCSI*sex interaction as the main predictors, with important pre-injury demographic and injury characteristics as covariates.

311 children (65.0% males; median age = 11.92 [IQR = 9.14–14.21 years]) were included in the analysis. After adjusting for covariates, higher symptom burden was associated with lower Backward Digit Span (χ2 = 9.85, p = .043) and Verbal Fluency scores (χ2 = 10.48, p = .033) across time points; these associations were not moderated by sex, ps ≥ .20. Symptom burden was not associated with performance on the Coding, Continuous Performance Test, and Color-Word Interference scores, ps ≥ .17.

Higher symptom burden is associated with lower working memory and cognitive flexibility following pediatric concussion, yet these associations were not moderated by sex. Findings may inform concussion management by emphasizing the importance of multifaceted assessments of EF.

Although remote neuropsychological assessments have become increasingly common, current research on the reliability and validity of scores obtained from remote at-home assessments are sparse. No studies have examined remote at-home administration of the National Alzheimer’s Coordinating Center (NACC) Uniform Data Set (UDS) even though this battery is being used to track over 45,000 participants over time. This study aimed to determine whether remote UDS scores can be combined with in-person data by assessing whether rates of score changes over time (i.e., reliability) differed by modality and whether remote and in-person scores converge (i.e., validity).

Data for UDS visits conducted from 09/2005 to 12/2021 from 43 Alzheimer’s Disease Research Centers were examined. We identified 311 participants (254 cognitively unimpaired, 7 impaired - not mild cognitive impairment, 25 mild cognitive impairment, 25 dementia) who completed 2 remote UDS visits 0.868 years apart (SD = 0.200 years). First, initial remote scores were correlated with most recent in-person scores. Second, we examined whether rates of change differed between remote and in-person assessments. Repeated-measure one-way ANOVA were used to compare rates calculated from the same individual from remote versus inperson assessments. We additionally identified a demographically- and visit-number-matched group of 311 participants with in-person UDS visits given that all remote visits occurred after in-person visits; one-way ANOVAs were used to compare remote rates to rates from in-person assessments from the matched in-person group. Finally, accuracy of remote scores were assessed by quantifying the difference between the actual remote scores and predicted scores based on repeated in-person assessments. These residual values were then divided by the maximum score to form error rates.

Remote UDS score on MoCA-blind, Craft story immediate and delayed recall, digits forward, digits backward, phonemic fluency (F, L, F + L), and semantic fluency (animals, vegetables, animals + vegetables) were all highly correlated (all ps < 0.001) with scores obtained from preceding in-person assessments. At the group level, within-subject comparisons between remote and in-person rates of change were not significantly different for 7/11 tests; between-subject comparisons were not significantly different for 10/11 tests. Vegetable fluency had slightly reduced rates of change with remote assessment compared to inperson assessments. Critically, remote scores were consistent with predicted scores based on the trajectory of each subject’s in-person assessments with group mean error rates ranging from 0.7% (Craft Delayed Recall) to 3.9% (Phonemic fluency - F).

Our results demonstrate adequate reliability and convergent validity for remotely administered verbally based tests from the NACC UDS battery. Importantly, our findings provide some support for combining remote and in-person scores for studies that transitioned to remote testing due to COVID-19. However, future research is needed for tests with visual stimuli that assess visual memory, visuospatial function, and aspects of executive function.

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

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.

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.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary form of cerebral small vessel disease leading to early cerebrovascular changes. These changes result from mutations in the NOTCH3 gene that cause progressive accumulations of granular osmiophilic material (GOM) deposits, thickening arterial walls and reducing or restricting blood flow in the brain. The clinical presentation of CADASIL is characterized by migraines with aura, early and recurrent strokes, progressive cognitive impairment, and psychiatric disturbances. CADASIL is rare but frequently underrecognized or misdiagnosed. A genetic condition with a 50% risk of inheritance from an affected parent, the gold standard for diagnosis is genetic testing to determine the presence of mutations in the NOTCH3 gene. This presentation aims to familiarize neuropsychologists with the condition of CADASIL through a unique case study highlighting important psychological, social, and ethical considerations raised by genetic testing.

This case study presents a 67-year-old, right-handed, married female diagnosed with CADASIL who was referred for neuropsychological evaluation of cognitive function and low mood concerns following multiple ischemic events.

Results revealed severe cognitive deficits in domains of attention, learning, and memory. Her superior verbal abilities and executive function remained largely intact. Assessment of mood revealed elevations in symptoms of depression and anxiety. The patient was aware of CADASIL in her father, paternal aunt, and younger brother, but elected to forego any genetic testing to confirm whether she had the condition until she experienced a stroke at age 61. She has two adult children who have also elected to forego testing and currently remain asymptomatic. Cognitive profile, mood disturbances, and patient perspectives on refraining from pre-symptomatic genetic testing for CADASIL diagnosis will be discussed.

Aspects of this case are consistent with a small body of literature evidencing distinct psychological, emotional, and social challenges among families carrying genetic risk of CADASIL. While providing an example of an often underrecognized neurological disorder with which neuropsychologists should be familiar, this case uniquely raises ethical questions relevant to care providers and current treatment guidelines regarding genetic testing among families carrying highly heritable neurological conditions. In particular, personal ethical challenges around deciding to pursue or forego pre-symptomatic testing, and implications for family planning, highlight the importance of genetic counseling for affected families.

Existing research has demonstrated that neuropsychiatric/behavioral-psychological symptoms of dementia (BPSD) frequently contribute to worse prognosis in patients with neurodegenerative conditions (e.g., increased functional dependence, worse quality of life, greater caregiver burden, faster disease progression). BPSD are most commonly measured via the Neuropsychiatric Inventory (NPI), or its briefer, informant-rated questionnaire (NPI-Q). Despite the NPI-Q’s common use in research and practice, there is disarray in the literature concerning the NPI-Q’s latent structure and reliability, possibly related to differences in methods between studies. Also, hierarchical factor models have not been considered, even though such models are gaining favor in the psychopathology literature. Therefore, we aimed to compare different factor structures from the current literature using confirmatory factor analyses (CFAs) to help determine the best latent model of the NPI-Q.

This sample included 20,500 individuals (57% female; 80% White, 12% Black, 8% Hispanic), with a mean age of 71 (SD = 10.41) and 15 average years of education (SD = 3.43). Individuals were included if they had completed an NPI-Q during their first visit at one of 33 Alzheimer Disease Research Centers reporting to the National Alzheimer Coordinating Center (NACC). All CFA and reliability analyses were performed with lavaan and semTools R packages, using a diagonally weighted least squares (DWLS) estimator. Eight single-level models using full or modified versions of the NPI-Q were compared, and the top three were later tested in bifactor form.

CFAs revealed all factor models of the full NPI-Q demonstrated goodness of fit across multiple indices (SRMR = 0.039-0.052, RMSEA = 0.025-0.029, CFI = 0.973-0.983, TLI = 0.9670.977). Modified forms of the NPI-Q also demonstrated goodness of fit across multiple indices (SRMR = 0.025-0.052, RMSEA = 0.0180.031, CFI = 0.976-0.993, TLI = 0.968-0.989). Top factor models later tested in bifactor form all demonstrated consistently stronger goodness of fit regardless of whether they were a full form (SRMR = 0.023-0.035, RMSEA = 0.015-0.02, CFI = 0.992-0.995, TLI = 0.985-0.991) or a modified form (SRMR = 0.023-0.042, RMSEA = 0.015-0.024, CFI = 0.985-0.995, TLI = 0.9770.992). Siafarikas and colleagues’ (2018) 3-factor model demonstrated the best fit among the full-form models, whereas Sayegh and Knight’s (2014) 4-factor model had the best fit among all single-level models, as well as among the bifactor models.

Although all factor models had adequate goodness of fit, the Sayegh & Knight 4-factor model had the strongest fit among both single-level and bifactor models. Furthermore, all bifactor models had consistently stronger fit than single-level models, suggesting that BPSD are best theoretically explained by a hierarchical, non-nested framework of general and specific contributors to symptoms. These findings also inform consistent use of NPI-Q subscales.

Risk factors that contribute to brain pathology and cognitive decline among older adults include demographic factors (e.g., age, educational attainment), genetic factors, health factors, and depression (Plassman et al., 2010). Variability within an individual’s performance across cognitive tasks is referred to as dispersion (Hultsch et al., 2002), which appears sensitive to subtle cognitive impairments associated with neurodegenerative pathology in older adults (Bangen et al., 2019; Kälin et al., 2014). Thaler and colleagues (2015) found that dispersion across domains of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was a useful indicator of cognitive changes associated with cardiovascular disease and mortality. Also, research by Manning and colleagues (2021) found that elevated ratings of depression and anxiety in older adults was associated with greater dispersion across neuropsychological testing. The present study aimed to replicate findings that greater dispersion in neuropsychological performance is associated with impaired neurocognitive performance and greater self-reported depression among older adults who present for neuropsychological evaluation with cognitive concerns.

Neuropsychological testing data was obtained from a university hospital. Chart reviews were conducted on 369 participants who met initial criteria (60 years or older with testing data from the RBANS Form A, Wechsler Test of Adult Reading, and Geriatric Depression Scale [GDS]). Retrospective analyses were conducted on a final sample of 293 participants from 60 to 94 years old (Mage = 74.41, SDage = 7.43; 179 females, 114 males). Diagnoses were used for group comparisons between cognitively intact individuals with subjective cognitive complaints (SCC, n = 49), persons with Mild Neurocognitive Disorder (mND, n =137), and persons with Major Neurocognitive Disorder (MND, n = 107).

As expected, results indicated that higher dispersion was related to lower Total RBANS Scores (r = -0.54, p < .001) and significant differences across diagnostic groupings (F(2, 289) = 29.19, p < 0.001; SCC, mND, MND) indicated that variability in performance was an indicator of greater neurocognitive impairment. Contrary to expectations, greater dispersion was very weakly associated with lower reported depressive symptomatology (r = -0.13, p = 0.03). A three-stage hierarchical linear regression was conducted with the RBANS Coefficient of Variation (CoV) as the dependent variable and three predictor variables (Age, Total RBANS, Total GDS). The regression analysis results indicated that age was not a significant predictor, but both Total RBANS and GDS Scores were. The most important predictor was Total RBANS Scores which uniquely explained 21% of the variation in dispersion.

This study adds to the current literature regarding the clinical utility of dispersion in neuropsychological performance as an indicator of early and subtle neurocognitive impairment. Depressive symptom reporting was expected to help predict the degree of variability, but this factor was only weakly associated with the RBANS CoV.

Limitations of this study include its retrospective use of archival data and the restricted range on some variables of interest. Further research is needed to examine the relative utility of different measures of dispersion and why increased cognitive performance variability is related to neurocognitive impairment and decline.

Improving the timeline for intervention in Alzheimer's disease (AD) has considerable potential to delay and mitigate disability and suffering. Neuropsychological assessment is useful for distinguishing AD from normal aging and other dementias but is less useful in preclinical detection due to its limited sensitivity. The N400 (N4), a language-based EEG event-related potential (ERP) related to semantic functioning, is a promising candidate marker of AD with potential to improve early detection and monitoring of AD. For example, studies have shown that individuals with AD show a reduced N4 "effect"—a smaller difference in the size of the N4 to semantically congruent vs. incongruent word-pairs. The goal of this study is to assess the presence of the N4 effect in healthy seniors, and those with amnestic mild cognitive impairment (MCI) or mild AD, and to evaluate associations between performance on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the N4 across these samples.

Fifty older adults (intact=27, combined MCI/mild AD group=23; "impaired") completed neuropsychological testing, including the RBANS, as part of a larger study. Participants were re-contacted and returned for EEG assessment between several weeks to one year later. During EEG recording, participants completed a word-pair judgement paradigm, which involved distinguishing between semantically congruent and incongruent word-pairs. Data was collected and analyzed according to customized N4 analysis scripts provided as part of ERPCORE, an online resource for acquiring and analyzing common ERP components (Kappenman et al., 2021; https://osf.io/thsqg/). The change in N4 amplitude between congruent and incongruent trials (the N4 effect) was used as an index of participants' semantic functioning. Participants' N4 effect was quantified using the mean amplitude from 300-550 milliseconds poststimulus at electrode Cz.

Repeated measures ANOVAs indicated a significant effect of trial type on the N400 amplitude in the intact individuals (F(1, 26)=77.66, p<.001), which remained significant in the sample as a whole (F(1, 48)=65.18, p<.001). Although intact participants numerically showed a larger N4 effect (intact: M=-4.02, SD=2.37; impaired: M=-2.60, SD=3.40), the expected group-by-trial interaction was not significant (F(1, 48)=3.01, p=.089). Correlational analyses revealed no significant associations between the N4 effect and the RBANS Total Scale scores (r=-.14, p=.32), nor for the Immediate Memory (r=-.002, p=.99), Visuospatial/Constructional (r=-.069, p=.63), Language (r=-.15, p=.30) Attention (r=-.21, p=.14), or Delayed Memory (r=-.18 p=.58) indexes.

Results confirmed the presence of the N4 effect in intact participants and in the sample as a whole. Although the N4 effect was numerically smaller in the impaired group as expected, this difference was not significant in the present sample. Likewise, we observed no evidence for associations between the size of N4 effect and performance on RBANS indexes. Overall, the present study provides mixed evidence for the utility of the N4 as a biomarker in mild AD. Factors that may have contributed to the lack of associations between the N4 effect and the RBANS include the limited sample size and variable lengths of time between participants' initial cognitive assessments and EEG testing.

In the field of neurocognitive disorders, the perspective offered by new disease-modifying therapy increases the importance of etiological diagnosis. The prescription of cerebrospinal fluid analysis (CSF) and imaging biomarkers is a common practice in the clinic but is often driven more by personal expertise and local availability of diagnostic tools than by evidence of efficacy and cost-effectiveness analysis. This leads to a widely heterogeneous dementia care across Europe. Therefore, a European initiative is currently being conducted to establish a consensus for biomarker-based diagnosis of patients with mild cognitive impairment (MCI) and mild dementia.

Since November 2020, a European multidisciplinary task force of 22 experts from 11 scientific societies have been defining a diagnostic workflow for the efficient use of biomarkers. The Delphi consensus procedure was used to bridge the gaps of incomplete scientific evidence on biomarker prioritization. The project has been in two phases. During Phase 1, we conducted a literature review on the accuracy of imaging, CSF, neurophysiological and blood biomarkers in predicting the clinical progression or in defining the underpinning aetiology of main neurocognitive disorders. Evidence was provided to support the panelists’ decisions. In phase 2, a modified Delphi procedure was implemented, and consensus was reached at a threshold of 70% agreement, or 50%+1 when a question required rediscussion.

In phase 1, 167 out of 2,200 screened papers provided validated measures of biomarker diagnostic accuracy compared with a gold standard or in predicting progression or conversion of MCI to the dementia stage (i.e., MRI, CSF, FDG-PET, DaT-imaging, amyloid-PET, tau-PET, and myocardial MIBG-scintigraphy and EEG). During phase 2, panelists agreed on the clinical workspace of the workflow, the stage of application, and the patient age window. The workflow is patient-centered and features three levels of assessment (W): W1 defines eleven clinical profiles based on integrated results of neuropsychology, MRI atrophy patterns, and blood tests; W2 describes the first-line biomarkers according to W1 versus clinical suspicion; and W3 suggests the second-line biomarkers when the results of first-line biomarkers are inconsistent with the diagnostic hypothesis, uninformative or inconclusive. CSF biomarkers are first-line in the suspect of Alzheimer’s disease (AD) and when inconsistent neuropsychological and MRI findings hinder a clear diagnostic hypothesis; dopamine SPECT/PET for those leading to suspect Lewy body spectrum. FDG-PET is first-line for the clinical profiles leading to suspect frontotemporal lobar degeneration and motor tauopathies and is followed by CSF biomarkers in the case of atypical metabolic patterns, when an underlying AD etiology is conceivable.

The workflow will promote consistency in diagnosing neurocognitive disorders across countries and rational use of resources. The initiative has some limitations, mainly linked to the Delphi procedure (e.g., kickoff questions were driven by the moderators, answers are driven by the Delphi panel composition, a subtle phrasing of the questions may drive answers, and 70% threshold for convergence is conventional). However, the diagnostic workflow will be able to help clinicians achieve an early and sustainable etiological diagnosis and enable the use of disease-modifying drugs as soon as they become available.

Metacognitive deficits are common following traumatic brain injury (TBI), and this has important implications for recovery, social relationships, and rehabilitative outcomes (Chiou et al., 2011; Flashman & McAllister, 2002; Ownsworth & Fleming, 2005). Metacognitive deficits have historically been measured using self-report (Allen & Ruff, 1990; Newman et al., 2000; Sherer et al., 1995; Sherer et al., 1998), which is problematic as individuals with an awareness of deficit cannot accurately reflect on their own condition (Akturk & Sahin, 2011). In the past two decades, studies have transitioned to using more objective measures to assess metacognition, including error monitoring tasks (McAvinue et al., 2005; Yeung & Summerfield, 2012) and tasks using retrospective confidence judgments (RCJs) (Busey et al., 2000). Importantly, both tasks are used to study “metacognition,” but clear distinctions as to what domains these tasks measure has not been elucidated. Additionally, both tasks have been linked to executive functioning broadly, but error detection tasks are uniquely associated with measures of attention and self-reported anxiety (Hoerold et al., 2008; O’Keefe et al., 2007), indicating that there may be distinct processes that comprise metacognition. It is a goal to determine what domains these tasks represent so proper assessments of metacognitive ability can be conducted in this population.

Participants included 23 older adults with moderate-severe TBI and 16 age, sex, and education matched healthy control (HC) individuals ages 53-80. All participants received identical neuropsychological test batteries, including two tasks of metacognition (error monitoring task, RCJ task), neurocognitive tasks of attention (Digit Span - Forward, Trail Making Test A) and executive functioning (Digit Span - Backward, Trail Making Test B), and a self-report measure of anxiety (Brief Symptom Inventory - Anxiety subscale). To determine overlapping constructs measured by the two metacognitive tasks, these tasks were correlated with each other and with an attention composite, executive functioning (EF) composite, and anxiety measure in the TBI and HC groups.

In the TBI group, the metacognitive tasks were significantly correlated with each other (r=-0.47, p=0.022). The RCJ task was associated with EF (r=0.47, p=0.025), but not with attention (r=0.20, p=0.358) or anxiety (r=0.25, p=0.248). The error detection task was associated with EF (r=-0.48, p=0.021) and attention (r=-0.46, p=0.026), but not with anxiety (r=-0.19, p=0.383). In the HC group, there were no significant associations between the metacognitive tasks, or between either metacognitive task and EF, attention, or anxiety.

For older adults sustaining TBI, tasks of error detection and tasks using retrospective confidence judgments measured an overlapping construct, with both having an association with executive functioning and only the error detection task being associated with attention. Interestingly, these associations were not found in a healthy control sample of older adults. Both metacognitive tasks have been used in the literature to measure errors of awareness, but this study provides insight that these tasks are measuring different domains of metacognitive ability in older individuals with TBI. Use of multiple tasks of metacognitive ability in this population can help to describe where the deficits of awareness occur following TBI.

Cognition has been identified as an area of priority in examining health impacts of COVID-19 infection, and evidence suggests the virus invades the brain, with potential for long-term cognitive impact. Studies utilizing screening measures have reported cognitive sequelae (e.g., attention disorder, executive dysfunction) of the post-COVID-19 condition (i.e., long-haulers). More extensive examination of cognitive difficulties via comprehensive neuropsychological assessment is critical to informing treatment for those experiencing cognitive or functional difficulties post-infection. We aimed to comprehensively evaluate cognitive resiliencies and vulnerabilities of acutely recovered COVID-19 patients, across key domains (i.e., attention, processing speed, language, visuospatial abilities, memory, executive functioning), compared to healthy controls.

Adults (N=103; aged 19-85; 69.2% female) who had COVID-19 at least three months prior (n=50) and those with no history of infection (n=53) completed demographic and health questionnaires via Qualtrics, along with measures of depressive (CES-D) and anxiety (GAD-7) symptoms, the Lawton-Brody Instrumental Activities of Daily Living (IADL) Scale, and a measure of subjective cognitive difficulties (SCD-Q). Participants (n=84) completed a teleneuropsychology assessment including a short interview and battery of neuropsychological tests assessing attention (BTA, Digit Span Forward), processing speed (DKEFS Colour Naming & Word Reading, SDMT), language (FAS, Animals, NAB Naming), visuospatial abilities (JLO, RCFT Copy), verbal and visual memory (HVLT-R, NAB Shape Learning, RCFT), and executive function (DKEFS Color-Word Interference & Switching, Digit Span Backward & Sequencing, BRIEF), and including multiple measures of cognitive effort/assessment validity (RFIT, RDS), and a self-report measure of symptom validity (SIMS). T-tests were used to examine demographic and health variables between COVID-19 and control groups. MANCOVA were used to examine group differences across each cognitive domain assessed, and across cognitive effort and symptom validity tasks, while controlling for English language status.

Group comparisons indicated that the COVID-19 group was slightly older (mean age = 40 vs. 34 yrs.; f=-2.101, p=0.04). Those who had COVID-19 reported more difficulties completing IADLs (f=2.204; p=0.03), more depressive symptoms (f=-2.299; p=0.02), and more subjective cognitive difficulties (f=-3.886; p<0.01). Examination of cognitive performance indicated a main effect of prior infection on executive function, controlling for language status (Wilks’ /\=0.817, F(6,73)=2.733, p=0.02). Specifically, having COVID-19 was associated with worse DKEFS Colour-Word Switching performance (p=0.01) and slightly higher selfreported difficulties on the BRIEF MI (p=0.04). No other significant group differences were seen across cognitive domains. There was also a main effect of COVID-19 infection on effort and symptom validity task performance (Wilks’ /\=0.705, F(10,70)=2.923, p<0.01). Specifically, prior infection was associated with higher SIMS Neurologic Impairment (p<0.01) and Amnestic Disorders (p<0.01) subscale scores, and paradoxically, slightly higher RFIT combined scores (p=0.02).

Interestingly, results indicate a significant role for subjective cognitive complaints and potential exaggeration of cognitive symptoms post-COVID-19 infection, in the absence of differences in objective performance in most cognitive domains. While subtle differences are seen on some executive function measures, mean group differences are small, and in the context of higher SIMS subscale scores, may not be readily interpretable. Studies employing similarly comprehensive neuropsychological assessments including validity measures in larger samples are needed to further disambiguate potential objective cognitive performance decrements from subjectively experienced difficulties.

We aim to highlight a unique case that required adaptation of a neuropsychological battery used as part of a pre-surgical workup for medically refractory epilepsy, to meet the needs of a culturally and linguistically-diverse patient with visual impairment.

Comprehensive pre-surgical neuropsychological evaluation for a 34-year-old Spanish-speaking patient with a past medical history of epilepsy, hydrocephalus, and a subependymal giant cell astrocytoma resection, with subsequent complete blindness. EEG findings demonstrated abnormal left frontal dysfunction. A neuropsychological evaluation was conducted utilizing components from the Neuropsychological Screening Battery for Hispanics (NeSBHIS) as well as additional supplemental Spanish language assessments. Due to the patient’s visual impairment, visuospatial measures were unable to be utilized. Hand dynamometer was used in place of the Grooved Pegboard Test.

Results from the evaluation indicated a generally intact cognitive profile with a few observed deficits. Relative and normative weaknesses were identified on tasks of verbal learning. His initial learning of a list of orally presented words was in the Low Average range, where he demonstrated a positive though somewhat flat learning profile. His performances on short- and long-delay free recall tasks were in the Exceptionally Low range. With a recognition format, he performed within normal limits and made no false positive errors. Importantly, during the initial learning of the word list, the patient demonstrated a significant number of repetitions (13) and semantically related intrusions (6). These likely led to downstream difficulties encoding information; however, he displayed a minimal loss of information over a delay. Similarly, his immediate and delayed recall of an orally presented story fell in the Exceptionally Low range. Additional relative weaknesses were observed on tasks of working memory (Low Average range) and on a task of phonemic fluency (Below Average range). This performance was a notable contrast to his performance on tasks of semantic fluency, which ranged from the Low Average to Average range. On a task of motor functioning, grip strength performances were intact bimanually (Low Average to Average range) without a significant asymmetry between his left and right hands. Lastly, formal assessment of emotional functioning on self-report measures revealed minimal depression, minimal anxiety, and no significant quality of life concerns.

Taken together, the weaknesses observed in the domains of verbal learning, working memory, and phonemic fluency, in addition to the learning profile observed during the verbal encoding task, suggest that his overall profile is indicative of dominant frontal systems dysfunction. This finding was concordant with prior EEG and MRI studies. Notably, given the patient’s visual impairment, visuospatial measures were unable to be utilized, and lateralization was unable to be fully assessed given the abbreviated battery. The neuropsychological battery used for this evaluation was based on established guidelines, and while there were limitations in administration of the present battery, it is imperative to highlight the necessity and feasibility for adaptation of protocols to best capture data in culturally-underrepresented and visually impaired populations.

Approximately half of people living with HIV (PWH) experience HIV-associated neurocognitive disorders (HAND), yet HAND often goes undiagnosed. There is an ongoing need to find efficient, cost-effective ways to screen for HAND and monitor its progression in order to intervene earlier in its course and more effectively treat it. Prior studies that analyzed brief HAND screening tools have demonstrated that certain cognitive test pairs are sensitive to HAND cross-sectionally and outperform other screening tools such as the HIV Dementia Scale (HDS). However, few studies have examined optimal tests for longitudinal screening. This study aims to identify the best cognitive test pairs for detecting cognitive decline longitudinally.

Participants were HIV+ adults (N=132; ages 25-68; 59% men; 92% Black) from the Temple/Drexel Comprehensive NeuroHIV Center cohort. Participants were currently well treated (98% on cART, 92% with undetectable viral load, and mean current CD4 count=686). They completed comprehensive neurocognitive assessments longitudinally (328 total visits, average follow-up time=4.9 years). Eighteen participants (14% of the cohort) demonstrated significant cognitive decline, defined as a decline in global cognitive z-score of 0.5 (SD) or more. In receiver operating characteristic (ROC) analyses, tests with an area under the curve (AUC) of greater than .7 were included in subsequent test pair analyses. Further ROC analyses examined the sensitivity and specificity of each test pair in detecting significant cognitive decline. Results were compared with the predictive ability of the Modified HIV Dementia Scale (MHDS).

The following test pairs demonstrated the best balance between sensitivity and specificity in detecting global cognitive decline: Grooved Pegboard dominant hand (GPD) and category fluency (sensitivity=.89, specificity=.60, AUC=.75, p<.001), GPD and Coding (sensitivity=.76, specificity=.70, AUC=.73, p<.001), letter fluency and Trail Making Test (TMT) B (sensitivity=.82, specificity=.63, AUC=.73, p<.001), and GPD and TMT B (sensitivity=.81, specificity=.64, AUC=.73, p<.001). Change in MHDS predicted significant decline no better than chance (sensitivity=.61, specificity=.47, AUC=.53, p=.65).

Several cognitive test pairs, particularly those that include GPD, are sensitive to HIV-associated cognitive change, and far more sensitive and specific than the MHDS. Cognitive test pairs can serve as valid, rapid, cost-effective screening tools for detecting cognitive change in PWH, thereby better enabling early detection and intervention. Future research should validate the present findings in other cohorts and examine the implementation of test pair screenings in HIV care settings. Most of the optimal tests identified are consistent with the well-established impact of HAND on frontal-subcortical motor and executive networks. The utility of category fluency is somewhat unexpected as it places more demands on temporal semantic networks; future research should explore the factors driving this finding, such as the potential interaction of HIV with aging and neurodegenerative disease.

Reduced hearing is associated with increased risk for social, emotional, and behavioral difficulties. Studies to date have typically compared DHH children with their hearing peers without regard for unilateral hearing loss (UHL) versus bilateral hearing loss (BHL). Children with UHL are often perceived as more like their typically hearing peers than their peers with BHL. Children with UHL typically access sound and spoken language which facilitates their functioning with fewer supports (e.g., interpreters, captioning). These children, however, show cognitive, academic, and communication profiles more similar to children with BHL than typically hearing peers. They may also experience similar social, emotional, and behavioral challenges as their BHL peers. We examined social, emotional, and behavioral functioning in a clinically referred sample of children with UHL versus BHL.

Parents of 100 children aged 2 to 17 years (M=7.12) with either UHL (n=30) or BHL (n=70) completed the Behavioral Assessment System for Children, Third Edition (BASC-3) as part of neuropsychological evaluation in a Deaf and Hard of Hearing Program within a tertiary pediatric hospital. BASC-3 scores based on General Combined norms were compared to an expected distribution of typically developing hearing children using non-parametric one-sample tests. Profiles of scores for children with UHL and BHL were examined in a repeated measures MANOVA.

The groups of children with UHL and BHL showed similar age, gender, race, ethnicity, and Area Deprivation Index compositions. Eighty four percent of BHL children communicated with spoken language, and 100% of UHL children communicated with spoken language (p=.02). There were similar rates of comorbid diagnoses for ADHD (20%), Anxiety/Depression (18%), Autism Spectrum Disorder (8%), and Intellectual Disability/Global Developmental Delay (9%). However, children with BHL tended to be at greater risk for Language Disorders (50%) than those with UHL (30%, = 3.41 p=.065). Together, children with hearing loss showed significantly higher scores on the BASC-3 Hyperactivity, Aggression, Attention Problems, Atypicality, and Withdrawal clinical scales than expected (One-Sample Kolmogorov-Smirnov Test; p<.01). Profile analysis showed that children with any type of hearing loss had a varied pattern of scores across scales (F(7,686)=4.33, p<.01), with highest scores on Hyperactivity and Attention Problems scales and lowest scores on Somatization. Scale profiles did not differ, however, between UHL and BHLgroups (p=.127).

Children with UHL have access to auditory input, typically enabling early language development more like their hearing peers compared to children with BHL. In turn, these children may be overlooked more so than their BHL peers. However, the likelihood of social, emotional, and behavioral difficulties is similar between the two groups of children with hearing loss, whether that is unilateral or bilateral. Our study showed both groups of children had similar profiles across BASC-3 scales with elevations relative to norms. Measuring these everyday functions in children with hearing loss is important for early detection of risks to promote early intervention.

Survivors of childhood brain tumor are historically thought to perform worse on measures of executive functioning, including cognitive flexibility (CF; e.g., set-shifting), when compared to their peers. Commonly utilized measures, such as subtests from the Delis-Kaplan Executive Function System (D-KEFS), have baseline conditions that attempt to measure performances independent of but critical for CF tasks (e.g., motor speed on trail making, letter fluency on verbal fluency). However, in research, conditions measuring CF are often included in analyses without accounting for these important baseline conditions. The aim of the current study is to explore differences in CF performance between survivors and their healthy peers when controlling for baseline conditions. The variance explained by each baseline condition on CF condition performance in survivors is also explored.

A sample of 107 long-term survivors of childhood brain tumor (Mage=21.81, SD=5.99, 50.5% female) and 142 healthy controls (Mage= 23.25, SD=6.61, 61.3% female) were administered the Trail Making Test (TMT), Color-Word Interference (CWI), and Verbal Fluency (VF) subtests from the D-KEFS. For the TMT, baseline conditions include visually scanning for a target, motor speed, and letter and number sequencing. For the CWI subtest, baseline conditions include rapid color naming, word reading, and reading words in a different colored ink. On the VF subtest, baseline conditions include rapidly naming words with a specific letter and from a specific category. An analysis of covariance was conducted for each subtest to determine if groups differed in performance on the CF condition (i.e., Number-Letter Switching, Inhibition/Switching, Category Switching Accuracy) when controlling for baseline conditions. In survivors only, linear regressions investigated the amount of variance explained by each baseline condition on the CF conditions of each subtest.

Groups did not differ in CF performance of each subtest when controlling for baseline conditions (ps>.10). Across subtests, baseline conditions significantly predicted CF performance in survivors. On the TMT, Letter Sequencing (p=.003, unique-R2=.05), but not Visual Scanning, Number Sequencing, or Motor Speed, was a significant predictor of Number-Letter Sequencing performance (p<.001, R2=.50). On the CWI subtest, Word Reading (p<.001, unique-R2=.09) and Inhibition (p<.001, unique-R2=.05), but not Color Naming, were significant predictors of Inhibition/Switching performance (p<.001, R2=.67). On the VF subtest, Letter Fluency (p=.009, unique-R2=.06) and Category Fluency (p<.001, unique-R2=.08) were significant predictors of Category Switching Accuracy performance (p<.001, R2=.37).

Findings suggest that CF may not differ between survivors and their healthy peers, but that other factors of executive functioning, such as processing speed, drive performance differences on measures of CF. As these tasks rely heavily on speed, survivors may be slower than their healthy counterparts, but may not perform worse on set-shifting. In addition, these results highlight the importance of controlling for lower-order processes in analyses to help isolate CF performance and more accurately characterize potential differences between groups. While replication of findings in survivors and other clinical groups (e.g., congenital heart disease, traumatic brain injury) is still needed, this work can help inform which processes are most important to account for, which is not yet established.

Prion disease is a rare, invariably fatal neurodegenerative disease characterized by rapid neuronal degeneration; Mutations to PRNP gene cause genetic prion disease (GPD). In animal models, microglial activation, astrocytosis, and release of neurofilament precede the onset of frank symptoms (Sorce & Nuvolone 2020, Minikel 2020). In humans at risk for GPD, prodromal pathology appears to occur in only a brief window prior to symptom onset (Vallabh et al. 2020, Thompson et al. 2021), but some data suggest that known PRNP mutation carriers may exhibit cognitive abnormalities prior to meeting clinical diagnostic criteria (Mole et al., 2021). We aim to examine pre-symptomatic differences in cognitive processing speed (CPS) and executive function (EF) in PRNP mutation carriers and controls.

Our sample includes two groups from an ongoing observational study on GPD (Vallabh et al., 2020): known PRNP mutation carriers (N = 32, Age M = 45.77, SD = 14.75) and control group of non-carriers with a family history of GPD and healthy controls with no known history (N = 11, Age M = 42.01, SD = 12.43). All participants completed a full cognitive battery at baseline and on an annual basis. We compared first visit cognitive testing measuring CPS and EF using: National Institute of Health (NIH) Toolbox [Pattern Comparison (NIH-PC), Flanker, Dimensional Card Sorting Task (NIH-DCCS)], Trail Making Test (TMT) A and B, and Delis-Kaplan Executive Function System (D-KEFS) Color-Word Interference Test (CWIT).

Independent t-tests and Mann-Whitney U tests compared cognitive test performance between groups. Across all cognitive test measures assessed, none exhibited significant differences between groups after Bonferroni correction for N=10 tests (corrected P > 0.05). Mean scores for mutation carriers were non-significantly lower than controls on TMT-B (Z-score Mdn = .29, SD = 1.33 vs. Z-score Mdn = .96, SD = .97), NIH-PC (Age-corrected Standard Score [ACSS] M = 100.13, SD = 20.76 vs. ACSS score M = 114.82, SD = 14.61) and NIH-Flanker (ACSS score M = 83.58, SD = 9.72 vs. ACSS score M = 90.64, SD = 10.94), and NIH-DCCS (ACSS M = 101.29, SD = 16.37 vs. ACSS score M = 112.00, SD = 16.28) but not for TMT-A or all four conditions of CWIT.

We did not detect any significant cognitive deficits in known PRNP mutation carriers. This is consistent with the lack of prodromal pathological biomarker changes or cognitive changes as reported in Vallabh et al 2020, and with the finding of Mole et al. 2021 that most tests reveal impairment only at a stage where carriers report subjective symptoms. Our results suggest an opportunity for primary prevention to preserve full cognitive health in at-risk individuals. However, small sample size and limited test sensitivity may leave us underpowered to detect subtle deficits. Future research is warranted to further investigate the neuropsychological profile of pre-symptomatic GPD.