The Apolipoprotein E (APOE) gene has been established in the Alzheimer’s disease (AD) literature to impact brain structure and function and may also show congruent effects in healthy older adults, although findings in this population are much less consistent. Magnetic Resonance Imaging (MRI), Diffusion Tensor Imaging (DTI), and neuropsychological measures present as useful, non-invasive tools to investigate the impact of APOE-e allele status on grey matter structure, white matter integrity, and cognitive functioning, respectively. Nonetheless, studies to date have revealed mix findings and few studies have taken a multimodal approach to investigating APOE’s effects. Thus, the objective of the current study was to replicate and expand upon the multimodal neuroimaging study conducted by Honea et al. (2009), that examined the impact of APOE-e4 presence on brain structure and cognitive function in healthy older adults, with the addition of APOE-e2 carriers and cognitive composite measures. The aim of the current replication study was to identify reliable changes to grey matter volume and white matter integrity in healthy older adults as it relates to APOE-e allele presence and cognitive performance. This represents one of the first studies to investigate both the risk and protective effects of APOE-e alleles (e4 and e2 respectively) on measures of cognitive performance, GMV and white matter integrity in healthy older adults.

Data were obtained from the Alzheimer’s Disease Initiative phase 3 (ADNI3) database. Baseline MRI, DTI and cognitive composite scores for memory (ADNI-Mem) and executive function (ADNI-EF) were acquired from 116 healthy controls. Participants were grouped according to APOE allele presence (APOE-e2+ N= 17, APOE-e3e3 N= 64, APOE-e4+ N=35). Voxel-based morphometry (VBM) and tract based spatial statistics (TBSS) were used to compare grey matter volume (GMV) and white matter integrity respectively between APOE-e2+ and APOE-e3e3 controls, and again between APOE-e4+ and APOE-e3e3 controls. Multivariate analysis of covariance (MANCOVA) was used to examine the effects of APOE polymorphism on memory and EF across all APOE groups with covariates of age, sex, education, and cognitive scores were correlated with imaging metrics within groups (Pearson r) to examine associations between cognitive performance and brain structure.

Consistent with findings from Honea et al. (2009), no significant differences were seen across APOE groups, within-groups in MRI metrics, or cognitive performance (p>0.05, corrected for multiple comparisons). Taking a similar approach to Honea and company, nonsignificant, trend-level results were examined (p<0.2, corrected for multiple comparisons) and suggested: 1) Decreased GMV and increased mean diffusivity (MD) were present in APOE-e4+ compared to APOE-e3e3 and 2) Increased GMV and fractional anisotropy (FA) were present in APOE-e2+ compared to APOE-e3e3.

The current study replicated and extended previous findings. Trend-level findings across both the current and replicated study suggests there may be subtle neurostructural differences in healthy aging as a function of APOE-e4 status. The current study additionally found potential subtle differences in GMV and white matter integrity in APOE-e2 carriers at the trend-level, consistent with previous reports of APOE-e2 's protective effects against neurodegeneration. Although these findings should be interpreted with caution, trend-level effects seen in the current study are consistent with previous research and may hold important implications for APOE neuromechanisms.

The current study aimed to evaluate the psychometric properties and diagnostic accuracy of the 32-item version of the Multilingual Naming Test (MINT) in a sample of English and Spanish monolinguals and bilingual older adults from two ethnic groups (EA; European Americans and HA; Hispanic American) with typical and atypical aging. An IRT model was used to identify 24 MINT Items assessed across ethnicity and language testing groups (Spanish and English). We analyzed the discriminant and predictive validity of the 32-item and 24-item scales across diagnostic groups (cognitively normal [CN], mild cognitive impairment [MCI], and dementia [AD]). Diagnostic accuracy was then assessed with both versions applying ROC (Receiver Operating Characteristics) curve reporting using AUC (Area Under the Curve). We expected the MINT to distinguish between the CN and AD groups but not between CN and MCI and the MCI and AD. We conducted IRT analyses to evaluate the cross-language validity of the items from the 32-item MINT in English and Spanish through Rasch Analysis across our two ethnic groups. Finally, we tested the association between MINT scores and MRI volumetric measures of language-related areas in both cerebral hemispheres’ temporal and frontal lobes.

The sample comprised 281 participants (178 females) enrolled in the 1Florida Alzheimer’s Disease Research Center (ADRC), with 175 participants self-identified as HA (51 tested in English and 124 in Spanish) and 106 EA, all of them monolingual English speakers. The participants were classified into three diagnostic groups: 1. CN (n = 94); 2. MCI (n = 148); and 3. AD (n = 39). Participants are evaluated yearly through a comprehensive neuropsychological battery, including the MINT is a standard CN task that requires patients to retrieve words upon presentation of a line drawing.

We obtained a ceiling effect in four items (Butterfly, Glove, Watch, and Candle). Four items were easier in English (Blind, Gauge, Porthole, and Pestle) and four in Spanish (Dustpan, Funnel, Anvil, and Mortar). In the 32-item version of the MINT, EA scored significantly higher than HA, but when removing those eight items, the ethnic difference was attenuated and no longer statistically significant (controlling for education). The ROC curves showed that both versions of the MINT had poor accuracy when identifying CN participants and were acceptable in identifying dementia participants but unacceptable for classifying MCI participants. The 32-item MINT in English and Spanish and the 24-item MINT in Spanish were significantly correlated with the bilateral MTG. However, the 24-item MINT in English was only correlated with this area’s volume in the right hemisphere. The left FG correlated with MINT scores regardless of language and MINT version. We also found some differential correlations depending on the language of administration. The bilateral hippocampi, STG, MTG and FG, and right ITG were significantly correlated only with MINT Spanish scores, while the left ITG was significant only when either version of the MINT was administered in English.

Our results highlight the importance of analyzing cross-cultural samples when implementing neuropsychological tests.

Late-life depression is prevalent among older adults and the presence of depressive symptoms has been shown to be associated cross-sectionally with worse verbal fluency performance. There is limited and mixed evidence as to whether depressive symptoms impact change in verbal fluency performance over time, and whether gender impacts this relationship.

Participants were community-dwelling older adults who were dementia-free at baseline (N = 522; M age = 75.96, SD + 6.46 years). Baseline depressive symptoms were measured using the Geriatric Depression Scale. Category fluency and letter fluency performance, using the Controlled Oral Word Association Test (COWAT), were examined annually. Linear mixed effects models stratified by gender examined whether associations between baseline depressive symptoms and changes in fluency performance over five years were different in female (n = 289) as compared to male (n = 233) participants. Sensitivity analyses excluding participants with prevalent or incident mild cognitive impairment (MCI) (n = 141), excluding participants with incident dementia (n = 28), and excluding participants with prevalent or incident MCI or incident dementia (n = 169) were run. All analyses were adjusted for age, years of education, estimated premorbid functioning, and health comorbidities.

Depression was minimal across participants (m = 4.72, SD + 3.96). A subset of participants (n = 44) reported “possible depression,” namely levels suggestive of subclinical depression, according to clinical cutoffs. The “possible depression” group included 31 females (10.73% of females) and 13 males (5.58% of males), and the “no depression” group included 258 females (89.27% of females) and 220 males (94.42% of males). Baseline levels of depressive symptoms suggestive of subclinical depression were associated with worse decline in category fluency performance during longitudinal follow-up in females (estimate = -0.16, p = .002) but not males (estimate = -0.03, p = .658). Results remained the same when excluding prevalent and incident MCI cases (estimate = -0.19, p = .005), excluding incident dementia cases (estimate = -0.12, p = .017), and excluding prevalent and incident MCI and incident dementia cases (estimate = -0.20, p = .004). Letter fluency performance did not decline over time and was not influenced by levels of depressive symptoms in females (estimate = -0.03, p = .502) or males (estimate = 0.05, p = .452).

Baseline presence of depressive symptoms suggestive of subclinical depression was associated with worse decline in category fluency performance during longitudinal follow-up in female but not male participants. Letter fluency performance did not decline and was not impacted by levels of depressive symptoms. Results remained significant when accounting for covariates and potential confounders. The present study elucidated the combined influence of gender and depressive symptoms on change in fluency performance in older adults and can aid in identifying individuals who may be at a greater risk of cognitive decline.

White matter microstructure (WMM) potentially mediates the relation between APOE4 and memory performance. This study’s purpose was to understand whether p-tau effects this mediation model and whether education level differentially impacts the relations between these genetic and biological biomarkers’ influence on memory.

Participants included 161 older adults (M=74 years, 40.4% female, 92% White, 74 e4 non-carriers, 87 e4 carriers) with subjective and objective cognitive impairment from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). A composite memory score created by ADNI was used as the outcome variable. Mean fractional anisotropy (FA) and radial diffusivity (RD) values of white matter tracts within regions of interest (i.e., fornix (FX), hippocampal cingulum (CGH)) were individually used as the measures of WMM. A moderated mediation was run to examine whether p-tau was a moderator of the mediation between APOE4, white matter microstructure, and memory. An exploratory dual moderated mediation analysis examined education as a moderator of the moderated mediation. Indirect effects were tested using bootstrapping procedures.

In the FA moderated mediation model, APOE4 was significantly related to FA of the fornix and memory performance. FA of the CGH and FX were also related to memory performance. With FA of the fornix as the mediator, the conditional indirect effect was not significant (95% CI[-.0009, .0070]). There was a trend suggesting at low (95% CI[-.2421, -.0140]) and average (95% CI[-.1658, -.0083]) levels of p-tau, FA of the fornix was a significant mediator but was non-significant at high levels of p-tau (95% CI [-.1322, .0341]). The RD moderated mediation model was non-significant. The FA and RD exploratory dual moderated mediation models were non-significant. However, the APOE4 x p-tau interaction with FA of the fornix as the mediator suggested a trend. At low levels of p-tau, increased education was related to a significant moderated mediation.

Results suggest that FA of the fornix is a significant mediator between the relation of APOE4 and memory, and this may be dependent upon p-tau levels. When p-tau burden load was high, the path by which APOE4 impacts memory performance was not through white matter microstructure degradation. Additionally, the potential buffering effects of education may be most robust at lower levels of p-tau burden.

The prevalence of memory complaints in older adults is between 25 and 50%, with poor memory associated with decreased quality of life and declines in daily functioning. Memory training programs are a method for training older adults on strategies and skills to improve memory performance. We conducted a feasibility study of a virtually-delivered adaptation of an Ecologically-Oriented Neurorehabilitation of Memory (EON-Mem) in improving memory for healthy older adults. The primary purposes of this study included: (1) determine the feasibility of conducting EON-Mem virtually with older adults, (2) determine whether a randomized control trial using EON-Mem in older adults is of value, and (3) determine whether electronic delivery of memory training programs with ecological validity is beneficial for older adults.

Twenty-five older adults 55 years of age and older were recruited for participation in a memory training program. All testing and intervention sessions were completed virtually through the Zoom platform. Measures of emotional functioning (Hospital Anxiety and Demographics Scale, health-related quality of life (Short Form-36) and cognitive functioning (Ecological Memory Simulations and Repeatable Battery for Neuropsychological Status; RBANS) were administered before and following the intervention. Participants attended one virtual treatment session per week, with sessions ranging between 60-90 minutes, for a total of six weeks. Between treatment sessions, participants were asked to complete daily homework assignments that allowed them to apply strategies to real-world situations. A priori, feasibility was set at an 80% completion rate and variables that influenced completion are reported.

To address questions regarding feasibility (e.g., adherence, attrition, etc.), we calculated descriptive statistics (i.e., count statistics, means, standard deviations, and range) on sample information. Of the 25 participants enrolled in the study, 21 participants completed all steps of the study (84% completion rate) showing the delivery format is feasible. The average age of our sample was 61.7 (SD = 5.9) years and average years of education was 17.06 (SD=2.36). Excluding those who dropped, average completion was 72.76 days (SD=18.65, range=47-124). Across all six weeks, homework completion averaged 66.4% (33/49). There were varying effects of the EON-Mem for the EMS memory outcomes with the greatest proportion showing reliable improvement on the ability to recall names (10 participants [42%]). Regarding the RBANS, the greatest proportion of participants showed reliable improvement on the Story Memory task (i.e., four participants [17%]), but only two (9%) showing reliable change on the total Memory Index score.

Overall, a virtual administration of EON-Mem in older adults was feasible.

Regarding memory changes, the majority of the sample did not demonstrate reliable improvement in memory which might have been due to a variety of reasons including the fact that our sample had a high level of education and low level of memory impairment. Notably, however, this was a feasibility study, not an intervention study. Therefore, future directions should focus on randomized controlled trials to determine efficacy.

Heart failure occurs when the heart is unable to support a flow of blood that meets the body’s needs, ultimately resulting in decreased oxygenation throughout the body— including the brain. Results of previous research suggest that individuals with heart failure exhibit both localized and diffuse neuropsychological deficits. The aims of this study are to meta-analytically examine a) the performance of participants with heart-failure and healthy controls on the Mini Mental State Examination (MMSE), a neuropsychological test of general cognition, and b) the role of depressive mood as a potential moderator of performance on the MMSE in these participants.

Two researchers independently searched eight databases for articles that examined the neuropsychological functioning of patients with heart failure.

Inclusion criteria identified studies that had a heart failure group with a comparable control group and reported on neuropsychological assessment for both groups. Studies were excluded if a heart failure group had any other type of major organ failure or if the comparison was between different classes of heart failure rather than between a heart failure group and healthy controls.

A meta-analysis using a random-effects model revealed a statistically significant and large effect size estimate (g= 0.727, p <.001) CI [.331, 1.123]. The heterogeneity was found to be statistically significant and in the large range, I2 = 83.027%, tau2 = .155, p < .001. A meta-regression analyzing the relationship between depressive mood and MMSE effect size estimates was statistically significant, Q residual = 8.715, df = 3, p = .03.

This study is the first to examine the relationship between depressive mood and general cognitive status (as measured by the MMSE) in participants with heart failure. The strong relationship between cognitive status and heart failure, and the role of depression in explaining a statistically significant portion of the heterogeneity in the relationship seen in primary studies, highlights the importance of accurately assessing depression when studying the effect of heart failure on cognition. Further research needs to examine the impact of depression on quality of life in patients with heart failure as potentially mediated by difficulties in cognition.

The COVID-19 pandemic has been a catalyst for a shift towards virtual forms of working, and specific support for the provision of virtual therapy (BPS, 2020). Remotely delivered therapy has known potential benefits, such as improving access to people living in underserved areas and for those who struggle to attend face-to-face appointments due to psychosocial, physical or geographical constraints. Those with neurological conditions frequently fall in these groups.

Acceptance and Commitment Therapy (ACT) is an evidence-based psychological intervention which aims to improve the physical and mental health of people living with neurological conditions. However, there are several considerations to translating this into a virtual therapy for this clinical group that have not yet been thoroughly empirically evaluated. Such considerations include: fatigue, cognitive difficulties in the context of virtual communication, adaptations within the therapeutic alliance, and translation of dynamic and interactive therapeutic exercises within a virtual medium.

This study aimed to describe the experiences of Clinical Psychologists delivering ACT remotely in the context of two randomised controlled feasibility and acceptability clinical trials for young people (aged 11 to 24) who have experienced a brain tumour or Tuberous Sclerosis Complex. Exploring therapist perceptions and experiences provides valuable insights into potential barriers and facilitators to engagement with remote ACT delivery.

Clinical Psychologists who were trained to deliver ACT via videoconferencing were invited to take part in virtual interviews. The semi-structured interview guide aimed to draw on their experience of ACT training, supervision, remote delivery, and perceived impact of ACT. Interviews were audio-recorded, transcribed verbatim and analysed using inductive thematic analysis.

Five Clinical Psychologists were interviewed. Interview data were coded into broad themes around the experience of delivering ACT, engaging with remote systems, the wider perceived impact of ACT and the adaptability of ACT. ACT training was reported to be an effective, positive experience and the opportunity for regular peer and group supervision worked to solidify the training and support fidelity to the ACT processes. It was largely acknowledged that while remote delivery of the intervention did create some initial challenges to the therapeutic process, this approach created opportunity for the young people to access psychological support that they might not have been able to engage with due to logistical considerations. Clinical Psychologists also shared that training in and experience of delivering ACT had a positive and meaningful impact on their clinical practice and personal conduct. They also reported that ACT was adaptable to the needs of the young people in the clinical trials and felt appropriate to deliver in this context.

This in-depth, qualitative study demonstrated the clinical promise of remotely delivered ACT. Clinical Psychologists viewed remotely delivered ACT as an appropriate, acceptable and feasible intervention for young people with experience of brain tumour and Tuberous Sclerosis Complex within the context of research, that would be generalisable to everyday clinical practice.

The CCoSI is a brief screening instrument that is designed to detect cognitive impairment in children aged 5y0m-16y11m shortly after acquired brain injury (ABI) by evaluating language, fluency, attention, memory, and visuospatial domains. Each domain translates to a CCoSI index and is composed of a series of brief subtests. This study assessed the feasibility of modifying the Children’s Cognitive Screening Instrument (CCoSI) into an electronic version (eCCoSI) and administering it using video teleconferencing (VTC).

Tasks and stimuli were modified for online administration. Typically developing children aged 5y0m-16y11 m were tested using the modified eCCoSI via VTC. The eCCoSI was administered using Skype for Business and Microsoft Teams. Participants attended one 25-minute video assessment session over either platform. Results of VTC-assessed healthy controls were compared to age-matched peers ([25] Female: [19] Male; mean age = [11.54], SD = [3.01], age range =5.00-15.75) who had been previously tested face-to-face (FTF) with the original CCoSI at the Bristol Royal Hospital for Children (BRHC).

Age-related trends in performance were also examined across FTF and VTC for comparability.

44 typically developing children were virtually assessed ([25] Female: [19] Male; mean age = [11.79], SD = [3.03], age range =5.05-16.92). Results from a 2x2 ANOVA with age-group and modality as independent factors showed no significant difference in performance between participants tested FTF and VTC over the CCoSI Attention, Fluency, Language, Memory, and Visuospatial indices. No significant result of interaction between age and modality was found; however, there was a significant result of age-group.

VTC assessment is a feasible alternative to FTF administration of the CCoSI within healthy controls. Results from the present study are promising for the use of the eCCoSI in clinical practice. Further research should attempt to replicate these results within clinical populations.

Baseline assessment of cognitive performance is common practice under many concussion management protocols and is required for collegiate athletes by the NCAA. The purpose of baseline cognitive assessment is to understand an athlete’s individual uninjured cognitive performance, as opposed to using population normative data. This baseline can then serve as a reference point for recovery after concussion and can inform return-to-play decisions. However, multiple factors, including lack of effort, can contribute to misrepresentation of baseline results which raises concern for reliability during return-to-play decision-making. Measuring effort across a continuum, rather than as a dichotomous variable (good versus poor effort) may provide informative insight related to cognitive performance at baseline.

Collegiate athletes (n = 231) completed the Immediate Post-Concussion Assessment and Cognitive Test (ImPACT) as part of their baseline pre-participation concussion evaluation. ImPACT creates composite scores of Verbal Memory, Visual Memory, Visual-Motor Speed, and Reaction Time. Baseline self-reported symptoms and total hours of sleep the night prior to testing are also collected through ImPACT. ImPACT has one embedded indicator within the program to assess effort, and research has identified an additional three embedded indicators. Athletes were also administered one stand-alone performance validity test, either the Medical Symptom Validity Test (n = 130) or the Rey Dot Counting Test (n = 101), to independently measure effort. Effort was estimated across a continuum (zero, one, two, or three or more failed effort indicators) with both stand-alone and embedded effort indicators. We evaluated the relationship between effort, symptoms, self-reported sleep, Reaction Time composite score and Visual-Motor Speed composite score using a linear regression model.

We found that 121 athletes passed all effort indicators, while 39 athletes failed only one effort indicator, 40 athletes failed two effort indicators, and 31 athletes failed three or four (three+) effort indicators. Self-reported symptoms and total hours of sleep were not related to effort, but Reaction Time and VisualMotor Speed composites were. Specifically, performance on the Visual-Motor Speed composite was significantly worse for athletes who failed two or three+ effort indicators compared to athletes who did not fail any, and performance on the Reaction Time composite was significantly worse only for athletes who failed three+ effort indicators. Additionally, athletes who failed one or more effort indicators and reported less sleep performed worse on both the Visual-Motor Speed and Reaction Time composites, compared to those who reported less sleep and did not fail any effort indicators.

Athletes who failed one effort indicator did not perform significantly worse on Reaction Time and Visual-Motor Speed composites compared to those who passed all effort indicators. However, 31% of athletes failed two or more effort indicators and these athletes performed worse on cognitive tests, likely due to factors impacting their ability to put forth good effort. These results suggest that effort is more complex than a previously used dichotomous variable and highlights the importance of using several indicators of effort throughout baseline assessments. In addition, the importance of sleep should be emphasized during baseline assessments, especially when effort is questionable.

Neuropsychological measures of verbal fluency help detect cognitive decline and neuropathology. The discrepancy between semantic verbal fluency and phonemic verbal fluency is commonly utilized to differentiate between cortical and subcortical processes. Understanding how other factors influence a patient’s verbal fluency scores is vital in informing clinical interpretation of neuropsychological test data. This study aimed to investigate how educational attainment and crystalized verbal skills (i.e., word reading and vocabulary) influence verbal fluency performance among a clinical sample of patients seen for neuropsychological evaluation services at a community-based outpatient neurology clinic.

We utilized data from N=26 patients [mean age = 50.5 (SD = 22.0), 31% female, mean education = 13.5 (SD = 2.3)] who completed neuropsychological evaluations as part of their clinical care at an outpatient neurology clinic. Participants were included in this study if they had complete data for all variables of interest. We used Pearson correlation analyses to investigate associations between each predictor variable of interest (years of education, WRAT-5 Reading, WASI-2 Vocabulary) and age-norm corrected D-KEFS Verbal Fluency scores. Prior to analysis, all variables were converted to z-scores.

We found that years of education (r = 0.49, p = 0.01) and vocabulary (r = 0.41, p = 0.04) were significantly positively correlated with category fluency performance. Reading was also positively correlated with category fluency at trend level, but this association was not statistically significant (r = 0.36, p = 0.07). We found that vocabulary (r = 0.47, p = 0.02) and reading (r = 0.51, p = 0.007) were significantly positively correlated with phonemic fluency performance, while the association between education and phonemic verbal fluency performance was not significant (r = 0.27, p = 0.18).

Our results suggest that educational attainment and crystalized verbal skills are positively associated with verbal fluency performance, though the degree of influence of these individual factors may differ for category fluency vs phonemic fluency performance. Our results have implications for the clinical practice of neuropsychology. Namely, appreciating a patient’s educational attainment and crystalized verbal skills can help guide clinical interpretation of whether or not a patient’s verbal fluency test scores reflect a decline from their baseline. This may be particularly important to consider among patients with high educational attainment or high premorbid verbal skills, as a subtle decline in their verbal fluency abilities may not be appreciated if relying only on age-based norms for interpretation. This is clinically relevant including when assessing for the early stages of neurodegenerative disorders (e.g., Alzheimer’s disease, Primary Progressive Aphasia) or for subtle changes associated with stroke or brain injury.

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.

Previous literature has studied the cognitive processes that contribute to performance on the Stroop interference condition in adults and found that the Stroop task performance (i.e., color-word interference) is comprised of multiple cognitive skills, including speed of visual search, working memory, and conflict monitoring (Perianez et al. 2020). However, the relationship of these cognitive processes to Stroop interference in youth remains understudied. Moreover, no studies have examined the contribution of effort measurement to the interference condition in healthy youth.

Golden Stroop Test interference performance was examined in healthy youth athletes (n=174) aged 8-16 years (mean age=12.07) who participated in a baseline neuropsychological evaluation as part of a clinical research program on sports concussion. Predictor variables included speed of visual search, working memory, processing speed, verbal fluency effort (i.e., validity tests), visuospatial abilities, visual processing, and executive functioning skills such as cognitive flexibility and reasoning.

Speed of visual search as measured by Trail Making Test visual scanning time (p<0.00), and effort as measured by Reliable Digit Span and Trail Making Test ratio (p=0.03; p<0.00, respectively) significantly contributed to Stroop interference performance in healthy youth. We provided three validity measures; however, only those requiring higher-order cognitive processes predicted Stroop performance: Reliable Digit Span (p=0.03) and the Trail Making Test ratio (p<0.00). The standalone validity measure (TOMM) was not a significant predictor of Stroop performance (p>0.05).

In contrast to adults, working memory and processing speed did not significantly predict Stroop performance, while visual search speed did predict Stroop interference. Furthermore, two embedded validity indicator (EVI) measures predicted Stroop interference, in contrast to a standalone validity measure requiring lower cognitive processes, which did not predict Stroop performance. Therefore, EVI’s that include an executive functioning component may not accurately represent effort in youth, perhaps due to their less developed executive functioning relative to adults (Lezak et al., 2012; Shanmugan & Satterthwaite, 2017). Overall, understanding the cognitive processes contributing to Stroop performance in healthy youth will allow clinicians to better detect deficits in those cognitive processes and understand how they may impact Stroop performance. This would lead to a better understanding of executive functioning and the accurate measurement of effort in healthy youth.

It has been established that capturing how an individual draws the Rey Complex Figure Task (RCF) is as important as assessing what is drawn (Rey, 1941, Osterrieth, 1944). Despite the development of multiple systems that have been designed to measure these qualitative characteristics there are still no systematic means to measure adherence to the temporal-spatial heuristic that represents a typical drawing practice in healthy, neurotypical adults (Visser, 1973; Hamby et al, 1993).This study sought to develop a system for scoring temporal-spatial adherence when drawing the figure to provide objective, continuous data.

Fifty-three English-speaking adults (mean age 44.61 yrs, SD 12.48; 44 female) were recruited. Exclusion criteria included vision and hearing impairment not corrected by aids; neurodivergent, neurological or psychiatric diagnosis, cancer or brain injury history. Participants completed the RCF copy phase as part of an extended neuropsychological battery. The RCF drawing process was recorded via video and a ball-point pen that digitally recorded drawing. Order data for the 18 RCF elements (Osterrieth, 1944,Taylor, 1959) was recorded by two scorers and analysed via Principal Component Analysis (PCA) with an equimax rotation to identify elements typically drawn together by a healthy, neurotypical adult. Using scoring methodology adapted from Geary et al (2011), the extent to which participants drew consecutively the member elements of each factor or 'strategy cluster’ was calculated and recorded. Strategy Cluster Scores across the population sample were examined to understand normative performance.

Order data was examined for interrater reliability via Pearson’s correlation coefficient and was considered good (r2 = 0.78, p < 0.001). PCA identified four factors or 'strategy clusters’ that were statistically robust and accounted for 67.34% of total variation. The strategy clusters were Core Structure (rectangle, diagonal, horizontal, vertical); Triangular Structure (triangle, horizontal in triangle, vertical in triangle, diamond); Internal Left-Hand Side (four horizontal lines, smaller rectangle, horizontal in top-left quad); and Internal Right-Hand Side (five lines, circle, vertical top-right quad, small triangle). The mean RCF Strategy Cluster Score was 6.23 (SD 1.94; possible range: 2.75 to 10). Population data spread indicated that healthy neurotypical adults only partially observed a temporal-spatial heuristic, rather than strict, absolute adherence.

Four strategy clusters were identified where cluster members were typically drawn consecutively. RCF Cluster Strategy scoring was shown to measure the temporal-spatial heuristic objectively, providing continuous data that lends itself to clinical standardisation. Further, the study demonstrated that whilst healthy, neurotypical adults copy the RCF using a temporal-spatial heuristic, it is only partially adhered to. Traditionally deviation from strict adherence to the four strategy clusters during drawing was deemed to be indicative of cognitive dysregulation, however our findings demonstrate a normal distribution of typical population performance. These findings have important implications for interpreting how RCF drawing strategy informs clinical assessment and diagnosis as both very strict and very weak adherence to a temporal-spatial heuristic can be indicative of atypical function. The study supports this novel scoring system as a fast and reliable means to systematically measure RCF Cluster Strategy that with further validation could be adopted within clinical practice.

Evidence regarding cognitive impairment following concussion/mild traumatic brain injury (mTBI) has been conflicting. Criticism has focused on what is being measured, how it is being measured, and who is being measured (Pertab et al, 2009; Iverson, 2010). However, literature suggests that clinicians and researchers should examine how individuals complete a task rather than what they achieve (Geary et al, 2011). Studies examining the drawing process used to complete the Rey-Osterrieth Complex Figure Task (RCF) have been inconclusive and methodologically weak. The current study addressed several criticisms and limitations by examining whether observing RCF drawing process, including a novel strategy construct, could support a diagnosis of persisting post-concussive symptoms.

Sixteen individuals with a history of concussion/mTBI and sixteen matched controls (age, sex, IQ) were included in multiple regression analyses to examine whether RCF drawing constructs predict post-concussive symptoms (mean age 43.59 years; 22 female). At least 3 months had passed since the concussive/mTBI event. Post-concussive symptoms were assessed with the Rivermead Post-Concussive Symptoms Questionnaire (RPCSQ) and the Mental Fatigue Scale (MFS). Separate regression analyses were conducted for each scale. Predictor variables were statistically selected from a catalogue of 4 RCF drawing process constructs - Wholeness, Order, Continuation and Strategy; 15 traditional measures of cognitive function; and 3 psychological state measures. 17 variables were included in the model for the RPCSQ, including Order and Strategy. 18 variables were included for the MFS, including Order, Continuation and Strategy.

Order scores were found to be one of the strongest predictors of RPCSQ scores (B = -2.06; ß= 0.20), and MFS scores (B = -1.54, ß = 0.26). Individuals drawing fewer core elements at the start of the drawing process were found to report more post-concussive symptoms. Participants who observed a stronger temporal-spatial strategy heuristic, as measured by the Strategy construct, reported more symptoms, particularly mental fatigue (RPCSQ: B = 0.49, ß = 0.09; MFS: B = 0.58, ß = 0.19). Continuation was also found to be predictive of MFS scores (B = -0.24, ß = -0.14), such that the fewer continuation points that were observed, the greater the MFS score.

Two constructs of RCF drawing process - Order and Strategy - were found to predict persisting post-concussive symptoms generally, and mental fatigue specifically. Continuation was also found to predict mental fatigue. Such findings provide a cognitive explanation for patient reports of mental fatigue following concussion - recognised as the most common and persistent symptom. Strict adherence to a temporal-spatial strategy may indicate cognitive inflexibility - a theory supported by the inclusion and influence of other cognitive tasks in the regression models that rely on cognitive flexibility. Individuals exert more effort to shift between perceptual planes and to override global bias, thereby expending cognitive resources more quickly and to a greater extent. These findings provide a credible explanation for the lack of evidence of cognitive impairments in previous research, where neuropsychological tasks focus on attainment rather than process. These findings highlight the clinical importance of assessing cognitive dysregulation, specific cognitive processes and cognitive deficits post-concussion/mTBI.

To investigate the informative value of nightmares on neurobehavioral functioning in individuals with mild traumatic brain injury (mTBI) beyond general sleep disturbance.

A sample of 146 adults with mTBI (mean age = 45.1±16.0), recruited from a specialized concussion treatment center, underwent an assessment of neurobehavioral functioning using the Behavioral Assessment Screening Tool (BAST), self-reported habitual sleep disturbance and quality (via the Pittsburgh Sleep Quality Index; PSQI), and reported nightmare frequency in the past two weeks.

Nightmare frequency was the strongest predictor of negative affect (ß = .362, p <.001), anxiety (ß = .332, p <.001), and impulsivity (ß = .270, p <.001) after controlling for sex and age. Sleep disturbance accounted for the greatest variance in depression (ß = .493, p <.001), burden from concussion (ß = .477, p <.001), and fatigue (ß = .449, p <.001) after controlling for sex and age.

Nightmares independently associate with neurobehavioral symptoms and likely have differential etiology from reported sleep disturbance. Nightmare frequency was more strongly related to positive neurobehavioral symptoms (i.e., added factors that impact functioning, e.g., anxiety), while general sleep disturbance was associated with negative neurobehavioral symptoms (i.e., factors taken away that impact functioning, e.g., lack of energy). Our findings suggest that neuropsychological evaluations of individuals with mTBI should assess for sleep disturbance and nightmare frequency as risk factors for neurobehavioral barriers to functioning.

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.

The purpose of this study was to explore overall recovery time and post-concussive symptoms (PCSS) of pediatric concussion patients who were referred to a specialty concussion clinic after enduring a protracted recovery (>28 days). This included patients who self-deferred care or received management from another provider until recovery became complicated. It was hypothesized that protracted recovery patients, who initiated care within a specialty concussion clinic, would have similar recovery outcomes as typical acute injury concussion patients (i.e., within 3 weeks).

Retrospective data were gathered from electronic medical records of concussion patients aged 6-19 years. Demographic data were examined based on age, gender, race, concussion history, and comorbid psychiatric diagnosis. Concussion injury data included days from injury to initial clinic visit, total visits, PCSS scores, days from injury to recovery, and days from initiating care with a specialty clinic to recovery. All participants were provided standard return-to-learn and return-to-play protocols, aerobic exercise recommendations, behavioral health recommendations, personalized vestibular/ocular motor rehabilitation exercises, and psychoeducation on the expected recovery trajectory of concussion.

52 patients were included in this exploratory analysis (Mean age 14.6, SD ±2.7; 57.7% female; 55.7% White, 21.2% Black or African American, 21.2% Hispanic). Two percent of our sample did not disclose their race or ethnicity. Prior concussion history was present in 36.5% of patients and 23.1% had a comorbid psychiatric diagnosis. The patient referral distribution included emergency departments (36%), local pediatricians (26%), neurologists (10%), other concussion clinics (4%), and self-referrals (24%).

Given the nature of our specialty concussion clinic sample, the data was not normally distributed and more likely to be skewed by outliers. As such, the median value and interquartile range were used to describe the results. Regarding recovery variables, the median days to clinic from initial injury was 50.0 (IQR=33.5-75.5) days, the median PCSS score at initial visit was 26.0 (IQR=10.0-53.0), and the median overall recovery time was 81.0 (IQR=57.0-143.3) days.

After initiating care within our specialty concussion clinic, the median recovery time was 21.0 (IQR=14.0-58.0) additional days, the median total visits were 2.0 (IQR=2.0-3.0), and the median PCSS score at follow-up visit was 7.0 (IQR=1-17.3).

Research has shown that early referral to specialty concussion clinics may reduce recovery time and the risk of protracted recovery. Our results extend these findings to suggest that patients with protracted recovery returned to baseline similarly to those with an acute concussion injury after initiating specialty clinic care. This may be due to the vast number of resources within specialty concussion clinics including tailored return-to-learn and return-to-play protocols, rehabilitation recommendations consistent with research, and home exercises that supplement recovery. Future studies should compare outcomes of protracted recovery patients receiving care from a specialty concussion clinic against those who sought other forms of treatment. Further, evaluating the influence of comorbid factors (e.g., psychiatric and/or concussion history) on pediatric concussion recovery trajectories may be useful for future research.

To determine the association between in-vivo spectroscopy metabolite data, the local connectome, and markers of initial injury severity (I.e., history of loss of consciousness; LoC) in traumatic brain injury (TBI), in a heterogenous sample of Veterans and non-Veterans with a history of remote mild-to-moderate TBI (I.e., >6 months).

Participants with complete PRESS magnetic resonance spectroscopy (MRS) and diffusion weighted imaging (DWI) data (N = 41) were sampled from a larger multisite study of chronic mild-to-moderate TBI (Nmiid = 38; Nmoderate = 3; 54% with LoC; 46% with multiple TBI). The sample was predominantly male (76%) with ages ranging from 23-59 (M = 36.9, SD = 10.1), with 98% holding at least a high school degree (M = 14.5 years of education, SD = 2.4). Fully tissue-and-relaxation-corrected metabolite concentration estimates in the dorsal anterior cingulate (30x30x30mm voxel) were modeled using Osprey 2.4.0. Total creatine (tCr), total choline (tCho), total N-acetylaspartate (tNAA), glutamate/glutamine (Glx), and myo-inositol (mI) were analyzed. Logistic regression was used to measure the association between metabolites and history of TBI with LoC. Correlational connectometry using the normalized spin distribution function was performed for metabolites associated with LoC, to characterize the local connectome associated with metabolites of interest, controlling for age and sex, and correcting for multiple comparisons (FDR < .050 with 4000 permutations). A profile approach was used to interpret diffusion metrics, contrasting quantitative anisotropy (QA) with fractional anisotropy (FA). Local connectome tracks were then clustered to identify the larger white matter tract.

Glx (p = .008) and tCr (p = .032) were significantly associated with history of TBI with LoC. Increased Glx was associated with increased QA in 11,001 tracks, accounting for 1.4% of the total white matter tracks in the brain. 90% of tracks were identified in bilateral cingulum (33%), bilateral thalamic (13%), bilateral corticospinal (13%), corpus callosum (12%), left arcuate fasciculus (9%), left frontoparietal aslant tracts (6%), and bilateral inferior fronto-occipital fasciculus (4%) tracts. In contrast, FA was not associated with Glx. The same pattern emerged for tCr, with 10,542 tracks identified predominantly in bilateral cingulum (29%), corpus callosum (21%), bilateral corticospinal (15%), bilateral corticostriatal (7%), bilateral medial lemniscus (7%), left cortico-pontine (3%), left thalamic (2%), and bilateral superior longitudinal fasciculus (2%) tracts. Post-hoc exploratory analyses of mean QA across regions of cingulum found that increased QA was associated with self-report measures of headache intensity, fatigue, and perceived change in executive functioning.

Results provided evidence that multimodal imaging can identify subtle markers of initial TBI severity years after injury. Neurometabolite concentrations were associated with diffuse changes in the local connectome; the pattern of discrepancy between FA and QA was suggestive of reduced potential for neuroplasticity. Exploratory analyses further indicated that variability in white matter density in the cingulum, an important connection for limbic regions, was associated with a range of problems commonly reported in clinical settings, which may be informative for diagnosis and treatment planning.

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

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

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

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

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

Pediatric brain tumor survivors treated with proton radiation therapy (PRT) prior to 4 years of age are at high risk for poor cognitive and developmental outcomes. This cross-sectional study examined developmental outcomes and educational service utilization at follow-up in a cohort of pediatric survivors treated with PRT before the age of 4 years.

A total of 46 patients (58.7% female, 93.5% White) were assessed using age-appropriate measures for executive, behavioral, and adaptive functioning. Mean age at PRT was 2.4 years (SD=0.9, range 1.0-3.9 years); mean age at follow-up was 7.0 years (SD=4.8, range 2.0-18.6 years). Mean follow-up interval was 4.57 years (SD=4.52, range 0.9-16.2 years). Diagnoses included ependymoma (n=26, 54.2%), medulloblastoma (n=7, 14.6%), craniopharyngioma (n=4, 8.3%), and a few other tumor types. Infratentorial tumors were most common (69.6%). Treatment included prior surgical resection (93.5%) and chemotherapy (60.9%). Posterior fossa syndrome was present in 10.9% (n=5). PRT field consisted of focal (n=41, 89.1%) or craniospinal irradiation (CSI) (n=5, 10.9%). The impact of demographic, diagnostic, and treatment-related factors was examined, including age at PRT, gender, time interval since PRT, radiation field, and tumor location, on intelligence quotient (IQ), adaptive skills, and executive functioning. Rates of impairment (T-scores >65) were calculated. The utilization of educational services was determined.

Mean IQ (SS = 97.6, SD=16.3), as well as mean global executive functioning (Mean T=53.4, SD=11.1) and adaptive skills (Mean SS = 92.5, SD=21.4), as assessed by parent rating scales (BRIEF; SIB), were in the average range. Despite mean scores being within the average range, a large proportion of patients demonstrated difficulties with social withdrawal (28.3%) and activities of daily living (28.3%) (BASC), and global executive dysfunction (17.4%) (BRIEF). Younger age at PRT was associated with lower global adaptive skills at follow-up (r=.39, p=.005), better activities of daily living (r=.53, p<.001), lower social skills (r=.43, p=.002), and more hyperactivity (r=-.37, p=.008), but not aggression, anxiety, depression, somatization, atypical behaviors, withdrawal, or attention problems. Longer follow-up interval was correlated with better activities of daily living (r=.46, p<.001), but more anxiety (r=.39, p=.006). Gender, SES, radiation field, history of hydrocephalus, and location of tumor were not significantly related to primary outcome variables. Posterior fossa syndrome was associated with lower adaptive skills (t=2.90, p=.003) and IQ (t=2.02, p=.026). Of those enrolled in school, 59% received special education services and/or accommodations (IEP n=18, Early Intervention n=6; 504 Plan n=3).

Overall, PRT before age 4 years was associated with difficulties with withdrawal, adaptive skills, and executive functioning. Younger age at PRT was associated with lower adaptive functioning, lower social skills, and higher hyperactivity, but not with IQ, attention, mood, or anxiety. While a longer time interval since treatment was associated with improvement in activities of daily living, anxiety was increased, suggesting some late emotional effects. Furthermore, posterior fossa syndrome after surgery was related to lower adaptive skills and IQ. Attention problems were not indicated. Approximately half received school services/accommodations. Young children treated with PRT require proactive support and services to foster their developmental outcomes.