Children with attention-deficit/hyperactivity disorder (ADHD) commonly exhibit impairments in their executive functions. Caregivers are primarily responsible for the daily management of their children's ADHD and executive functioning difficulties. Psychoeducation, a cornerstone of ADHD treatment, can empower caregivers by providing them the knowledge and resources they require to support their child with ADHD. This study examined the efficacy of a suite of six caregiver psychoeducation sessions delivered by a specialised ADHD service. Two of these sessions pertained to (i) Understanding ADHD and (ii) Executive Functioning in ADHD. The other four covered information around Family Self-Care and Stress Management, Social Connectedness and Communication, Sensory Processing and Self-Regulation in ADHD and, Medication.

All sessions were delivered between May 2016 and July 2022, in 2 to 3-hour sessions each. Caregivers completed pre and post-session questionnaires, rating (i) their understanding of each of the topics, (ii) whether they identified effective strategies to help their child with ADHD meet their needs, and (iii) whether they improved their knowledge of resources they can access to assist with ADHD management. Altogether, 666 caregiver responses were collected across all sessions, 35% (n=234) of which were from the Understanding ADHD sessions and 4.2% (n = 28) from the Executive Functioning sessions.

Wilcoxon signed-rank tests with Bonferroni adjusted alpha level of 0.016 were conducted to examine each session's pre- and post-session responses. Results showed that the Understanding ADHD workshops impelled significant improvements in attendee-rated levels of topic understanding (z = -8.79, p <.001, r = -.41), strategies gained (z = -8.54, p <.001, r = -.40) and perceived resource accessibility (z = -6.40, p <.001, r = -.30). Attendees reported moderate to large improvements following the Executive Functioning in ADHD sessions, including in their topic understanding (z = -4.18, p <.001, r = -.57), strategies gained (z = -3.93, p <.001, r = -.54) and perceived resource accessibility (z = -4.23, p <.001, r = -.61). Improvements across all three areas were also noted across the other four caregiver sessions, except for the medication session where no significant changes in strategies gained and perceived access to resources were noted.

This study provides evidence that caregiver sessions within a Tier-4 service are efficacious and can (i) meet caregivers' needs to better understand ADHD, executive functioning difficulties as well as of other ADHD-related issues, and (ii) may equip caregivers with the knowledge to access resources to appropriately manage their children with ADHD - a possible precursor to improved clinical and functional outcomes in children. That the session on ADHD medications only led to improved understanding of the topic but not to perceived gains in strategies or perceived access to strategies could be attributed to low pre-and post-session questionnaire response rates as well as to the nature of those sessions which were purely informative and did not discuss strategies and resources. Nonetheless, longitudinal studies, with control groups, should determine whether any post-intervention improvements are sustained over time and should establish whether these are associated with improved outcomes in children.

Prospective memory (PM) is the ability to remember to produce an action at a specific moment in the future signaled by the occurrence of a specific event (EB condition), a time or a time interval (TB condition). Detection of the appropriate moment corresponds to the prospective component (PC), while production of the appropriate action corresponds to the retrospective (RC) component. Although PM difficulties have been reported in healthy aging and in association with Multiple Sclerosis (MS), PM has not been examined in elderly people with MS (PwMS), which is particularly relevant since their life expectancy has improved significantly in recent years due to available treatments, and PM is essential to daily functioning. The main objective of this study was to investigate whether the decline in PM performance with advancing age is influenced by the presence of multiple sclerosis (MS). This study also aimed to clarify the type of PM impairment (PC vs RC in TB and EB conditions) in MS as a function of age.

A total of 80 participants were recruited and separated into four groups: elderly PwMS (n = 20), young PwMS (n = 20), elderly healthy controls (HC) (n = 20) and young HC (n = 20). PM and its components were measured using the TEMP, an experimental ecological tool developed by our laboratory that has been validated in previous studies. In addition, all participants underwent a series of neuropsychological tests specific to MS (MACIFMS) and aging (Boston Naming Test, Clock Drawing Test, Towers of London, Trail making Test, Stroop, MoCA).

On the TEMP total score, a two-way ANOVA showed a main effect of age (F[1,75]=47.4, p<0.001, n2 = .40), a main effect of the presence of MS (F[1,75]=19.51, p<0.001, n2 = .21) as well as a significant Age X Disease interaction (F[2,74] =5.40, p=0.023, n2 = .07). Direct comparison between EB and TB conditions revealed that for the PC, only elderly PwMS had more difficulty in the TB than in the EB condition (Z = -2.51, p = 0.012), whereas RC score was significantly lower in the TB than in the EB condition in all groups except in younger controls (younger PwMS : Z = -2.56, p = 0.01; elderly HC : Z = -3.31, p < 0.001; elderly PwMS :Z = -3.04, p = 0.002).

The TEMP revealed a marked impairment in PM in elderly PwMS compared to elderly HC and young PwMS. This impairment was particularly evident on the PC component in the TB condition. RC difficulties noted in the TB condition in all but younger controls reflect the arbitrary nature of the cue-action link that is particularly sensitive to episodic memory difficulties often observed in aging and MS.

Parental history (PH) of problematic substance use has been identified as a risk factor for adolescent substance use, which can lead to increased use in adulthood. Researchers hypothesize that individuals with PH exhibit premorbid differences in their reward processing, increasing their likelihood of engaging in reward-driven behavior. Studies have shown that preadolescents with PH have greater activation in their putamen and nucleus accumbens (NA); however, most research has only investigated PH of alcohol use (PHA), not PH of drug use (PHD). Additionally, limited research has assessed whether reward processing develops differently among youth with (PH+) to youth without (PH-). The present study utilizes the national, prospective Adolescent Brain Cognitive Development SM (ABCD) Study to examine whether reward anticipation in the nucleus accumbens (NA) differs in preadolescents with and without parental substance use history and whether patterns of reward anticipation change over time during a two-year follow-up period. Further, it will also examine whether PHA and PHD predict similar activation patterns.

The current sample (N=6,600, Mage = 10.9; range = 9-13.8 years old; 46.7% female) was drawn from the national ABCD Study. To assess reward processing, the Monetary Incentive Delay Task (MID), a fMRI task-based paradigm, was administered at baseline and 2 year follow-up. The primary regions of interest (ROI) were the left and right NA and neutral vs anticipation of large rewards was the selected contrast. The Family History Assessment was used to assess problematic parental alcohol and drug use for both parents, with scores ranging from 0-2, with two indicating that both parents demonstrate problematic use. Three PH contrasts (PH- vs.PH+1, PH-vs.PH+2, & PH+1 vs. PH+2) were created for each group (PHA and PHD) (Martz et al., 2022). Separate linear mixed-effect models with predictors variables (parental contrasts, timepoint, and parental contrasts-by-time-point) and covariates (age, sex, race/ethnicity, income, parental education, parental warmth, parental monitoring, and the random effects of MRI model, family status, and subject) were run to predict reward anticipation.

Results indicated that PHA and,not PHD, was predictive of reward anticipation. PHA+1 youth showed greater activation in the l-NA (b= .02827, p= .03) and r-NA (b= .03476, p=.005), compared to PH- youth. Additionally, PHA+1 youth showed greater activation in the r-NA (b=-.07029, p=.008) compared to PHA+2 youth, but not in the l-NA. Those with PHA+2 demonstrated blunted activity in both the l-NA (b= -.07244, p=.02) and right nucleus accumbens (b= -.1091, p=001) when compared to those with PH-. No interactions with time were found.

Preadolescents with a PHA+ for both parents had blunted activity in reward anticipation, conferring a unique risk not seen in youth with only one parent with problematic alcohol use, or in youth with a PH of drug use. Future research should attempt to disentangle both genetic and environmental factors that may explain these discrepancies in reward processing, as well as the protective factors that may mitigate it. The current study found no interaction between PHA+ and time, suggesting that during preadolescents, the pattern of reward functioning remains consistent, but future work should assess if this pattern holds up across adolescence

Inhibitory control impairment is highly prevalent following traumatic brain injury (TBI). There have not been any empirical investigations into whether this could explain social disinhibition following severe TBI, i.e. socially inappropriate behaviour of verbal, physical or sexual nature. Further, social context has proven to be important in studying social disinhibition and using a social version of an established task for the assessment of inhibitory control may provide a new perspective. Therefore, the objectives of this research study were to investigate the role of inhibitory control impairment in social disinhibition following severe TBI, using a social and a non-social task. We hypothesized that people with TBI and clinical levels of social disinhibition would perform worse on both task versions, when compared to those with low disinhibition levels. Further, we hypothesized that participants high on social disinhibition would perform worse on the social, when compared to the non-social version.

We conducted a between-group comparative study. Twenty-six adult participants with severe TBI were matched with 27 adult, healthy controls based on gender, age and education. Frontal Systems Behavior Scale and Social Disinhibition Interview were used to assess social disinhibition. A computerized task based on the cued go/no-go paradigm was used to assess inhibitory control. We included two versions of this task – a coloured (non-social) Go/No-Go with different colored rectangles, and an emotional (social) Go/No-Go with emotional faces serving as ‘go‘ and ‘no-go‘ cues. Two-way mixed ANCOVAs were used to test between-group differences in errors of commission and response speed.

Unexpectedly, the TBI and the control group did not significantly differ on their levels of depression, anxiety, stress, or their level of social disinhibition. Overall, participants were slower (F(1,47) = 15.212, p<.001, ηp2 = .245) and made more errors of commission on no-go trials (F(1,44) = 11.560, p = .001, ηp2 = .208) on the social Go/No-Go task. There was no main effect of participants‘ brain injury status on errors of commission on no-go trials or mean reaction times. When categorized based on disinhibition level (high vs low), participants in the highdisinhibition group made more errors on the social task (F(1,41) = 4.095, p = .050, ηp2 = .091) than those in the low-disinhibition group, and more errors on the social, compared to the non-social task (task-group interaction (F(1,41) = 7.233, p = .010, ηp2 = .150)).

Based on these initial results, social disinhibition is associated with inhibitory control impairment, although this is only evident when a social inhibitory control task is used for assessment. We did not find any relationship between social disinhibition and the speed with which people react to stimuli. The results of this study add to the conceptualization of social disinhibition that is commonly present after severe TBI.

Prospective memory (PM) tasks are common in everyday life and have been implicated in optimal daily functioning. However, less is known about the parameters of PM tasks that most influence functional decline, as well as the domains of everyday functioning most sensitive to PM impairment. The present study sought to examine these questions in individuals with traumatic brain injury (TBI).

Participants included 30 adults with chronic moderate-to-severe TBI who were at least one year removed from their injury (median [IQR] = 8.1 years [10.8]). Participants completed the Memory for Intentions Test (MIST), which is a 30-minute task that assesses time- and event-based PM with varying cue-intention delay length (2 versus 15 min) in the context of an ongoing task. Total scores were generated for each delay length and cue type. Additionally, participants completed a comprehensive neuropsychological battery, including assessments of processing speed, executive functions, attention, working memory, verbal fluency, and episodic learning and memory. Participants also completed questionnaires of self-reported cognitive and everyday functioning, including the Functional Behavior Profile (FBP), Prospective and Retrospective Memory Questionnaire (PRMQ) and a modified Lawton & Brody Instrumental Activities of Daily Living (IADL) Scale, which separately assessed 11 domains of everyday functioning.

Pearson’s r correlations revealed that total number of domains showing decline on the modified Lawton & Brody IADL scale was strongly correlated with MIST 15-min delay (MIST-15; r=-0.503, p=0.005), such that worse PM performance on long delay items was associated with more domains of IADL decline; this relationship was also reflected in the MIST Total Score (r=-0.389; p=0.033). No other MIST index was associated with IADL decline (ps>0.10). MIST-15 did not significantly correlate with any other measure of self-reported functioning (PRMQ, FBP; all ps>0.10), but was associated with specific declines in buying groceries (p=0.009), performing home repairs (p=0.021), shopping (p=0.033), and doing laundry (p=0.035). Relationships at a trend level included declines in housekeeping (p=0.05), managing finances (p=0.097), cooking (p=0.092), and taking medication (p=0.066). To determine specificity of the relationship between MIST-15 and everyday functioning, a linear regression was conducted using covariates that were significantly correlated with total number of domains of IADL decline (i.e., Selective Reminding Test total learning trials, CVLT-II Long Delay Free Recall, Symbol Digit Modalities Test total). This regression was statistically significant [F(4,24)=4.263; p=0.10; R2=0.415), and MIST-15 remained an independent predictor (p=0.047; R2 change=0.107).

Results suggest that the ability to remember to carry out intended actions after longer delay periods may be uniquely related to severity of declines in everyday functioning. Longer PM delays place higher demands on both memory and executive processes, as the encoded intention must survive a longer decay wherein monitoring for the appropriate cue is extended, and likely better mimic PM tasks in daily life (e.g., remembering to pick up milk after the workday). In light of these findings, clinicians may seek to include brief trials of long delay PM tasks as part of a comprehensive battery to screen for functional decline.

We measured sex differences in emotion regulation (ER) abilities – relying on exercise of cognitive reappraisal – during an image rating task in adults over 55 years of age with varying degrees of depression symptom severity. We also collected a self-report measure on participants' views of their own ER capacities. Previous research by this group has demonstrated the importance of emotion processing in the context of sex and aging in depression. We hypothesized that females would (1) score higher on the Cognitive Reappraisal Facet of the ERQ, (2) be more successful in utilizing cognitive reappraisal skills in response to negative stimuli; and (3) have self-report scores on the ERQ that more closely match their success at cognitive reappraisal than would males.

capacities. Previous research by this group has demonstrated the importance of emotion processing in the context of sex and aging in depression. We hypothesized that females would (1) score higher on the Cognitive Reappraisal Facet of the ERQ, (2) be more successful in utilizing cognitive reappraisal skills in response to negative stimuli; and (3) have self-report scores on the ERQ that more closely match their success at cognitive reappraisal than would males.

Only the first of our three outcome measures was successfully predicted by the model including age, MADRS scores, and sex as predictors. Scores on the ERQ cognitive reappraisal facet with sex accounted for 11.3% of the variance (F=7.344, p=.009). Age and depression symptom severity did not reach significance. Performance on the ERT itself and the correlation between the two were not meaningfully modeled.

Women showed both better cognitive reappraisal abilities overall and more insight into the level of those abilities, findings that fall in line with most ER literature. However, we found that females were also more likely than males to be skewed in the positive or “overconfident” direction; to overestimate those same abilities. This information is useful for clinicians interpreting self-report information in the emotion regulation domain. These findings may not generalize to a more diverse (racially and socioeconomically) population and given the cognitive nature of the reappraisal strategy; these results may not extend to a less educated population. These data will be useful to inform the interpretation of fMRI images from this same experiment.

Semantic fluency measures comprise a differing number of trials depending on the test battery and/or normative data used. Using semantic fluency trials from the Delis Kaplan Executive Function System (D-KEFS; Animals and Boys’ names), we sought to examine whether: 1) there was incremental benefit of multiple trials in associations with aggregated temporal cortical thickness and 2) patterns of neuroanatomical associations with specific temporal lobe structures differed between Animals and Boys’ names trials.

Archival records of adults who completed a neuropsychological evaluation which included the semantic fluency measures of interest and had undergone structural MRI were identified (n=243, Mage=72.35 years, SDage=6.74, Female=46.9%). Cortical thickness values were obtained using FreeSurfer and averaged across sub-regions, separately for the left and right temporal lobe, per recommendations from the FreeSurfer group. Multiple linear regression models were fit to examine separate and incremental contribution of both Animals and Boys’ names, on temporal lobe thickness, including age, sex, and education in the models. Zero order correlations with each of the temporal cortical thickness areas (inferior, middle, and superior temporal; banks of the superior temporal sulcus, fusiform, transverse temporal, entorhinal, temporal pole, and parahippocampal cortices) were also computed to identify more focal neuroanatomical correlates.

Animals and Boys’ names trials individually accounted for a significant proportion of variance when predicting temporal cortical thickness over and above demographics, but Animals was a considerably stronger predictor for left temporal cortical thickness (Left: Animals AR2 =.127*, Boys’ names AR2 = .067*; Right: Animals AR2 =.074*, Boys’ names AR2 = .065*). The variance accounted for by Boys’ names incrementally over Animals was not significant (AR2 = .004 for left and .015 for right hemispheres, respectively). Similarly, though the composite Category fluency index accounted for a significant proportion of the variance independently, it did not add incrementally over and above Animals alone when predicting cortical thickness in either hemisphere. When examining simple correlations with specific temporal cortices, Animals consistently had correlations of a greater magnitude than Boys’ names within the left hemisphere (Animals r>.3 for superior, middle, inferior, and fusiform gyri; Boys’ names r< .3 for all cortical thickness regions). Greater variability was noted for associations with right temporal thickness but Animals continued to show associations of a greater magnitude of associations than Boys’ names for several sub-regions. * denotes significance at p < .01.

The additional Boys’ names trial does not confer significant benefit over Animals alone, when predicting cortical thickness in either temporal lobe. Additionally, overall category fluency provided little incremental utility over and above the Animals trial alone in predicting temporal thickness. Psychometrically, it is expected that composites derived from multiple trials are more robust. However, this study demonstrates that it is important to examine whether the administration of additional trials is truly beneficial, particularly in a climate where brevity of neuropsychological assessment is critically desired. Further, psychometric tests have historically been validated against other neuropsychological measures, but it is critical we also validate measures against neuroanatomical correlates.

Few concussion studies have investigated the psychological domain of concussions. Of the 22 postconcussion symptoms assessed on the Graded Symptom Checklist of the SCAT-5, five do not overlap with core symptoms of anxiety and depression. 43% of patients report at least one psychiatric symptom, the median is four after injury. Previous studies focus on total scores and not individual items; furthermore, few consider resilience as part of psychological factors that impact recovery. This research aims to describe general and specific characteristics of psychological functioning in males/females ages 12-18 after concussion to help guide treatment. We compared total scores for each measure between males/females and looked at the differences between the genders for individual items in each measure.

Participants were evaluated at an outpatient concussion clinic participating in the North Texas Concussion Registry (ConTex; N=1238, 53% female, mean age=15.4 years, SD=1.16 years). The Generalized Anxiety Disorder 7-item Scale (GAD-7, the Patient Health Questionnaire-8 (PHQ-8), the Brief Resilience Scale (BRS), and the Pittsburgh Sleep Quality Index (PSQI) were used to determine levels of anxiety, depression, resilience, and sleep quality.

Utilizing Mann-Whitney U tests (median, interquartile range) to examine group distributions for the GAD-7, PHQ-8, and BRS, females had significantly higher scores than males for the GAD (p<0.001; Female: 4, 1-9 v. Male: 2, 0-5) and PHQ (p<0.001; Female: 5, 210 v. Male: 3, 1-7). For the BRS, total scores for females were significantly lower than males (p<0.001; Female: 3.67, 3-4 v. Male: 3.83, 3.214.33). The PSQI media score was significantly different between males and females: item 2, p=.016 and item 4 p=.007 using an exact sampling distribution for U. Pearson Chi square tests were used to examine sex differences for each item of the psychological measures. Items 1-7 within the GAD-7 were significant between sexes (i.e. male or female). The seven items assess (1) Feelings of nervousness, (2) Inability to stop/control worry, (3) Worrying too much about different things, (4) Trouble relaxing, (5) Inability to sit still due to restlessness, (6) Irritability, and (7) Feeling afraid. Items 2-8 within the PHQ were significant between sexes. The items assess (2) Feeling down/depressed/hopeless, (3) Trouble falling/staying asleep, (4) Feeling tired/no energy, (5) Appetite changes, (6) Lowered/poor self-esteem, (7) Concentration issues, and (8) Feeling slowed down or unable to be still. There was a statistically significant difference between genders and Items 2 and 4 within the BRS were significant between sexes. The items assess (2) Difficulty surviving hard times and (4) Difficulty snapping back from something bad.

Like other studies, this study found females have higher levels of negative affect (i.e., depressive and anxious symptoms). Females displayed lower resilience and reported poorer sleep. By analyzing psychiatric measures, treatment protocols can be tailored to address specific problems, and mental health difficulties can be mitigated by teaching specific coping techniques. These results suggest clinicians should consistently be providing education on depression, anxiety, sleep, and resilience, particularly to female patients, who appear at greater risk for psychological distress.

Blood pressure variability (BPV), independent of traditionally targeted average blood pressure levels, is an emerging vascular risk factor for stroke, cerebrovascular disease, and dementia, possibly through links with vascular-endothelial injury. Recent evidence suggests visit-to-visit (e.g., over months, years) BPV is associated with cerebrovascular disease severity, but less is known about relationships with short-term (e.g., < 24 hours) fluctuations in blood pressure. Additionally, it is unclear how BPV may be related to angiogenic growth factors that play a role in cerebral arterial health.

We investigated relationships between short-term BPV, white matter hyperintensities on MRI, and levels of plasma vascular endothelial growth factor (VEGF) in a sample of community-dwelling older adults (n = 57, ages 55-88) without history of dementia or stroke. Blood pressure was collected continuously during a 5-minute resting period. BPV was calculated as variability independent of mean, a commonly used index of BPV uncorrelated with average blood pressure levels. Participants underwent T2-FLAIR MRI to determine severity of white matter lesion burden. Severity of lesions was classified as Fazekas scores (0-3). Participants also underwent venipuncture to determine levels of plasma VEGF. Ordinal logistic regression examined the association between BPV and Fazekas scores. Multiple linear regression explored relationships between BPV and VEGF. Models controlled for age, sex, and average blood pressure.

Elevated BPV was related to greater white matter lesion burden (i.e., Fazekas score) (systolic: OR = 1.17 [95% CI 1.01, 1.37]; p = .04; diastolic: OR = 2.47 [95% CI 1.09, 5.90]; p = .03) and increased levels of plasma VEGF (systolic: ß = .39 [95% CI .11, .67]; adjusted R2 = .16; p = .007; diastolic: ß = .48 [95% CI .18, .78]; adjusted R2 = .18; p = .003).

Findings suggest short-term BPV may be related to cerebrovascular disease burden and angiogenic growth factors relevant to cerebral arterial health, independent of average blood pressure. Understanding the role of BPV in cerebrovascular disease and vascular-endothelial health may help elucidate the increased risk for stroke and dementia associated with elevated BPV.

Participation in sports likely confers multiple benefits for children and adolescents with autism spectrum disorder (ASD). Adolescent student athletes often undergo preseason testing as part of a broader concussion management program for schools. This study compares preseason neurocognitive functioning and symptom reporting between high school athletes with and without ASD.

Participants were derived from a database of 60,751 adolescent student athletes from Maine (aged 13-18) who completed preseason testing between 2009 and 2019 and did not have missing data on the history question relating to ASD. There were 425 students (0.7%) who self-reported having been diagnosed with ASD in their health history. Cognitive functioning was measured by ImPACT, and the Post-Concussion Symptom Scale (PCSS) was used to obtain symptom ratings. Group differences between the ASD and the population control group on the five ImPACT cognitive test composite raw scores and the total symptom score from the PCSS were examined using Mann-Whitney U tests.

Compared to the population control sample, those with ASD reported much greater rates of comorbid conditions: attention deficit/hyperactivity disorder (50.1% vs. 10.3%), special education (39.2% vs. 4.4%), learning disabilities (43.8% vs. 4.4%), and prior treatment for a psychiatric condition (23.4% vs. 7.5%). Groups differed significantly across all neurocognitive composites (p values <.002). However, all differences were negligible in terms of the magnitude of the effects (r values range from 0.01-0.03). The groups also differed significantly on the PCSS total symptom score (p<.001), but the magnitude of the difference was negligible (r=.031). Among boys, the ASD group endorsed 21 of the 22 symptoms at a greater rate. Among girls, the ASD group endorsed 11 of the 22 individual baseline symptoms at a greater rate than the control group. Examples of symptoms that were endorsed at a higher rate among both boys and girls with ASD: sensitivity to noise (girls: odds ratio, OR=4.38; boys: OR=4.99), numbness or tingling (girls: OR=3.67; boys: OR=3.25), difficulty remembering (girls: OR=2.01; boys: OR=2.49), difficulty concentrating (girls: OR=1.82; boys: OR=2.40), sleeping more than usual (girls: OR=1.94; boys: OR=1.97), sensitivity to light (girls: OR=1.82; boys: OR=1.76), sadness (girls: OR=1.72; boys: OR=2.56), nervousness (girls: OR=1.80; boys: OR=2.27), and feeling more emotional (girls: OR=1.79; boys: OR=2.84).

Students with ASD participating in organized sports are likely high functioning, on average. There were small differences in their cognitive test scores compared to the population control sample. They endorsed more symptoms, however, during baseline preseason testing. If they sustain a concussion, their clinical management should be more intensive to maximize the likelihood of swift and favorable recovery.

Quantitative Susceptibility Mapping (QSM) is an MRI-based technique that sensitively measures in-vivo iron deposition via relaxation and magnetic susceptibility of brain tissue. Iron is essential for brain homeostasis, including oxidative metabolism, formation and maintenance of neural networks, and myelin synthesis. While increased levels of iron deposition occur during normal aging, high levels may have detrimental effects. Previous work has linked excessive brain iron accumulation to oxidative stress, beta-amyloid and tau toxicity, neurodegeneration, and cognitive dysfunction, particularly memory loss. Physical activity, on the other hand, correlates with higher synaptic integrity and memory performance, even in the presence of neuropathology. To date, it is unknown how physical activity may affect iron deposition-related cognition changes. We examined the moderating role of physical activity on the relationship between QSM hippocampal iron deposition and verbal memory in typically aging adults.

62 cognitively unimpaired older adults from the UCSF Memory and Aging Center (age mean(SD) = 78.34(7.28) years; 56% women; education mean(SD) = 17.94(1.72) years; 85% non-Hispanic White) completed neuropsychological testing and brain MRI during annual research visits, followed by Fitbit™ physical activity monitoring for 30 days. Average total daily steps were aggregated. Participants completed 3T Prisma neuroimaging with QSM, and regional iron deposition levels were quantified. All subjects also underwent diffusion tensor imaging (fractional anisotropy). Verbal memory was assessed via long delay free recall scores from the California Verbal Learning Test II (CVLT-II). Linear regression examined verbal memory as a function of hippocampal QSM (bilateral), physical activity, and their interaction. Models covaried for age, sex, and education. Additional models separately examined left and right hippocampal QSM, as well as subcortical QSM to determine lateralization and specificity of verbal memory effects to hippocampal iron deposition, respectively.

Univariably, higher bilateral hippocampal QSM correlated with worse verbal memory (r= 0.35; p= 0.015). Adjusting for demographics, physical activity moderated the relationship between bilateral hippocampal QSM and verbal memory (ß= 0.41, p= 0.011), such that at higher levels of physical activity, the negative relationship between hippocampal QSM and verbal memory was significantly attenuated. Results persisted when adjusting for DTI integrity of the uncinate fasciculus and fornix white matter tracts. Lateralization models were both significant, suggesting that results were not dominantly driven by either left (ß= 0.34, p= 0.048), or right (ß=0.31, p= 0.035) hippocampal QSM. In contrast, subcortical QSM did not correlate with memory performance (r= 0.13, p > 0.05) or interact with physical activity on verbal memory outcomes (p > 0.05).

Physical activity significantly moderated the negative relationship between hippocampal QSM and verbal memory performance. Higher exercise engagement may buffer the adverse effect of hippocampal iron deposition on memory, potentially through its role in maintenance of myelin and synaptic integrity and/or protecting against other neurotoxic events (e.g., oxidative stress, neuronal cell death). Our results support that physical activity continues to be a modifiable risk factor that may offer a protective role in neurobiological pathways of memory and cognitive decline.

With the emergence of the coronavirus 2019 pandemic, investigating the validity of tele-screenings for neuropsychological status has become increasingly necessary. While the telephone version of the Montreal Cognitive Assessment (MoCA-T) has been validated for use in patients with Parkinson’s and stroke/cerebrovascular disease, the clinical utility of this instrument in geriatric patients with other suspected cognitive disorders has yet to be determined. Thus, the present study aimed to examine the classification accuracy of the MoCA-T in a mixed clinical sample of patients with mild cognitive impairment (MCI) or dementia.

Ninety-one older adults were administered the MoCA-T via videoconferencing technology as part of a comprehensive neurocognitive evaluation performed by a multidisciplinary treatment team within a dementia specialty clinic. Based on this evaluation, 51 (56.0%) patients were diagnosed with dementia, 27 (29.7%) with MCI, and 13 (14.3%) with no neurocognitive diagnosis (i.e., subjective cognitive complaints). In addition to MoCA-T total and item scores, we also computed subscale scores for between-group comparisons as the sum of items assessing orientation, language, attention/executive function, and memory. ANOVA/ANCOVA and ROC curve analyses were used to examine between-group differences on the MoCA-T and its psychometric properties in discriminating patients with MCI or dementia, respectively.

Participants had a mean age of 74.3 ± 8.7 and education of 16 ± 2.9 years. Patients with dementia were significantly older than those with MCI and no diagnosis, but there were no other significant between-group differences in clinical characteristics. MoCA-T total [F(2,86)=28.5, p<0.001] and all subscale scores (p<0.01) differed significantly between groups and in the expected direction (dementia<MCI<no diagnosis) even after controlling for age. The only exception was language for which there was initially a statistical trend (p=0.06) that reached significance (p<0.05) after controlling for age. In terms of individual items, abstraction, fluency, orientation to place/city, and category cued recall were the only items that did not differ significantly between groups. ROC curve analyses revealed -5 points to be the optimum cut-off for distinguishing between cognitively normal individuals from patients with MCI (Sensitivity=0.67; Specificity=0.77; AUC=0.78), and a cut-off of -8 points optimally distinguished between patients with MCI and dementia (Sensitivity=0.77; Specificity=0.74; AUC=0.81).

The current study provides further evidence for the clinical utility of the MoCA-T as a screening instrument for neurocognitive disorders in older adults and extends prior work to include administration via videoconferencing technology. While previous studies have focused on the use of MoCA-T in specific patient populations, here, we demonstrate the validity of this screening tool in a mixed-clinical sample, which suggests its broader use in clinical settings for distinguishing between neurocognitive disorders, regardless of the underlying etiology.

Many people with HIV (PWH) are at risk for age-related neurodegenerative disorders such as Alzheimer’s disease (AD). Studies on the association between cognition, neuroimaging outcomes, and the Apolipoprotein E4 (APOE4) genotype, which is associated with greater risk of AD, have yielded mixed results in PWH; however, many of these studies have examined a wide age range of PWH and have not examined APOE by race interactions that are observed in HIV-negative older adults. Thus, we examined how APOE status relates to cognition and medial temporal lobe (MTL) structures (implicated in AD pathogenesis) in mid- to older-aged PWH. In exploratory analyses, we also examined race (African American (AA)/Black and non-Hispanic (NH) White) by APOE status interactions on cognition and MTL structures.

The analysis included 88 PWH between the ages of 45 and 68 (mean age=51±5.9 years; 86% male; 51% AA/Black, 38% NH-White, 9% Hispanic/Latinx, 2% other) from the CNS HIV Antiretroviral Therapy Effects Research multi-site study. Participants underwent APOE genotyping, neuropsychological testing, and structural MRI; APOE groups were defined as APOE4+ (at least one APOE4 allele) and APOE4- (no APOE4 alleles). Eighty-nine percent of participants were on antiretroviral therapy, 74% had undetectable plasma HIV RNA (<50 copies/ml), and 25% were APOE4+ (32% AA/Black/15% NH-White). Neuropsychological testing assessed seven domains, and demographically-corrected T-scores were calculated. FreeSurfer 7.1.1 was used to measure MTL structures (hippocampal volume, entorhinal cortex thickness, and parahippocampal thickness) and the effect of scanner was regressed out prior to analyses. Multivariable linear regressions tested the association between APOE status and cognitive and imaging outcomes. Models examining cognition covaried for comorbid conditions and HIV disease characteristics related to global cognition (i.e., AIDS status, lifetime methamphetamine use disorder). Models examining the MTL covaried for age, sex, and

relevant imaging covariates (i.e., intracranial volume or mean cortical thickness).

APOE4+ carriers had worse learning (ß=-0.27, p=.01) and delayed recall (ß=-0.25, p=.02) compared to the APOE4- group, but APOE status was not significantly associated with any other domain (ps>0.24). APOE4+ status was also associated with thinner entorhinal cortex (ß=-0.24, p=.02). APOE status was not significantly associated with hippocampal volume (ß=-0.08, p=0.32) or parahippocampal thickness (ß=-0.18, p=.08). Lastly, race interacted with APOE status such that the negative association between APOE4+ status and cognition was stronger in NH-White PWH as compared to AA/Black PWH in learning, delayed recall, and verbal fluency (ps<0.05). There were no APOE by race interactions for any MTL structures (ps>0.10).

Findings suggest that APOE4 carrier status is associated with worse episodic memory and thinner entorhinal cortex in mid- to older-aged PWH. While APOE4+ groups were small, we found that APOE4 carrier status had a larger association with cognition in NH-White PWH as compared to AA/Black PWH, consistent with studies demonstrating an attenuated effect of APOE4 in older AA/Black HIV-negative older adults. These findings further highlight the importance of recruiting diverse samples and suggest exploring other genetic markers (e.g., ABCA7) that may be more predictive of AD in some races to better understand AD risk in diverse groups of PWH.

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.

Chronic musculoskeletal pain is associated with neurobiological, physiological, and cellular measures. Importantly, we have previously demonstrated that a biobehavioral and psychosocial resilience index appears to have a protective relationship on the same biomarkers. Less is known regarding the relationships between chronic musculoskeletal pain, protective factors, and brain aging. This study investigates the relationships between clinical pain, a resilience index, and brain age. We hypothesized that higher reported chronic pain would correlate with older appearing brains, and the resilience index will attenuate the strength of the relationship between chronic pain and brain age.

Participants were drawn from an ongoing observational multisite study and included adults with chronic pain who also reported knee pain (N = 135; age = 58.3 ± 8.1; 64% female; 49% non-Hispanic Black, 51% non-Hispanic White; education Mdn = some college; income level Mdn = $30,000 - $40,000; MoCA M = 24.27 ± 3.49). Measures included the Graded Chronic Pain Scale (GCPS), characteristic pain intensity (CPI) and disability, total pain body sites; and a cognitive screening (MoCA). The resilience index consisted of validated biobehavioral (e.g., smoking, waist/hip ratio, and active coping) and psychosocial measures (e.g., optimism, positive affect, negative affect, perceived stress, and social support). T1-weighted MRI data were obtained. Surface area metrics were calculated in FreeSurfer using the Human Connectome Project's multi-modal cortical parcellation scheme. We calculated brain age in R using previously validated and trained machine learning models. Chronological age was subtracted from predicted brain age to generate a brain age gap (BAG). With higher scores of BAG indicating predicated age is older than chronological age. Three parallel hierarchical regression models (each containing one of three pain measures) with three blocks were performed to assess the relationships between chronic pain and the resilience index in relation to BAG, adjusting for covariates. For each model, Block 1 entered the covariates, Block 2 entered a pain score, and Block 3 entered the resilience index.

GCPS CPI (R2 change = .033, p = .027) and GCPS disability (R2 change = 0.038, p = 0.017) significantly predicted BAG beyond the effects of the covariates, but total pain sites (p = 0.865) did not. The resilience index was negatively correlated and a significant predictor of BAG in all three models (p < .05). With the resilience index added in Block 3, both GCPS CPI (p = .067) and GCPS disability (p = .066) measures were no longer significant in their respective models. Additionally, higher education/income (p = 0.016) and study site (p = 0.031) were also significant predictors of BAG.

In this sample, higher reported chronic pain correlated with older appearing brains, and higher resilience attenuated this relationship. The biobehavioral and psychosocial resilience index was associated with younger appearing brains. While our data is cross-sectional, findings are encouraging that interventions targeting both chronic pain and biobehavioral and psychosocial factors (e.g., coping strategies, positive and negative affect, smoking, and social support) might buffer brain aging. Future directions include assessing if chronic pain and resilience factors can predict brain aging over time.

The COVID-19 pandemic increased utilization of remote assessment to allow clinicians and researchers to continue valuable work while maintaining quarantine guidelines. With guidelines relaxing, researchers have returned to in-person assessment. Information is needed regarding the effect of remote assessments on test-retest reliability. COGNET, a longitudinal study of cognition in participants with essential tremor, transitioned from in-person to remote assessments during the pandemic, and has now returned to in-person assessment. The current study investigates the extent to which remote assessment affected test-retest reliability across a range of neuropsychological assessments administered in COGNET.

Participants included 27 older adults enrolled in COGNET (mean age=75.0 (9.1), education=16.2 (2.6), 67% female, and 100% white). Memory tests included: California Verbal Learning Test II, Logical Memory subtest of the Wechsler Memory Scales - Revised, and Verbal Paired? Associates. Executive function tests included: Digit Span Backwards and the Delis-Kaplan Executive Function System subtests of Verbal Fluency, Sorting, and Color-Word. Attention tests included Oral Symbol Digit Modalities Test and Digit Span Forward. Language was assessed with the Boston Naming Test. Intraclass correlation coefficients (ICCs) were calculated to examine test-retest reliability of InPerson to In-Person visits (P-P), and combination visits (e.g., In-Person to Remote (PR), and Remote to In-Person (R-P)). Following Koo & Li (2016), ICCs were interpreted as: >.90 excellent, .75-.90 good, .50-.74 moderate, and <.50 poor reliability. The Feldt approach was used to compare ICCs from P-P visits against ICCs calculated for combination visits (P-R or R-P), with the test statistic compared to an F distribution.

ICCs for person-to-person assessment ranged from .51 to .89. Memory test ICCs ranged from moderate to good (.51 to .80). Executive function test ICCs ranged from moderate to good (.55 to .89). The attention domain had moderate ICCs (.67 - .68). Language ICC was moderate (.70). ICCs for person-to-remote assessment ranged from .42 to .89. Memory tests ranged from moderate to good ICCs (.59 to .83). Executive function tests ranged from poor to good ICCs (.42 to .89). Attention ICCs were moderate to good (.55 to .79). The Language ICC was moderate (.72). ICCs for remote-to-person ranged from .48 to 86. Memory ICCs ranged from moderate to good (.59 to .86). Executive function ICCs ranged from poor to good (.48 to .83). Attention ICCs were moderate to good (.56 to .79). The Language ICC was good (.78). The only test for which an ICC from a combination visit was significantly lower than a person to person visit was Digit Span Backwards.

Test-retest reliability was moderate or better for all P-P assessments, consistent with the known psychometrics of these tests. Only one test of executive function showed lower reliability when remote assessment was introduced. From a broad standpoint, current results suggest that remote administration of neuropsychological tests can be used as a reliable substitute for in-person assessment for many measures, and suggest that caution be used when interpreting any change in Digit Span Backwards across person and remote assessments.

Little research exists characterizing the neuropsychological profile of pediatric insular epilepsy. Accurate diagnosis of insular epilepsy is challenging due to difficulties localizing deep brain structures with current non-invasive neurodiagnostic tools, as well as seizure semiology that may mimic temporal, frontal, and parietal seizures for this patient population [1]. Therefore, we investigated trends across neuropsychological data to help characterize the cognitive profile of pediatric insular epilepsy. This is important because studies that could accurately characterize insular epilepsy into cognitive phenotypes could potentially provide supporting evidence for insular localization during epilepsy surgery work-up. The insula is situated underneath the temporal, parietal, and frontal opercula, and has a number of diffuse projections to key brain structures involved in language, executive functioning, motor coordination, and sensory function [2]. Therefore, we hypothesized that children with insular epilepsy will demonstrate particular weaknesses in language and executive functioning skills.

Retrospective medical records review identified 19 children with insular epilepsy who completed neuropsychological assessment (Age: M=8.2 years, SD=3.4) at Boston Children’s Hospital. Insular epilepsy was defined by ictal insular localization on long-term monitoring EEG. The current sample includes 59% males and 41% females. The majority of participants (69%) had left sided lateralization and more than one seizure type (63%). MRI findings were widely distributed across frontal, temporal, and multiple lobes as well as insular and perisylvian brain regions. A lesion was identified on MRI findings for most participants (63%).

Descriptive analyses showed that overall IQ (FSIQ: M=84, SD=12, range=68-102) fell in the Low Average range. Verbal and visual reasoning skills were equally developed in the Low Average range (VIQ: M=88, SD=12, range=70-104; PIQ: M=88, SD=16, range=53-117). Participants exhibited lower performance on speeded expressive language measures, including measures of phonemic fluency (M=5.5, SD=1.5, range=2-8) and semantic fluency (M=6.7, SD=2.5, range=3-11). With regard to executive functioning, reduced cognitive flexibility was observed on D-KEFS Trail Making Test (Trial 4, Number-Letter Switching: M=5.9, SD=4.9, range=1-12). Additionally, working memory skills fell in the Below Average range (WMIQ: M=77, SD=8.5, range=67-88).

Our results indicate that pediatric patients with insular epilepsy present with reduced scores across aspects of speeded expressive language and executive functioning, including working memory and cognitive flexibility. Additional research is needed to replicate these preliminary findings with a larger sample size and determine whether these trends in cognitive profile would help with seizure localization. Future research should investigate whether insular epilepsy has a clearly identifiable and distinct cognitive phenotype that could be helpful in differential diagnostic workup.

Behavioral interventions are a non-pharmacological treatment that shows improvement in the everyday functioning of people with Mild Cognitive Impairment (MCI). Multiple studies have focused on examining factors that can reduce or enhance adherence to behavioral interventions. However, few studies use adherence as a predictor of functional changes. The goal of this study was to analyze the association between adherence, age, and education in factor score changes of participant impairment, participant adjustment, and partner adjustment in a sample of participants with amnestic MCI (aMCI) and their study partners.

We included fifty-two dyads of a person with aMCI and their study partner with intervention data at baseline and 24-week follow-up from the Physical Exercise and Cognitive Engagement Outcomes for Mild Neurocognitive Disorder (PEACEOFMND) study. At baseline, participants were randomized to one of three behavioral interventions: computerized cognitive training (BrainHQ; n=19), yoga (n=15), or wellness education (n=18). Factors were established from a larger clinical sample that used the same measures as PEACEOFMND. The three-factor latent structure was constructed as the following: 1) participant adjustment combined scores of the Center for Epidemiologic Studies Depression Scale (CES-D), Quality of Life in Alzheimer’s Disease (QoL-AD), and Self-Efficacy for managing MCI scales; 2) partner adjustment included study partner’s scores in CES-D, QoLAD and Caregiving Competence and Mastery Components (CCMC) of the Pearlin scales; 3) participant impairment included participant’s scores in E-Cog memory domain, and study partner’s scores in the Functional Activity Questionnaire (FAQ) and Zarit Burden Interview. We calculated factor changes by obtaining the difference between factor scores at follow-up and baseline. Bayesian correlation analysis was performed to investigate the association between age, education, adherence to the combined behavioral interventions, participant adjustment, participant impairment, and partner adjustment.

The Bayesian correlation results showed moderate evidence (BF10=6.8, Pearson’s r=0.38) supporting a positive correlation between adherence and change in participant adjustment. Additionally, there was moderate evidence (BF10=2.18, Pearson’s r=0.32) supporting a positive correlation between change in participant impairment and participant level of education as well as participant age and change in partner adjustment (BF10=2.8, Pearson’s r=0.33).

Bayesian correlations replicated results from previous analysis using a traditional method, showing that increased adherence to combined behavioral interventions is associated with an increase in participant’s quality of life, self-efficacy, and better mood. Thus, commitment to behavioral intervention completion in aMCI participants is related to overall participant adjustment.

Spontaneous speech undergoes subtle but significant changes years before the onset of Alzheimer's dementia (AD). In monolinguals, these changes, or linguistic markers of AD, include the use of syntactically simpler structures, reduced lexical diversity, reduced semantic detail/specificity, and increased disfluencies (Ostrand & Gunstad, 2020; Slegers et al., 2018; Venneri et al., 2018). No studies have examined if bilinguals exhibit similar changes in their language output prior to diagnosis of AD though this question has important clinical relevance and can also shed light on which cognitive abilities decline first with AD pathology. Of particular interest, changes in semantic representations might affect both languages (because semantics are shared between the two), but changes in executive control might be more prominent in the nondominant language (because of interference from the dominant language).

Seventeen older Spanish-English bilinguals completed an interview in which they described a picture in each language and answered a series of questions beginning with "warm-up" questions and progressing to questions that elicited higher level language (e.g., defending an opinion). All participants were considered cognitively healthy at the time of testing, but 8 participants later developed Alzheimer's Disease (i.e., converters) on average after 4.1 (SD=2.5) years, while 9 matched controls remained cognitively healthy on average for 5.7 (SD=3.6) years (for as long as they were followed). Converters and controls were matched for age, education, language proficiency, and cognitive status at the time of testing. Language samples were transcribed word for word and analyzed using the Systematic Analysis of Language (Miller & Iglesias, 2012).

Converters and controls were compared on measures of syntactic complexity, lexical diversity, abandoned utterances, errors, and disfluencies. In the dominant language, the number of different words (using a moving window average; a measure of lexical diversity), showed promise for classifying who would eventually convert (Area Under the Curve = 77), though the difference between converters and controls was significant only in a 1-tailed test (t(15)=-1.96, p=.034). In the nondominant language, converters showed a higher percent of Maze words compared to controls (2-tailed t (15) = 2.27, p = 0.039). Mazes combine repetitions, filled pauses, and revisions. Further exploration of Maze subcomponents revealed that filled pauses and revisions produced no differences between groups in either language (all ps3.18), but converters produced more repetitions (e.g., "the the boy" or "the cou-counter") than controls, (2-tailed t-tests in both languages were significant; ps <.03). However, variability in repetitions was high, making it less sensitive in the ROC analysis.

Changes in bilinguals' spoken language output occur years before diagnosis, in agreement with literature on monolinguals. However, in bilinguals, the two languages may be differentially affected by cognitive changes. The dominant language may be more sensitive for discriminating groups possibly reflecting semantic decline and decreased ability to quickly access a variety of words. But changes in the nondominant language reveal a broader nature of cognitive deficits in prodromal AD, including decreased circumlocution abilities to avoid disfluencies when faced with word-finding difficulties.