Mean levels of cognitive functioning typically do not show an association with self-reported cognitive fatigue in persons with multiple sclerosis (PwMS), but some studies indicate that cognitive variability has an association with cognitive fatigue. Additionally, coping has been shown to be a powerful moderator of some outcomes in multiple sclerosis (MS). To date, however, coping has not been considered as a possible moderator of the relationship between cognitive fatigue and cognitive variability in MS. The current study examined this relationship.

We examined 52 PwMS. All participants were administered the Fatigue Impact Scale, the Coping Orientation to Problems Experienced Questionnaire, and cognitive tests. Indices of variability for memory and attention/executive functioning tests were used as outcome variables. Avoidant coping, active coping, and composite coping indices were used as moderators.

The interaction analyses for the avoidant coping and composite coping indices were significant and accounted for 8 and 11% of the attention/executive functioning variability outcome, respectively. The interactions revealed that at low levels of cognitive fatigue, attention/executive functioning variability was comparable between the low and high avoidant and composite coping groups. However, at high levels of cognitive fatigue, PwMS using lower levels of avoidant coping (less maladaptive coping) showed less variable attention/executive functioning scores compared with those using higher levels of avoidant coping. We found a similar pattern for the composite coping groups.

At high levels of cognitive fatigue, PwMS using adaptive coping showed less attention/executive functioning variability. These findings should be considered in the context of treatment implications.

Executive dysfunction, including working memory deficits, is prominent in posttraumatic stress disorder (PTSD) and can impede treatment effectiveness. Intervention approaches that target executive dysfunction alongside standard PTSD treatments could boost clinical response. The current study reports secondary analyses from a randomized controlled trial testing combined PTSD treatment with a computerized training program to improve executive dysfunction. We assessed if pre-treatment neurocognitive substrates of executive functioning predicted clinical response to this novel intervention.

Treatment-seeking veterans with PTSD (N = 60) completed a working memory task during functional magnetic resonance imaging prior to being randomized to six weeks of computerized executive function training (five 30-minute sessions each week) plus twelve 50-minute sessions of cognitive processing therapy (CEFT + CPT) or placebo training plus CPT (PT + CPT). Using linear mixed effects models, we examined the extent to which the neurocognitive substrates of executive functioning predicted PTSD treatment response.

Results indicated that veterans with greater activation of working memory regions (e.g. lateral prefrontal and cingulate cortex) had better PTSD symptom improvement trajectories in CEFT + CPT v. PT + CPT. Those with less neural activation during working memory showed similar trajectories of PTSD symptom change regardless of treatment condition.

Greater activity of frontal regions implicated in working memory may serve as a biomarker of response to a novel treatment in veterans with PTSD. Individuals with greater regional responsiveness benefited more from treatment that targeted cognitive dysfunction than treatment that did not include active cognitive training. Clinically, findings could inform our understanding of treatment mechanisms and may contribute to better personalization of treatment.

Accurate appraisal of one’s own abilities (i.e., insight) is necessary for appropriate compensatory behaviors and sustained independence during aging. Although insight is often purported to be related to executive functioning (EF), nuanced understanding of the cognitive correlates of insight for functional abilities among nondemented older adults is lacking. Because insight shares neuroanatomic underpinnings with time-based prospective memory (PM), the present study examined the contributions of time-based PM, beyond event-based PM and other potential cognitive confounds (i.e., episodic memory, time estimation, and EF), in predicting insight into one’s own performance on instrumental activities of daily living (IADLs) among community-dwelling older adults.

A group of 88 nondemented, community-dwelling older adults completed performance-based measures of time- and event-based PM, episodic memory, time estimation, and EF, as well as IADL tasks followed by self-appraisals of their own IADL performance as indices of insight.

Time-based PM was moderately-to-strongly associated with insight, beyond event-based PM, time estimation, and episodic memory [F(1,83) = 11.58, p = .001, ηp2 = .122], as well as beyond EF and demographic covariates [F(1,79) = 10.72, p = .002, ηp2 = .119].Specifically, older adults who performed more poorly on a time-based PM task overestimated the efficiency of their own IADL performance to a greater extent.

Findings suggest that nondemented older adults with poorer time-based PM may be more prone to inaccurately appraising their functional abilities and that this vulnerability may not be adequately captured by traditional EF measures.

Theory and research indicated that executive functioning (EF) correlated with, preceded, and stemmed from worry in generalized anxiety disorder (GAD). The present secondary analysis (Zainal & Newman, 2023b) thus determined whether EF domains mediated the effect of a 14-day (5 prompts/day) mindfulness ecological momentary intervention (MEMI) against a self-monitoring control (SM) for GAD.

Participants (N = 110) diagnosed with GAD completed self-reported (Attentional Control Scale, GAD Questionnaire, Perseverative Cognitions Questionnaire) and performance-based tests (Letter-Number Sequencing, Stroop, Trail Making Test-B, Verbal Fluency) at baseline, post-treatment, and one-month follow-up (1MFU). Causal mediation analyses determined if pre-post changes in EF domains preceded and mediated the effect of MEMI against SM on pre-1MFU changes in GAD severity and trait repetitive negative thinking (RNT).

MEMI was more efficacious than SM in improving pre–post inhibition (β = −2.075, 95% [−3.388, −0.762], p = .002), working memory (β = 0.512, 95% [0.012, 1.011], p = .045), and set-shifting (β = −2.916, 95% [−5.142, −0.691], p = .010) but not verbal fluency and attentional control. Within groups, MEMI but not SM produced improvements in all examined pre–post EF outcomes except attentional control. Only pre–post improvements in inhibition mediated the effect of MEMI against SM on pre-1MFU reductions in GAD severity (β = −0.605, 95% [−1.357, −0.044], p = .030; proportion mediated = 7.1%) and trait RNT (β = −0.024, 95% [−0.054, −0.001], p = .040; proportion mediated = 7.4%). These patterns remained after conducting sensitivity analyses with non-linear mediator-outcome relations.

Optimizing MEMI for GAD might entail specifically boosting inhibition plausibly by augmenting it with dialectical behavioral therapy, encouraging high-intensity physical exercises, and targeting negative emotional contrast avoidance.

Loss of empathy is a hallmark feature of behavioral variant frontotemporal dementia (bvFTD). Change in socioemotional functioning identified by others is often the primary initial presenting concern in this disorder, in contrast to more subtle early cognitive changes and limited patient insight. The present study examined the predictive utility of an empathy informant-report measure for discriminating clinician-diagnosed bvFTD from other dementia syndromes.

Data from the National Alzheimer’s Coordinating Center (NACC) database were used to study individuals with bvFTD (n = 406) and other dementia syndromes (n = 385). Participants were administered neuropsychological measures and collateral informants completed an informant-report of empathy.

Informants reported that patients with bvFTD demonstrated significantly lower levels of empathic concern [F(1, 789) = 120.91, p < .001, η 2 = 0.13] and perspective taking [F(1, 789) = 153.08, p < .001, η 2 = 0.16] than patients with other dementia syndromes. These differences were not attributable to the level of global cognitive impairment. Empathy scores were not significantly associated with any neurocognitive measure when controlling for age. ROC curve analyses showed fair to good clinical utility of the informant-report empathy measure for distinguishing bvFTD from non-bvFTD, whereas a traditional measure of executive functioning failed to differentiate the groups.

These findings indicate that informant ratings of empathy offer a unique source of clinical information that may be useful in detecting neurobehavioral changes specific to bvFTD before a clear neurocognitive pattern emerges on testing.

Wiedemann-Steiner syndrome (WSS) is a rare Mendelian disorder of the epigenetic machinery caused by heterozygous pathogenic variants in KMT2A. Currently, the specific neurocognitive profile of this syndrome remains unknown. This case series provides insight into the cognitive phenotype of WSS.

This study involves a retrospective medical chart review of 10 pediatric patients, each with a molecularly confirmed diagnosis of WSS who underwent clinical neuropsychological evaluation at an academic medical center.

The majority of patients performed in the below average to very low ranges in Nonverbal Reasoning, Visual/Spatial Perception, Visuoconstruction, Visual Memory, Attention, Working Memory and Math Computation skills. In contrast, over half the sample performed within normal limits on Receptive Vocabulary, Verbal Memory, and Word Reading. Wilcoxon signed rank test showed weaker Nonverbal versus Verbal Reasoning skills (p = .005). Most caregivers reported deficits in executive functioning, most notably in emotion regulation.

Nonverbal reasoning/memory, visuospatial/construction, attention, working memory, executive functioning, and math computation skills are areas of weakness among those with WSS. These findings overlap with research on Kabuki syndrome, which is caused by variants in KMT2D, and suggest disruption in the neurogenesis of the hippocampal formation may drive shared pathogenesis of the two syndromes.

Patients with remitted Cushing’s Disease (CD) often present persisting impairments in executive and cognitive functioning domains. Little research has been conducted regarding the functional neural correlates of an important executive functioning skill, namely the ability to plan, in these patients.

To examine visuospatial planning related brain activity in remitted CD patients and matched controls using functional magnetic resonance imaging (fMRI).

fMRI scans were made using a 3-Telsa scanner while remitted CD patients (n=21) and age-, gender-, and education matched healthy controls (HCs; n=21) completed a parametric Tower of London (ToL) task. Psychological and cognitive functioning were assessed using validated questionnaires. Clinical severity was assessed retrospectively using the Cushing’s syndrome Severity Index (CSI).

CD Patients were on average 45.1 (SD=7.1) years old, 81% female, and in remission for mean 10.68 (SD=7.69) years. No differences were found in number of correct trials, response times per ToL trial, or in the region of interest analyses. Exploratory wholebrain analyses found that CD patients showed more activation in several brain regions associated with higher cognitive processes on 2-, 3-, and 5-step trials compared to HCs. Over-recruitment of the right parietal operculum cortex in the patients was significantly negatively associated with the prior active disease state on the CSI (r=-0.519, p=0.02).

The increased brain activation during the ToL in remitted CD patients versus controls signals over-recruitment of certain brain areas involved in higher cognitive processes. CD may thus result in long-lasting, subtle scarring effects during demanding executive functioning tasks, despite remission.

No significant relationships.

This study evaluated: (1) apolipoprotein E (APOE) ϵ4 prevalence among Black, Latino, and White older adults, (2) associations of APOE ϵ4 status with baseline level and change over time of cognitive outcomes across groups, and (3) combined impact of APOE ϵ4 prevalence and magnitude of effect on cognitive decline within each racial/ethnic group.

Participants included 297 White, 138 Latino, and 149 Black individuals from the longitudinal UC Davis Diversity Cohort who had APOE genotyping and ≥2 cognitive assessments. Magnitude of associations of ϵ4 with cognitive baseline and change across racial/ethnic groups was tested with multilevel parallel process longitudinal analyses and multiple group models.

ϵ4 prevalence in Black (46%) and White participants (46%) was almost double that of Latino participants (24%). ϵ4 was associated with poorer baseline episodic memory only in White participants (p = .001), but had a moderately strong association with episodic memory change across all racial/ethnic groups (Blacks= −.061 SD/year, Latinos = −.055,Whites= −.055). ϵ4 association with semantic memory change was strongest in White participants (−.071), intermediate in Latino participants (−.041), and weakest in Black participants (−.022).

Calculated cognitive trajectories across racial/ethnic groups were influenced in an additive manner by ϵ4 prevalence and strength of association with cognitive decline within the group. Group differences in ϵ4 prevalences and associations of ϵ4 with cognition may suggest different pathways from APOE to cognitive decline, and, AD possibly having less salient impact on cognitive decline in non-White participants. Differential effects of APOE on episodic memory and non-memory cognition have important implications for understanding how APOE influences late life cognitive decline.