Meta-analysis of Cognitive Function Following Non-severe SARS-CoV-2 Infection.

To effectively diagnose and treat subjective cognitive symptoms in post-acute sequalae of COVID-19 (PASC), it is important to understand objective cognitive impairment across the range of acute COVID-19 severity. Despite the importance of this area of research, to our knowledge, there are no current meta-analyses of objective cognitive functioning following non-severe initial SARS-CoV-2 infection. The aim of this meta-analysis is to describe objective cognitive impairment in individuals with non-severe (mild or moderate) SARS-CoV-2 cases in the post-acute stage of infection. This meta-analysis was pre-registered with Prospero (CRD42021293124) and utilized the PRISMA checklist for reporting guidelines, with screening conducted by at least two independent reviewers for all aspects of the screening and data extraction process. Fifty-nine articles (total participants = 22,060) with three types of study designs met our full criteria. Individuals with non-severe (mild/moderate) initial SARS-CoV-2 infection demonstrated worse objective cognitive performance compared to healthy comparison participants. However, those with mild (nonhospitalized) initial SARS-CoV-2 infections had better objective cognitive performance than those with moderate (hospitalized but not requiring ICU care) or severe (hospitalized with ICU care) initial SARS-CoV-2 infections. For studies that used normative data comparisons instead of healthy comparison participants, there was a small and nearly significant effect when compared to normative data. There were high levels of heterogeneity (88.6 to 97.3%), likely reflecting small sample sizes and variations in primary study methodology. Individuals who have recovered from non-severe cases of SARS-CoV-2 infections may be at risk for cognitive decline or impairment and may benefit from cognitive health interventions.

Meta-analysis of Cognitive Rehabilitation Interventions in Veterans and Service Members With Traumatic Brain Injuries.

MAIN OBJECTIVE: Cognitive difficulties are some of the most frequently experienced symptoms following mild-to-moderate traumatic brain injuries (TBIs). There is meta-analytic evidence that cognitive rehabilitation improves cognitive functioning after TBI in nonveteran populations but not specifically within the veteran and service member (V/SM) population. The purpose of the current meta-analysis was to examine the effect of cognitive rehabilitation interventions for V/SMs with a history of mild-to-moderate TBI. DESIGN AND MAIN MEASURES: This meta-analysis was preregistered with PROSPERO (CRD42021262902) and used the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) checklist for reporting guidelines. Inclusion criteria required studies to have (1) randomized controlled trials; (2) used adult participants (aged 18 years or older) who were US veterans or active-duty service members who had a history of mild-to-moderate TBI; (3) cognitive rehabilitation treatments designed to improve cognition and/or everyday functioning; (4) used objective neuropsychological testing as a primary outcome measure; and (5) been published in English. At least 2 reviewers independently screened all identified abstracts and full-text articles and coded demographic and effect size data. The final search was run on February 24, 2023, using 4 databases (PubMed, PsycINFO, Web of Science, and Google Scholar). Study quality and bias were examined using the revised Cochrane Risk-of-Bias Tool for Randomized Trials. RESULTS: We identified 8 articles meeting full criteria (total participants = 564; 97% of whom had a history of mild TBI). Compared with control groups, participants showed a small, but significant, improvement in overall objective neuropsychological functioning after cognitive rehabilitation interventions. Interventions focusing on teaching strategies had a larger effect size than did those focusing on drill-and-practice approaches for both objective neuropsychological test performance and performance-based measures of functional capacity. CONCLUSION: There is evidence of cognitive improvement in V/SMs with TBI histories after participation in cognitive rehabilitation. Clinician-administered interventions focusing on teaching strategies may yield the greatest cognitive improvement in this population.

Research Letter: Characterizing Lifetime Mild TBI Exposure Among Female and Male Military Service Members and Veterans in the LIMBIC-CENC Study.

OBJECTIVE: To (1) characterize lifetime mild traumatic brain injury (TBI) exposures among male and female US military service members and Veterans (SMVs) and (2) evaluate sex-related differences in mild TBI exposures. SETTING: Clinical research laboratory. PARTICIPANTS: Participants were enrolled in the ongoing Long-term Impact of Military-relevant Brain Injury Consortium-Chronic Effects of Neurotrauma Consortium (LIMBIC-CENC) Prospective Longitudinal Study. DESIGN: Cross-sectional. MAIN MEASURES: Lifetime history of mild TBI was measured via structured interview. All mild TBI characteristics were collected as part of this interview, including total lifetime number; environment (deployment vs. non-deployment); timing of injury (relative to military service and age); and mechanism of injury (blast-related vs. non-blast). RESULTS: Most participants (n = 2323; 87.5% male; 79.6% Veteran) reported ≥1 lifetime mild TBI (n = 1912; 82%), among whom, many reported ≥2 lifetime mild TBIs. Female SMVs reported fewer total lifetime mild TBIs than male participants (P < 0.001), including fewer deployment-related (P < 0.001) and non-deployment (P < 0.001) mild TBIs. There were significant sex differences for total number of mild TBIs sustained before (P = 0.005) and during (P < 0.001) military service but not after separation from military service (P = 0.99). Among participants with a lifetime history of mild TBI, female SMVs were less likely to report ≥2 mTBIs (P = 0.003); however, male SMVs were more likely to report a mild TBI during military service (P = 0.03), including combat-related mild TBI (P < 0.001) and mild TBI involving blast (P < 0.001). CONCLUSIONS: These findings inform clinical and research efforts related to mild TBI in US military SMVs. It may not be sufficient to simply measure the total number of mild TBIs when seeking to compare clinical outcomes related to mild TBI between sexes; rather, it is important to measure and account for the timing, environment, and mechanisms associated with mild TBIs sustained by female and male SMVs.

Altered lateralization of the cingulum in deployment-related traumatic brain injury: An ENIGMA military-relevant brain injury study.

Traumatic brain injury (TBI) in military populations can cause disruptions in brain structure and function, along with cognitive and psychological dysfunction. Diffusion magnetic resonance imaging (dMRI) can detect alterations in white matter (WM) microstructure, but few studies have examined brain asymmetry. Examining asymmetry in large samples may increase sensitivity to detect heterogeneous areas of WM alteration in mild TBI. Through the Enhancing Neuroimaging Genetics Through Meta-Analysis Military-Relevant Brain Injury working group, we conducted a mega-analysis of neuroimaging and clinical data from 16 cohorts of Active Duty Service Members and Veterans (n = 2598). dMRI data were processed together along with harmonized demographic, injury, psychiatric, and cognitive measures. Fractional anisotropy in the cingulum showed greater asymmetry in individuals with deployment-related TBI, driven by greater left lateralization in TBI. Results remained significant after accounting for potentially confounding variables including posttraumatic stress disorder, depression, and handedness, and were driven primarily by individuals whose worst TBI occurred before age 40. Alterations in the cingulum were also associated with slower processing speed and poorer set shifting. The results indicate an enhancement of the natural left laterality of the cingulum, possibly due to vulnerability of the nondominant hemisphere or compensatory mechanisms in the dominant hemisphere. The cingulum is one of the last WM tracts to mature, reaching peak FA around 42 years old. This effect was primarily detected in individuals whose worst injury occurred before age 40, suggesting that the protracted development of the cingulum may lead to increased vulnerability to insults, such as TBI.

Cognitive performance in functional seizures compared with epilepsy and healthy controls: a systematic review and meta analysis.

BACKGROUND: Cognition is a core component of functional seizures, but the literature on cognition in this disorder has been heterogeneous, with no clear unifying profile emerging from individual studies. The aim of this study was to do a systematic review and meta-analysis of cognitive performance in adults with functional seizures compared with epilepsy (including left temporal lobe epilepsy) and compared with healthy non-seizure cohorts. METHODS: In this systematic review and meta-analysis, starting Feb 6, 2023, replicated and updated on Oct 31, 2023, a medical librarian searched MEDLINE, Embase, PsycINFO, and Web of Science. Inclusion criteria were full reports documenting raw or standardised cognitive test data in adults with functional seizures compared with adults with epilepsy, prospectively recruited healthy comparisons, or published norms. Grey literature was retained and there were no language or date restrictions. We excluded studies only reporting on mixed functional seizures and epilepsy, or mixed functional neurological samples, with no pure functional seizures group. Risk of bias was evaluated using a modified version of the Newcastle-Ottawa Scale. People with lived experiences were not involved in the design or execution of this study. This study is registered as CRD42023392385 in PROSPERO. FINDINGS: Of 3834 records initially identified, 84 articles were retained, including 8654 participants (functional seizures 4193, epilepsy 3638, and healthy comparisons 823). Mean age was 36 years (SD 12) for functional seizures, 36 years (12) for epilepsy, and 34 years (10) for healthy comparisons, and the proportion of women per group was 72% (range 18-100) for functional seizures, 59% (range 15-100) for epilepsy, and 69% (range 34-100) for healthy comparisons. Data on race or ethnicity were rarely reported in the individual studies. Risk of bias was moderate. Cognitive performance was better in people with functional seizures than those with epilepsy (Hedges' g=0·17 [95% CI 0·10-0·25)], p<0·0001), with moderate-to-high heterogeneity (Q[56]=128·91, p=0·0001, I2=57%). The functional seizures group performed better than the epilepsy group on global cognition and intelligence quotient (g=0·15 [0·02-0·28], p=0·022) and language (g=0·28 [0·14-0·43], p=0·0001), but not other cognitive domains. A larger effect was noted in language tests when comparing functional seizures with left temporal lobe epilepsy (k=5; g=0·51 [0·10 to 0·91], p=0·015). The functional seizures group underperformed relative to healthy comparisons (g=-0·61 [-0·78 to -0·44], p<0·0001), with significant differences in all cognitive domains. Meta regressions examining effects of multiple covariates on global cognition were not significant. INTERPRETATION: Patients with functional seizures have widespread cognitive impairments that are likely to be clinically meaningful on the basis of moderate effect sizes in multiple domains. These deficits might be slightly less severe than those seen in many patients with epilepsy but nevertheless argue for consideration of clinical assessment and treatment. FUNDING: Department of Veterans Affairs, Veterans Health Administration.

Neuropsychological functioning, neurobehavioral symptoms, and community reintegration in unstably housed veterans with mental health conditions.

Objective: Returning Veterans often have conditions (e.g. posttraumatic stress disorder [PTSD], depression, and history of traumatic brain injury [TBI]) associated with cognitive dysfunction and problems with work, school, housing, and relationships. Rehabilitative efforts in Veterans aim to promote community reintegration, or successful adjustment in one's home, community, and desired social roles. We examined associations between neuropsychological performance, neurobehavioral symptoms, and community reintegration in Veterans. Method: 89 Iraq/Afghanistan Veterans at risk for homelessness and receiving residential mental healthcare completed a neuropsychological assessment and the Community Reintegration for Service Members-Computer Adaptive Test (CRIS-CAT). Neuropsychological components were derived using Principal Component Analysis. Bivariate Pearson correlations between neuropsychological variables, neurobehavioral symptoms, and CRIS-CAT scales (Extent of Participation, Perceived Limitations, and Satisfaction) were used to determine significant correlates of community reintegration. Regression models were used to examine associations between bivariate-significant neuropsychological components, neurobehavioral symptoms, and CRIS-CAT scales. Results: Bivariate analyses revealed that better community reintegration was associated with better performance in attention/executive functioning and fewer neurobehavioral symptoms. Three regression models examining predictors of variance in Extent of Participation, Perceived Limitations, and Satisfaction in community reintegration were statistically significant overall, with only fewer affective symptoms emerging as significantly and uniquely associated with greater participation and greater satisfaction in community functioning. Conclusions: Veterans with fewer affective symptoms reported greater participation and satisfaction with community functioning. Future longitudinal research examining associations between neurobehavioral symptoms, cognition, and risk factors of poorer community reintegration in unstably housed Veterans is warranted.

The utility of the Wisconsin card sorting test, 64-card version to detect noncredible attention-deficit/hyperactivity disorder.

Clinicians who evaluate patients with concerns related to attention-deficit/hyperactivity disorder (ADHD) are encouraged to include validity indicators throughout clinical assessment procedures. To date, no known previous literature has examined the Wisconsin Card Sorting Test (WCST) specifically to address noncredible ADHD, and none has attempted to identify an embedded PVT within the 64-card version. The present study sought to address these gaps in the literature with a simulation study. Sixty-seven undergraduate participants (M age = 19.30) were grouped as credible (combining healthy controls and individuals with ADHD) or noncredible (combining coached and uncoached participants simulating ADHD-related impairment) and administered a battery of neuropsychological tests. Results revealed the noncredible group performed significantly worse on several WCST-64 variables, including failure to maintain set, number of trials to first category, and total categories. Raw scores from these variables were entered as predictors as one set in a logistic regression (LR) with group membership as the outcome variable. An exponentiated equation (EE) derived from LR results yielded acceptable discriminability (area under receiver operating characteristic curve = .73) with modest sensitivity (.38) while maintaining ideal specificity (.91), generally commensurate with a standalone forced-choice memory PVT and better than an embedded attention-based PVT. These findings suggested the WCST-64 may be sensitive to noncredible performance in the context of ADHD and reiterates the importance of considering tests of various cognitive abilities in the evaluation of performance validity. Implications of these findings, limitations of the present study, and directions for future inquiry, including cross-validation in clinical samples, were discussed.

The dimensionality of the Behavior Rating Inventory of Executive Function, Second Edition in a clinical sample.

The parent-report Behavior Rating Inventory of Executive Function, Second Edition (BRIEF-2) is a widely used pediatric neuropsychological measure. Unfortunately, despite meaningful changes from its predecessor, few studies have examined its internal factor structure (now with Behavioral Regulation [BRI], Emotion Regulation [ERI], and Cognitive Regulation [CRI]), and no available literature has investigated higher order models for the BRIEF-2. This study sought to address this shortcoming in the literature by investigating and reporting on the dimensionality of the parent-report BRIEF-2 in a clinical sample. Two hundred and two (202) pediatric neuropsychology examinees (M age = 9.90; 68% males) with complete data for the parent-report BRIEF-2 were included. Descriptive results revealed generally elevated scores across BRIEF-2 scales (Global Executive Composite M T = 70.16). Exploratory factor analyses suggested two factors (CRI and BRI/ERI) should be extracted, and that higher order models should be considered. Confirmatory factor analyses suggested that a direct hierarchical/bifactor two-factor structure (which was more parsimonious than the theoretical three-factor model) provided the best fit, with a bulk of the variance explained by the general GEC factor. The BRIEF-2 may be best interpreted at the overall level, with relatively less weight given to the index variables, particularly within clinical samples with high levels of reported executive functioning difficulties. Implications of these findings, limitations of the present study, and appropriate directions for future inquiry were discussed.

Examination of five- and four-subtest short form IQ estimations for the Wechsler Intelligence Scale for Children-Fifth edition (WISC-V) in a mixed clinical sample.

Evaluating general cognitive ability (i.e., intelligence) is common in neuropsychological practice, and identifying abbreviated assessments of intelligence is often advantageous. Despite the Wechsler Intelligence Scale for Children, Fifth Edition's (WISC-V) widespread contemporary use, limited research has identified clinically useful short form (SF) full scale IQ (FSIQ) estimations in clinical samples. This study sought to address this gap in the literature. Two hundred sixty-eight pediatric participants (M age = 9.79; 69% male; 88% Caucasian/White) who underwent psychological/neuropsychological evaluation were included. Mean scores for WISC-V scores fell in the low average-to-average ranges, consistent with the clinical nature of this sample (e.g., M FSIQ = 85.3). Ten unique SF combinations with five (pentad) and four (tetrad) subtests, each intentionally selected to represent a breadth of domains subsumed by WISC-V FSIQ, were described by summing subtest age-corrected scaled scores. Regression-based and prorated FSIQ estimates were calculated, and mean differences suggested some prorated estimates should be arithmetically adjusted. Both regression-based and prorated/adjusted methods provided FSIQ estimates that were accurate within five Standard Score points of true FSIQ for approximately 81-92% (pentad) and 65-76% (tetrads) of participants. Prorated/adjusted estimates appeared to provide somewhat better accuracy than regression-based estimates. Relationships between SFs and true FSIQ did not appear to be moderated by participant age, gender, nor how many WISC-V subtests were administered to participants within this archival sample (i.e., 7 vs. 10). Implications of these findings, including benefits, detriments, and other considerations of each SF combination, in addition to limitations of this study, are discussed in detail.