A meta-analysis of the relationship between symptom severity of Posttraumatic Stress Disorder and executive function.

INTRODUCTION: Some studies of Posttraumatic Stress Disorder (PTSD) find executive dysfunction, whereas others do not. We meta-analytically examined the association between executive function and PTSD and used meta-regression to examine the potential moderating effect of PTSD severity on executive function. METHODS: We conducted a meta-analysis according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We identified published peer-reviewed articles containing measures of executive function and PTSD symptom severity in subjects with PTSD compared to trauma-unexposed controls or trauma-exposed controls without PTSD, or both. We calculated an effect size for each study containing at least one measure of executive function and PTSD symptom severity. RESULTS: PTSD subjects for whom the Clinician-Administered PTSD Scale (CAPS) score was available had worse executive function compared to both trauma-unexposed controls (g = 0.464, p < .001) and to trauma-exposed controls without PTSD (g = 0.414, p = .001), as did PTSD subjects for whom the Mississippi Scale for Combat-Related PTSD (M-PTSD) score was available (g = 0.390, p < .001). Neither CAPS nor M-PTSD scores significantly moderated the effect size of executive function. CONCLUSIONS: PTSD is associated with executive dysfunction, but this association was not moderated by PTSD symptom severity, suggesting that once PTSD occurs, executive dysfunction may occur regardless of PTSD severity.

Day of injury CT and late MRI findings: Cognitive outcome in a paediatric sample with complicated mild traumatic brain injury.

OBJECTIVES: Complicated mild traumatic brain injury (mTBI) or cmTBI is based on the presence of visibly identifiable brain pathology on the day-of-injury computed tomography (CT) scan. In a paediatric sample the relation of DOI CT to late MRI findings and neuropsychological outcome was examined. METHODS: MRI (>12 months) was obtained in paediatric cmTBI patients and a sample of orthopaedically injured (OI) children. Those children with positive imaging findings (MRI+) were quantitatively compared to those without (MRI-) or with the OI sample. Groups were also compared in neurocognitive outcome from WASI sub-tests and the WISC-IV Processing Speed Index (PSI), along with the Test of Everyday Attention for Children (TEA-Ch) and a parent-rated behavioural functioning measure (ABAS-II). RESULTS: Despite the MRI+ group having significantly more DOI CT findings than the MRI- group, no quantitative differences were found. WASI Vocabulary and Matrix Reasoning scores were significantly lower, but not PSI, TEA-Ch or ABAS-II scores. MRI+ and MRI- groups did not differ on these measures. CONCLUSIONS: Heterogeneity in the occurrence of MRI-identified focal pathology was not associated with uniform changes in quantitative analyses of brain structure in cmTBI. Increased number of DOI CT abnormalities was associated with lowered neuropsychological performance.

Psychiatric Disease as a Potential Risk Factor for Dementia: A Narrative Review.

Neurodegenerative disease is a major global health problem with 150 million people predicted to have dementia by 2050. Genetic factors, environmental factors, demographics, and some diseases have been associated with dementia. In addition to associations between diseases such as hypertension and cerebrovascular disease and dementia, emerging findings associate some psychiatric disorders with incident dementia. Because of the high and increasing global prevalence of dementia and the high worldwide prevalence of psychiatric disorders, the primary objective of this narrative review was to evaluate published findings that evaluate the association between bipolar disorder, depression, anxiety, post-traumatic stress disorder, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorder, schizophrenia and other psychosis syndromes, and personality disorders and personality traits and incident dementia. Here, we highlight findings indicating possible associations between these psychiatric disorders and subsequent dementia and suggest that some psychiatric disorders may be risk factors for incident dementia. Further research, including more large longitudinal studies and additional meta-analyses, however, is needed to better characterize the associations between psychiatric disorders and incident dementia, to identify possible mechanisms for these putative associations, and to identify risk factors within psychiatric disorders that predispose some people with a psychiatric disorder but not others to subsequent dementia. Additional important questions concern how the treatment of psychiatric disorders might affect the risk of incident dementia.

Human Cytomegalovirus Infection and Neurocognitive and Neuropsychiatric Health.

A common infection, human cytomegalovirus (HCMV) has been associated with a variety of human diseases, including cardiovascular disease and possibly certain cancers. HCMV has also been associated with cognitive, psychiatric, and neurological conditions. Children with congenital or early-life HCMV are at risk for microcephaly, cerebral palsy, and sensorineural hearing loss, although in many cases sensorineural loss may resolve. In addition, HCMV can be associated with neurodevelopmental impairment, which may improve with time. In young, middle-aged, and older adults, HCMV has been adversely associated with cognitive function in some but not in all studies. Research has linked HCMV to Alzheimer's and vascular dementia, but again not all findings consistently support these associations. In addition, HCMV has been associated with depressive disorder, bipolar disorder, anxiety, and autism-spectrum disorder, although the available findings are likewise inconsistent. Given associations between HCMV and a variety of neurocognitive and neuropsychiatric disorders, additional research investigating reasons for the considerable inconsistencies in the currently available findings is needed. Additional meta-analyses and more longitudinal studies are needed as well. Research into the effects of antiviral medication on cognitive and neurological outcomes and continued efforts in vaccine development have potential to lower the neurocognitive, neuropsychiatric, and neurological burden of HCMV infection.

Prevalence of traumatic brain injury in the general adult population: a meta-analysis.

Traumatic brain injury (TBI) is a significant public-health concern. To understand the extent of TBI, it is important to assess the prevalence of TBI in the general population. However, the prevalence of TBI in the general population can be difficult to measure because of differing definitions of TBI, differing TBI severity levels, and underreporting of sport-related TBI. Additionally, prevalence reports vary from study to study. In this present study, we used meta-analytic methods to estimate the prevalence of TBI in the adult general population. Across 15 studies, all originating from developed countries, which included 25,134 adults, 12% had a history of TBI. Men had more than twice the odds of having had a TBI than did women, suggesting that male gender is a risk factor for TBI. The adverse behavioral, cognitive and psychiatric effects associated with TBI coupled with the high prevalence of TBI identified in this study indicate that TBI is a considerable public and personal-health problem.

Improving post-intensive care unit neuropsychiatric outcomes: understanding cognitive effects of physical activity.

Critical illness and its treatment often result in long-term neuropsychiatric morbidities. Consequently, there is a need to focus on means to prevent or ameliorate these morbidities. Animal models provide important data regarding the neurobiological effects of physical activity, including angiogenesis, neurogenesis, and release of neurotrophic factors that enhance plasticity. Studies in noncritically ill patients demonstrate that exercise is associated with increased cerebral blood flow, neurogenesis, and brain volume, which are associated with improved cognition. Clinically, research in both healthy and diseased human subjects suggests that exercise improves neuropsychiatric outcomes. In the critical care setting, early physical rehabilitation and mobilization are safe and feasible, with demonstrated improvements in physical functional outcomes. Such activity may also reduce the duration of delirium in the intensive care unit (ICU) and improve neuropsychiatric outcomes, although data are limited. Barriers exist regarding implementing ICU rehabilitation in routine care, including use of sedatives and lack of awareness of post-ICU cognitive impairments. Further research is necessary to determine whether prior animal and human research, in conjunction with preliminary results from existing ICU studies, can translate into improvements for neuropsychiatric outcomes in critically ill patients. Studies are needed to evaluate biological mechanisms, risk factors, the role of pre-ICU functional level, and the timing, duration, and type of physical activity for optimal patient outcomes.

A prospective randomized study examining the impact of intravenous versus inhalational anesthesia on postoperative cognitive decline and delirium.

The present prospective randomized study was designed to investigate whether the development of Post Operative Cognitive Decline (POCD) is related to anesthesia type in older adults. All patients were screened for delirium and mental status, received baseline neuropsychological assessment, and evaluation of activities of daily living (ADLs). Follow-up assessments were performed at 3-6 months and 12-18 months. Patients were randomized to receive either inhalation anesthesia (ISO) with isoflurane or total intravenous anesthesia (TIVA) with propofol for maintenance anesthesia. ISO (n = 99) and TIVA (n = 100) groups were similar in demographics, preoperative cognition, and incidence of post-operative delirium. Groups did not differ in terms of mean change in memory or executive function from baseline to follow-up. Pre-surgical cognitive function is the only variable predictive of the development of POCD. Anesthetic type was not predictive of POCD. However, ADLs were predictive of post-operative delirium development. Overall, this pilot study represents a prospective, randomized study demonstrating that when examining ISO versus TIVA for maintenance of general anesthesia, there is no significant difference in cognition between anesthetic types. There is also no difference in the occurrence of postoperative delirium. Postoperative cognitive decline was best predicted by lower baseline cognition and functional status.

Scheltens ratings, clinical white matter hyperintensities and executive functioning in the Cache County Memory Study.

OBJECTIVE: Examine the association between neuropsychologically assessed executive function and clinically identifiable white matter burden from magnetic resonance imaging, using a visual rating system (Scheltens Rating System) applied to the Cache County Memory Study (CCMS) archival database. METHOD: We used the Scheltens Ratings Scale to quantify white matter lesion burden in the CCMS sample and used this metric as a predictor of executive function. The sample included 60 individuals with dementia and 13 healthy controls. RESULTS: Higher Scheltens ratings were associated with poorer task performance on an Executive Function composite score of common neuropsychological tests. This association held true for both controls and dementing cases. CONCLUSIONS: The current findings support extensive prior literature demonstrating the association between brain vascular health determined by white matter burden and clinical outcomes based on neuropsychological assessment of cognitive performance.

Interhemispheric transfer time and concussion in adolescents: A longitudinal study using response time and event-related potential measures.

Introduction: Concussion in children and adolescents is a public health concern with higher concussion incidence than adults and increased susceptibility to axonal injury. The corpus callosum is a vulnerable location of concussion-related white matter damage that can be associated with short- and long-term effects of concussion. Interhemispheric transfer time (IHTT) of visual information across the corpus callosum can be used as a direct measure of corpus callosum functioning that may be impacted by adolescent concussion with slower IHTT relative to matched controls. Longitudinal studies and studies testing physiological measures of IHTT following concussion in adolescents are lacking. Methods: We used the N1 and P1 components of the scalp-recorded brain event-related potential (ERP) to measure IHTT in 20 adolescents (ages 12-19 years old) with confirmed concussion and 16 neurologically-healthy control participants within 3 weeks of concussion (subacute stage) and approximately 10 months after injury (longitudinal). Results: Separate two-group (concussion, control) by two-time (3 weeks, 10 months) repeated measures ANOVAs on difference response times and IHTT latencies of the P1 and N1 components showed no significant differences by group (ps ≥ 0.25) nor by time (ps ≥ 0.64), with no significant interactions (ps ≥ 0.15). Discussion: Results from the current sample suggest that measures of IHTT may not be strongly influenced at 3 weeks or longitudinally following adolescent concussion using the current IHTT paradigm.

Performance monitoring and cognitive control in individuals with mild traumatic brain injury.

Literature suggests that individuals with mild traumatic brain injury (mTBI) show subtle abnormalities in the cognitive control process of performance monitoring. The neural bases of performance monitoring can be measured using the error-related negaitivity (ERN) and post-error positivity (Pe) components of the scalp-recorded event-related potential (ERP). Thirty-six individuals with mTBI and 46 demographically similar controls completed a modified color-naming Stroop task while ERPs were recorded. Separate repeated-measures analyses of variance were used to examine the behavioral (response times [RT] and error rates) and ERP (ERN and Pe amplitudes) indices of performance monitoring. Both groups showed slower RTs and increased error rates on incongruent trials relative to congruent trials. Likewise, both groups showed more negative ERN and more positive Pe amplitude to error trials relative to correct trials. Notably, there were no significant main effects or interactions of group for behavioral and ERP measures. Subgroup and correlational analyses with post-concussive symptoms and indices of injury severity were also not significant. Findings suggest comparable performance to non-injured individuals in some aspects of cognitive control in this sample. Neuropsychological implications and comparison with other cognitive control component processes in individuals with TBI are provided.

Assessment of brain activity during memory encoding in a narcolepsy patient on and off modafinil using normative fMRI data.

We present behavioral and functional magnetic resonance imaging (fMRI) findings of a 20-year-old female with narcolepsy who completed a standardized fMRI-adapted face memory task both 'off' and 'on' modafinil compared to a normative sample (N = 38). The patient showed poor recognition performance off modafinil (z = -2.03) but intact performance on modafinil (z = 0.78). fMRI results showed atypical activation during memory encoding off modafinil, with frontal lobe hypoactivity, but hippocampal hyperactivity, whereas all brain regions showed more normalized activation on modafinil. Results from this limited study suggest hippocampal and frontal alterations in individuals with narcolepsy. Further, the results suggest the hypothesis that modafinil may affect brain activation in some people with narcolepsy.

Association between C-reactive protein and cognitive deficits in elderly men and women: a meta-analysis.

BACKGROUND: Certain risk factors for cognitive decline appear modifiable. A potentially modifiable marker of inflammation, C-reactive protein may be associated with cognitive deficits, although not all studies have found a relationship between C-reactive protein and cognitive ability. Further, few research papers have examined whether gender may affect any association between C-reactive protein and cognitive deficit. METHODS: To better understand the association between C-reactive protein, cognitive deficit, and gender in elderly people, we meta-analyzed cross-sectional studies that reported cognitive ability assessed by the Mini-Mental State Examination or an equivalent measure, C-reactive protein concentrations, and gender. RESULTS: While we identified no studies containing only male subjects, the two identified studies containing both female and male subjects (n = 2,525) showed an effect size for cognition of -0.1809 (95% confidence interval, -0.2652 to -0.0967, p = 0.000025) between high and low C-reactive-protein groups. In contrast, the two identified studies containing only female subjects (n = 1,754) showed an effect size for cognition of 0.0345 (95% confidence interval, -0.0594 to 0.1285, not significant). CONCLUSIONS: In the context of a small number of source studies and lack of an all-male group, these results suggest that any association between C-reactive protein and cognitive deficits may be stronger in elderly men than in elderly women.

Long-Term Sequelae in Young Convalescent COVID-19 Patients.

As of March 2022, over 78 million cases of COVID-19 and 900,000 deaths have been reported in the United States. The consequences in the acute phase due to the SARS-COV-2 infection are well defined. Beyond the direct effects of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) involving the lung parenchyma, the post-viral complications within the central nervous system are still largely unknown, and a comprehensive evaluation regarding the long-term neuropsychological sequelae from this disease is not well characterized. An increasing number of patients previously diagnosed with COVID-19 have now presented with ongoing symptoms of inattention, executive function, and memory difficulties. These symptoms are collectively and commonly known by the public as 'brain fog', with many expressing concerns over their inability to engage in the workplace due to these symptoms. Here, we describe three patients who were seen in the Memory Disorders Clinic at Duke University to characterize the long-term neuropsychological symptoms, neuropsychological test results and brain MRI findings after infection with SARS-CoV-2 in a cohort of patients under the age of 60.

Are effort measures sensitive to cognitive impairment?

The basic premise of symptom validity tests (SVTs) is that appropriate effort can be assessed because the designs of SVT measures are thought to be insensitive to all but the most extreme forms of impairment of memory. In patients with mild traumatic brain injury in particular, it is thought that failure on effort measures consistently reflects poor effort or even conscious exaggeration of symptoms. This study examines the issue of SVT failure as a reflection of cognitive impairment and/or neuropsychiatric impairment by presenting cases of three patients who were given full neuropsychological batteries but in each case failed the Word Memory Test (WMT), a verbal recognition SVT measure. One patient who failed the WMT was probably in the early stages of dementia. The WMT fit the "Genuine Memory Impaired Profile". Two mild traumatic brain injury patients failed the WMT but their patterns of performance suggested that cognitive deficits influenced WMT performance. In determining the validity of neuropsychological test data in the individual case, it is recommended that the examiner consider whether cognitive impairment could affect performance on effort measures and the recommended cut score. Also, it is recommended that examiners use multiple indicators of effort.

Cohort differences on the CVLT-II and CVLT3: Evidence of a negative Flynn effect on the attention/working memory and learning trials.

OBJECTIVE: Although cohort effects on IQ measures have been investigated extensively, studies exploring cohort differences on verbal memory tests, and the extent to which they are influenced by socioenvironmental changes across decades (e.g. educational attainment; ethnic makeup), have been limited. METHOD: We examined differences in performance between the normative samples of the CVLT-II from 1999 and the CVLT3 from 2016 to 2017 on the immediate- and delayed-recall trials, and we explored the degree to which verbal learning and memory skills might be influenced by the cohort year in which norms were collected versus demographic factors (e.g. education level). RESULTS: Multivariate analysis of variance tests and follow-up univariate tests yielded evidence for a negative cohort effect (also referred to as negative Flynn effect) on performance, controlling for demographic factors (p = .001). In particular, findings revealed evidence of a negative Flynn effect on the attention/working memory and learning trials (Trial 1, Trial 2, Trial 3, Trials 1-5 Total, List B; ps < .007), with no significant cohort differences found on the delayed-recall trials. As expected, education level, age group, and ethnicity were significant predictors of CVLT performance (ps < .01). Importantly, however, there were no interactions between cohort year of norms collection and education level, age group, or ethnicity on performance. CONCLUSIONS: The clinical implications of the present findings for using word list learning and memory tests like the CVLT, and the potential role of socioenvironmental factors on the observed negative Flynn effect on the attention/working memory and learning trials, are discussed.

Trail-Making Test Part B: Evaluation of the Efficiency Score for Assessing Floor-Level Change in Veterans.

OBJECTIVE: The Trail Making Test - Part B (TMT-B) is a commonly used executive control measure with a known floor effect, limiting the ability to distinguish impairment among individuals unable to complete this task in the standard time limit. Our group previously proposed the TMT-B Efficiency Score (TMT-Be), which captures performance variability among examinees who fail to complete the task. The present study assesses the TMT-Be in a longitudinal clinical sample. METHOD: Data were collected via record review of veterans who underwent two clinical neuropsychological evaluations. We identified 30 veterans (mean age Visit 1:69 ± 8.7 years) who were unable to complete TMT-B during at least one evaluation (mean days between visits = 615). Two scoring systems were utilized to examine performance variability: TMT-Be and TMT-B Prorated Score (TMT-Bpr). RESULTS: TMT-Be distribution was less skewed, but more platykuric, compared to TMT-Bpr. TMT-Be and TMT-Bpr were highly correlated. Both metrics correlated with psychomotor speed and another executive task, but not confrontation naming, providing both convergent and discriminant evidence of validity. TMT-Be, but not TMT-Bpr, detected significant decline in performance longitudinally. Age and education were significant predictors of the TMT-Be, but not TMT-Bpr, difference scores. CONCLUSIONS: Both metrics captured performance variability in a clinical sample and provided sufficient variance for examining floor-level performance on the TMT-B. TMT-Be appeared to be less prone to creating outliers and more likely to detect change. The results support the utility of the TMT-Be metric in research and clinical settings.

Lowering the Floor on Trail Making Test Part B: Psychometric Evidence for a New Scoring Metric.

The Trail Making Test Part B (TMT-B) is widely used in clinical and research settings as a measure of executive function. Standard administration allows a maximal time score (i.e., floor score) of 300 s. This practice potentially masks performance variability among cognitively impaired individuals who cannot complete the task. For example, performances that are nearly complete receive the same 300-s score as a performance of only a few moves. Such performance differences may have utility in research and clinical settings. To address this, we propose a new TMT-B efficiency metric designed to capture clinically relevant performance variability below the standard administration floor. Our metric takes into account time, correct moves, and errors of commission and omission. We demonstrate that the metric has concurrent validity, permits statistical analysis of performances that fall below the test floor, and captures clinically relevant performance variability missed by alternative methods.

Prevalence of traumatic brain injury in juvenile offenders: a meta-analysis.

Studies of traumatic brain injury (TBI) among adult populations demonstrate that such injuries can lead to aggressive behaviors. Related findings suggest that incarcerated individuals have high rates of brain injuries. Such studies suggest that traumatic brain injury may be related to the etiology and recidivism of criminal behavior. Relatively few studies have examined the prevalence of TBI using a delinquent juvenile sample. In order to assess the relationship between TBI and juvenile offender status, the current study used meta-analytic techniques to examine the odds of having a TBI among juvenile offenders. Across 9 studies, we found that approximately 30% of juvenile offenders have sustained a previous brain injury. Across 5 studies that used a control group, a calculated summary odds ratio of 3.37 suggests that juvenile offenders are significantly more likely to have a TBI compared to controls. Results suggest that the rate of TBIs within the juvenile offender population is significant and that there may be a relationship between TBIs and juvenile criminal behavior.

Reaffirmed limitations of meta-analytic methods in the study of mild traumatic brain injury: a response to Rohling et al.

In 2009 Pertab, James, and Bigler published a critique of two prior meta-analyses by Binder, Rohling, and Larrabee (1997) and Frencham, Fox, and Maybery (2005) that showed small effect size difference at least 3 months post-injury in individuals who had sustained a mild traumatic brain injury (mTBI). The Binder et al. and Frencham et al. meta-analyses have been widely cited as showing no lasting effect of mTBI. In their critique Pertab et al. (2009) point out many limitations of these two prior meta-analyses, demonstrating that depending on how inclusion/exclusion criteria were defined different meta-analytic findings occur, some supporting the persistence of neuropsychological impairments beyond 3 months. Rohling et al. (2011) have now critiqued Pertab et al. (2009). Herein we respond to the Rolling et al. (2011) critique reaffirming the original findings of Pertab et al. (2009), providing additional details concerning the flaws in prior meta-analytic mTBI studies and the effects on neuropsychological performance.

Heterogeneity of brain lesions in pediatric traumatic brain injury.

OBJECTIVE: Magnetic resonance imaging (MRI) provides a method to identify and quantify abnormalities resulting from traumatic brain injury (TBI). MRI abnormalities in children with TBI have not been fully characterized according to the frequency, location, and quantitative measurement of a range of pathologies critical for studies of neuropsychological outcome. Here, we report MRI findings from a large, multicenter study of childhood TBI, the Social Outcomes of Brain Injury in Kids (SOBIK) study, which compared qualitative and quantitative neuroimaging findings in 72 children with complicated mild-to-severe TBI to 52 children with orthopedic injury (OI). METHOD: Qualitative analyses of MRI scans coded white matter hyperintensities (WMHs), hemosiderin deposits reflecting prior hemorrhagic lesions, regions of encephalomalacia and/or atrophy, and corpus callosum atrophy and traumatic shear lesions. Two automated quantitative analyses were conducted: (a) FreeSurfer methods computed volumes for total brain, white matter (WM), gray matter (GM), corpus callosum, ventricles, amygdala, hippocampus, basal ganglia, and thalamus along with a ventricle-to-brain ratio (VBR); and (b) voxel-based morphometry (VBM) to identify WM, GM, and cerebrospinal fluid. We also examined performance on the Processing Speed Index (PSI) from the Wechsler Intelligence Scale for Children, Fourth Edition, in relation to the above-mentioned neuroimaging variables. RESULTS: WMHs, hemosiderin deposits, and focal areas of encephalomalacia or atrophy were common in children with TBI, were related to injury severity, and were mostly observed within a frontotemporal distribution. Quantitative analyses showed volumetric changes related to injury severity, especially ventricular enlargement and reduced corpus callosum volume. VBM demonstrated similar findings, but, in addition, GM reductions in the inferior frontal, basal forebrain region, especially in the severe TBI group. The complicated mild TBI group showed few differences from the OI group. PSI was significantly associated with global atrophy, as measured by VBR. CONCLUSION: MRI findings after childhood TBI are diverse and particularly influenced by injury severity, and they involve common features, group heterogeneity, and individual variability.