The UCLA longitudinal study of neurocognitive outcomes following mild pediatric traumatic brain injury.

Comprehensive reviews of neurocognitive outcomes following mild, uncomplicated traumatic brain injury (TBI) in children have shown minimal effects on neurocognition, especially in methodologically rigorous studies. In this study, we report longitudinal (1, 6, and 12 months post injury) results in four domains of neurocognitive functioning in a large sample of children with mild TBI (n = 124, ages 8-17 at injury) relative to two demographically matched control groups (other injury: n = 94 and non-injury: n = 106). After accounting for age and parental education, significant main effects of group were observed on 7 of the 10 neurocognitive tests. However, these differences were not unique to the TBI sample but were found between both the TBI and other injury groups relative to the non-injured group, suggesting a general injury effect. Effects were primarily within the domains measuring memory, psychomotor processing speed, and language. This is the largest longitudinal study to date of neurocognitive outcomes at discrete time points in pediatric mild TBI. When controlling for pre-injury factors, there is no evidence of long-term neurocognitive impairment in this group relative to another injury control group. The importance of longitudinal analyses and use of appropriate control groups are discussed in the context of evaluating the effects of mild TBI on cognition.

Brain and cognitive reserve: mediator(s) and construct validity, a critique.

The concept of "reserve" has traditionally been defined on the basis of a single indicator (e.g., education or intracranial volume) that purports to moderate or buffer the effects of brain damage on different clinical outcomes. While studies have shown modest effects for some indicators, it has left the concept of "reserve" wanting as an explanatory construct. More recently efforts have been made to identify groups of indicators hypothesized to represent a construct for brain or cognitive reserve. These efforts have also proved wanting because of the lack of evidence to justify such a priori groupings of variables into a brain or cognitive reserve construct. This theoretical paper addresses the issue of construct validity (convergent and discriminant) for both brain and cognitive reserve as single or multiple reserve factors. Conceptual models are proposed that are (a) derived from the current extant reserve literature and (b) empirically testable in order to facilitate establishment of construct validity for the commonly used, and perhaps misused, brain and cognitive reserve concepts.

Children's Color Trails Test 1 & 2: test-retest reliability and factorial validity.

This investigation examined the test-retest reliability and the factorial validity of the Children's Color Trails Test 1 & 2 (CCTT) using two distinct and independent studies and their respective research samples. The reliability of the CCTT was evaluated in a study with 6-12-year-old children (n = 54) strictly selected and diagnosed with attention-deficit/hyperactivity disorder from an interventional protocol using test-retest coefficients at 8- and 16-week time intervals. Factorial validity was investigated using groups of children with traumatic brain injury (TBI) (n = 137), children with other types of trauma than brain or head injury (Other Injury) (n = 132), and healthy controls (n = 114) from a protocol assessing the neuropsychological sequelae of traumatic brain injury. The results revealed completion time test-retest reliability in the moderate range, which may be considered modest (r(tt) =.46-.68) in this sample of children with ADHD. Interference reliability coefficients were greater and in the moderate-high range (r(tt) =.75-.78). Factorial analytic results revealed a three-factor structure solution for all three groups (TBI, Other Injury, and controls). As a result of CCTT's factorial loadings, Factor 1 was labeled speed of perceptual tracking and susceptibility to interference, Factor 2 was labeled inattention and impulsivity, and Factor 3 was labeled simple inattention. Relative limitations and strengths associated with this investigation including practice effects associated with repeated CCTT administrations also were addressed within the context of the extant findings and existing trail-making test literature.

Neuropsychological exploration of alleged mold neurotoxicity.

Cognitive and emotional correlates of toxic mold exposure and potential dose-response effects for both outcomes were investigated. Self-reported length of exposure, time since last exposure, and serum immunoglobulin (IgG) levels were assessed. Despite CNS complaints often seen with mold exposed individuals, overall results did not uncover concomitant cognitive deficits suggested in previous studies or a significant reduction in intellectual functioning. Fewer subjects were excluded as result of failing effort/motivation assessment than expected. Correlations of IgG and cognitive function are discussed. A dose-effect for self-reported length of exposure and cognitive outcome was not seen. The sample's overall Minnesota Multiphasic Personality Inventory II (MMPI-2) profile indicated elevations on scales 1, 2, 3, 7 and 8. MMPI-2 clinical scales 1 and 3 were significantly correlated with length of exposure. The MMPI-2 may be sensitive to increasing physical and emotional sequelae as length of exposure increases. A potential subgroup of cognitively impaired outliers within mold exposure litigants is explored. Limitations of self-reported and objective measurements for mold exposure and exploratory statistical methodology are discussed.

Childhood cognitive performance and risk of generalized anxiety disorder.

BACKGROUND: Perception of control over one's environment, particularly when faced with an ambiguous situation, has been identified as a critical cognitive process involved in worry and generalized anxiety disorder (GAD). Similarly, it is thought that individuals with lower cognitive skills feel less in control, and do not cope as well as individuals with higher cognitive skills. This study tests the hypothesis that individuals with higher cognitive skills are less likely to develop a lifetime diagnosis of GAD, and considers onset in three developmental periods: childhood, adolescence and adulthood. METHODS: Survival analysis and multivariate regression models were used to evaluate the relationship between cognitive performance at age seven, and DSM-IV diagnosis of GAD. Study participants were 689 individuals in their mid-30s, who had been followed since birth as part of the National Collaborative Perinatal Project in Providence, RI, USA. RESULTS: A 15-point (1 SD) advantage in childhood cognitive performance was significantly associated with a 50% reduced risk of lifetime GAD and an 89 and 57% reduction in risk of GAD in childhood and adolescence, respectively, after adjusting for relevant covariates including socio-economic status and parent history of mental health problems. These results were not affected by behavioural inhibition or learning disabilities in childhood. CONCLUSIONS: Childhood cognitive performance is associated with a diagnosis of GAD in childhood and adolescence. Further research on the association between childhood cognitive performance and GAD is warranted.

Components of depression in HIV-1 infection: their differential relationship to neurocognitive performance.

Both depression and neurocognitive compromise are commonly observed among persons infected with the Human Immunodeficiency Virus (HIV). To date, the majority of studies have failed to find a consistent relationship between mood and cognition among HIV-seropositive (HIV+) individuals, suggesting that these constructs are independent of one another. However, depression is a multi-dimensional syndrome and its measurement often utilizes multi-factorial instruments containing cognitive, affective, somatic, and motivational components. The degree to which various symptoms or dimensions of depression might be related to neuropsychological performance in HIV-1 infection is not typically explored and was a main objective of the current study. A sample of 247 HIV+ persons completed both a comprehensive neurocognitive battery and the Beck Depression Inventory (BDI) as part of a standard clinical evaluation at a major community hospital. To examine the dimensionality of the BDI, a principal components analysis was conducted which suggested a three-factor solution comprised of factors representing Self-Reproach (SR), Mood-Motivation Disturbance (MM), and Somatic Disturbance (SOM). The relationship between each of these three factors and neurocognitive performance was examined using both regression and analysis of variance techniques. These analyses showed the MM factor, more so than either the SR or SOM factors, to be associated with several aspects of neurocognitive performance, including verbal memory, executive functioning, and motor speed. These findings suggest that certain items on depression rating scales may be more indicative of central nervous system (CNS) involvement than others. The association between disturbance in mood and motivation and neurocognitive compromise may suggest that each are sequelae of disease specific mechanisms.

Functional outcome in TBI I: neuropsychological, emotional, and behavioral mediators.

Literature exists to suggest that the severity of traumatic brain injury (TBI) is positively associated with the severity of functional impairment. However, potential mediators of this relationship have not been studied systematically. In the present study, we evaluated a model hypothesized to explain the relationship between TBI severity and functional impairment in 87 patients with moderate-to-severe TBI, studied longitudinally. Using structural equation modeling, we found that only neuropsychological status (but not emotional or behavioral difficulties) consistently mediated the relationship between TBI severity and functional outcome at 12-months post-injury. These findings suggest that, of the factors examined here, neurocognitive compromise plays the most prominent role in mediating post-TBI adaptive functioning in moderate-to-severe TBI, which has important implications for post-injury interventions.

Functional outcome in TBI II: verbal memory and information processing speed mediators.

Following traumatic brain injury (TBI), patients often report memory difficulties, as well as reduced information processing speed. However, it remains unclear the extent to which these deficits contribute to functional impairment. In the present study, we compared the relative contribution of verbal memory and information processing speed to functional impairment at 12-month post-injury, in 87 patients with moderate-to-severe TBI. Employing structural equation modeling, we found that information processing speed, but not verbal memory functions, significantly mediated the relationship between TBI severity and post-TBI adaptive functioning. These findings suggest that despite the pervasive memory complaints among patients with TBI, it is the impact of neurotrauma on frontal systems that appears to be primarily responsible for patients' difficulties in social and occupational functioning.

Psychosocial risk factors of HIV morbidity and mortality: findings from the Multicenter AIDS Cohort Study (MACS).

Despite the use of laboratory markers in estimating HIV prognosis, significant variation in the natural history of HIV-1 infection remains unexplained. Recent studies suggest psychosocial risk factors have important prognostic significance in HIV disease. The objective of the present study was to examine the prognostic influence of age, general intellectual functioning, and emotional distress across the spectrum of HIV disease progression. The study sample was drawn from the Multicenter AIDS Cohort Study (MACS), a 13-year, prospective study of HIV-seropositive men recruited from four study centers across the country. The participants were 1,231 HIV-seropositive MACS participants, followed from baseline (median 8/15/87) to the end of the observation period (12/15/98). HIV disease progression was evaluated with respect to three outcome measures: (1) number of years from baseline testing to the first AIDS defining illness (progression to AIDS), (2) years from baseline to HIV-dementia (progression to dementia), and (3) years from baseline to death (survival). The influence of psychosocial risk factors on outcome measures was evaluated using survival analyses. General intellectual functioning, age, and somatic symptoms of depression, were found to be significant predictors of HIV disease progression and survival. Older age at baseline was associated with a more rapid progression to dementia and death. Lower Shipley IQ estimates were associated with a more rapid disease progression (AIDS and dementia) and shortened survival. Somatic symptoms of depression were associated with shortened survival. In addition, age, IQ, and somatic symptoms of depression, had an additive effect with an increase in the number of risk factors associated with accelerated disease progression and shortened time to death. These findings remained consistent, despite controlling for baseline CD4 and HIV medication use. Psychosocial cofactors are important in understanding HIV disease progression. Methods for estimating HIV prognosis may become more reliable if psychosocial factors are considered. Future research will clarify if psychosocial risk factors reflect central nervous system integrity, brain reserve capacity or mediate morbidity and mortality through social economic status, access to health care and other social correlates.