Variance In Cognitive Performance Research Articles

Explaining individual differences in cognitive processes underlying hindsight bias.

After learning an event's outcome, people's recollection of their former prediction of that event typically shifts toward the actual outcome. Erdfelder and Buchner (Journal of Experimental Psychology: Learning, Memory, and Cognition, 24, 387-414, 1998) developed a multinomial processing tree (MPT) model to identify the underlying processes contributing to this hindsight bias (HB) phenomenon. More recent applications of this model have revealed that, in comparison to younger adults, older adults are more susceptible to two underlying HB processes: recollection bias and reconstruction bias. However, the impact of cognitive functioning on these processes remains unclear. In this article, we extend the MPT model for HB by incorporating individual variation in cognitive functioning into the estimation of the model's core parameters in older and younger adults. In older adults, our findings revealed that (1) better episodic memory was associated with higher recollection ability in the absence of outcome knowledge, (2) better episodic memory and inhibitory control and higher working memory capacity were associated with higher recollection ability in the presence of outcome knowledge, and (3) better inhibitory control was associated with less reconstruction bias. Although the pattern of effects was similar in younger adults, the cognitive covariates did not significantly predict the underlying HB processes in this age group. In sum, we present a novel approach to modeling individual variability in MPT models. We applied this approach to the HB paradigm to identify the cognitive mechanisms contributing to the underlying HB processes. Our results show that working memory capacity and inhibitory control, respectively, drive individual differences in recollection bias and reconstruction bias, particularly in older adults.

Patterns of change in nonverbal cognition in adolescents with Down syndrome.

This study was designed to examine longitudinal change in nonverbal cognitive abilities across adolescence for 20 males with Down syndrome (DS). We used hierarchical linear modeling to examine the rate of change in performance on the subtests of the Leiter-R Brief IQ across four annual time points and to determine the relation between maternal IQ and level and rate of change in performance. Results indicated no significant change in IQ (standard scores) with age in the sample, suggesting IQ stability during adolescence for individuals with DS, although several participants performed at floor level on the standard scores for the Leiter-R, limiting interpretation. Growth scores, however, provide a metric of absolute ability level, allow for the examination of change in Leiter-R performance in all participants, and minimize floor effects. Results from the analysis of growth scores indicated significant gain in absolute nonverbal cognitive ability levels (growth score values) over time for the adolescents with DS, although the growth varied by subdomain. Maternal IQ did not explain variability in cognitive performance or change in that performance over time in our sample of adolescents with DS.

Cortical atrophy, reduced integrity of white matter and cognitive impairment in subcortical vascular dementia of Binswanger type.

An association between white matter hyperintensities (WMH) and cognitive dysfunction has long been recognized. However, subjects with identically appearing WMH on magnetic resonance imaging present with a wide variance in cognitive function ranging from normal cognition to dementia. The aim of this study was to compare cortical atrophy and integrity of white matter of patients with subcortical vascular dementia of Binswanger type (SVaD-BT) with those of the normal cognition group with WMH (ncWMH). Eleven patients with SVaD-BT and 11 age-, sex-, education- and grade of WMH-matched ncWMH underwent magnetic resonance imaging, including 3-D volumetric images for cortical atrophy and diffusion tensor imaging for integrity of white matter. Compared to ncWMH, SVaD-BT patients showed cortical atrophies in frontal (i.e. frontal pole, precentral gyrus and frontal medial cortex) and occipital areas (i.e. lingual gyrus) followed by atrophies in temporal (i.e. fusiform cortex and middle temporal gyrus) areas. Along with cortical atrophies, reduced integrity with low fractional anisotropy and high mean diffusivity values in genu and splenium of the corpus callosum were detected in SVaD-BT patients. Our findings suggest that cognitive decline from ncWMH to SVaD-BT may be associated with cortical atrophy and reduced integrity of white matter.

Short-term memory development: Differences in serial position curves between age groups and latent classes

In studies on the development of cognitive processes, children are often grouped based on their ages before analyzing the data. After the analysis, the differences between age groups are interpreted as developmental differences. We argue that this approach is problematic because the variance in cognitive performance within an age group is considered to be measurement error. However, if a part of this variance is systematic, it can provide very useful information about the cognitive processes used by some children of a certain age but not others. In the current study, we presented 210 children aged 5 to 12years with serial order short-term memory tasks. First we analyze our data according to the approach using age groups, and then we apply latent class analysis to form latent classes of children based on their performance instead of their ages. We display the results of the age groups and the latent classes in terms of serial position curves, and we discuss the differences in results. Our findings show that there are considerable differences in performance between the age groups and the latent classes. We interpret our findings as indicating that the latent class analysis yielded a much more meaningful way of grouping children in terms of cognitive processes than the a priori grouping of children based on their ages.

Diurnal variation of cognitive performance and perceived difficulty in dart-throwing performance in 9–10-year-old boys

The aim of this study was to investigate variations in cognitive performance and difficulty perception in 9–10-year-old boys. Fifteen healthy boys (Age = 9.8 ± 0.4 years; Height = 146 ± 5.2 cm; Body mass = 34.2 ± 2.9 kg) performed three cognitive tasks, the reaction time (RT), the trail-making test, TMT (to evaluate flexibility), and the barrage tests (to evaluate selective attention [SA]). The tests were performed at 07:00 and 17:00 h. The results demonstrated that oral temperature, RT, and flexibility were significantly higher at 17:00 h than at 07:00 h. A significant main effect of diurnal variation was found for RT (t = 3.075, p = 0.008), SA (t = 2.43, p = 0.029), and executive function (TMT, Parts A and B) (t = 5.86, p < 0.001; t = 4.85, p < 0.001, respectively). However, these rhythms of cognitive performance were not correlated with the rhythm of core temperature at 07:00 h. In conclusion perceived difficulty was correlated with executive function in situations with higher level of difficulties.

The dynamic relationship between cognitive function and positive well-being in older people: a prospective study using the English Longitudinal Study of Aging.

There is evidence that having a stronger sense of positive well-being may be a potential resource for healthier aging as represented by slower physical decline, reduced risk of frailty and longer survival. However, it is unclear whether positive well-being is protective of another crucial component of healthy aging, cognitive function, or whether it has a bidirectional relationship with cognitive function. We use multilevel models with within-person centering to estimate the within- and between-person association between cognitive function and positive well-being in 4 waves of data from the English Longitudinal Study of Ageing (ELSA), (N = 10985, aged 50–90 years at wave 1). Our findings show that, although most variation in cognitive function was explained by age, and most variation in well-being was explained by depression, small but significant associations between cognition and well-being remained after variation in age and depression were controlled. In models where cognition was the outcome, the association was mainly because of variation in mean levels of well-being between persons. In models where well-being was the outcome, the association was mainly because of within-person fluctuation in cognitive test performance. Exercise and depression were the most important moderating influences on the association between cognition and positive well-being. Depression had greater effect upon this association for those with higher well-being, but exercise protected cognitive performance against the adverse effects of lower well-being.

Mitochondrial DNA Mutations and Cognition: A Case-Series Report

Mutations in the mitochondrial genome can impair normal metabolic function in the central nervous system (CNS) where cellular energy demand is high. Primary mitochondrial DNA (mtDNA) mutations have been linked to several mitochondrial disorders that have comorbid psychiatric, neurologic, and cognitive sequelae. Here, we present a series of cases with primary mtDNA mutations who were genotyped and evaluated across a common neuropsychological battery. Nineteen patients with mtDNA mutations were genotyped and clinically and cognitively evaluated. Pronounced deficits in nonverbal/visuoperceptual reasoning, verbal recall, semantic word generativity, and processing speed were evident and consistent with a "mitochondrial dementia" that has been posited. However, variation in cognitive performance was noteworthy, suggesting that the phenotypic landscape of cognition linked to primary mtDNA mutations is heterogeneous. Our patients with mtDNA mutations evidenced cognitive deficits quite similar to those commonly seen in Alzheimer's disease and could have clinical relevance to the evaluation of dementia.

Altered thalamocortical functional connectivity in idiopathic generalized epilepsy

Aberrant thalamocortical network has been hypothesized to play a crucial role in the fundamental pathogenesis underlying idiopathic generalized epilepsy (IGE). We aimed to investigate alterations of thalamocortical functional network in patients with IGE using thalamic seed-based functional connectivity (FC) analysis, and their relationships with frontal cognitive functions and clinical characteristics. Forty-nine IGE patients (31 with juvenile myoclonic epilepsy, 17 with IGE with generalized tonic-clonic seizures only, one with juvenile absence epilepsy) and 42 control subjects were prospectively recruited. Voxel-based morphometry (VBM) was first performed to detect thalamic region of gray matter (GM) reduction in patients compared to controls. Between-group comparison of thalamocortical FC was then carried out using resting-state functional magnetic resonance imaging (MRI) analysis seeding at thalamic region of volume difference. In addition, thalamocortical FC was correlated with frontal cognitive performance and clinical variables. Neuropsychological assessment revealed that patients with IGE had poorer performance than controls on most of the frontal cognitive functions. VBM detected a reduction in GM in the anteromedial thalamus in patients relative to controls. FC analysis seeding at the anteromedial thalamus revealed a reduction of thalamocortical FC in the bilateral medial prefrontal cortex and precuneus/posterior cingulate cortex in patients with IGE compared to controls. Thalamocortical FC strength of bilateral medial prefrontal cortex correlated negatively with disease duration, but did not correlate with seizure frequency or frontal cognitive functions in patients with IGE. Our results indicate that IGE is associated with decreased thalamocortical FC between anteromedial thalamus and medial prefrontal cortex and precuneus/posterior cingulate cortex. Our finding of greater reduction of medial prefrontal FC in relation to increasing disease duration suggests that thalamoprefrontal network abnormality, the proposed pathophysiologic mechanism underlying IGE, may be the consequence of the long-standing burden of the disease.

Hair cortisol and cognitive performance in healthy older people.

Worse cognitive performance in older people has been associated with hypothalamic-pituitary-adrenal axis dysregulation (in particular, higher cortisol levels). Analysis of hair cortisol concentrations (HCC) is a novel method to measure long-term cortisol exposure, and its relationship with cognition in healthy older people has not yet been studied. We investigated whether HCC (measured in hair scalp) and diurnal salivary cortisol levels (awakening, 30min after awakening, and evening, across two days) were related to cognitive performance (assessed with the Trail-making Test A and B, Digit Span Forward and Backward, word list-RAVLT and Stories subtest of the Rivermead) in 57 healthy older people (mean age=64.75 years, SD=4.17). Results showed that lower HCC were consistently related to worse working memory, learning, short-term verbal memory (RAVLT first trial and immediate recall) and long-term verbal memory. In contrast, higher mean levels and higher diurnal area under the curve of diurnal salivary cortisol were related to worse attention and short-term verbal memory (immediate story recall), respectively. Interestingly, a higher ratio of mean levels of diurnal salivary cortisol over HCC were related to worse performance on working memory and short-term verbal memory, suggesting that those individuals with lower long-term cortisol exposure might be more vulnerable to the negative effect of HPA-axis dysregulation on these cognitive processes. Our findings suggest that both low long-term cortisol exposure and a possible dysregulation of the diurnal rhythm of the HPA-axis may account, at least in part, for the inter-individual variability in cognitive performance in healthy older people.

The Role of Education and Verbal Abilities in Altering the Effect of Age-Related Gray Matter Differences on Cognition

Evidence suggests that individual variability in lifetime exposures influences how cognitive performance changes with advancing age. Brain maintenance and cognitive reserve are theories meant to account for preserved performance despite advancing age. These theories differ in their causal mechanisms. Brain maintenance predicts more advantageous lifetime exposures will reduce age-related neural differences. Cognitive reserve predicts that lifetime exposures will not directly reduce these differences but minimize their impact on cognitive performance. The present work used moderated-mediation modeling to investigate the contributions of these mechanisms at explaining variability in cognitive performance among a group of 39 healthy younger (mean age (standard deviation) 25.9 (2.92) and 45 healthy older adults (65.2 (2.79)). Cognitive scores were computed using composite measures from three separate domains (speed of processing, fluid reasoning, and memory), while their lifetime exposures were estimated using education and verbal IQ measures. T1-weighted MR images were used to measure cortical thickness and subcortical volumes. Results suggest a stronger role for cognitive reserve mechanisms in explaining age-related cognitive variability: even with age-related reduced gray matter, individuals with greater lifetime exposures could perform better given their quantity of brain measures.

Is white matter integrity associated with speed or variability in cognitive performance?

Intra-individual variability (IIV), that is the inconsistency of responding across multiple trials of a test, has been suggested as a measure of cognitive performance alternative to the commonly-used mean level of performance. IIV in reaction time (RT) is a trait-like characteristic of an individual and has been purported as an index of the central nervous system functioning. In this study we investigated whether white matter integrity explains individual differences in RT IIV. Volume and severity of white matter lesions were assessed from MRI brain scans of 671 73-year-olds. Individuals with greater volume of lesions and more severe lesions in frontal regions had higher RT IIV. However, these associations were eradicated by controlling for mean RT. We conclude that white matter integrity does not explain variance in RT IIV that is independent of mean RT.

Altered resting state functional connectivity in young survivors of acute lymphoblastic leukemia

Chemotherapy treatment for pediatric acute lymphoblastic leukemia (ALL) has been associated with long-term cognitive impairments in some patients. However, the neurobiologic mechanisms underlying these impairments, particularly in young survivors, are not well understood. This study aimed to examine intrinsic functional brain connectivity in pediatric ALL and its relationship with cognitive status. We obtained resting state functional magnetic resonance imaging (rsfMRI) and cognitive testing data from 15 ALL survivors age 8-15 years and 14 matched healthy children. The ALL group had a history of intrathecal chemotherapy treatment but were off-therapy for at least 6 months at the time of enrollment. We used seed-based analyses to compare intrinsic functional brain network connectivity between the groups. We also explored correlations between connectivity and cognitive performance, demographic, medical, and treatment variables. We demonstrated significantly reduced connectivity between bilateral hippocampus, left inferior occipital, left lingual gyrus, bilateral calcarine sulcus, and right amygdala in the ALL group compared to controls. The ALL group also showed regions of functional hyperconnectivity including right lingual gyrus, precuneus, bilateral superior occipital lobe, and right inferior occipital lobe. Functional hypoconnectivity was associated with reduced cognitive function as well as younger age at diagnosis in the ALL group. This is the first study to demonstrate that intrinsic functional brain connectivity is disrupted in pediatric ALL following chemotherapy treatment. These results help explain cognitive dysfunction even when objective test performance is seemingly normal. Children diagnosed at a younger age may show increased vulnerability to altered functional brain connectivity.

Altered functional connectivity and performance variability in relapsing–remitting multiple sclerosis

Background: Patients with multiple sclerosis (MS) demonstrate slower and more variable performance on attention and information processing speed tasks. Greater variability in cognitive task performance has been shown to be an important predictor of neurologic status and provides a unique measure of cognitive performance in MS patients. Objectives: This study investigated alterations in resting-state functional connectivity associated with within-person performance variability in MS patients. Methods: Relapsing–remitting MS patients and matched healthy controls completed structural MRI and resting-state fMRI (rsfMRI) scans, as well as tests of information processing speed. Performance variability was calculated from reaction time tests of processing speed. rsfMRI connectivity was investigated within regions associated with the default mode network (DMN). Relations between performance variability and functional connectivity in the DMN within MS patients were evaluated. Results: MS patients demonstrated greater reaction time performance variability compared to healthy controls (p<0.05). For MS patients, more stable performance on a complex processing speed task was associated with greater resting-state connectivity between the ventral medial prefrontal cortex and the frontal pole. Conclusions: Among MS patients, greater functional connectivity between medial prefrontal and frontal pole regions appears to facilitate performance stability on complex speed-dependent information processing tasks.

Reply

This paper represents the third paper generated from a protocol that included HIV seropositive and seronegative participants. As discussed in the methods section, more specific detail regarding the full protocol and methods has been published previously. This includes the protocol for measuring sleep based on well-established methods and validated tools including in lab polysomnography, 2 week ambulatory actigraphy monitoring, electronic sleep diaries and clinical sleep evaluations conducted by sleep medicine trained experts.1,2,3 The reviewer's suggestions regarding the merit of including a control group in this subgroup analysis paper raises an issue that the scientific community is now beginning to openly discuss. This issue has been raised in other disciplines, such as cognitive aging, particularly when exploring cross-ethnic groups in cognitive performance. For example, in the cognitive aging literature, researchers have often explored cognitive function in minority samples by conducting cross-group research, in which a control group of white participants is included in the study. However, some researchers have proposed that these studies do not appreciate the unique cognitive attributes of the minority group of interest.4,5 Furthermore, they do not account for factors that may explain the within-group variability in cognitive function often observed in minority groups.6 As a result, these researchers suggest that within-group research is a more reliable and valid approach than cross-group research for identifying the underlying sources of poor cognitive functioning within minority samples, and subsequently, explaining the racial group differences in cognitive performance often reported in previous literature. This same theoretical perspective could also be applied to clinical samples, such as our HIV sample. Cognitive deficits have been long recognized as a being prevalent in HIV seropositive individuals, even those who are aviremic. Indeed, the NeuroAIDS research community is actively searching for underlying pathophysiologic mechanisms, despite virological stability on cART. Furthermore, the cognitive functioning and/or deficits are likely to vary greatly within a diverse HIV cohort much less between seropositive HIV subjects and seronegative “controls.” The within-group approach will be useful in identifying the factors that explain the within-group variability in cognitive function observed in HIV samples, and, subsequently, will assist researchers in understanding the mechanisms for cognitive deficits within HIV individuals. The cross-group approach of making comparisons between a HIV sample and non-HIV control sample would ignore this within-group variability and would not adequately address the nature of variability in cognitive performance among the HIV individuals. As a result, a cross-group approach may limit the potential for identifying mechanisms for the cognitive deficits observed in HIV individuals and strategies of intervention for this population. In summary we appreciate the interest in our paper. As highlighted by the reviewer's comments, we believe that the overarching message is the need for further investigations into this relationship; as it certainly encompasses a complex inter-relationship both physiologically, environmentally, and socio-culturally.

Variability of Cognitive Performance during Hemodialysis: Standardization of Cognitive Assessment

Background/Aims: Up to 70% of hemodialysis patients over the age of 54 have relevant cognitive impairment. No standardized protocol for the evaluation and monitoring of this population is available today. We hypothesized that the dialysis procedure and the testing environment induce fluctuations of cognitive performance. Methods: 26 hemodialysis patients were randomly tested using the Montreal Cognitive Assessment (MoCA) before, during and after hemodialysis and inside the dialysis room or alone in a separate room. Tests were performed at weekly intervals using five test variations to prevent learning effects. The Mini-Mental State Examination (MMSE) was performed as a reference test. Results: MoCA scores significantly differed between the conditions: ‘before hemodialysis' revealed the best MoCA score as compared to ‘during hemodialysis' or ‘after hemodialysis' (p = 0.013). During the combined condition ‘before dialysis AND separate room', best performance was achieved (p < 0.001). The BP decline had no significant influence on cognitive performance, whereas the fluid shift showed a significant impact (p = 0.008). Conclusion: Cognitive performance in hemodialysis patients highly depends on the time point and testing environment. Therefore, we strongly suggest a standardization, using the MoCA before hemodialysis in a separate room, in order to make testing results of future research in this field comparable.

Associations Between Cognitive and Gait Performance During Single- and Dual-Task Walking in People With Parkinson Disease

Cognitive impairments in Parkinson disease (PD) manifest as deficits in speed of processing, working memory, and executive function and attention abilities. The gait impairment in PD is well documented to include reduced speed, shortened step lengths, and increased step-to-step variability. However, there is a paucity of research examining the relationship between overground walking and cognitive performance in people with PD. This study sought to examine the relationship between both the mean and variability of gait spatiotemporal parameters and cognitive performance across a broad range of cognitive domains. A cross-sectional design was used. Thirty-five participants with no dementia and diagnosed with idiopathic PD completed a battery of 12 cognitive tests that yielded 3 orthogonal factors: processing speed, working memory, and executive function and attention. Participants completed 10 trials of overground walking (single-task walking) and 5 trials of overground walking while counting backward by 3's (dual-task walking). All gait measures were impaired by the dual task. Cognitive processing speed correlated with stride length and walking speed. Executive function correlated with step width variability. There were no significant associations with working memory. Regression models relating speed of processing to gait spatiotemporal variables revealed that including dual-task costs in the model significantly improved the fit of the model. Participants with PD were tested only in the on-medication state. Different characteristics of gait are related to distinct types of cognitive processing, which may be differentially affected by dual-task walking due to the pathology of PD.

Abstract T P364: Longitudinal Evaluation of Functional Magnetic Resonance Imaging on Working Memory in Patients after Transient Ischemic Attack

OBJECTIVE: Transient ischemic attack (TIA) can increase the risk of cognitive decline, especially in attention-executive-psychomotor functioning. However, whether TIA patients have altered patterns of brain activation during this function, and whether there is a dynamic change on cerebral activity patterns, have not been examined to date. This study is designed to using functional magnetic resonance imaging (fMRI) to investigate longitudinal changes in brain activation during a verbal working memory (VWM) task in patients with TIA. METHODS: The current study included 25 patients with first-ever TIA in right hemisphere and 25 healthy volunteers. N-Back VWM task-related fMRI were conducted one week and three months after TIA onset. The brain activity evoked by n-back task in the patients was assessed and compared with that of the controls. Significant changes in cerebral activation over time were also observed in TIA patients. RESULTS: The groups did not differ on any demographic, cognitive and task performance variables. Compared with healthy subjects, patients at one week after TIA demonstrated increased activity in bilateral inferior frontal gyrus (IFG), right dorsolateral prefrontal cortex (DLPFC), insula, inferior parietal lobe (IPL) and cerebellum during the task. However, at 3-month follow-up, the task-related brain activity in patients was clearly less recruited, and only right IFG still exhibited increased activity. Moreover, a direct comparison of fMRI data between one week and three months after TIA showed that there was increased activation in bilateral middle temporal gyrus (MTG), right DLPFC, IPL, cerebellum and left IFG in patients at one week after TIA. CONCLUSIONS: These findings support the hypotheses that the patterns of brain activity during VWM performance may change for a period of time post-TIA despite the cessation of clinical symptoms. They also provide evidence of a progressive normalization of the VWM activation pattern after transient episodes of ischemia in patients with first-ever TIA.

Predicting cognitive ability in ageing cohorts using Type 2 diabetes genetic risk

To investigate whether there is overlap in the genetic determinants of Type 2 diabetes and cognitive ageing by testing whether a genetic risk score for Type 2 diabetes can predict variation in cognitive function in older people without dementia. Type 2 diabetes genetic risk scores were estimated using various single nucleotide polymorphism significance inclusion criteria from an initial genome-wide association study, the largest in Type 2 diabetes to date. Scores were available for 2775-3057 individuals, depending on the cognitive trait. Type 2 diabetes genetic risk was associated with self-reported diabetes mellitus. Across varying single nucleotide polymorphism-inclusion levels, a significant association between Type 2 diabetes genetic risk and change in general cognitive function was found (median r = 0.04); however, this was such that higher Type 2 diabetes genetic risk related to higher cognitive scores. To investigate more fully the source of the often observed comorbidity between Type 2 diabetes and cognitive impairment, one direction for future research will be to use cognitive ability polygenic risk scores to predict Type 2 diabetes in line with the reverse causation hypothesis that people with lower pre-morbid cognitive ability are more likely to develop Type 2 diabetes.

Polygenic scores from the MiR137 pathway explain variability in cognitive performance in patients with schizophrenia and controls.

Introduction Genome-wide association studies have identified rs1622579, a common variant located within an intronic region of MiR137, as a risk variant for schizophrenia. MiR137 has a hypothesized role in neural cell proliferation, migration and maturation. Cognitively, this variant is associated with deficits in verbal episodic memory, and altered fronto-amygdala connectivity. As MiR137 interacts with several other genome wide associated variants (e.g. ZNF804A, TCF4, CACNA1C, CSMD1 and WBP1L), we tested whether these cognitive effects were associated with polygenic risk in a set of identified downstream targets of MiR137. Methodology Polygene scores were calculated by (1) selecting all identified downstream genetic targets of MiR137 (Hill et al., 2014); (2) selecting risk SNPs within each of these genes based on risk estimates from the Psychiatric Genomics Consortium (Ripke et al., 2011), and (3) ascribing a polygenic risk score to each participant based on the total number of risk alleles they carried. To define risk, we used 3 arbitrary p-value thresholds (p < 10-5, p < 0.05, and p < 0.5) from the PGC1 case-control analysis. To estimate these polygene effects on cognitive deficits associated with SZ (IQ, episodic and working memory, attention control, and theory of mind) linear regression analyses was performed, with age and gender entered as variables of no interest. We carried out three separate analyses: all cases and controls (n=586), patients with a broad diagnosis of psychosis including non-schizophrenia psychosis (n=489) and patients with schizophrenia and schizoaffective disorder (n=379). Results MiR137 polygenic risk scores were significantly higher in the broad and narrow diagnosis groups compared to the controls (F(2,1081) =5.52, p<0.01). Poorer performance on measures of IQ, memory, and attention were each found to be associated with higher MiR137 polygene scores thresholded at p=0.05, including paired associated learning (p<0.001); faces, letter-number sequencing (LNS) sustained attention to reaction time (SART) (p<0.01); full-scale IQ, logical memory (LM) and spatial working memory (SWM) (p<0.05). The amount of variance explained on the measures varied between 1% and 2.6% Discussion These data support a modest but significant influence of this MiR137 'pathway' on cognition, across multiple measures of cognition. These widespread cognitive effects are consistent with MiR137’s previously described role in brain development. Greater variance was explained when all cases and controls were included, rather than considering narrow, broad, and controls separately. Extending on previous findings, MiR137's effects on cognition were significantly more apparent when considered in combination with the other risk variants with which it interacts rather than when the rs1622579 risk variant was considered in isolation.

Factors associated with neurocognitive performance in OIF/OEF servicemembers with postconcussive complaints in postdeployment clinical settings.

Cognitive difficulties are frequently reported by Operation Enduring Freedom /Operation Iraqi Freedom military personnel who sustained mild traumatic brain injuries (TBIs). The current study examined several potential factors that may contribute to self-reported cognitive difficulties in postdeployment clinical settings. Eighty-four subjects who sustained a mild or moderate TBI and reported cognitive difficulties underwent neurocognitive testing. Multiple regression analyses were used to determine the amount of variance in neurocognitive performance accounted for by the predictor variables (demographic, mechanism of injury, time since injury, headache severity, combat stress, postconcussive complaints, and effort/performance validity). The predictor variables collectively accounted for 51.7% of the variance in cognitive performance (F (8,72) = 11/99, p < 0.001). The most potent predictor of cognitive functioning was performance validity/effort, which uniquely accounted for 16.3% of the variance (p < 0.01). Self-reported symptom severity, including postconcussive complaints, combat stress, and headache intensity, accounted for 7.2% of the variance (p < 0.05). Demographic factors and injury characteristics, such as time since injury and mechanism of injury, were not significant predictive factors of cognitive performance. The findings of the current study underscore the need to include measurement of effort as part of neurocognitive evaluation in postdeployment settings when evaluating cognitive complaints associated with mild TBI.