Complaints of neuropsychological dysfunction have emerged among subsets of military personnel after almost every major deployment involving western nations in recent history. Although deployments have been characterized by a range of neural risk factors, psychological stress is common to most prolonged deployments. This review uses a public health framework to address associations between deployment-related stress and neuropsychological performance. Specifically, the review covers mechanisms by which deployment-related psychological stress may affect neuropsychological functioning, considers the advantages and disadvantages of approaching the question from a public health perspective, and discusses how epidemiological research may sort out questions regarding course, cause, and effect. (JINS, 2011, 17, 000–000)

Neuropsychology is poised for transformations of its concepts and methods, leveraging advances in neuroimaging, the human genome project, psychometric theory, and information technologies. It is argued that a paradigm shift toward evidence-based science and practice can be enabled by innovations, including (1) formal definition of neuropsychological concepts and tasks in cognitive ontologies; (2) creation of collaborative neuropsychological knowledgebases; and (3) design of Web-based assessment methods that permit free development, large-sample implementation, and dynamic refinement of neuropsychological tests and the constructs these aim to assess. This article considers these opportunities, highlights selected obstacles, and offers suggestions for stepwise progress toward these goals. (JINS, 2011, 17, 000–000)

Schizophrenia is associated with executive dysfunction. Yet, the degree to which executive functions are impaired differentially, or above and beyond underlying basic cognitive processes is less clear. Participants included 145 matched pairs of individuals with schizophrenia (SCs) and normal comparison subjects (NCs). Executive functions were assessed with 10 tasks of the Delis-Kaplan Executive Function System (D-KEFS), in terms of “achievement scores” reflecting overall performance on the task. Five of these tasks (all measuring executive control) were further examined in terms of their basic component (e.g., processing speed) scores and contrast scores (reflecting residual higher order skills adjusted for basic component skills). Group differences were examined via multivariate analysis of variance. SCs had worse performance than NCs on all achievement scores, but the greatest SC-NC difference was that for the Trails Switching task. SCs also had worse performance than NCs on all basic component skills. Of the executive control tasks, only Trails Switching continued to be impaired after accounting for impairments in underlying basic component skills. Much of the impairment in executive functions in schizophrenia may reflect the underlying component skills rather than higher-order functions. However, the results from one task suggest that there might be additional impairment in some aspects of executive control. (JINS, 2010, 17, 000–000)

Traumatic axonal injury (TAI) is a common mechanism of traumatic brain injury not readily identified using conventional neuroimaging modalities. Novel imaging modalities such as diffusion tensor imaging (DTI) can detect microstructural compromise in white matter (WM) in various clinical populations including TAI. DTI-derived data can be analyzed using global methods (i.e., WM histogram or voxel-based approaches) or a regional approach (i.e., tractography). While each of these methods produce qualitatively comparable results, it is not clear which is most useful in clinical research and ultimately in clinical practice. This study compared three methods of analyzing DTI-derived data with regard to detection of WM injury and their association with clinical outcomes. Thirty patients with TAI and 19 demographically similar normal controls were scanned using a 3 Tesla magnet. Patients were scanned approximately eight months postinjury, and underwent an outcomes assessment at that time. Histogram analysis of fractional anisotropy (FA) and mean diffusivity showed global WM integrity differences between patients and controls. Voxel-based and tractography analyses showed significant decreases in FA within centroaxial structures involved in TAI. All three techniques were associated with functional and cognitive outcomes. DTI measures of microstructural integrity appear robust, as the three analysis techniques studied showed adequate utility for detecting WM injury. (JINS, 2011, 17, 000–000)

Blast-related head injuries are one of the most prevalent injuries among military personnel deployed in service of Operation Iraqi Freedom. Although several studies have evaluated symptoms after blast injury in military personnel, few studies compared them to nonblast injuries or measured symptoms within the acute stage after traumatic brain injury (TBI). Knowledge of acute symptoms will help deployed clinicians make important decisions regarding recommendations for treatment and return to duty. Furthermore, differences more apparent during the acute stage might suggest important predictors of the long-term trajectory of recovery. This study evaluated concussive, psychological, and cognitive symptoms in military personnel and civilian contractors (N = 82) diagnosed with mild TBI (mTBI) at a combat support hospital in Iraq. Participants completed a clinical interview, the Automated Neuropsychological Assessment Metric (ANAM), PTSD Checklist-Military Version (PCL-M), Behavioral Health Measure (BHM), and Insomnia Severity Index (ISI) within 72 hr of injury. Results suggest that there are few differences in concussive symptoms, psychological symptoms, and neurocognitive performance between blast and nonblast mTBIs, although clinically significant impairment in cognitive reaction time for both blast and nonblast groups is observed. Reductions in ANAM accuracy were related to duration of loss of consciousness, not injury mechanism. (JINS, 2011, 17, 000–000)

Elucidating the relationship between fatigue and depression in multiple sclerosis (MS) patients is complicated by ambiguity regarding how these two constructs should be delineated. Neurovegetative symptoms of depression may reflect depression in MS patients, as they do in non-neurological populations; instead these items may measure disease-related fatigue; or disease-related fatigue and depression may reflect the same syndrome in MS patients. The present study sought to evaluate these possibilities by characterizing the underlying factor structure of self-report items designed to measure fatigue and depression symptoms. Questionnaires designed to measure fatigue and depression were administered to 174 MS patients and 84 healthy controls, and these items were subject to factor analysis. Results suggest that neurovegetative symptoms are poor indicators of depression in MS patients. Neurovegetative depression items were removed from the final model due to poor psychometric properties, or they loaded on Fatigue or Sleep Disturbance factors. The correlation between latent factors Depression and Fatigue was large (.47), but does not indicate that these phenomena are manifestations of the same construct. Hence, the results of this study support the notion that vegetative symptoms of depression do not reflect depression in MS patients, but instead measure symptoms of fatigue and sleep disturbance. (JINS, 2010, 17, 000–000)

Measures of brain and hippocampal volume in 40 healthy young (aged 18–30 years) and 36 healthy elderly (aged 60–83 years) subjects were compared with composite cognitive function scores in three conceptual domains: memory ability, processing speed, and general fluid intelligence. Through a series of general linear models testing the relationship between these brain measures and cognitive performance scores, a significant positive relationship between hippocampal volume and fluid intelligence ability was found in elderly subjects but not in young. No relationship between the other cognitive domains and brain or hippocampal volume was found. The findings suggest a role of hippocampal atrophy in the decline in fluid intelligence in the elderly. (JINS, 2011, 17, 000–000)

A strong tendency toward left hemisphere (LH) language dominance has been well established, as evidenced by the high prevalence of language impairment following sudden onset lesions in the LH. In the presence of progressive LH pathology, such as epilepsy, substantial deviations in language organization can occur. However, the question regarding whether reorganization involves both expressive and receptive language functions or only the one directly affected by the primary location of pathology has not been settled. Using Wada testing scores from 296 epilepsy patients and estimated rates of typical dominance in the normal population, we assessed the frequency with which left frontal and temporal pathology resulted in reorganization of only the expressive or receptive language function or both. The comparisons revealed: (1) a significantly higher prevalence of atypical organization (i.e., deviations from LH dominance) among the LH patients compared to normal population estimates and right hemisphere patients, and (2) that regardless of pathology location within the LH, the rates of atypical reorganization for both expressive and receptive language were essentially equal. These results constitute evidence that the two language functions are intimately yoked and that when disruption to the system results in reorganization, it usually yields functional changes throughout the system. (JINS, 2010, 17, 000–000)

Story recall in Alzheimer disease (AD) is typically used as a measure of episodic memory, but the degree to which recall is dependent on available attentional resources is not fully understood. The current study investigated how measures of attention were associated to verbatim recall (exact reproduction) or gist recall (relevant semantic meaning). Sixteen participants with AD and 16 age-matched healthy older adults recalled a story on immediate free recall and recognition. Controls recalled more units overall than AD. A group × response interaction revealed more gist than verbatim recall in AD, but those with mild disease generated approximately the same number gist responses as controls. For each group, qualitatively different attentional resources were associated with recall units. In controls, verbatim units correlated positively with primacy serial position items of the California Verbal Learning Test II (CVLTII), suggesting that episodic buffer resources may be associated with story recall. In AD, gist units were positively correlated with digits forward, but inversely related to the CVLTII primacy region items, suggesting reliance on low-level capacity resources. Possible explanations of the impaired performance in AD may be a bias in favor of gist processing, poor verbatim encoding, and/or processing failure at the level of the episodic buffer. (JINS, 2011, 17, 000–000)

Chronic kidney disease (CKD) is a common and debilitating illness that impacts neurocognitive function. However, the majority of previous studies varied in methodologic design and rigor, thus minimizing definitive conclusions. The present study was designed to determine the impact of CKD on neurocognitive function through specific examination of CKD factors and therapeutic interventions. We evaluated 120 CKD outpatients and 41 healthy donors (controls) in terms of neurocognitive function, anxiety, and depressive symptomatology, and somnolence. Information regarding medical and treatment history was recorded. Twenty-three percent of CKD patients presented with cognitive impairment. Stage 5 patients had lower scores (p < .05) compared with controls and patients in stage 3 and 4 on measures of global cognitive function. No differences in global cognitive function were found between stage 3 and 4 patients and controls. A greater proportion of patients undergoing hemodialysis relative to those treated with peritoneal dialysis showed impairment on measures of memory functions. Results suggest that stage 5 CKD patients may present with impaired cognitive functions. Anemia appeared to be a key variable that may explain the memory impairment in this sample. Future longitudinal investigations of CKD are warranted to determine the trajectory of cognitive impairment. (JINS, 2010, 17, 000–000)

The cognitive profile of early onset Parkinson’s disease (EOPD) has not been clearly defined. Mutations in the parkin gene are the most common genetic risk factor for EOPD and may offer information about the neuropsychological pattern of performance in both symptomatic and asymptomatic mutation carriers. EOPD probands and their first-degree relatives who did not have Parkinson’s disease (PD) were genotyped for mutations in the parkin gene and administered a comprehensive neuropsychological battery. Performance was compared between EOPD probands with (N = 43) and without (N = 52) parkin mutations. The same neuropsychological battery was administered to 217 first-degree relatives to assess neuropsychological function in individuals who carry parkin mutations but do not have PD. No significant differences in neuropsychological test performance were found between parkin carrier and noncarrier probands. Performance also did not differ between EOPD noncarriers and carrier subgroups (i.e., heterozygotes, compound heterozygotes/homozygotes). Similarly, no differences were found among unaffected family members across genotypes. Mean neuropsychological test performance was within normal range in all probands and relatives. Carriers of parkin mutations, whether or not they have PD, do not perform differently on neuropsychological measures as compared to noncarriers. The cognitive functioning of parkin carriers over time warrants further study. (JINS, 2011, 17, 1–10)

Practice Effects (PE) have been gaining interest as an early marker of pathological cognitive decline among older adults, with cognitively compromised individuals exhibiting diminished or absent PE, presumably due to reduced ability to learn. However, the opposite pattern has also been observed, with MCI participants showing larger PEs than controls. In this prospective cohort study, we examined the possibility that individuals with incipient cognitive decline may be more “thrown” by task novelty, which may inflate PE due to diminished performance during the first exposure to the task. We assessed Novelty Effect (NE) and Learning (LRN) on a motor task in 50 community-dwelling independent older adults who expressed a concern about their cognition. Results showed that larger NE was associated with greater cognitive decline 17 months later, reliably classifying participants into decliners and nondecliners. LRN did not independently explain any variance in future cognitive change, but moderated the relationship between NE and decline and correlated with the level of cognition at baseline and follow-up. These findings highlight the differing contributions of NE and LRN to PE, and demonstrate that NE may be sensitive to depletion of cognitive reserve among individuals who are on the verge of exhibiting a reliable cognitive decline. (JINS, 2011, 17, 000–000)

The early onset of depression following traumatic brain injury (TBI) is associated with poorer psychosocial outcomes; however, the direction of this relationship is unclear. This study investigated the relationship between progress in resuming preinjury lifestyle (transition events), change in perceived functioning and level of depressive symptoms at discharge and 3-months postdischarge. As part of a prospective longitudinal study of brain injury outcomes, 96 consecutively discharged patients with TBI completed measures of transition events (Sentinel Events Questionnaire) and perceived functioning (Mayo-Portland Adaptability Inventory-4 Ability and Adjustment indices) at discharge and 3-months follow-up. Level of depressive symptoms was assessed at discharge and 3-months follow-up using the Depression Anxiety Stress Scale 21. After controlling for age and discharge depressive symptoms, change in perceived functioning was found to mediate the relationship between total transition events and depressive symptoms at 3-months postdischarge (β reduced from .21 to .14), with a significant indirect effect observed. The present findings indicate that lack of progress in resuming preinjury lifestyle contributes to postdischarge depressive symptoms through an influence on perceived functioning, thus providing an improved conceptualization of reactive depression in the context of brain injury. (JINS, 2011, 17, 000–000)

The association between family socioeconomic status (SES) and child executive functions is well-documented. However, few studies have examined the role of potential mediators and moderators. We studied the independent and interactive associations between family SES and single parenthood to predict child executive functions of inhibitory control, cognitive flexibility, and working memory and examined child expressive language abilities and family home environment as potential mediators of these associations. Sixty families from diverse SES backgrounds with a school-age target child (mean [SD] age = 9.9 [0.96] years) were evaluated. Child executive functioning was measured using a brief battery. The quality of the home environment was evaluated using the Home Observation for the Measurement of the Environment inventory. Family SES predicted the three child executive functions under study. Single parent and family SES were interactively associated with children’s inhibitory control and cognitive flexibility; such that children from low SES families who were living with one parent performed less well on executive function tests than children from similarly low SES who were living with two parents. Parental responsivity, enrichment activities and family companionship mediated the association between family SES and child inhibitory control and working memory. This study demonstrates that family SES inequalities are associated with inequalities in home environments and with inequalities in child executive functions. The impact of these disparities as they unfold in the lives of typically developing children merits further investigation and understanding. (JINS, 2011, 17, 000–000)

Prenatal exposure to sodium valproate (VPA) and polytherapy has been linked with increased risk of birth defects and cognitive impairment in young children. We evaluated the cognitive impact of prenatal exposure to VPA and polytherapy in school-aged children. Fifty-seven children exposed to VPA (n = 23), polytherapy with VPA (n = 15), or polytherapy without VPA (n = 19) were assessed using the Wechsler Intelligence Scale for Children—Fourth Edition. Information on maternal epilepsy, pregnancy, and medical history was obtained prospectively through the Australian Pregnancy Register for Women with Epilepsy and Allied Disorders. All groups had elevated frequencies of Extremely Low (<70) or Borderline (70–79) Full-Scale IQ (15.8–40.0%). Verbal Comprehension and Working Memory scores in all groups fell significantly below the standardized test mean, while Perceptual Reasoning and Processing Speed scores were relatively intact. Multivariate analysis of covariance analysis revealed significant main effects of VPA on Verbal Comprehension and Working Memory, and of polytherapy on Verbal Comprehension and Processing Speed. Our results suggest that VPA has a dose-dependent negative impact on verbal intellectual abilities, and may also affect working memory. The possibility that inclusion of VPA in many polytherapy regimens may underlie reduced mean scores of polytherapy-exposed children is discussed. (JINS, 2011, 17, 000–000)

Mild cognitive impairment (MCI), especially amnestic, often represents pre-dementia Alzheimer’s disease, characterized by medial temporal lobe atrophy, while white matter (WM) alterations are insufficiently described. We analyze both cortical morphometric and WM diffusivity differences in amnestic versus non-amnestic subtypes and ask if memory and WM tract affection are related independently of cortical atrophy. Forty-nine patients from a university-hospital based memory clinic with a score of 3 on the Global Deterioration Scale aged 43–77 years (45% female) were included. Two neuropsychologists have classified cases as amnestic (aMCI), non-amnestic (naMCI), or less advanced (laMCI), not satisfying criteria for aMCI/naMCI. Diffusion tensor imaging (DTI) WM tract and morphometric data of the temporal-parietal memory network were compared among patient subtypes and related to story, word list, and visual memory. WM radial and mean diffusivity (DR and MD), underlying the entorhinal cortex, were higher in aMCI compared with laMCI. WM DR and MD, underlying the entorhinal, parahippocampal, and middle temporal cortex, explained unique variance in word list and story memory, and this was not due to secondary effects of cortical thinning. DTI may thus potentially aid diagnosis in early disease stages. (JINS, 2011, 17, 000–000)

We used data from two population-based longitudinal studies to estimate time of onset and rate of accelerated decline across cognitive domains before dementia diagnosis. The H70 includes an age-homogeneous sample (127 cases and 255 non-cases) initially assessed at age 70 with 12 follow-ups over 30 years. The Kungsholmen Project (KP) includes an age-heterogeneous sample (279 cases and 562 non-cases), with an average age of 82 years at initial assessment, and 4 follow-ups spanning 13 years. We fit mixed linear models to the data and determined placement of change points by a profile likelihood method. Results demonstrated onset of accelerated decline for fluid (speed, memory) versus crystallized (verbal, clock reading) abilities occurring approximately 10 and 5 years before diagnosis, respectively. Although decline before change points was greater for fluid abilities, acceleration was more pronounced for crystallized abilities after the change points. This suggests that onset and rate of acceleration vary systematically along the fluid-crystallized ability continuum. There is early onset in fluid abilities, but these changes are difficult to detect due to substantial age-related decline. Onset occurred later and acceleration was greater in crystallized abilities, suggesting that those markers may provide more valid identification of cases in later stages of the prodromal phase. (JINS, 2011, 17, 000–000)

Age, education, and gender are the most common covariates used to define normative standards against which neuropsychological (NP) performance is interpreted, but influences of other demographic factors have begun to be appreciated. In developing nations, urban versus rural residence may differentially affect numerous factors that could influence cognitive test performances, including quality of both formal and informal educational experiences and employment opportunities. Such disparities may necessitate corrections for urban/rural (U/R) status in NP norms. Prior investigations of the U/R effect on NP performance typically have been confounded by differences in educational attainment. We addressed in this by comparing the NP performance of large, Chinese urban (Yunnan Province, n = 201) and rural (Anhui Province, n = 141) cohorts of healthy adults, while controlling for other demographic differences. Although the groups did not differ in global NP scores, a more complex pattern was observed within specific NP ability domains and tests. Urban participants showed better performance in select measures of processing speed and executive functions, verbal fluency, and verbal learning. Self-reported daily use of academic skills was predictive of many U/R differences. Controlling for academic skill use abrogated most U/R differences but revealed rural advantages in select measures of visual reasoning and motor dexterity. (JINS, 2011, 17, 000–000)

The Val158Met polymorphism of the catechol-O-methyltransferase (COMT) gene may be related to individual differences in cognition, likely via modulation of prefrontal dopamine catabolism. However, the available studies have yielded mixed results, possibly in part because they do not consistently account for other genes that affect cognition. We hypothesized that COMT Met allele homozygosity, which is associated with higher levels of prefrontal dopamine, would predict better executive function as measured using standard neuropsychological testing, and that other candidate genes might interact with COMT to modulate this effect. Participants were 95 healthy, right-handed adults who underwent genotyping and cognitive testing. COMT genotype predicted executive ability as measured by the Trail-Making Test, even after covarying for demographics and Apolipoprotein E (APOE), brain-derived neurotrophic factor (BDNF), and ankyrin repeat and kinase domain containing 1 (ANKK1) genotype. There was a COMT-ANKK1 interaction in which individuals having both the COMT Val allele and the ANKK1 T allele showed the poorest performance. This study suggests the heterogeneity in COMT effects reported in the literature may be due in part to gene–gene interactions that influence central dopaminergic systems. (JINS, 2011, 17, 1–7)

Difficulty in inhibition or cognitive control is a common and significant sequela of pediatric traumatic brain injury (TBI). The present study used functional MRI to examine one specific inhibitory function, interference control, in 11 adolescents, aged 12–16 years, (mean age, 15.7 years) with TBI who were at least 1 year postinjury and 11 age-matched typically developing control participants (TC) (mean age, 15.2 years). Participants completed a Counting Stroop task with 2 main conditions: (1) a neutral condition requiring the counting of animal words and (2) an interference condition in which mismatched number words were counted. Both TBI and TC adolescents activated similar networks of brain regions relevant to interference control, but the TBI group showed higher levels of activation relative to the TC group in multiple brain areas within this network, including predominantly right frontal and parietal regions. Findings of greater activation of the relevant neural network in the TBI group are consistent with recent fMRI findings using other interference control paradigms with individuals with a history of TBI. (JINS, 2011, 17, 000–000.)