Lack of Association of Informant-Reported Traumatic Brain Injury and Chronic Traumatic Encephalopathy.

Repetitive head impacts (RHIs) from football are associated with the neurodegenerative tauopathy chronic traumatic encephalopathy (CTE). It is unclear whether a history of traumatic brain injury (TBI) is sufficient to precipitate CTE neuropathology. We examined the association between TBI and CTE neuropathology in 580 deceased individuals exposed to RHIs from football. TBI history was assessed using a modified version of the Ohio State University TBI Identification Method Short Form administered to informants. There were 22 donors who had no TBI, 213 who had at least one TBI without loss of consciousness (LOC), 345 who had TBI with LOC, and, of those with a history of TBI with LOC, 36 who had at least one moderate-to-severe TBI (msTBI, LOC >30 min). CTE neuropathology was diagnosed in 405. There was no association between CTE neuropathology status or severity and TBI with LOC (odds ratio [OR] = 0.95, 95% confidence interval [CI] = 0.64-1.41; OR = 1.22, 95% CI = 0.71-2.09) or msTBI (OR = 0.70, 95% CI = 0.33-1.50; OR = 1.01, 95% CI = 0.30-3.41). There were no associations with other neurodegenerative or cerebrovascular pathologies examined. TBI with LOC and msTBI were not associated with CTE neuropathology in this sample of brain donors exposed to RHIs from American football.

Research utility of a CAPS-IV and CAPS-5 hybrid interview: Posttraumatic stress symptom and diagnostic concordance in recent-era U.S. veterans.

The Clinician-Administered PTSD Scale (CAPS) is used to measure posttraumatic stress symptoms (PTSS) and diagnose posttraumatic stress disorder (PTSD). However, its use, particularly in settings involving longitudinal assessment, has been complicated by changes in the diagnostic criteria between the fourth and fifth editions of the Diagnostic and Statistical Manual of Mental Disorders (i.e., DSM-IV and DSM-5, respectively). The current sample included trauma-exposed U.S. veterans who were deployed in support of military operations following the September 11, 2001, terrorist attacks (N = 371) and were enrolled in a longitudinal study focused on deployment-related stress and traumatic brain injury. A hybrid clinical interview using item wording from the CAPS for DSM-IV (CAPS-IV) with the addition of items unique to the CAPS for DSM-5 (CAPS-5) was used to assess both DSM-IV and DSM-5 PTSD diagnostic criteria, allowing for the calculation of separate total scores and diagnoses. Diagnostic agreement, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and interrater reliability between CAPS-IV and CAPS-5 were evaluated for the entire sample and stratified by gender. We found high diagnostic agreement (92.9%-95.4%), sensitivity (94.4%-98.2%), specificity (91.7%-92.8%), PPV (89.5%-93.0%), NPV (95.7%-98.1%), and interrater reliability,κ = 0.86-0.91,) for both men and women. The current study supports the use of a hybrid PTSD diagnostic interview assessing both DSM-IV and DSM-5 diagnostic criteria, particularly in situations such as longitudinal studies that may require a feasible method of incorporating changes in diagnostic criteria from the DSM-IV to the DSM-5.

Integrating Neuropsychology into Interprofessional Geriatrics Clinics.

Interprofessional healthcare teams are increasingly viewed as a clinical approach to meet the complex medical, psychological, and psychosocial needs of older adult patients. Despite the fact that older adults are at risk for cognitive difficulties, neuropsychologists are not routinely included on Geriatrics consult teams. The primary aim of this paper is to highlight the utility of neuropsychology within an interprofessional Geriatrics consult clinic. To address this aim, we describe specific benefits to patient care that may be associated with the inclusion of neuropsychologists on Geriatrics consult teams, including differential diagnosis, enhanced patient care, and reduced barriers to care. We provide a description of the integration of neuropsychology within a Veterans Health Administration (VA) interprofessional Geriatrics consult clinic team in order to illustrate the implementation of this model.

Associations Among Increases in Posttraumatic Stress Symptoms, Neurocognitive Performance, and Long-Term Functional Outcomes in U.S. Iraq War Veterans.

Cross-sectional research suggests that posttraumatic stress symptoms (PTSS) among war zone veterans are associated with functional impairment and poor quality of life. Less is known about the long-term functional repercussions of PTSS. This study of Iraq War veterans examined the associations between increases in PTSS and long-term functional outcomes, including the potential contributions of neurocognitive decrements. Service members and veterans (N = 594) completed self-report measures of functioning and PTSS severity before Iraq War deployment and again after their return (M = 9.3 years postdeployment). Some participants (n = 278) also completed neurocognitive testing at both times. Multiple regression analyses with the full sample-adjusted for TBI, demographic characteristics, military variables, and predeployment PTSS and functioning-revealed that increased PTSS severity over time was significantly associated with unemployment, aOR = 1.04, 95% CI [1.03, 1.06]; poorer work performance; and poorer physical, emotional, and cognitive health-related functioning at long-term follow-up, f2 s = 0.37-1.79. Among participants who completed neurocognitive testing, a decline in select neurocognitive measures was associated with poorer functioning; however, neurocognitive decrements did not account for associations between increased PTSS and unemployment, aOR = 1.04, 95% CI [1.02, 1.07], with the size and direction upheld after adding neurocognitive variables, or poorer functional outcomes, with small increases after adding neurocognitive measures to the models, f2 s = 0.03-0.10. War zone veterans experiencing long-term increased PTSS and/or neurocognitive decrements may be at elevated risk for higher-level functional impairment over time, suggesting that early PTSS management may enhance long-term functioning.

Reporting of symptoms associated with concussion by OEF/OIF/OND Veterans: Comparison between research and clinical contexts.

OBJECTIVE: Veterans from recent military conflicts frequently report persisting symptoms associated with concussion well beyond the expected period of recovery following mild traumatic brain injury. This study examined differences in the reporting of symptoms associated with concussion between clinical and research contexts. METHODS: This naturalistic comparison included 91 Veterans from Operations Enduring Freedom (OEF), Iraqi Freedom (OIF) and New Dawn (OND). All participants were enrolled in a longitudinal study focused on traumatic brain injury and stress-related disorders and had also completed a VHA Comprehensive TBI Evaluation. Individuals completed the Neurobehavioral Symptom Inventory (NSI) during their research and clinical evaluations; additional measures of performance and symptom validity were also available for a subset of participants. RESULTS: NSI mean total and subscale scores were significantly higher when assessed in the clinical compared to the research setting, irrespective of the order and duration of time between evaluations. Rates of over-reporting on the NSI and performance validity test failure were also higher during the clinical evaluation. CONCLUSION: Clinicians and researchers must appreciate the possible effects of context on the reporting of symptoms commonly associated with concussion. Future research identifying and mitigating factors influencing the effect of context on symptom reporting is needed.

The Clock-in-the-Box, a brief cognitive screen, is associated with failure to return home in an elderly hospitalized sample.

PURPOSE: Cognitive screening upon hospital admission can provide important information about the patient's ability to process information during the inpatient stay. The Clock-in-the-Box (CIB) is a rapidly administered cognitive screening measure which has been previously validated with cognitive screening and neuropsychological assessments. The purpose of this study is to demonstrate the predictive validity of the CIB for discharge location among a sample of older medical inpatients. PATIENTS AND METHODS: Hospitalized Veterans (N=218), aged 55 years and older, were recruited on the day after admission after they gave their consent. These participants completed the CIB, the Montreal Cognitive Assessment, and self-report measures of daily functioning. Using logistic regression models, the bivariable and multivariable impact of the cognitive screening and functional assessments were examined for their ability to predict whether the participants did not return home after hospitalization (eg, admission to subacute rehabilitation facilities or nursing facilities). RESULTS: The participants were older (mean 71.5±9.5 years) and predominantly male (92.7%). The CIB score was independently associated with discharge to locations other than home (odds ratio =0.72, 95% confidence interval =0.60-0.87, P=0.001) and remained associated after adjusting for demographics, prehospitalization functional abilities, and Montreal Cognitive Assessment score (adjusted odds ratio =0.55, 95% confidence interval =0.36-0.83, P=0.004). CONCLUSION: The current evidence, combined with its brevity and ease of use, supports the use of the CIB as a cognitive screen for inpatient older adults, in order to help inform clinical treatment decisions and discharge planning.

Mild Traumatic Brain Injury, PTSD, and Psychosocial Functioning Among Male and Female U.S. OEF/OIF Veterans.

This study examined the unique and combined relationship between mild traumatic brain injury (mTBI) and posttraumatic stress disorder (PTSD) with psychosocial functioning in a cohort of 1,312 U.S. male and female veterans of Operations Enduring Freedom (OEF) and Iraqi Freedom (OIF) enrolled in the Veterans After-Discharge Longitudinal Registry (Project VALOR). We assessed mTBI with structured screening questions reflective of current TBI classification standards and PTSD via the SCID-IV PTSD module; all other variables were assessed by self-report questionnaires. We identified significant diagnostic group differences in psychosocial functioning for both sexes. Individuals with PTSD, with or without a history of mTBI, reported significantly worse psychosocial functioning than individuals with mTBI alone or neither mTBI nor PTSD (males, η(2) p = .11, p < .001; females, η(2) p = .14, p < .001), even after adjusting for demographics and severity of chronic pain. The results suggested that veterans experiencing PTSD, regardless of whether they had a history of mTBI, were at increased risk for long-term psychosocial impairment. Further research examining possible benefits from improved access to resources and treatment to address these needs would be valuable.

Validation of the use of video teleconferencing technology in the assessment of PTSD.

The Veterans Health Administration (VHA) has promoted the use of telehealth technologies to deliver mental health care to veterans with limited access to services on account of geographic and other barriers. The use of technology to deliver interventions to veterans with posttraumatic stress disorder (PTSD) has been a particular focus within VHA. Much less attention has been paid to the use of telehealth technologies to diagnose veterans with PTSD for both treatment and/or disability compensation purposes, in spite of the need for such services. The literature evaluating the use of video teleconferencing methods in the assessment of PTSD is limited; to our knowledge, only 1 previous study has been published. The current study evaluated the psychometric characteristics of the Clinician Administered PTSD Scale (CAPS) administered by video teleconferencing with a larger and more diverse sample of veterans. The CAPS raters had high interrater reliability and there were strong correlations between face-to-face CAPS assessments and video teleconferencing CAPS assessments for diagnosis and total severity. The results suggest that the CAPS can and should be used via video teleconferencing with veterans who have barriers to face-to-face evaluations.

Massed versus spaced visuospatial memory in cognitively healthy young and older adults.

BACKGROUND: The present study examined the effect of massed versus spaced learning trials on 24-hour delayed recall for a visuospatial learning task. To determine the utility of measuring the incremental benefit of spaced training as a cognitive assay that may be useful in early clinical trials, we used a within-subject crossover design, with two small samples (typical sample sizes for phase I clinical trials). METHODS: Young adults and cognitively healthy older adults without significant physical, neurological, or psychiatric illness were trained on a visuospatial paired-associate learning task under a massed condition (learning trials were presented in immediate succession) and a spaced condition (learning trials were presented with 15-minute intertrial delays). RESULTS: Statistically significant differences between training conditions on the visuospatial task, such that young adult participants performed better on delayed recall after spaced training, were identified. Large effect sizes for young and older adults on this task suggest meaningful differences between training conditions, reflecting the expected "spacing effect." The role of amyloid aggregation was also considered for a subset of participants; as amyloid levels increased, the benefit of spaced training decreased, suggesting that the effect of this training paradigm is modulated by disease burden. CONCLUSIONS: The utility of this paradigm as a potential assay for phase I proof-of-concept trials, targeting molecular mechanisms that are central to the encoding and consolidation of new learning, is discussed.

Assessment of cognition in mild cognitive impairment: a comparative study.

The demand for rapidly administered, sensitive, and reliable cognitive assessments that are specifically designed for identifying individuals in the earliest stages of cognitive decline (and to measure subtle change over time) has escalated as the emphasis in Alzheimer's disease clinical research has shifted from clinical diagnosis and treatment toward the goal of developing presymptomatic neuroprotective therapies. To meet these changing clinical requirements, cognitive measures or tailored batteries of tests must be validated and determined to be fit-for-use for the discrimination between cognitively healthy individuals and persons who are experiencing very subtle cognitive changes that likely signal the emergence of early mild cognitive impairment. We sought to collect and review data systematically from a wide variety of (mostly computer-administered) cognitive measures, all of which are currently marketed or distributed with the claims that these instruments are sensitive and reliable for the early identification of disease or, if untested for this purpose, are promising tools based on other variables. The survey responses for 16 measures/batteries are presented in brief in this review; full survey responses and summary tables are archived and publicly available on the Campaign to Prevent Alzheimer's Disease by 2020 Web site (http://pad2020.org). A decision tree diagram highlighting critical decision points for selecting measures to meet varying clinical trials requirements has also been provided. Ultimately, the survey questionnaire, framework, and decision guidelines provided in this review should remain as useful aids for the evaluation of any new or updated sets of instruments in the years to come.

Commentary on "a roadmap for the prevention of dementia II. Leon Thal Symposium 2008." Recruitment of participants for Alzheimer's disease clinical trials: the role of trust in caregivers, clinical researchers, regulatory authorities, and industry sponsors.

A major barrier to progress in Alzheimer's disease treatment research is the increasingly difficult task of recruiting elderly participants into clinical trials. We conducted an anonymous online survey of 676 adults (average age, 50 years) to examine perceived trust in different components of our healthcare-delivery and clinical-research systems, as well as willingness to participate in clinical trials. Respondents indicated the greatest amount of trust in family members, followed by family physicians. Only 3% of respondents "completely" trusted clinical researchers, whereas 62% of respondents trusted them "somewhat" to care for them during the course of a clinical trial. Trust in clinical researchers was modestly negatively correlated with income (r = -0.165, P < .001), but was not significantly related to sex, race, or education. Respondents indicated the least amount of trust in industry sponsors, followed by regulatory authorities.

Stability of cognitive impairment in chronic schizophrenia over brief and intermediate re-test intervals.

OBJECTIVE: This study examined between- and within-subject stability of cognitive performance in individuals with chronic schizophrenia. METHODS: Thirty individuals with schizophrenia and 20 healthy controls matched by age, sex, education, and estimated IQ underwent repeated cognitive assessments at baseline and 30 days using computerized tests of psychomotor function, visual attention/information processing, non-verbal learning, and executive function. RESULTS: Compared to healthy controls, individuals with schizophrenia scored lower on all cognitive measures and demonstrated greater variability in cognitive performance. Within-subject variability in cognitive performance in both the schizophrenia and healthy control groups remained stable at brief (i.e., hours) and intermediate (i.e., one month) assessments. CONCLUSIONS: These results demonstrate the stability of between- and within-subject variability in cognitive performance in schizophrenia, and suggest that variability in cognitive performance may reflect an inherent characteristic of the disorder, rather than differences in test-retest reliability/error of cognitive measures.

Electroencephalography and event-related potentials as biomarkers of mild cognitive impairment and mild Alzheimer's disease.

BACKGROUND: Successful early detection of mild cognitive impairment (MCI) and Alzheimer's disease demands the identification of biomarkers capable of distinguishing individuals with prodromal or early cognitive impairment from healthy aging adults. Many laboratories are engaged in the discovery and validation of a wide array of potential genetic, proteomic, cognitive, and other types of biomarkers. METHODS: This review focuses on the application of quantitative electroencephalography (qEEG) and event-related potential (ERP) technologies as markers of prodromal impairment and early disease progression. It is the aim of this review to critically assess where this field currently stands, as well as future directions for EEG biomarker development. RESULTS: As a neuroimaging tool that is relatively inexpensive, potentially portable, and capable of providing high-density spatial mapping, qEEG offers a noninvasive, rapid, and replicable method for assessing age-related and disease-related neurophysiologic change. CONCLUSIONS: As different signature changes associated with particular stages of disease burden are identified and validated, we anticipate expanded application of qEEG as a reliable and sensitive biomarker(s) of MCI and early Alzheimer's disease.

Specific impairments in visuospatial working and short-term memory following low-dose scopolamine challenge in healthy older adults.

Scopolamine-induced deficits in cognitive and motor processes have been widely demonstrated in animals and humans, although the role of acetylcholine in working memory is not as well understood. This study examined the role of acetylcholine neurotransmission in visuospatial short term and working memory using the Groton Maze Learning Test (GMLT). The GMLT is a computerized hidden maze learning test that yields measures of component cognitive processes such as spatial memory, working memory, and visuomotor function, as well as their integration in trial-and-error problem solving. Healthy older adults were administered scopolamine (0.3 mg subcutaneous), the acetlycholinesterase inhibitor donepezil (5 mg oral), scopolamine with donepezil, or placebo. Compared to placebo, low-dose scopolamine led to performance deficits on all measures of the GMLT. The greatest scopolamine-induced deficits were observed in errors reflecting working memory processes (e.g., perseverative errors d=-2.98, and rule-break errors d=-2.49) and these impairments remained robust when statistical models accounted for scopolamine-related slowing in visuomotor speed. Co-administration of donepezil partially ameliorated scopolamine-related impairments and this effect was greatest for measures of working memory than short-term memory. By itself, donepezil was associated with a small improvement in visuomotor function. These results suggest that scopolamine disrupts processes required for rule maintenance and performance monitoring, in combination with visuomotor slowing and sequential location learning.

Spatial working memory and problem solving in schizophrenia: the effect of symptom stabilization with atypical antipsychotic medication.

Reasoning and problem solving in the spatial domain are important aspects of executive function that are reliably impaired in schizophrenia, and the Groton Maze Learning Test(c) (GMLT) provides a valid measure of spatial working memory. In the current study, 34 patients with first-episode schizophrenia and 20 matched controls were assessed for baseline spatial working memory abilities using this hidden maze learning test. Approximately one month after baseline assessment, allowing for symptoms to stabilize in response to treatment with therapeutic doses of atypical antipsychotic medications for individuals with schizophrenia, all participants were again assessed with the GMLT. Prior to pharmacologic intervention, patients with schizophrenia showed significant impairments in performance of all aspects of the GMLT, including measures of learning efficiency and error monitoring. One month of treatment was associated with a reliable improvement in these domains, although impairments in accuracy and error monitoring on this spatial working memory test persisted despite symptomatic improvement. These results indicate that impairments in spatial working memory are present at the earliest stages of the illness, and that such deficits in performance remain present, albeit ameliorated, after treatment with atypical antipsychotic medication.