Colleen E. Jackson

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

Successful early detection of mild cognitive impairment (MCI) and Alzheimers 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.

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 Alzheimers 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 Alzheimers 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.

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.

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

This study examined between‐ and within‐subject stability of cognitive performance in individuals with chronic schizophrenia.

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.

Longitudinal associations between post-traumatic stress disorder and metabolic syndrome severity.

BACKGROUND Post-traumatic stress disorder (PTSD) is associated with elevated risk for metabolic syndrome (MetS). However, the direction of this association is not yet established, as most prior studies employed cross-sectional designs. The primary goal of this study was to evaluate bidirectional associations between PTSD and MetS using a longitudinal design. METHOD A total of 1355 male and female veterans of the conflicts in Iraq and Afghanistan underwent PTSD diagnostic assessments and their biometric profiles pertaining to MetS were extracted from the electronic medical record at two time points (spanning ~2.5 years, n = 971 at time 2). RESULTS The prevalence of MetS among veterans with PTSD was just under 40% at both time points and was significantly greater than that for veterans without PTSD; the prevalence of MetS among those with PTSD was also elevated relative to age-matched population estimates. Cross-lagged panel models revealed that PTSD severity predicted subsequent increases in MetS severity (β = 0.08, p = 0.002), after controlling for initial MetS severity, but MetS did not predict later PTSD symptoms. Logistic regression results suggested that for every 10 PTSD symptoms endorsed at time 1, the odds of a subsequent MetS diagnosis increased by 56%. CONCLUSIONS Results highlight the substantial cardiometabolic concerns of young veterans with PTSD and raise the possibility that PTSD may predispose individuals to accelerated aging, in part, manifested clinically as MetS. This demonstrates the need to identify those with PTSD at greatest risk for MetS and to develop interventions that improve both conditions.

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 Alzheimers 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.

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

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).

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

ABSTRACT 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.

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.