Effect of blast-related mTBI on the working memory system: a resting state fMRI study.

Reduced working memory is frequently reported by Veterans with a history of blast-related mild traumatic brain injury (mTBI), but can be difficult to quantify on neuropsychological measures. This study aimed to improve our understanding of the impact of blast-related mTBI on the working memory system by using resting state functional magnetic resonance imaging (fMRI) to explore differences in functional connectivity between OEF/OIF/OND Veterans with and without a history of mTBI. Participants were twenty-four Veterans with a history of blast-related mTBI and 17 Veterans who were deployed but had no lifetime history of TBI.

Retrospective and Prospective Memory Among OEF/OIF/OND Veterans With a Self-Reported History of Blast-Related mTBI.

Objectives: To evaluate prospective and retrospective memory abilities in Operation Enduring Freedom (OEF), Operation Iraqi Freedom (OIF), and Operation New Dawn (OND) Veterans with and without a self-reported history of blast-related mild traumatic brain injury (mTBI).

Methods: Sixty-one OEF/OIF/OND Veterans, including Veterans with a self-reported history of blast-related mTBI (mTBI group; n=42) and Veterans without a self-reported history of TBI (control group; n=19) completed the Memory for Intentions Test, a measure of prospective memory (PM), and two measures of retrospective memory (RM), the California Verbal Learning Test-II and the Brief Visuospatial Memory Test-Revised.

Results: Veterans in the mTBI group exhibited significantly lower PM performance than the control group, but the groups did not differ in their performance on RM measures.

Effect of simvastatin on CSF Alzheimer disease biomarkers in cognitively normal adults.

Objective: To examine potential disease-modifying effects of statin drugs, we conducted a 12-month randomized, placebo-controlled clinical trial of simvastatin in cognitively normal adults using change in CSF Alzheimer disease biomarkers as primary outcome measure.

Methods: Participants were 45-64 years old and statin-naive with normal cognition and normal or mildly elevated cholesterol. Forty-six participants completed the 1-year study per protocol (25 in the simvastatin and 21 in the placebo group).

Cerebrospinal fluid biomarkers for Alzheimer's and vascular disease vary by age, gender, and APOE genotype in cognitively normal adults.

Background: This study sought to evaluate gender and APOE genotype-related differences in the concentrations of cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease (AD) and cerebrovascular injury across the life span of cognitively normal adults.

Methods: CSF amyloid beta (Aβ), phospho-tau-181 (p-tau), and total tau were measured in 331 participants who were between the ages of 21 and 100. CSF E-selectin and vascular cell adhesion protein 1 (VCAM1) were measured in 249 participants who were between the ages of 50 and 100.

Higher Pretreatment Blood Pressure Is Associated With Greater Posttraumatic Stress Disorder Symptom Reduction in Soldiers Treated With Prazosin.

Background: In a previously reported positive randomized controlled trial of the α-adrenoreceptor (αAR) antagonist prazosin for combat posttraumatic stress disorder (PTSD) in 67 active duty soldiers, baseline symptoms did not predict therapeutic response. If increased brain αAR activation in PTSD is the target of prazosin treatment action, higher brain αAR activation should predict greater prazosin efficacy. Although brain αAR activation is not measurable, coregulated peripheral αAR activation could provide an estimate of brain αAR activation.

Repetitive blast exposure in mice and combat veterans causes persistent cerebellar dysfunction.

Blast exposure can cause mild traumatic brain injury (TBI) in mice and other mammals. However, there are important gaps in our understanding of the neuropathology underlying repetitive blast exposure in animal models compared to the neuroimaging abnormalities observed in blast-exposed veterans. Moreover, how an increase in the number of blast exposures affects neuroimaging endpoints in blast-exposed humans is not well understood.

Neuroimaging, behavioral, and psychological sequelae of repetitive combined blast/impact mild traumatic brain injury in Iraq and Afghanistan war veterans.

Abstract Whether persisting cognitive complaints and postconcussive symptoms (PCS) reported by Iraq and Afghanistan war veterans with blast- and/or combined blast/impact-related mild traumatic brain injuries (mTBIs) are associated with enduring structural and/or functional brain abnormalities versus comorbid depression or posttraumatic stress disorder (PTSD) remains unclear. We sought to characterize relationships among these variables in a convenience sample of Iraq and Afghanistan-deployed veterans with (n=34) and without (n=18) a history of one or more combined blast/impact-related mTBIs. Participants underwent magnetic resonance imaging of fractional anisotropy (FA) and macromolecular proton fraction (MPF) to assess brain white matter (WM) integrity; [(18)F]-fluorodeoxyglucose positron emission tomography imaging of cerebral glucose metabolism (CMRglu); structured clinical assessments of blast exposure, psychiatric diagnoses, and PTSD symptoms; neurologic evaluations; and self-report scales of PCS, combat exposure, depression, sleep quality, and alcohol use.

Blast exposure causes early and persistent aberrant phospho- and cleaved-tau expression in a murine model of mild blast-induced traumatic brain injury.

Mild traumatic brain injury (mTBI) is considered the 'signature injury' of combat veterans that have served during the wars in Iraq and Afghanistan. This prevalence of mTBI is due in part to the common exposure to high explosive blasts in combat zones. In addition to the threats of blunt impact trauma caused by flying objects and the head itself being propelled against objects, the primary blast overpressure (BOP) generated by high explosives is capable of injuring the brain.

A trial of prazosin for combat trauma PTSD with nightmares in active-duty soldiers returned from Iraq and Afghanistan.

Objective: The authors conducted a 15-week randomized controlled trial of the alpha-1 adrenoreceptor antagonist prazosin for combat trauma nightmares, sleep quality, global function, and overall symptoms in active-duty soldiers with posttraumatic stress disorder (PTSD) returned from combat deployments to Iraq and Afghanistan.

Method: Sixty-seven soldiers were randomly assigned to treatment with prazosin or placebo for 15 weeks. Drug was titrated based on nightmare response over 6 weeks to a possible maximum dose of 5 mg midmorning and 20 mg at bedtime for men and 2 mg midmorning and 10 mg at bedtime for women.

Loss of olfactory tract integrity affects cortical metabolism in the brain and olfactory regions in aging and mild cognitive impairment.

Unlabelled: Olfactory dysfunction is an early feature of Alzheimer disease. This study used multimodal imaging of PET and (18)F-FDG combined with diffusion tensor imaging (DTI) to investigate the association of fiber tract integrity in the olfactory tract with cortical glucose metabolism in subjects with mild cognitive impairment (MCI) and normal controls. We hypothesized that MCI subjects would show loss of olfactory tract integrity and may have altered associations with glucose metabolism.

Cerebrospinal fluid norepinephrine and cognition in subjects across the adult age span.

Adequate central nervous system noradrenergic activity enhances cognition, but excessive noradrenergic activity may have adverse effects on cognition. Previous studies have also demonstrated that noradrenergic activity is higher in older than younger adults. We aimed to determine relationships between cerebrospinal fluid (CSF) norepinephrine (NE) concentration and cognitive performance by using data from a CSF bank that includes samples from 258 cognitively normal participants aged 21-100 years.

High prevalence of chronic pituitary and target-organ hormone abnormalities after blast-related mild traumatic brain injury.

Studies of traumatic brain injury from all causes have found evidence of chronic hypopituitarism, defined by deficient production of one or more pituitary hormones at least 1 year after injury, in 25-50% of cases. Most studies found the occurrence of posttraumatic hypopituitarism (PTHP) to be unrelated to injury severity. Growth hormone deficiency (GHD) and hypogonadism were reported most frequently.

Cerebrocerebellar hypometabolism associated with repetitive blast exposure mild traumatic brain injury in 12 Iraq war Veterans with persistent post-concussive symptoms.

Disagreement exists regarding the extent to which persistent post-concussive symptoms (PCS) reported by Iraq combat Veterans with repeated episodes of mild traumatic brain injury (mTBI) from explosive blasts represent structural or functional brain damage or an epiphenomenon of comorbid depression or posttraumatic stress disorder (PTSD). Objective assessment of brain function in this population may clarify the issue. To this end, twelve Iraq war Veterans (32.

Adrenocortical responsiveness to infusions of physiological doses of ACTH is not altered in posttraumatic stress disorder.

Early studies of posttraumatic stress disorder (PTSD) reported that abnormal function of the hypothalamic-pituitary-adrenocortical (HPA) system was associated with the disorder. However, subsequent studies attempting to identify a specific aspect of HPA dysfunction that characterizes PTSD have been marked by considerable inconsistency of results. A facet of HPA regulation that has been considered but not definitively investigated is the possibility that the responsiveness of the adrenal cortex to physiological concentrations of adrenocorticotropin (ACTH) is diminished in PTSD.

Preclinical evidence of Alzheimer changes: convergent cerebrospinal fluid biomarker and fluorodeoxyglucose positron emission tomography findings.

Background: Alterations in cerebrospinal fluid (CSF) tau and beta-amyloid peptide 1-42 (Abeta(42)) levels and rates of cerebral glucose metabolism (CMRglu) on fluorodeoxyglucose positron emission tomography (FDG-PET) occur years before clinical symptoms of Alzheimer disease (AD) become manifest, but their relationship remains unclear.

Objective: To determine whether CSF AD biomarker levels and CMRglu in healthy individuals correlate in brain structures affected early in AD.

Design: Cohort study.

Apolipoprotein E highly correlates with AbetaPP- and tau-related markers in human cerebrospinal fluid.

We assessed cerebrospinal fluid (CSF) levels of apolipoprotein E (apoE), phospholipid transfer protein (PLTP) activity, cholesterol, secreted amyloid-beta protein precursor alpha and beta (sAbetaPPalpha, sAbetaPPbeta), amyloid-beta peptides 1-40 (Abeta_{40}) and 1-42 (Abeta_{42}), total tau and tau phosphorylated at threonine 181 (pTau) in neurologically healthy, cognitively intact adults. ApoE significantly correlated with sAbetaPPalpha (r = 0.679), sAbetaPPbeta (r = 0.

Effect of statins on Alzheimer's disease biomarkers in cerebrospinal fluid.

Background: Treatment with HMG-CoA reductase inhibitors ("statins") has been variably associated with a reduced risk of Alzheimer's disease (AD) in epidemiologic studies and reduced amyloid-beta (Abeta) deposition in animal models of AD. Putative neuroprotective effects of statins may vary in relation to their ability to penetrate into the central nervous system (CNS).

Methods: We measured levels of cerebrospinal fluid (CSF) AD biomarkers following 14 weeks of treatment with simvastatin (a CNS permeant statin; n=10) at 40 mg/day or pravastatin (a CNS impermeant statin; n=13) at 80 mg/day in hypercholesterolemic subjects without dementia.

Lewy body pathology in late-onset familial Alzheimer's disease: a clinicopathological case series.

Background: Lewy body pathology (LBP) is a common finding in Alzheimer's disease (AD), but the pathophysiology for this coexistent pathology remains unclear.

Methods: We ascertained late-onset dementia (mean age > 60 years old) families with at least 3 autopsies. We then conducted systematic alpha-synuclein (SNCA) immunostaining to determine the frequency and distribution of LBP in families with late-onset AD.

Salivary cortisol and memory function in human aging.

Objective: To examine the association of salivary cortisol with cognitive changes in a 3 year longitudinal study. Previous studies have suggested that elevated glucocorticoid concentrations alter hippocampal neuronal morphology, inhibit neurogenesis, and impair cognition.

Methods: Salivary cortisol samples were collected at home by 79 cognitively intact older persons (mean age 78+/-7 years) at 08:00, 15:00 and 23:00h, and collections were repeated annually for 3 years.

Reduction of nightmares and other PTSD symptoms in combat veterans by prazosin: a placebo-controlled study.

Objective: Prazosin is a centrally active alpha(1) adrenergic antagonist. The authors' goal was to evaluate prazosin efficacy for nightmares, sleep disturbance, and overall posttraumatic stress disorder (PTSD) in combat veterans.

Method: Ten Vietnam combat veterans with chronic PTSD and severe trauma-related nightmares each received prazosin and placebo in a 20-week double-blind crossover protocol.

Neuroimaging in dementia with Lewy bodies: metabolism, neurochemistry, and morphology.

Dementia with Lewy bodies (DLB) is recognized as one of the most common forms of neurodegenerative dementia. Neuroimaging contributes to a better understanding of the pathophysiology of DLB by examining alterations in brain metabolism, neurochemisty, and morphology in living patients. Neuroimaging can provide objective and quantifiable antemortem markers for the presence of and the progression of DLB and permits differentiation from other dementias.

Prazosin reduces nightmares in combat veterans with posttraumatic stress disorder.

Background: Preclinical and clinical observations suggest that the centrally active alpha1-adrenergic antagonist prazosin might alleviate trauma content nightmares and other symptoms in combat veterans with chronic posttraumatic stress disorder (PTSD).

Method: In this retrospective chart review study, we analyzed data from 59 consecutive combat veterans with previously treatment-resistant chronic PTSD (DSM-IV criteria) and severe intractable trauma content nightmares to whom prazosin had been prescribed. Nightmare severity was quantified using the recurrent distressing dreams item of the Clinician Administered PTSD Scale (CAPS).