Articles: brain.
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J. Psychopharmacol. (Oxford) · Jun 2014
Randomized Controlled Trial Multicenter StudyEvaluation of antidepressant properties of the p38 MAP kinase inhibitor losmapimod (GW856553) in Major Depressive Disorder: Results from two randomised, placebo-controlled, double-blind, multicentre studies using a Bayesian approach.
Pro-inflammatory cytokines (PICs) may play important pathophysiological roles in some forms of Major Depressive Disorder (MDD). The p38 MAPK inhibitor losmapimod (GW856553) attenuates the pro-inflammatory response in humans by reducing PIC production. Losmapimod (7.5 mg BD) was administered for 6 weeks in two randomised, placebo-controlled trials in subjects with MDD enriched with symptoms of loss of energy/interest and psychomotor retardation (Studies 574 and 009). ⋯ A subsequent study, Study 009 (n=128), designed using a Bayesian approach based on a prior derived from Study 574, showed no advantage for losmapimod (Bech, 6 weeks: endpoint drug vs. placebo difference = 1.11; 95% credible interval, -0.22, 2.50). Biomarker data showed no significant changes. In conclusion 7.5 mg BID losmapimod was not effective in MDD.
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Multicenter Study
Association of Traumatic Brain Injuries With Vomiting in Children With Blunt Head Trauma.
We aimed to determine the prevalence of traumatic brain injuries in children who vomit after minor blunt head trauma, particularly when the vomiting occurs without other findings suggestive of traumatic brain injury (ie, isolated vomiting). We also aimed to determine the relationship between the timing and degree of vomiting and traumatic brain injury prevalence. ⋯ Traumatic brain injury on CT is uncommon and clinically important traumatic brain injury is very uncommon in children with minor blunt head trauma when vomiting is their only sign or symptom. Observation in the emergency department before determining the need for CT appears appropriate for many of these children.
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Multicenter Study
Effects of traumatic brain injury and posttraumatic stress disorder on Alzheimer's disease in veterans, using the Alzheimer's Disease Neuroimaging Initiative.
Both traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) are common problems resulting from military service, and both have been associated with increased risk of cognitive decline and dementia resulting from Alzheimer's disease (AD) or other causes. This study aims to use imaging techniques and biomarker analysis to determine whether traumatic brain injury (TBI) and/or PTSD resulting from combat or other traumas increase the risk for AD and decrease cognitive reserve in Veteran subjects, after accounting for age. Using military and Department of Veterans Affairs records, 65 Vietnam War veterans with a history of moderate or severe TBI with or without PTSD, 65 with ongoing PTSD without TBI, and 65 control subjects are being enrolled in this study at 19 sites. ⋯ To date, 19 subjects with TBI only, 46 with PTSD only, and 15 with TBI and PTSD have been recruited and referred to 13 clinics to undergo the study protocol. It is expected that cohorts will be fully recruited by October 2014. This study is a first step toward the design and statistical powering of an AD prevention trial using at-risk veterans as subjects, and provides the basis for a larger, more comprehensive study of dementia risk factors in veterans.
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Multicenter Study Clinical Trial
Increased Brain Volume Among Good Grade Patients with Intracerebral Hemorrhage. Results from the Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH) Study.
We ascertained the occurrence of global cerebral edema manifesting as increased brain volume in subjects with intracerebral hemorrhage (ICH) and explored the relationship between subject characteristics and three month outcomes. ⋯ We found preliminary evidence of increased cerebral brain volume in subjects with good grade and small ICHs, which may be suggestive of global cerebral edema.
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Multicenter Study
Association of brain amyloid-β with cerebral perfusion and structure in Alzheimer's disease and mild cognitive impairment.
Patients with Alzheimer's disease have reduced cerebral blood flow measured by arterial spin labelling magnetic resonance imaging, but it is unclear how this is related to amyloid-β pathology. Using 182 subjects from the Alzheimer's Disease Neuroimaging Initiative we tested associations of amyloid-β with regional cerebral blood flow in healthy controls (n = 51), early (n = 66) and late (n = 41) mild cognitive impairment, and Alzheimer's disease with dementia (n = 24). Based on the theory that Alzheimer's disease starts with amyloid-β accumulation and progresses with symptoms and secondary pathologies in different trajectories, we tested if cerebral blood flow differed between amyloid-β-negative controls and -positive subjects in different diagnostic groups, and if amyloid-β had different associations with cerebral blood flow and grey matter volume. ⋯ The associations of amyloid-β with cerebral blood flow and volume differed across the disease spectrum, with high amyloid-β being associated with greater cerebral blood flow reduction in controls and greater volume reduction in late mild cognitive impairment and dementia. In addition to disease stage, amyloid-β pathology affects cerebral blood flow across the span from controls to dementia patients. Amyloid-β pathology has different associations with cerebral blood flow and volume, and may cause more loss of blood flow in early stages, whereas volume loss dominates in late disease stages.