Lack of effect of pravastatin on cerebral blood flow or parenchymal volume loss in elderly at risk for vascular disease

<p><b>Background and Purpose:</b> Ageing is associated with a decline in cerebral blood flow. Animal studies have shown that cholesterol-lowering therapy with statins might preserve cerebral blood flow (CBF). We examined the effect of 40 mg pravastatin on the decline in CBF and brain volume in a subset of elderly subjects participating in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) trial.</p> <p><b>Methods:</b> Randomization was not stratified according to whether or not subjects participated in the MRI substudy. In 391 men (n=226) and women (n=165) aged 70 to 82 years (mean±SD, 75±3.2), we measured total CBF (in mL/min) at baseline and after a mean±SD follow-up of 33±1.4 months with a gradient-echo phase-contrast MRI technique. Total CBF was defined as the summed flows in both internal carotid and vertebral arteries. Parenchymal volume (whole brain) was segmented with the use of in-house–developed semiautomatic software.</p> <p><b>Results:</b> Total CBF significantly declined in the placebo-allocated group, from 521±83 to 504±92 mL/min (P=0.0036) and in the pravastatin-allocated group from 520±94 to 506±92 mL/min (P=0.018). This decline was not significantly different between treatment groups (P=0.56). There was also a significant reduction in brain volume over time (P<0.001), which was not different between the treatment groups (P=0.47). When expressed per unit of parenchymal volume, the decline in CBF over time was no longer statistically significant.</p> <p><b>Conclusions:</b> Elderly people at risk for cerebral vascular disease had a significant decline in CBF with increasing age that was explained by a concomitant reduction in brain volume. Treatment with 40 mg pravastatin daily had no beneficial effect on total CBF.</p&gt

A Critical Examination of the Environmental Mastery Scale

The Psychological well being Inventory (PWBI) is a multidimensional instrument that has enjoyed widespread use in a variety of research initiatives, from small-scale studies to national surveys. Recent empirical investigation of the measure has raised questions about its validity. This study examines the factorial validity of the Environmental Mastery Scale of the PWBI, a construct that receives much attention in mental health research. The results of a confirmatory factor analysis did not support the unidimensional factor structure of the measure. Correlated uniqueness models were also examined, which did not reveal evidence of a method effect. There are problems with the measure at the item level, which also raises significant questions about the underlying theory of its parent measure.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/61157/1/EMS.pd

The AURORA Study: a longitudinal, multimodal library of brain biology and function after traumatic stress exposure

Adverse posttraumatic neuropsychiatric sequelae (APNS) are common among civilian trauma survivors and military veterans. These APNS, as traditionally classified, include posttraumatic stress, postconcussion syndrome, depression, and regional or widespread pain. Traditional classifications have come to hamper scientific progress because they artificially fragment APNS into siloed, syndromic diagnoses unmoored to discrete components of brain functioning and studied in isolation. These limitations in classification and ontology slow the discovery of pathophysiologic mechanisms, biobehavioral markers, risk prediction tools, and preventive/treatment interventions. Progress in overcoming these limitations has been challenging because such progress would require studies that both evaluate a broad spectrum of posttraumatic sequelae (to overcome fragmentation) and also perform in-depth biobehavioral evaluation (to index sequelae to domains of brain function). This article summarizes the methods of the Advancing Understanding of RecOvery afteR traumA (AURORA) Study. AURORA conducts a large-scale (n = 5000 target sample) in-depth assessment of APNS development using a state-of-the-art battery of self-report, neurocognitive, physiologic, digital phenotyping, psychophysical, neuroimaging, and genomic assessments, beginning in the early aftermath of trauma and continuing for 1 year. The goals of AURORA are to achieve improved phenotypes, prediction tools, and understanding of molecular mechanisms to inform the future development and testing of preventive and treatment interventions