The adverse effects of reduced cerebral perfusion on cognition and brain structure in older adults with cardiovascular disease

BACKGROUND: It is well established that aging and vascular processes interact to disrupt cerebral hemodynamics in older adults. However, the independent effects of cerebral perfusion on neurocognitive function among older adults remain poorly understood. We examined the associations among cerebral perfusion, cognitive function, and brain structure in older adults with varying degrees of vascular disease using perfusion magnetic resonance imaging (MRI) arterial spin labeling (ASL). MATERIALS AND METHODS: 52 older adults underwent neuroimaging and were administered the Mini Mental State Examination (MMSE), the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and measures of attention/executive function. ASL and T1-weighted MRI were used to quantify total brain perfusion, total brain volume (TBV), and cortical thickness. RESULTS: Regression analyses showed reduced total brain perfusion was associated with poorer performance on the MMSE, RBANS total index, immediate and delayed memory composites, and Trail Making Test B. Reduced frontal lobe perfusion was associated with worse executive and memory function. A similar pattern emerged between temporal lobe perfusion and immediate memory. Regression analyses revealed that decreased total brain perfusion was associated with smaller TBV and mean cortical thickness. Regional effects of reduced total cerebral perfusion were found on temporal and parietal lobe volumes and frontal and temporal cortical thickness. DISCUSSION: Reduced cerebral perfusion is independently associated with poorer cognition, smaller TBV, and reduced cortical thickness in older adults. CONCLUSION: Prospective studies are needed to clarify patterns of cognitive decline and brain atrophy associated with cerebral hypoperfusion

Cerebrovascular Perfusion among Older Adults with and Without Cardiovascular Disease

BACKGROUND AND PURPOSECardiovascular disease (CVD) encompasses a range of disorders that affect health and functioning in older adults. While cognitive declines have been linked to both cardiovascular and cerebral blood perfusion, protective neurovascular mechanisms raise the question whether cerebrovascular perfusion differs as a function of cardiovascular health status. The present study examined whether cerebrovascular perfusion significantly differs between healthy older adults with and without diagnosed CVD. The study also examined whether previously documented sex differences in cerebral perfusion would be replicated.METHODSTwenty CVD patients without significant heart failure and 39 healthy controls were recruited to undergo a comprehensive assessment, including an interview, echocardiogram, and magnetic resonance imaging). Arterial spin labeling was used to quantify cerebral blood perfusion.RESULTSBoth groups exhibited mean left ventricular ejection fractions that fell within normal limits. In line with previous research, women exhibited significantly higher cerebral perfusion than men. There were no significant group differences in whole brain cerebrovascular perfusion, regional perfusion, or white matter perfusion by patient status after accounting for sex and age.CONCLUSIONSThese findings suggest that the effects of mild CVD on cerebrovascular perfusion are minimal. Future studies are needed to investigate the mechanisms involved in maintaining cerebrovascular perfusion in the context of altered peripheral perfusion and to determine whether this finding extends to more acute or severe CVD.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163612/2/jon12757.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163612/1/jon12757_am.pd

Gender norms and economic empowerment intervention to reduce intimate partner violence against women in rural Côte d'Ivoire: a randomized controlled pilot study.

BACKGROUND: Gender-based violence against women, including intimate partner violence (IPV), is a pervasive health and human rights concern. However, relatively little intervention research has been conducted on how to reduce IPV in settings impacted by conflict. The current study reports on the evaluation of the incremental impact of adding "gender dialogue groups" to an economic empowerment group savings program on levels of IPV. This study took place in north and northwestern rural Côte d'Ivoire. METHODS: Between 2010 and 2012, we conducted a two-armed, non-blinded randomized-controlled trial (RCT) comparing group savings only (control) to "gender dialogue groups" added to group savings (treatment). The gender dialogue group consisted of eight sessions that targeted women and their male partner. Eligible Ivorian women (18+ years, no prior experience with group savings) were invited to participate. 934 out of 981 (95.2%) partnered women completed baseline and endline data collection. The primary trial outcome measure was an overall measure of past-year physical and/or sexual IPV. Past year physical IPV, sexual IPV, and economic abuse were also separately assessed, as were attitudes towards justification of wife beating and a woman's ability to refuse sex with her husband. RESULTS: Intent to treat analyses revealed that compared to groups savings alone, the addition of gender dialogue groups resulted in a slightly lower odds of reporting past year physical and/or sexual IPV (OR: 0.92; 95% CI: 0.58, 1.47; not statistically significant). Reductions in reporting of physical IPV and sexual IPV were also observed (not statistically significant). Women in the treatment group were significantly less likely to report economic abuse than control group counterparts (OR = 0.39; 95% CI: 0.25, 0.60, p < .0001). Acceptance of wife beating was significantly reduced among the treatment group (β = -0.97; 95% CI: -1.67, -0.28, p = 0.006), while attitudes towards refusal of sex did not significantly change Per protocol analysis suggests that compared to control women, treatment women attending more than 75% of intervention sessions with their male partner were less likely to report physical IPV (a OR: 0.45; 95% CI: 0.21, 0.94; p = .04) and report fewer justifications for wife beating (adjusted β = -1.14; 95% CI: -2.01, -0.28, p = 0.01) ; and both low and high adherent women reported significantly decreased economic abuse (a OR: 0.31; 95% CI: 0.18, 0.52, p < 0.0001; a OR: 0.47; 95% CI: 0.27, 0.81, p = 01, respectively). No significant reductions were observed for physical and/or sexual IPV, or sexual IPV alone. CONCLUSIONS: Results from this pilot RCT suggest the importance of addressing household gender inequities alongside economic programming, because this type of combined intervention has potential to reduce levels of IPV. Additional large-scale intervention research is needed to replicate these findings. TRIAL REGISTRATION: REGISTRATION NUMBER: NCT01629472

R-MPV followed by high-dose chemotherapy with TBC and autologous stem-cell transplant for newly diagnosed primary CNS lymphoma

High-dose methotrexate-based chemotherapy is the mainstay of treatment of primary central nervous system lymphoma (PCNSL), but relapses remain frequent. High-dose chemotherapy (HDC) with autologous stem-cell transplant (ASCT) may provide an alternative to address chemoresistance and overcome the blood-brain barrier. In this single-center phase-2 study, newly diagnosed PCNSL patients received 5 to 7 cycles of chemotherapy with rituximab, methotrexate (3.5 g/m(2)), procarbazine, and vincristine (R-MPV). Those with a complete or partial response proceeded with consolidation HDC with thiotepa, cyclophosphamide, and busulfan, followed by ASCT and no radiotherapy. Primary end point was 1-year progression-free survival (PFS), N = 32. Median age was 57, and median Karnofsky performance status 80. Following R-MPV, objective response rate was 97%, and 26 (81%) patients proceeded with HDC-ASCT. Among all patients, median PFS and overall survival (OS) were not reached (median follow-up: 45 months). Two-year PFS was 79% (95% confidence interval [CI], 58-90), with no events observed beyond 2 years. Two-year OS was 81% (95% CI, 63-91). In transplanted patients, 2-year PFS and OS were 81%. There were 3 treatment-related deaths. Prospective neuropsychological evaluations suggested relatively stable cognitive functions posttransplant. In conclusion, this treatment was associated with excellent disease control and survival, an acceptable toxicity profile, and no evidence of neurotoxicity thus far. This trial was registered at www.clinicaltrials.gov as NCT00596154

The Liquid Biopsy Consortium: Challenges and opportunities for early cancer detection and monitoring

The emerging field of liquid biopsy stands at the forefront of novel diagnostic strategies for cancer and other diseases. Liquid biopsy allows minimally invasive molecular characterization of cancers for diagnosis, patient stratification to therapy, and longitudinal monitoring. Liquid biopsy strategies include detection and monitoring of circulating tumor cells, cell-free DNA, and extracellular vesicles. In this review, we address the current understanding and the role of existing liquid-biopsy-based modalities in cancer diagnostics and monitoring. We specifically focus on the technical and clinical challenges associated with liquid biopsy and biomarker development being addressed by the Liquid Biopsy Consortium, established through the National Cancer Institute. The Liquid Biopsy Consortium has developed new methods/assays and validated existing methods/technologies to capture and characterize tumor-derived circulating cargo, as well as addressed existing challenges and provided recommendations for advancing biomarker assays