Background and Purose Disruption of the blood-brain barrier (BBB) has been proposed to be important in vascular cognitive impairment (VCI). Increased cerebrospinal fluid (CSF) albumin and contrast-enhanced MRI provide supporting evidence, but quantification of the BBB permeability in patients with VCI is lacking. Therefore, we acquired dynamic contrast-enhanced MRI (DCEMRI) to quantify BBB permeability in VCI. Method We studied 60 patients with suspected VCI. They had neurological and neuropsychological testing, permeability measurements with DCEMRI and lumbar puncture to measure albumin index (Qalb). Patients were separated clinically into subcortical ischemic vascular disease (SIVD), multiple and lacunar infarcts (MI/LAC), and leukoaraiosis (LA). Twenty volunteers were controls for the DCEMRI studies, and control CSF was obtained from 20 individuals undergoing spinal anesthesia for non-neurological problems. Results Thirty-six patients were classified as SIVD, 8 as MI/LAC and 9 as LA. The Qalb was significantly increased in the SIVD group compared to 20 controls. Permeabilities for the VCI patients measured by DCEMRI were significantly increased over controls (p<0.05). Patient age correlated with neither the BBB permeability nor Qalb. Highest Qalb values were seen in SIVD group (p<0.05), and were significantly increased over MI/LAC. Ki values were elevated over controls in SIVD, but were similar to MI/LAC. Conclusions There was abnormal permeability in white matter in patients with SIVD as shown by DCEMRI and Qalb. Future studies will be needed to determine the relationship of BBB damage and development of WMHs.

Background and Purpose Subcortical ischemic vascular disease (SIVD) is a major form of vascular cognitive impairment (VCI) due to small vessel disease. Matrix metalloproteinases (MMPs) are neutral proteases that disrupt the blood-brain barrier (BBB) and degrade myelin basic protein under conditions of neuroinflammation. Brain tissues and CSF of patients with VCI have increased levels of MMPs. We hypothesized that patients with SIVD have increased MMPs in the CSF, which are associated with increased CSF albumin. Methods We studied 60 patients with suspected VCI. Twenty-five were classified as SIVD, while other groups included mixed Alzheimer’s disease AD and VCI (MX), multiple strokes (MI), and leukoaraiosis (LA) when white matter lesions were present and the diagnosis of VCI was uncertain. MMP-2 and MMP-9 in CSF and plasma were measured by gel zymography and indexed to CSF and plasma albumin. MMP-3 activity was measured by fluorescent assay. Results We found reduced MMP-2 index (p<0.001) in the CSF for the full group of patients (SIVD, MI, MX and LA) compared to controls, whose CSF was obtained during spinal anesthesia. MMP-3 activity was increased in VCI compared to controls (p<0.01). In SIVD, MMP-2 index showed a negative correlation with Qalb, which was absent with the MMP-9 index. Combining MMP-2 index and MMP-3 activity separated the SIVD patients from the controls with high specificity (p<0.0005). Conclusions Our results support the hypothesis that MMPs are associated with increased CSF albumin and suggest that they may contribute to the pathophysiology of SIVD.

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This article evaluates the efforts of three teachers at a predominantly white middle school to create a multicultural U.S. history curriculum by focusing on the experiences of enslaved African Americans during the Civil War. I argue that this focus unintentionally undermines students' ability to use history as a resource for thinking about contemporary race relations. 1 conclude with some suggestions for creating a multicultural history curriculum that will benefit both white students and students of color.

To study the fluctuation of suicides around the holidays, we examined 188,047 U.S. suicides from 1973 to 1979. Correcting for the effects of extraneous variables, such as seasons and days of the week, we found that suicides dropped by an annual average of -102.5 in the period surrounding the holidays. One set of holidays (Memorial Day, Thanksgiving, and Christmas) was associated with an unusually low risk of suicide before, during, and after the holiday. Another set of holidays (New Year's Day, July 4th, and Labor Day) was associated with a low risk of suicide before the holiday and a high risk just afterwards. Almost all demographic groups experienced a low risk of suicide around the holidays: whites, blacks, males, females, retired persons, and persons of working age. Only white teenagers deviated from this pattern. Thus, the evidence does not support the widespread popular assumption that holidays are a risk factor in suicide.

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