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Greater cognitive and affective decline occurs in patients with AD-MetS than in those without. Further, insulin resistance and vascular endothelial dysfunction are strongly correlated with AD-MetS before pathological white matter changes can be observed.

Pericytes play a pivotal role in contraction, mediating inflammation and regulation of blood flow in the brain. In this study, changes of pericytes in the neurovascular unit (NVU) were examined in relation to the effects of exogenous tissue plasminogen activator (tPA) and a free radical scavenger, edaravone. Immunohistochemistry and Western blot analyses showed that the overlap between platelet-derived growth factor receptor β-positive pericytes and N-acetylglucosamine oligomers (NAGO)-positive endothelial cells increased significantly at 4 days after 90 min of transient middle cerebral artery occlusion (tMCAO). The number of pericytes and the overlap with NAGO decreased with tPA but recovered with edaravone 4 days after tMCAO with proliferation. Thus, tPA treatment damaged pericytes, resulting in the detachment from astrocytes and a decrease in glial cell line-derived neurotrophic factor secretion. However, treatment with edaravone greatly improved tPA-induced damage to pericytes. The present study demonstrates that exogenous tPA strongly damages pericytes and destroys the integrity of the NVU, but edaravone treatment can greatly ameliorate such damage after acute cerebral ischemia in rats. © 2014 The Authors. Journal of Neuroscience Research Published by Wiley Periodicals, Inc.

Aims:The world is rapidly aging, and is facing an increase of late-elderly dementia patients. It is important to investigate the characteristic features of late-elderly dementia in the super-aged country. Methods: We examined 1,554 patients with cognitive decline in our clinic, dividing into 3 subgroups according to the age; young-(≤64 years old [y.o.]), middle-(65-74 y.o.), and late-elderly (75 y.o.≤), and investigated the cognitive, affective, and activities of daily living functions (ADL), especially in late-elderly patients comparing with young-and middle-elderly patients. Results: Among 1,554 patients, Alzheimer's disease (AD) dominated 62%, and which was age-dependently increased up to 69% in late-elderly group. Total scores of 4 cognitive tests were significantly worse with aging with specific subscales of orientation, recall, visual retention, word fluency, etc. On the other hand, total scores of the affective tests showed only an increase in apathy scale in the late-elderly group. Each subgroup showed depressive/depression in 63.2-55.2 %, and apathy in 44.2-54.8%. Furthermore, instrumental ADL items significantly deteriorated in the late-elderly group, which statistically correlated with mini-mental state examination (MMSE) score. Conclusions: These results demonstrates that late-elderly group is characterized by significant cognitive declines, increasing apathy, more than half in depressive/depression and apathy, and instrumental ADL decrease. The cognitive decline may be related to such affective and ADL declines.

Background and Purpose-This study aimed to assess the risk and benefit of tissue-type plasminogen activator treatment after oral anticoagulation with rivaroxaban or apixaban compared with warfarin or placebo. Methods-Pretreatment with warfarin (0.2 mg/kg per day), rivaroxaban (2 mg/kg per day), apixaban (10 mg/kg per day), or vehicle (0.5% carboxymethyl cellulose sodium salt) was performed for 7 days. Transient middle cerebral artery occlusion was then induced for 120 minutes, followed by reperfusion with tissue-type plasminogen activator (10 mg/ kg per 10 mL). Clinical parameters, including cerebral infarction volume, hemorrhagic volume, and blood coagulation, were examined. Twenty-four hours after reperfusion, markers for the neurovascular unit at the peri-ischemic lesion were immunohistochemically examined in brain sections, and matrix metalloproteinase-9 activity was measured by zymography. Results-The paraparesis score was significantly improved in the rivaroxaban-pretreated group compared with the warfarinpretreated group. Intracerebral hemorrhage was observed in the warfarin-pretreated group, and this was reduced in the rivaroxaban and apixaban-pretreated groups compared with the vehicle group. Marked dissociation of astrocyte foot processes and the basal lamina or pericytes was observed in the warfarin-pretreated group, and this was improved in the rivaroxaban and apixaban-pretreated groups. Furthermore, activation of matrix metalloproteinase-9 in the ipsilateral warfarin-pretreated brain was greatly reduced in rivaroxaban-and apixaban-pretreated rats. Conclusions-This study shows a lower risk of intracerebral hemorrhage after tissue-type plasminogen activator treatment in rats with ischemic stroke that are pretreated with rivaroxaban and apixaban compared with pretreatment with warfarin. Reducing neurovascular dissociation by rivaroxaban and apixaban compared with warfarin could partly explain a reduction in hemorrhagic complications reported in clinical studies.