Microbleeds in fronto-subcortical circuits are predictive of dementia conversion in patients with vascular cognitive impairment but no dementia

Cerebral small vessel disease（CSVD） is a common etiology of vascular cognitive impairment with no dementia（V-CIND）. Studies have revealed that cerebral microbleeds（CMBs）, a feature of CSVD, contribute to cognitive impairment. However, the association between CMBs and dementia conversion in individuals with V-CIND is still unclear. Here, we analyzed the predictive role of CMBs in the conversion from V-CIND to dementia in CSVD patients. We recruited and prospectively assessed 85 patients with CSVD and V-CIND. V-CIND was evaluated using a series of comprehensive neuropsychological scales, including the Chinese version of the Montreal Cognitive Assessment and the Clinical Dementia Rating. MRI assessments were used to quantify lacunar infarcts, white matter hyperintensities, CMBs, and medial temporal lobe atrophy. Eighty-two of the 85 patients completed the assessment for dementia conversion at a 1-year follow-up assessment. Multivariate logistic regression analyses were conducted to examine independent clinical and MRI variables associated with dementia conversion. Twenty-four patients（29.3%） had converted to dementia at the 1-year follow-up, and these individuals had significantly more CMBs in the fronto-subcortical circuits. Multivariate logistic regression analyses revealed that the patients with CMBs in the fronto-subcortical circuits（odds ratio = 4.4; 95% confidence interval： 1.602-12.081, P = 0.004） and 5 or more CMBs overall（odds ratio = 17.6, 95% confidence interval： 3.23-95.84, P = 0.001） had a significantly increased risk of dementia at the 1-year follow-up. These findings indicate that CMBs in the fronto-subcortical circuits may be predictive of dementia conversion in CSVD patients with V-CIND, and thus extend the clinical significance of CMBs.

Neuroprotective effects of tetrandrine against vascular dementia

Tetrandrine is one of the major active ingredients in Menispermaceae Stephania tetrandra S.Moore,and has specific therapeutic effects in ischemic cerebrovascular disease.Its use in vascular dementia has not been studied fully.Here,we investigated whether tetrandrine would improve behavioral and cellular impairments in a two-vessel occlusion rat model of chronic vascular dementia.Eight weeks after model establishment,rats were injected intraperitoneally with 10 or 30 mg/kg tetrandrine every other day for 4 weeks.Behavioral assessment in the Morris water maze showed that model rats had longer escape latencies in training trials,and spent less time swimming in the target quadrant in probe trials,than sham-operated rats.However,rats that had received tetrandrine showed shorter escape latencies and longer target quadrant swimming time than untreated model rats.Hematoxylin-eosin and Nissl staining revealed less neuronal necrosis and pathological damage,and more living cells,in the hippocampus of rats treated with tetrandrine than in untreated model rats.Western blot assay showed that interleukin-1β expression,and phosphorylation of the N-methyl-D-aspartate 2B receptor at tyrosine 1472,were lower in model rats that received tetrandrine than in those that did not.The present findings suggest that tetrandrine may be neuroprotective in chronic vascular dementia by reducing interleukin-1β expression,N-methyl-D-aspartate receptor 2B phosphorylation at tyrosine 1472,and neuronal necrosis.

MRI Features and Site-specific Factors of Ischemic Changes in White Matter： A Retrospective Study

Brain magnetic resonance imaging （MRI） of the elderly often reveals white matter changes （WMCs） with substantial variability across individuals. Our study was designed to explore MRI features and site-specific factors of ischemic WMCs. Clinical data of consecutive patients diagnosed with ischemic cerebral vascular disease who had undergone brain MRI were collected and analyzed. Multi-logistic regression analysis comparing patients with mild versus severe WMCs was performed to detect independent associations. Analyses of variance （ANOVAs） were used to detect regionally specific differences in lesions. We found that lesion distribution differed significantly across five cerebral areas, with lesions being predominant in the frontal lobe and parieto-occipital area. To explore WMCs risk factors, after adjusting for gender, diabetes mellitus, and hypertension, only age （P〈0.01）, creatinine （P=0.01）, alkaline phosphatase （ALP） （P=0.01） and low-density lipoprotein cholesterol （LDL-C） （P=0.03） were found to be independently associated with severe WMCs. Age （P〈0.001） was strongly associated with WMCs in the frontal lobe while hypertension was independently related to lesions in the basal ganglia （P=0.048） or infratentorial area （P=0.016）. In conclusion, MRI of WMCs showed that ischemic WMCs occurred mostly in the frontal lobe and parieto-occipital area. The infratentorial area was least affected by WMCs. Typically, age-related WMCs were observed in the frontal lobes, while hypertension-related WMCs tended to occur in the basal ganglia and infratentorial area.

Buyanghuanwu decoction promotes angiogenesis after cerebral ischemia/reperfusion injury：mechanisms of brain tissue repair

Buyanghuanwu decoction has been shown to protect against cerebral ischemia/reperfusion injury,but the underlying mechanisms remain unclear.In this study,rats were intragastrically given Buyanghuanwu decoction,15 m L/kg,for 3 days.A rat model of cerebral ischemia/reperfusion injury was established by middle cerebral artery occlusion.In rats administered Buyanghuanwu decoction,infarct volume was reduced,serum vascular endothelial growth factor and integrin αvβ3 levels were increased,and brain tissue vascular endothelial growth factor and CD34 expression levels were increased compared with untreated animals.These effects of Buyanghuanwu decoction were partially suppressed by an angiogenesis inhibitor（administered through the lateral ventricle for 7 consecutive days）.These data suggest that Buyanghuanwu decoction promotes angiogenesis,improves cerebral circulation,and enhances brain tissue repair after cerebral ischemia/reperfusion injury.