Protective effect of carnosine on cognitive impairment induced by subcortical ischemic vascular dementia / 中国药理学通报

Aim Subcortical ischemic vascular demen-tia ( SIVD ) induced by chronic hypoperfusion due to small-artery disease is a common cause of vascular de-mentia ( VaD) , which is recognized as the second most prevalent type of dementia. The aim of this study was to determine whether carnosine played a protective role in cognitive impairment induced by permanent occlu-sion of the right unilateral common carotid arteries ( rUCCAO ) in SIVD. Methods Adult male mice ( C57BL/6 strain ) were subjected to rUCCAO, and treated with carnosine or saline. Locomotor test, open field test, hot plate test, freezing test and Morris water maze were performed after rUCCAO. Results There were no differences among rUCCAO group, carnosine group and sham group for total distance traveled in lo-comotor test. In the open field test, carnosine (200, 500 mg · kg-1 ) significantly revised the decrease of latency spent in the center induced by SIVD . There were no differences between rUCCAO and sham groups for the pain threshold. In freezing test, rUCCAO in-duced a significant reduction in content memory, which was completely reversed by treatment of carnosine. In Morris water maze training trials, rUCCAO-treated mice showed prolonged escape latency in acquisition phase, carnosine ( 200, 500 mg · kg-1 ) markedly shortened the escape latency. Conclusion These data suggest that carnosine has a neuroprotective effect on cognitive impairment induced by rUCCAO in mice.

Recent Updates on Subcortical Ischemic Vascular Dementia / 대한뇌졸중학회지

Vascular dementia (VaD) is a history-laden disease entity that dates back to the 19th century when arteriosclerotic brain atrophy due to hardening of the arteries was perceived as the major cause of senile dementia. Its existence had been overshadowed by the emergence of Alzheimer's disease (AD) in the past century and research on AD dominated the field of dementia. Interest in VaD has been revived in recent years as vascular lesions have been shown to make great contributions to the development of dementia, particularly in the elderly. VaD has now evolved into the concept of vascular cognitive impairment (VCI), which encompasses not only VaD but also AD with cerebrovascular disorder and VCI with no dementia. The concept of VCI is intended to maximize the therapeutic potential in dementia management because the vascular component may be amenable to therapeutic intervention particularly in the early stages of cognitive impairment. Subcortical ischemic vascular dementia (SIVD) is pathologically driven by severe stenosis and the occlusion of small vessels that culminate into white matter ischemia and multiple lacunar infarctions in the subcortical structures. The relatively slow progression of symptoms and clinical manifestations associated with cholinergic deficits often make the differentiation of SIVD from AD difficult. The recent development of in vivo amyloid imaging enabled further pathological breakdown of SIVD into pure SIVD and mixed dementia with subcortical ischemia based on the absence or existence of amyloid pathology in the brain. In this article, the authors reviewed the emerging concepts of VaD/VCI and the clinical manifestations, biomarkers, treatments, and preclinical models of SIVD based on the pathophysiologic mechanisms of the disease.

Analysis of SPECT in Two Sub-types of Subcortical Ischemic Vascular Dementia

BACKGROUND: The brain imaging criteria for subcortical ischemic vascular dementia (SIVD), as proposed by Eurkinjuntti, incorporates the two familiar entities, "the lacunar state" and "Binswanger's disease". However, it has not been proven whether these two subtypes of SIVD have common pathophysiological features. This study investigated the changes of the regional cerebral blood flow (rCBF) in the two subsets of SIVD. METHODS: 12 SIVD patients with predominant white matter lesions, 13 patients with predominant multiple lacunar infarctions and 17 controls were evaluated. The general cognitive function and the severity of dementia were measured by using the K-MMSE and the clinical dementia rating scale. The patients simultaneously met both the NINDS-AIREN criteria for probable or possible vascular dementia (VaD) and the Eurkinjuntti's brain imaging criteria for SIVD. 99mTc-ethyl cysteinate dimmer (ECD)-SPECT was performed to measure the rCBF, and statistical parametric mapping (SPM) was applied to the objective analysis of the SPECT data. RESULTS: SPM analysis of the SPECT images revealed that decreased rCBF in the bilateral thalami, anterior cingulated gyri, superior temporal gyri, caudate heads and left parahippocampal gyrus was significant in the patients with SVaD compared to the controls (uncorrected P=0.001). This pattern of rCBF reduction was the same in both the SIVD patients with predominant white matter lesions and with predominant lacunar infarctions. CONCLUSIONS: Our study suggests that the two subsets of SIVD proposed by Eurkinjuntti may have a common functional abnormality, and the Eurkinjuntti's criteria offers a solution for researchers to identify the more homogeneous group of VaD patients.

Relationship between characteristics of brain-imaging and cognitive disorders in vascular dementia patients / 第三军医大学学报

Objective To investigate the characteristics of brain imaging and its relationship with the cognitive disorders in vascular dementia patients. Methods The volumes of cerebral lobes and hippocampus formation in 30 ischemic vascular dementia patients and 30 normal controls were measured with MRI based technique. The indices of ventricles and cerebral sulci in 30 ischemic vascular dementia patients and 30 patients with ischemic stroke were calculated with CT based technique. The cognitive functions were assessed by psychometric testing (Mini Mental State Examination MMSE, Brief Screening Scale for Dementia BSSD, Raven's Standard Progress Matric RSPM) in all subjects. Results The volumes of frontal and temporal lobes in vascular dementia patients were smaller than those in ischemic stroke patients and normal control subjects ( P 0.05). The decrease of the volumes of the frontal and temporal lobes were positively correlated with the decrease of MMSE and BSSD scores. The cognitive disorders were more severe in the ischemic vascular dementia patients with pathological foci in the frontal and temporal lobes, multiple infarcts, and the total volume of infarcts greater than 50 mm 3 ( P