Peak width of skeletonized mean diffusivity and its association with age-related cognitive alterations and vascular risk factors.

INTRODUCTION: Only two studies investigated the associations between peak width of skeletonized mean diffusivity (PSMD) and age-related cognitive alterations, whereas none of the studies investigated the association with vascular risk factors. METHODS: We evaluated 801 stroke- and dementia-free elderlies with baseline and 3-year follow-up assessments. Regression analyses were used to assess the association between age-related cognitive functions and PSMD. Simple mediation models were used to study the mediation effect of PSMD between vascular risk factors and age-related cognitive outcomes. RESULTS: PSMD was negatively associated with processing speed at baseline and negatively associated with processing and memory scores at 3-year follow-up. The association between vascular risk factors and age-related cognition was mediated by PSMD, as well as other diffusion tensor imaging markers. DISCUSSION: PSMD is preferred over other diffusion tensor imaging markers as it is sensitive to age-related cognitive alterations and calculation is fully automated. PSMD is proposed as a research tool to monitor age-related cognitive alterations.

Proteomic analysis and comparison of intra­ and extracranial cerebral atherosclerosis responses to hyperlipidemia in rabbits.

The present study aimed to investigate protein expression levels of intra­ and extracranial atherosclerosis in rabbits following administration of a high­fat diet. Rabbits were randomly divided into control (group A; n=9) and high­fat diet (group B; n=9) groups. At week 12, tissues were sectioned from the common carotid artery (CCA) and middle cerebral artery (MCA). Pathological analysis was performed. Differential protein expression levels were examined by 2­D gel electrophoresis (2­DE) and mass spectrometry (MS) analysis and validated by western blotting. Serum lipid levels, the intima­media thickness (IMT) and degree of atherosclerosis of the CCA and MCA were increased at week 12 in the high­fat diet group compared with rabbits that received a normal diet. 2­DE and MS analysis of the protein extracted from CCA and MCA detected >439 different proteins; the expression of 25 proteins was altered, and 8 proteins [albumin A chain, tropomyosin α­1 chain (TPM1), heat shock protein 70 (HSP70), α­smooth muscle actin, ß­galactose binding agglutinin, TPM4 isoform 2, cell keratin 9, single octylic acid glyceride ß­2) demonstrated significant alterations in expression levels. Due to limited antibody sources, only three differentially expressed proteins (TPM1, HSP70 and α­smooth muscle actin) were examined by western blotting. The results of our previous study demonstrated that hyperlipidemia affected the IMT of intracranial and extracranial cerebral arteries. In the present study, protein expression levels of TPM1 and α­smooth muscle actin from extracranial cerebral arteries were significantly increased compared with intracranial cerebral arteries; however, protein expression levels of HSP70 from intracranial cerebral arteries was increased compared with extracranial cerebral arteries. The differences may be closely associated with cell proliferation and metastasis, and oxidoreduction, in intra­ and extracranial cerebral atherosclerosis. HSP70 may have protective properties against atherosclerosis via underlying anti­inflammatory mechanisms, furthermore, differential protein expression levels (TPM1, HSP70 and α­smooth muscle actin) between intra­ and extracranial cerebral arteries may facilitate the identification of novel biological markers for the diagnosis and treatment of cerebral arteriosclerosis.

Evaluation of age-related white matter changes using transcranial Doppler ultrasonography.

BACKGROUND: Age-related white matter changes (WMC) increase risk of cognitive and functional decline. They are considered as target for preventive trials. However, using magnetic resonance imaging (MRI) to screen for subclinical WMC is not cost-effective. We explored the clinical utility of transcranial Doppler ultrasound (TCD) in the evaluation of WMC. We hypothesized that the pulsatility index (PI) of TCD correlates with severity of WMC. METHODS: Among 100 stroke patients with WMC, we obtained the mean PI of middle cerebral artery (MCA) and vertebral basilar artery (VB). We investigated the association between PI and WMC volume. We also obtained PI of 50 subjects who had no WMC on MRI and explored the ability of PI values in differentiating subjects with and without WMC. RESULTS: Multivariate linear regressions found that mean MCA PI and mean VB PI were independent predictors for total WMC volume (beta = .43, P < .001 and beta = .37, P < .001, respectively). Mean MCA PI significantly differentiated patients with WMC from those without WMC (area under curve [AUC] .85 [95% confidence interval .78-.91]) with an optimal cut-off value at 1.15 that yielded sensitivity and specificity of 73.7% and 82%, respectively. AUC for mean VB PI was .81 (95% confidence interval .74-.88) with cut-off value at 1.06 that yielded sensitivity and specificity of 70% and 75%, respectively. CONCLUSIONS: PI correlates with volume of WMC. It may help to differentiate those with and without WMC in stroke patients. Further study evaluating the clinical utility of TCD in screening for subclinical WMC among community elderly is warranted.

Coexisting small vessel disease predicts poor long-term outcome in stroke patients with intracranial large artery atherosclerosis.

BACKGROUND AND PURPOSES: Until now, limited data are available about the potential effect of coexisting small vessel disease (SVD) on the long-term outcome of stroke patients with intracranial large artery atherosclerosis (ILAA). METHODS: A prospective study was performed on 293 patients with symptomatic ILAA, who were divided into 4 groups (group I, single intracranial large artery atherosclerosis (SILAA) without SVD; group II, multiple intracranial large arteries atherosclerosis (MILAA) without SVD; group III, SILAA with SVD; group IV, MILAA with SVD) and followed up for recurrent stroke or death. RESULTS: The 3-year cumulative risks of recurrent stroke were 18% for SILAA without SVD, 38% for MILAA without SVD, 21% for SILAA with SVD and 34% for MILAA with SVD. The 3-year cumulative risks of death were 6, 7, 20 and 22%, respectively. Compared with SILAA without SVD, more recurrent stroke occurred in MILAA without SVD (log-rank 3.83; p = 0.050) and MILAA with SVD (log-rank 7.79; p = 0.014), and the higher risk of death (log-rank 9.472; p = 0.002) was found in group MILAA with SVD. A Cox proportional-hazards regression model showed that MILAA with SVD may be a predictor of recurrent stroke (hazard ratio 2.001; 95% CI 1.108-3.934; p = 0.044), and a borderline predictor for death (hazard ratio 3.180; 95% CI 0.895-10.987; p = 0.073). CONCLUSION: Coexisting SVD is very common and may predict poor outcome in stroke patients with symptomatic ILAA.

Effects of statins on progression of subclinical brain infarct.

BACKGROUND: Subclinical brain infarct (SBI) is associated with subsequent stroke and cognitive decline. A longitudinal epidemiological study suggests that statins may prevent development of SBI. We investigated the effects of statins upon development of brain infarct by performing a post-hoc analysis of the Regression of Cerebral Artery Stenosis (ROCAS) study. METHODS: The ROCAS study is a randomized, double-blind, placebo-controlled study evaluating the effects of simvastatin 20 mg daily upon progression of asymptomatic middle cerebral artery stenosis among stroke-free individuals over 2 years. A total of 227 subjects were randomized to either placebo (n = 114) or simvastatin 20 mg daily (n = 113). The number of brain infarcts as detected by MRI was recorded at baseline and at the end of the study. The primary outcome measure was the number of new brain infarcts at the end of the study. RESULTS: Among the 227 randomized subjects, 33 (14.5%) had SBI at baseline. At the end of the study, significantly fewer subjects in the active group (n = 1) had new brain infarcts compared with the placebo group (n = 8; p = 0.018). The new brain infarcts of subjects in the active group were subclinical. Among the placebo group, the new brain infarcts of 3 subjects were symptomatic while those of the remaining 5 subjects were subclinical. Among putative variables, multivariate regression analysis showed that only the baseline number of SBIs (OR = 6.27, 95% CI 2.4-16.5) and simvastatin treatment (OR = 0.09, 95% CI 0.01-0.82) independently predicted the development of new brain infarcts. CONCLUSIONS: Consistent with findings of the epidemiological study, our study suggests that statins may prevent the development of a new brain infarct.

Validation of the ABCD2 score to identify the patients with high risk of late stroke after a transient ischemic attack or minor ischemic stroke.

BACKGROUND AND PURPOSE: The ABCD(2) score is able to predict the short-term risk of stroke after a transient ischemic attack/minor stroke. We aimed to explore its predictive value for long-term recurrent stroke. METHODS: Consecutive patients with a transient ischemic attack/minor stroke, hospitalized during a 2-year period, were followed up to document any further stroke and death stratified by a 7-point ABCD(2) score. Result- A total of 490 patients were followed for an average of 40.5 months (SD, 10.7 months). Further stroke were identified in 76 (15.5%) patients and 62 (12.7%) patients died during follow-up. Multivariate Cox regression analysis showed that an ABCD(2) score >4 was found to be an independent risk factor for further stroke (hazard ratio, 2.27; 95% CI, 1.36 to 3.80) and for death (hazard ratio, 1.68; 95% CI, 0.99 to 2.85). CONCLUSIONS: In addition to predicting short-term stroke risk, ABCD(2) score is a useful tool to predict long-term stroke risk after a transient ischemic attack or minor ischemic stroke.

Predictors of vascular events after ischemic stroke: the China ischemic stroke registry study.

BACKGROUND/AIMS: To measure the risk of vascular event occurrence among postischemic stroke patients in mainland China. METHODS: In this multicenter prospective stroke registry study, we enrolled 1,951 patients diagnosed with acute ischemic stroke. Demographic data, prestroke risk factors, severity of neurological deficits and disability graded on the National Institutes of Health Stroke Scale (NIHSS), and modified Rankin Scale scores of each patient were measured and recorded. Patients were followed up regularly for 12 months after recruitment. Clinical endpoints were defined as occurrence of vascular events or death. RESULTS: We detected 103 cases with nonfatal vascular events and 27 cases that died of vascular events. Cumulative incidences of total vascular events, cerebrovascular events, and coronary artery diseases were 7.2, 5.0, and 1.8%, respectively, at 12 months after the initial ischemic stroke. Concomitant atherosclerotic-thrombotic diseases (HR, 1.68; 95% CI, 1.14-2.43) and baseline NIHSS (HR, 1.07; 95% CI, 1.03-1.11) were found to be the best predictors for further occurrence of a vascular event. Antiplatelet therapy (HR, 0.52; 95% CI, 0.35-0.77) is associated with a lower risk of further vascular events. CONCLUSION: Our study provided valuable data on prognosis of acute ischemic stroke in Chinese patients.

Neuroimaging predictors for depressive symptoms in cerebral small vessel disease.

OBJECTIVE: Although cerebral small vessel disease (SVD) is closely associated with late life depression, patients with even severe SVD may have no depressive symptoms. We postulate that concurrent brain atrophy may also involve in the pathogenesis of depressive symptoms in SVD. We aimed to investigate the relevance of brain atrophy in predicting depressive symptoms among patients with severe SVD. METHODS: We recruited 45 lacunar stroke patients who had diffuse white matter lesion (WML) and varying severity levels of depressive symptoms. We used a quantitative hybrid warping method to determine the volume of 99 brain regions for each patient. We assessed severity of depressive symptoms using the depression score of the hospital anxiety and depression scale (HADS-D). We first performed correlation analysis of each brain variable with the depression score. Significant variables were then entered separately into linear regression analysis to explore predictors of HADS-D, with adjustment of relevant clinical variables. RESULTS: The mean age (SD) of the 45 participants was 74.6 (8.3) years. The mean HADS-D score was 3.5, with score ranging from 0 to 15. Variables that had a significant correlation coefficient with HADS-D were gender, hypertension, Oxford handicap scale, left inferior frontal gyrus, right subthalamic nucleus, left posterior limb of internal capsule, and right cerebellum. Regression analyses showed that only left inferior frontal gyrus atrophy (ß = -0.354, p = 0.017) predicted HADS-D score after adjusted for other relevant clinical variables. CONCLUSION: Concurrent atrophy of left inferior frontal gyrus is associated with depressive symptoms in elderly patients with severe SVD.

Association of antiplatelet therapy with lower risk of death and recurrent cerebrovascular events after ischemic stroke--results from the China Ischemic Stroke Registry Study.

BACKGROUND: Evidence of the beneficial effects of antiplatelet therapy after ischemic stroke is currently lacking in China. METHODS AND RESULTS: Demographic data, pre-stroke risk factors, severity of neurological deficit, and disability graded by the National Institutes of Health Stroke Scale (NIHSS) and Modified Rankin Scale (MRS) of 1,951 patients were measured and recorded at baseline. Regular follow-up by interview was performed for 12 months post-recruitment. The all-cause mortality was 1.88 per 100 person-years during the follow-up period. Recurrent fatal and nonfatal cerebrovascular events occurred in 90 patients, accounting for 4.24 per 100 person-years of cumulative incidence. After adjustment by other variables, antiplatelet therapy was identified as an independent protective predictor of all-cause death (hazard ratio (HR) 0.42; 95% confidence interval (CI) 0.21-0.86; P=0.017) and recurrent cerebrovascular events (HR 0.58; 95%CI 0.36-0.92; P=0.021). Among survivors, antiplatelet therapy was also an independent predictor for improvement in the NIHSS (HR 1.27; 95%CI 1.07-1.51; P=0.006) and the MRS (HR 1.25; 95%CI 1.02-1.52; P=0.031). CONCLUSIONS: The data from this multicenter, prospective study confirmed the association between antiplatelet therapy and decreased risk of all-cause mortality and recurrent cerebrovascular events after ischemic stroke in Chinese patients.

Plasma level of sICAM-1 is associated with the extent of white matter lesion among asymptomatic elderly subjects.

OBJECTIVE: Inflammatory endothelial activation mediated by intercellular adhesion molecule-1 (ICAM-1) plays a role in the pathogenesis of large- and small-vessel disease. We explored the association between soluble ICAM-1 (sICAM-1) and white matter lesion (WML) as a manifestation of cerebral small-vessel disease. METHODS: One hundred and seventy-five elderly individuals aged >or= 60 without neurological deficits were studied. Subcortical deep white matter hyperintensity (SDWMH) and periventricular hyperintensity (PVH) were rated separately. Lesions in each category were then divided into three groups (grade 0-I, grade II, grade III) according to the Fazekas scale. RESULTS: Plasma sICAM-1 levels were positively associated with grades of WML (for SDWMH: 297.4+/-135.6ng/mL in grade 0-I, 391.3+/-145.5ng/mL in grade II, and 450.2+/-232.9ng/mL in grade III, p<0.001; for PVH: 282.5+/-116.5ng/mL in grade 0-I, 402.3+/-160.4ng/mL in grade II, and 428.1+/-227.7ng/mL in grade III, p<0.001). Multivariate analysis showed higher sICAM-1 levels, age and hypertension were the independent risk factors associated with the presence and severity of WML. More than 4-fold increased risk of WML was observed in patients with the highest quartile of sICAM-1 (all WML OR=4.694, 95% CI: 1.805-12.204; moderate WML OR=4.618, 95% CI: 1.543-13.825; severe WML OR=4.893, 95% CI: 1.236-19.368). CONCLUSION: Increased plasma sICAM-1 suggests inflammatory process may be involved in the pathogenesis of WML.

[Quantitative analysis of regional cerebral blood flow in elderly with white matter lesions].

OBJECTIVE: To observe whether the severity of white matter lesions (WML) is related to ischemia in elderly. METHODS: WML were divided into 2 categories (centrum semiovale and periventricular regions) and four grades (grade 0, grade 1, grade 2 and grade 3) according to the severity of WML showing on the FLAIR sequence of MRI using modified Fazekas scale. The values of regional cerebral blood flow (rCBF) within WML and other brain regions were measured using Xenon contrast CT. RESULTS: Mean rCBF (ml x 100 g(-1) x min(-1)) within lesions around periventricular areas, in right and left centrum semiovale were 20.8 +/- 2.8, 22.3 +/- 1.9 and 22.2 +/- 2.1 in grade 0; 20.3 +/- 2.5, 21.3 +/- 1.0 and 21.0 +/- 1.8 in grade1; 16.3 +/- 2.0, 15.6 +/- 1.7 and 15.9 +/- 0.9 in grade 2; 14.1 +/- 2.6, 14.5 +/- 2.2 and 14.2 +/- 1.9 in grade 3 respectively. The severity of WML is associated significantly with reduction of rCBF within lesions both in centrum semiovale and periventricular regions (all P < 0.05). There was no significant difference in rCBF values between grade 0 and 1, but significant differences existed between grade 0 and grades 2 and 3, between grade 1 and grades 2 and 3 (all P < 0.05). Statistical significance also existed between the severity of white matter lesions and rCBF in bilateral temporal lobes and lentiform nucleases (P < 0.05). CONCLUSIONS: The severity of WML both in centrum semiovale and periventricular regions is associated significantly with reduction of rCBF within lesions.

[The effects of statins on the cerebral haemodynamics measured by transcranial Doppler in ischemic stroke patients].

OBJECTIVE: To evaluate the effects of statins on the cerebral haemodynamics of ischemic stroke patients with transcranial Doppler (TCD). METHODS: 70 inpatients with acute ischemic stroke were divided into two groups according whether they had taken statins after stroke. The change of the cerebral haemodynamics was studied in the two groups with TCD three months after stroke. RESULTS: Three months later, the systolic flow velocities and mean flow velocities of bilateral middle cerebral arteries in the statins groups significantly increased (P <0.05). The pulse index of bilateral middle cerebral arteries in statins group significantly decreased (P <0.05). The flow velocities and pulse index of bilateral middle cerebral arteries in control group don't change significantly (P > 0.05). CONCLUSIONS: Statins may have the effects of improving the situation of cerebral haemodynamics of patients with ischemic stroke.

Relationship between cerebral vasomotor reactivity and white matter lesions in elderly subjects without large artery occlusive disease.

BACKGROUND AND PURPOSE: The relationships between cerebral vasomotor reactivity (CVR) and white matter lesions (WMLs) were investigated mainly in patients with carotid stenosis. We aimed to study the relationship in asymptomatic elderly subjects without large artery occlusive disease. METHODS: A total of 33 elderly individuals (mean age was 76.2 years) who were free from neurological deficit or cognitive impairment were studied. Bilateral mean blood flow velocity was measured in the middle cerebral artery using a 2-MHz pulsed transcranial Doppler (TCD) system together with intravenous administration of acetazolamide as vasodilatory stimuli. WMLs on a fluid-attenuated inversion recovery (FLAIR) sequence of MRI were classified into two categories: subcortical deep white matter hyperintensity (SDWMH) and periventricular hyperintensity (PVH). The lesions in each category were then divided into three grades (grade 0-I, grade II, grade III) according to the Fazekas scale. RESULTS: CVR was inversely associated with the extent of SDWMH and PVH. The differences in CVR were statistically significant among different severity of WMLs: for SDWMH (70%+/- 10% in grade 0-I, 60%+/- 10% in grade II, and 40%+/- 10% in grade III, P < .001); for PVH (80%+/- 10% in grade 0-I, 60%+/- 10% in grade II, and 40%+/- 10% in grade III, P < .001). CONCLUSIONS: Impaired CVR is related to the extent of WMLs in asymptomatic elderly individuals without large artery stenosis. The findings in our study suggest that dysfunction of cerebral vascular autoregulation might be an important factor in the development of WMLs in the asymptomatic elderly without large artery occlusive disease.

[Study of regional cerebral blood flow around hematoma in acute intracerebral hemorrhage by xenon-CT].

OBJECTIVE: To study the change of regional cerebral blood flow (rCBF) around hematoma in acute intracerebral hemorrhage. METHODS: Xenon-CT was performed on 5 patients of basal ganglia hemorrhage with the hematoma volume less than 30 ml, 3 males and 2 females, aged 56.8 +/- 5.6. within 36 hours of the onset and 13 days after to measure the rCBF was measured by 27 pixel rings respectively in the core of hematoma, edema region around the hematoma and compared with rCBF in the uninvolved hemisphere. RESULTS: (1) all the 5 patients had a history of hypertension, the mean intracerebral hemorrhage volume was 13 ml +/- 7 ml (6.4 approximately 23.7 ml). The first examination was conducted 23 h +/- 6 h (19 approximately 34 h) after the onset and the second examination was conducted 13.0 d +/- 0.7 d (12 approximately 14 d) after the onset. (2) Within 36 hours of the onset, the mean rCBF in the core of hematoma was 15 ml.100 g(-1).min(-1) +/- 8 ml.100 g(-1).min(-1), and the mean rCBF in edema region around the hematoma was 30 ml.100 g(-1).min(-1) +/- 8 ml.100 g(-1).min(-1). Thirteen days after the onset the mean rCBF in the core of hematoma was 9 ml.100 g(-1).min(-1) +/- 4 ml.100 g(-1).min(-1), significantly reduced in comparison with that measured in the first examination (P = 0.014), and the mean rCBF in the edema region around the hematoma was 23 ml.100 g(-1).min(-1) +/- 13 ml.100 g(-1).min(-1), reduced in comparison with those measured in the first examination too, however, not significantly (P = 0.055). The rCBF reduction was more significant in the edema region adjacent to the hematoma (P = 0.004), but not in the distant edema region. During the first examination the rCBF in the edema region around the hematoma was lower than the enantiomorph rCBF by 20.9%. Thirteen days after, the rCBF in the edema region around the hematoma was lower than the enantiomorph rCBF by 46.3%, significantly greater than the reduction during the first examination (P = 0.324). There was no difference between the values of enantiomorph rCBF during the first and second examinations (P = 0.038). CONCLUSION: There exists reduced perihematoma rCBF after intracerebral hemorrhage by xenon-CT examination, this phenomenon lasts 14 days and have the tendency of further reduced.

Astragaloside IV protects against ischemic brain injury in a murine model of transient focal ischemia.

Astragalus membranaceus is a herbal medicine that has been used clinically in stroke patients in China for decades, but its potential neuroprotective effect against ischemic brain injury has not been experimentally tested. In this study, we investigated the effect of Astragaloside IV, a purified extract from Astragalus membranaceus, in a murine model of focal cerebral ischemia/reperfusion produced by transient (1.5 h) middle cerebral artery occlusion. As determined at 72 h after ischemia, post-ischemic treatment of Astragaloside IV (20 or 40 mg/kg) markedly and significantly (P < 0.03 vs. vehicle-treated animals) reduced infarct volume. Astragaloside IV treatment also decreased the levels of malondialdehyde, an indicator of lipid peroxidation, and increased the levels of the antioxidant enzymes glutathione peroxidase and superoxide dismutase in ischemic tissues. The results presented here provide the first evidence of a neuroprotective effect of Astragaloside IV in the model of ischemic brain injury. We suggest that the anti-infarction effect by Astragaloside IV may be derived at least in part from its antioxidant properties.