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Diabetes mellitus is associated with an increased risk of Alzheimer’s dementia and cognitive decline. The cause of neurodegeneration in chronic diabetic patients remains unclear. Changes in brain microglial activity due to glycemic fluctuations may be an etiological factor. Here, we examined the impact of acute ambient glucose fluctuations on BV-2 microglial activity. Biochemical parameters were assayed and showed that the shift from normal glucose (NG; 5.5 mM) to high glucose (HG; 25 mM) promoted cell growth and induced oxidative/inflammatory stress and microglial activation, as evidenced by increased MTT reduction, elevated pro-inflammatory factor secretion (i.e., TNF-α and oxygen free radicals), and upregulated expression of stress/inflammatory proteins (i.e., HSP70, HO-1, iNOS, and COX-2). Also, LPS-induced inflammation was enlarged by an NG-to-HG shift. In contrast, the HG-to-NG shift trapped microglia in a state of metabolic stress, which led to apoptosis and autophagy, as evidenced by decreased Bcl-2 and increased cleaved caspase-3, TUNEL staining, and LC3B-II expression. These stress episodes were primarily mediated through MAPKs, PI3K/Akt, and NF-κB cascades. Our study demonstrates that acute glucose fluctuation forms the stress that alters microglial activity (e.g., inflammatory activation or self-degradation), representing a novel pathogenic mechanism for the continued deterioration of neurological function in diabetic patients.

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The AD8 questionnaire developed by Washington University in St Louis is a screening tool with 8 questions to reliably differentiate nondemented from demented individuals even at the very mild stage. We recruited 239 participants, including 114 cognitively normal, 73 very mild dementia, and 52 mild dementia to validate its application in Taiwanese. The cut-off value of AD8 was 2 in discriminating cognitively normal from demented individuals with the area under curve (AUC) = 0.961, sensitivity = 97.6%, specificity = 78.1%, positive likelihood ratio (PLR) = 4.5, and negative likelihood ratio (NLR) = 0.03. The cut-off value also was 2 in discriminating nondemented from very mild dementia with the AUC = 0.948, sensitivity = 95.9%, specificity = 78.1%, PLR = 4.4, and NLR = 0.05. The Chinese AD8 is effective in discriminating individuals with dementia, even at its mildest stages from those without dementia with properties identical to the original English version. The cAD8 is a quick dementia screening tool that can be applied across cultures.

Susceptibility weighted imaging (SWI) is a newly developed magnetic resonance (MR) protocol. Recent studies have found that SWI may be useful in the field of cerebrovascular diseases, especially for detecting the presence of prominent veins, microbleeds and the susceptibility vessel sign (SVS). Some authors have even suggested that SWI can be used to predict outcome. We conducted a prospective study of patients hospitalized with middle cerebral artery territory infarction receiving MRI within 2 days of stroke onset. The presence of prominent veins, microbleeds and SVS in SWI was analyzed along with hospital characteristics of the patients. A total of 44 patients were enrolled. Among the 44 patients, 15 (34.1%) patients showed prominent veins, 19 (43.2%) showed SVS, and 14 (31.8%) showed microbleeds. The presence of SVS and prominent veins was not associated with prognosis. Though not statistically significant (p = 0.06), patients with SVS were more likely to develop later brain edema. SVS was significantly associated with arterial occlusion (p = 0.008) based on the MR angiogram, and microbleeds were significantly associated with later hemorrhagic transformation (p = 0.018). In our study, SWI could not be used to predict outcome as previously suggested. However, the presence of microbleeds may predict further hemorrhagic transformation, and the presence of SVS could be used to detect intra-arterial thrombus. Patients with SVS were also more likely to develop later brain edema. Including SWI in routine MR protocols for major acute ischemic stroke would be worthwhile.

In America and Europe, the current recommended dose of recombinant tissue-type plasminogen activator (r-tPA) for acute ischemic stroke is 0.9 mg/kg, but a similar study with this dosage has never been replicated in a controlled trial in East Asia. A lower dose (0.6 mg/kg) of r-tPA was used in Japan and was proved to have similar outcomes compared with a dose of 0.9 mg/kg in Western countries.1,2 However, the Safe Implementation of Thrombolysis in Stroke-Non-European Union World (SITS-NEW) study demonstrated that the safety and efficacy of the dose of 0.9 mg/kg of r-tPA in an Asian population was similar to those of the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST) study in the European population. 3,4 Our previous study, the Taiwan Thrombolytic Therapy for Acute Ischemic Stroke (TTT-AIS) study, was the first to determine whether the thrombolytic therapy in routine clinical use was as safe and effective in Chinese patients as in white patients. 5 The preliminary results showed that the group receiving a dose of 0.9 mg/kg had higher rates of symptomatic intracerebral hemorrhage (SICH), dependence, and mortality within 3 months than the low-dose group (<0.85 mg/kg). This finding was more prominent in older patients aged ≥70 years.Background and Purpose-The relationship between the dose of recombinant tissue-type plasminogen activator (r-tPA) and its safety/efficacy for ischemic stroke has not been well evaluated in the East Asian population. We assessed the safety/efficacy of different doses of r-tPA for acute ischemic stroke in Chinese patients. Methods-A total of 1004 eligible patients were classified according to the dose of r-tPA received for managing acute ischemic stroke: 0.9 mg/kg (n=422), 0.8 mg/kg (n=202), 0.7 mg/kg (n=199), and 0.6 mg/kg (n=181). The safety outcome was symptomatic intracerebral hemorrhage and death within 3 months. The efficacy outcome was good functional outcome (modified Rankin Scale ≤1) at 3 months. Results-There was a significant trend for symptomatic intracerebral hemorrhage with age (P=0.002). With multivariate logistic regression analysis, a dose of 0.9 mg/kg was a predictor of symptomatic intracerebral hemorrhage (P=0.0109), and a dose ≤0.65 mg/kg was a predictor of good functional outcome (P=0.0369). In patients aged 71 to 80 years, there was a significant trend of increasing symptomatic intracerebral hemorrhage (P=0.0130) and less good functional outcome (P=0.0179) with increasing doses of r-tPA. There was also a trend of increasing mortality (P=0.0971) at 3 months in these patients. Conclusions-These

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Obstructive sleep apnea (OSA) has been considered as one of the risk factors for ischemic stroke, but the impact of OSA on wake-up stroke (WUS) is not well studied. We aimed to determine the relationship between OSA and WUS. We prospectively recruited 71 patients with mild to moderate ischemic stroke during hospitalization. Patients were classified into WUS and non-WUS. A full-night sleep respiratory study was performed between 3 and 14 days after stroke onset. Demographic data, sleep respiratory data, heart rate variability, stroke risk factors, stroke classification and sleep-related scales were recorded. We compared the differences in the variables between the two groups and determined the independent variables associated with WUS. Of the 71 patients, 26 (36.6%) had WUS. The patients with WUS had a significantly higher apnea-hypopnea index (23.1 ± 19.4 vs. 12.5 ± 11.9, p = 0.016), obstructive apnea index (7.8 ± 9.7 vs. 3.0 ± 4.0, p = 0.021) and lower mean blood oxygen saturation (95.1 ± 1.5 vs. 95.8 ± 1.3, p = 0.046) than the non-WUS patients. There were no significant differences in demographic data, stroke risk factors, sleep-related scales or heart rate variability. Logistic regression revealed that severe sleep-disordered breathing (apnea-hypopnea index ≥30) was the only independent variable associated with WUS (OR 6.065, 95% CI 1.451-25.350; p = 0.014). We conclude that in patients with mild to moderate ischemic stroke, OSA is the only risk factor associated with WUS, which cannot be distinguished clinically from non-WUS.