We investigated the association between glucose tolerance status defined by a 75-g oral glucose tolerance test (OGTT) and the development of dementia.
A total of 1,017 community-dwelling ...dementia-free subjects aged ≥60 years who underwent the OGTT were followed up for 15 years. Outcome measure was clinically diagnosed dementia.
The age- and sex-adjusted incidence of all-cause dementia, Alzheimer disease (AD), and vascular dementia (VaD) were significantly higher in subjects with diabetes than in those with normal glucose tolerance. These associations remained robust even after adjustment for confounding factors for all-cause dementia and AD, but not for VaD (all-cause dementia: adjusted hazard ratio HR = 1.74, 95% confidence interval CI = 1.19 to 2.53, p = 0.004; AD: adjusted HR = 2.05, 95% CI = 1.18 to 3.57, p = 0.01; VaD: adjusted HR = 1.82, 95% CI = 0.89 to 3.71, p = 0.09). Moreover, the risks of developing all-cause dementia, AD, and VaD significantly increased with elevated 2-hour postload glucose (PG) levels even after adjustment for covariates, but no such associations were observed for fasting plasma glucose (FPG) levels: compared with those with 2-hour PG levels of <6.7 mmol/L, the multivariable-adjusted HRs of all-cause dementia and AD significantly increased in subjects with 2-hour PG levels of 7.8 to 11.0 mmol/L or over, and the risk of VaD was significantly higher in subjects with levels of ≥11.1 mmol/L.
Our findings suggest that diabetes is a significant risk factor for all-cause dementia, AD, and probably VaD. Moreover, 2-hour PG levels, but not FPG levels, are closely associated with increased risk of all-cause dementia, AD, and VaD.
We examined the association between diabetes-related factors and pathology of Alzheimer disease (AD) to evaluate how diabetes affects the pathogenic process of AD.
This study included specimens from ...a series of 135 autopsies of residents of the town of Hisayama in Fukuoka prefecture (74 men and 61 women) performed between 1998 and 2003, who underwent a 75-g oral glucose tolerance test in clinical examinations in 1988. We measured diabetes-related factors including fasting glucose, 2-hour post-load plasma glucose, fasting insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) in 1988. Neuritic plaques (NPs) were assessed according to the Consortium to Establish a Registry for Alzheimer's Disease guidelines and neurofibrillary tangles (NFTs) were assessed according to Braak stage. The associations between each factor and AD pathology were examined by analysis of covariance and logistic regression analyses.
Higher levels of 2-hour post-load plasma glucose, fasting insulin, and HOMA-IR were associated with increased risk for NPs after adjustment for age, sex, systolic blood pressure, total cholesterol, body mass index, habitual smoking, regular exercise, and cerebrovascular disease. However, there were no relationships between diabetes-related factors and NFTs. Regarding the effects of APOE genotype on the risk of AD pathology, the coexistence of hyperglycemia and APOE epsilon4 increased the risk for NP formation. A similar enhancement was observed for hyperinsulinemia and high HOMA-IR.
The results of this study suggest that hyperinsulinemia and hyperglycemia caused by insulin resistance accelerate NP formation in combination with the effects of APOE epsilon4.
High-power density is required in power conversion systems used in various applications, especially in electric vehicles. Driving the power devices with high frequency is one of the successful ...solutions to downsize a circuit's magnetic components, and hence an overall high-power density of the circuit can be realised. Therefore, GaN high electron mobility transistor (HEMT) is widely used in many applications, owing to its high-speed switching characteristics, low power losses, and high heat and radiation resistances. However, the high-speed switching of GaN HEMT comes with a drawback. For instance, in a full-bridge inverter configuration, high-speed turn-on of one device may cause a false turn-on of the complementary device. If a power device has encountered a false turn-on, the GaN HEMT devices will suffer from overcurrent, excessive heat and is eventually destructed due to the short circuit. This phenomenon can be tackled by modifying the circuit conditions. In this Letter, the theoretical analysis of a three-phase full-bridge inverter is developed to figure out the behaviour of the GaN HEMT gate voltage, which is the key-factor parameter causing a false turn-on. On the basis of the proposed theoretical analysis, the circuit conditions which minimise the gate voltage spike are derived.
Sekita A, Ninomiya T, Tanizaki Y, Doi Y, Hata J, Yonemoto K, Arima H, Sasaki K, Iida M, Iwaki T, Kanba S, Kiyohara Y. Trends in prevalence of Alzheimer’s disease and vascular dementia in a Japanese ...community: the Hisayama Study.
Objective: To examine secular trends in the prevalence of Alzheimer’s disease (AD) and vascular dementia (VD) in a general Japanese population.
Method: Four cross‐sectional examinations were conducted among residents of a Japanese community aged ≥65 in 1985, 1992, 1998 and 2005.
Results: The age‐ and sex‐adjusted prevalence of all‐cause dementia significantly increased with time (6.0% in 1985, 4.4% in 1992, 5.3% in 1998 and 8.3% in 2005; P for trend = 0.002). A similar trend was observed for AD (1.1%, 1.3%, 2.3% and 3.8% respectively; P for trend < 0.001), while the age‐ and sex‐adjusted prevalence of VD and other/unclassified dementia showed J‐shaped patterns (for VD: 2.3%, 1.5%, 1.5% and 2.5%, respectively, P for trend = 0.82; for other/unclassified dementia: 2.6%, 1.7%, 1.5% and 2.0%, P for trend = 0.26). The prevalence of AD was likely to increase with time from 1985 to 2005 among subjects aged 75 or older. The ratio of the prevalence of VD to that of AD decreased with time (2.1 in 1985, 1.2 in 1992, 0.7 in 1998 and 0.7 in 2005).
Conclusion: Our findings suggest that the prevalence of all‐cause dementia and AD significantly increased over the past two decades in the general Japanese population.
To estimate the incidence and survival rates of total and cause specific dementia in a general Japanese population.
A total of 828 subjects without dementia, aged 65 years or over, were followed-up ...prospectively for 17 years. Dementia was subdivided into cause specific subtypes: namely, Alzheimer's disease (AD), vascular dementia (VD), dementia with Lewy bodies (DLB), combined dementia and other types of dementia. During the follow-up, 275 subjects developed dementia; of these, 251 (91.2%) were evaluated morphologically, with 164 subjected to brain autopsy examination and the remaining 87 to neuroimaging.
The incidences of total dementia, AD, VD, DLB, combined dementia and other types of dementia were 32.3 (n = 275), 14.6 (124), 9.5 (81), 1.4 (12), 3.8 (33), and 3.1 (16) per 1000 person years, respectively. The incidences of AD, combined dementia and other types of dementia rose with increasing age, particularly after the age of 85 years, but this tendency was not observed for VD or DLB. The survival curve of dementia cases aged 65-89 years was significantly lower than that of age and sex matched controls (10 year survival rate, 13.6% vs 29.3%; hazard ratio 1.67; 95% confidence interval 1.31 to 2.13). The 10 year survival rates were not significantly different among dementia subtypes.
Our findings suggest that the Japanese elderly population has a high risk for the development of dementia, specifically AD and VD, and once dementia is established, the risk of death is considerable.
Intravoxel incoherent motion imaging, which simultaneously measures diffusion and perfusion parameters, is promising for brain tumor grading. However, intravoxel incoherent motion imaging has not ...been tested in children. The purpose of this study was to evaluate the correlation between intravoxel incoherent motion parameters and histology to assess the accuracy of intravoxel incoherent motion imaging for pediatric intracranial tumor grading.
Between April 2013 and September 2015, 17 children (11 boys, 6 girls; 2 months to 15 years of age) with intracranial tumors were included in this retrospective study. Intravoxel incoherent motion parameters were fitted using 13 b-values for a biexponential model. The perfusion-free diffusion coefficient, pseudodiffusion coefficient, and perfusion fraction were measured in high- and low-grade tumors. These intravoxel incoherent motion parameters and the ADC were compared using the unpaired
test. The correlations between the intravoxel incoherent motion parameters and microvessel density or the MIB-1 index were analyzed using the Spearman correlation test. Receiver operating characteristic analysis was used to evaluate diagnostic performance.
The perfusion-free diffusion coefficient and ADC were lower in high-grade than in low-grade tumors (perfusion-free diffusion coefficient, 0.85 ± 0.40 versus 1.53 ± 0.21 × 10
mm
/s,
< .001; ADC, 1.04 ± 0.33 versus 1.60 ± 0.21 × 10
mm
/s,
< .001). The pseudodiffusion coefficient showed no difference between the groups. The perfusion fraction was higher in high-grade than in low-grade tumors (21.7 ± 8.2% versus 7.6 ± 4.3%,
< .001). Receiver operating characteristic analysis found that the combined perfusion-free diffusion coefficient and perfusion fraction had the best diagnostic performance for tumor differentiation (area under the curve = 0.986).
Intravoxel incoherent motion imaging reflects tumor histology and may be a helpful, noninvasive method for pediatric intracranial tumor grading.
The relationship between lipid profiles and Alzheimer disease (AD) pathology at the population level is unclear. We searched for evidence of AD-related pathologic risk of abnormal lipid metabolism.
...This study included brain specimens from a series of 147 autopsies performed between 1998 and 2003 of residents in Hisayama town, Japan (76 men and 71 women), who underwent clinical examinations in 1988. Lipid profiles, such as total cholesterol (TC), triglycerides, and high-density lipoprotein cholesterol (HDLC), were measured in 1988. Low-density lipoprotein cholesterol (LDLC) was calculated using the Friedewald formula. Neuritic plaques (NPs) were assessed according to the Consortium to Establish a Registry for Alzheimer's Disease guidelines (CERAD) and neurofibrillary tangles (NFTs) were assessed according to Braak stage. Associations between each lipid profile and AD pathology were examined by analysis of covariance and logistic regression analyses.
Adjusted means of TC, LDLC, TC/HDLC, LDLC/HDLC, and non-HDLC (defined as TC-HDLC) were significantly higher in subjects with NPs, even in sparse to moderate stages (CERAD = 1 or 2), compared to subjects without NPs in multivariate models including APOE ε4 carrier and other confounding factors. The subjects in the highest quartiles of these lipid profiles had significantly higher risks of NPs compared to subjects in the lower respective quartiles, which may suggest a threshold effect. Conversely, there was no relationship between any lipid profile and NFTs.
The results of this study suggest that dyslipidemia increases the risk of plaque-type pathology.
We investigated the relationship between tumor blood-flow measurement based on perfusion imaging by arterial spin-labeling (ASL-PI) and histopathologic findings in brain tumors.
We used ASL-PI to ...examine 35 patients with brain tumors, including 11 gliomas, 9 meningiomas, 9 schwannomas, 1 diffuse large B-cell lymphoma, 4 hemangioblastomas, and 1 metastatic brain tumor. As an index of tumor perfusion, the relative signal intensity (SI) of each tumor (%Signal intensity) was determined as a percentage of the maximal SI within the tumor per averaged SI within normal cerebral gray matter on ASL-PI. Relative vascular attenuation (%Vessel) was determined as the total microvessel area per the entire tissue area on CD-34-immunostained histopathologic specimens. MIB1 indices of gliomas were also calculated. The differences in %Signal intensity among different histopathologic types and between high- and low-grade gliomas were compared. In addition, the correlations between %Signal intensity and %Vessel or MIB1 index were evaluated in gliomas.
Statistically significant differences in %Signal intensity were observed between hemangioblastomas versus gliomas (P < .005), meningiomas (P < .05), and schwannomas (P < .005). Among gliomas, %Signal intensity was significantly higher for high-grade than for low-grade tumors (P < .05). Correlation analyses revealed significant positive correlations between %Signal intensity and %Vessel in 35 patients, including all 6 histopathologic types (rs = 0.782, P < .00005) and in gliomas (rs = 0.773, P < .05). In addition, in gliomas, %Signal intensity and MIB1 index were significantly positively correlated (rs = 0.700, P < .05).
ASL-PI may predict histopathologic vascular densities of brain tumors and may be useful in distinguishing between high- and low-grade gliomas and in differentiating hemangioblastomas from other brain tumors.
Although the emotional expression of faces is believed to be accessed rapidly, previous ERP studies hardly found correlates of these processes. Here, we report findings from a study that investigated ...dichoptic binocular interaction using emotional face stimuli. Thirty-one subjects were briefly presented with schematic normal and scrambled faces (of neutral, positive, or negative expression) that occurred simultaneously in the left and right visual fields. Stimuli for both eyes could be congruent (control) or incongruent (dichoptic). Subjects decided which of the superimposed images in both hemi-fields appeared more “face-like” and during this task, the EEG was recorded from 30 channels. VEPs were analysed topographically according to the influence of the different experimental conditions (defined by presentation form, emotional expression, and location). Behavioural responses to the ambiguous dichoptic stimuli demonstrated a functional eye dominance not related to visual acuity and conventional eye preference. Electrophysiological data revealed three components with mean latencies of 85, 160, and 310
ms. Topography of the second component (equivalent to the face-related N170) differed in left–right and anterior–posterior direction compared with simple checkerboard stimuli. Dichoptic presentation caused reduced field strength of all three, and increased latency of the first component. Faces with negative expression yielded largest field strength of the second and third components. Besides that, emotional expression affected topography not only of late, but also the first component. This provides new evidence about the timing of perceptual processes related to facial expression, indicating that already VEP components occurring at 80–90
ms are sensitive to emotional content.
Background: Plasminogen activator inhibitor‐1 (PAI‐1) is the primary physiological regulator of urokinase plasminogen activator (uPA) and tissue plasminogen activator (tPA) activity. A number of ...studies have shown that elevated levels of PAI‐1 are related to pathological states such as an increased risk of arterial thrombotic events and a poor prognosis for cancer patients; however, there are few reports about PAI‐1 deficiency in humans because the disorder is very rare. Objective: To understand the in vivo impact of a complete PAI‐1 deficiency, Serpine1−/− mice were generated; a number of in vivo studies have been conducted to elucidate the function of PAI‐1 using Serpine1−/− mice. The phenotypes demonstrated in Serpine1−/− mice, however, were quite different from those in humans. Therefore, it is necessary to find out and analyze SERPINE1 deficiency in humans. Patient and methods: The patient is a 47‐year‐old woman who has had multiple episodes of major bleeding. Although most of the patient’s blood coagulation factors were functionally normal, her PAI‐1 antigen levels were undetectable. Therefore, DNA sequencing of the SERPINE1 gene were analyzed. Results: The proband had a homozygous 1‐bp duplication (C) at exon 3 (c.356dupC; p.Ile120AspfsX42). Both wild‐type PAI‐1 (42.7 kDa) and mutated (Mut) PAI‐1 (14.7 kDa) were expressed in COS‐1 cells, although the level of Mut PAI‐1 expressed in the cell lysates was much lower. Wild‐type PAI‐1 was observed in the culture supernatant, whereas no Mut PAI‐1 was detected in the supernatant. Conclusions: Considering the results of the present study, the translation of mouse studies to humans must be performed with great care.
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