CD133-containing microvesicles promote cancer progression by inducing M2-like tumor-associated macrophage polarization in the tumor microenvironment of colorectal cancer.

Tumor-associated macrophages (TAMs) are among the most abundant cell types in the tumor microenvironment (TME). The immunosuppressive TME formed by TAMs is an essential prerequisite for cancer progression. Tumor-derived microvesicles (MVs), a subtype of extracellular vesicle shed directly from the plasma membrane, are important regulators of intercellular communication and TME modulation during tumorigenesis. However, the exact mechanism by which tumor-derived MVs induce the generation of the immunosuppressive TME and polarization of TAMs remains unclear. Here, we investigated the role of CD133-containing MVs derived from colorectal cancer (CRC) cells in macrophage polarization and cancer progression. CD133-containing MVs from CRC cells were incorporated into macrophages, and M0 macrophages were morphologically transformed into M2-like TAMs. CD133-containing MVs were found to increase the mRNA expression of M2 macrophage markers. Additionally, cytokine array analysis revealed that M2-like TAMs induced by CD133-containing MVs increased the secretion of interleukin 6, which activated the STAT3 pathway in CRC cells. Furthermore, the conditioned medium of M2-like TAMs promoted cell motility, epithelial-mesenchymal transition, and cell proliferation. However, MVs from CD133-knockdown cells had little effect on TAM polarization and CRC progression. These results demonstrate that CD133-containing MVs induce M2-like TAM polarization and contribute to cancer progression by mediating crosstalk between tumor cells and TAMs in the TME of CRC.

Reproductive and developmental toxicity screening of bisphenol F by oral gavage in rats.

Bisphenol F (BPF, 4,4'-methylenediphenol) has recently been selected as an alternative to bisphenol A (BPA), which is used in the manufacturing of polycarbonates and epoxy resins. This study aimed to investigate the general, and reproductive/developmental effects of BPF. Therefore, BPF at dose levels of 0, 1, 5, 20, and 100 mg/kg/day was administered daily by oral gavage to Sprague-Dawley rats during the pre-mating, mating, gestation, and early lactation periods, and reproductive and developmental toxicities including general systemic toxicities were investigated. A decrease in body weight and food consumption was observed in the female rats treated with BPF at 20 and 100 mg/kg/day during the pre-mating and gestation periods. Additionally, gamma glutamyl transpeptidase levels were increased in the female rats administered 100 mg/kg/day. At 100 mg/kg/day, ovarian weight decreased and vaginal mucification increased according to a necropsy and histopathological examination, respectively. Moreover, the number of implantation sites and litter size decreased at 100 mg/kg/day. However, no significant BPF-related changes were observed in the male rats. Based on the results of this study, the no-observed-adverse-effect levels (NOAELs) of BPF for general systemic and reproductive effects were 5 and 20 mg/kg/day, respectively.

Prenatal developmental toxicity study of 2,4-dichlorobenzyl alcohol in rats.

Sore throat lozenges, which are over-the-counter drugs, contain 2,4-dichlorobenzyl alcohol (DCBA) as the primary ingredient. However, comprehensive data on the prenatal developmental toxicity of DCBA is limited. Therefore, this study was conducted to determine the effects of DCBA on pregnant rats and prenatal development. Sprague-Dawley rats were administered different doses of DCBA (0, 25, 100, 400, and 800 mg/kg/day) daily via an oral gavage from gestation day (GD) 6-19. Thereafter, all the live dams were sacrificed on GD 20, and caesarean sections were conducted. Live fetuses and their placenta were weighed and then examined for external, visceral, and skeletal malformations and variations. Based on the results obtained, dams at 800 mg/kg/day showed systemic toxicities, including a decrease in body weight and food consumption, and liver changes. Additionally, this treatment induced decreases in fetal and placental weights, as well as the increased incidence of retarded ossifications and full supernumery rib, and the decreased number of ossification centers. Therefore, based on these findings, the no-observed-adverse-effect level of DCBA was determined to be 400 mg/kg/day for dams and prenatal development.

Serial blood sampling effects in rat embryo-fetal development studies for toxicokinetics.

Serial blood sampling for toxicokinetics is generally conducted in regulatory embryo-fetal development (EFD) studies in rats. EFD studies are designed to detect the potential adverse effects of pharmaceuticals on pregnant females and their fetuses; this information is useful for understanding the relationships between systemic exposure levels and toxicity profiles. However, additional satellite pregnant females are needed for toxicokinetics because comprehensive information regarding the potential impact of serial blood sampling on pregnant females is scarce. Here, in this study, we investigated the potential impact of serial blood sampling in pregnant female rats using a typical EFD study design. Additionally, we investigated the additional endpoints (clinical pathology, organ weights, and histopathology) that were deemed likely to be sensitive to blood sampling. Results indicated that serial blood sampling in pregnant females induced physiological adaptive changes and did not affect the general endpoints in EFD studies. Nevertheless, inclusion of satellite groups in EFD studies may be a more prudent approach considering the physiological changes in pregnant females and potential off-target effects of candidate pharmaceuticals. These results provide background information on the impact of serial blood sampling in pregnant females and will be useful to design the regulatory EFD studies.

The qSOFA score combined with the initial red cell distribution width as a useful predictor of 30 day mortality among older adults with infection in an emergency department.

PURPOSE: This study aimed to investigate whether the qSOFA and initial red cell distribution width (RDW) in the emergency department (ED) are associated with mortality in older adults with infections who visited the ED. METHODS: This was a retrospective study conducted in 5 EDs between November 2016 and February 2017. We recorded age, sex, comorbidities, body temperature, clinical findings, and initial laboratory results, including the RDW. The initial RDW values and the qSOFA criteria were obtained at the time of the ED visit. The primary outcome was 30 day mortality. RESULTS: A total of 1,446 patients were finally included in this study, of which 134 (9.3%) died within 30 days and the median (IQR) age was 77 (72, 82) years. In the multivariable analysis, the RDW (14.0-15.4%) and highest RDW (> 15.4%) quartile were shown to be independent risk factors for 30 day mortality (OR 2.12; 95% CI 1.12-4.02; p = 0.021) (OR 3.35; 95% CI 1.83-6.13; p < 0.001). The patients with qSOFA 2 and 3 were shown to have the high odds ratios of 30-day mortality (OR 3.50; 95% CI 2.09-5.84; p < 0.001) (OR 11.30; 95% CI 5.06-25.23; p < 0.001). The qSOFA combined with the RDW quartile for the prediction of 30 day mortality showed an AUROC value of 0.710 (0.686-0.734). CONCLUSION: The qSOFA combined with the initial RDW value was associated with 30-day mortality among older adults with infections in the ED. The initial RDW may help emergency physicians predict mortality in older adults with infections visiting the ED.

Analysis of Sagittal Position Changes of the Condyle After Mandibular Setback Surgery Across the Four Different Types of Plating Systems.

ABSTRACT: The authors analyzed the three-dimensional postoperative condylar position change across the plating systems. This retrospective study was conducted with the patients who underwent bilateral sagittal split ramus osteotomy with setback surgery. The condylar change was analyzed from preoperative cone-beam computed tomography to postoperative 1 month (T1) and postoperative 6 months (T2) using superimposition software, automatically merging based on the anterior cranial base. The condylar changes during T1 and T2 were analyzed across the four types of plates (4-hole sliding, heart-shaped, 3-hole sliding, and 4-hole conventional) Mean intraclass correlation coefficient values were consistently high for each measurement (>0.850). During T1, the conventional plate had a decreased condylar anterior distance when compared with the 3-hole sliding plate (P = 0.032). During T2, the conventional plate had an increased condylar posterior distance when compared with the 3-hole sliding plate (P = 0.031). Superimposition software based on the anterior cranial base could be available for measurement of condylar position with highly reproducible results. After bilateral sagittal split ramus osteotomy, the 3-hole sliding plate could effectively compensate for the anterior displacement of the condyle compared to other plates.

A pathogenic PSEN1 Trp165Cys mutation associated with early-onset Alzheimer's disease.

BACKGROUND: Presenilin-1 (PSEN1) is one of the causative genes for early onset Alzheimer's disease (EOAD). Recently, emerging studies reported several novel PSEN1 mutations among Asian. We describe a male with EOAD had a pathogenic PSEN1 mutation. CASE PRESENTATION: A 53-year-old male presented with memory decline, followed by difficulty in finding ways. Patient had positive family history, since his mother and one of his brother was also affected with dementia. Brain magnetic resonance imaging (MRI) scan showed mild degree of atrophy of bilateral hippocampus and parietal lobe. 18F-Florbetaben-PET (FBB-PET) revealed increased amyloid deposition in bilateral frontal, parietal, temporal lobe and precuneus. Whole exome analysis revealed a heterozygous, probably pathogenic PSEN1 (c.695G > T, p.W165C) mutation. Interestingly, Trp165Cys mutation is located in trans membrane (TM)-III region, which is conserved between PSEN1/PSEN2. In vitro studies revealed that PSEN1 Trp165Cys could result in disturbances in amyloid metabolism. This prediction was confirmed by structure predictions and previous in vitro studies that the p.Trp165Cys could result in decreased Aß42/Aß40 ratios. CONCLUSION: We report a case of EOAD having a pathogenic PSEN1 (Trp165Cys) confirmed with in silico and in vitro predictions.

Titanium dioxide nanoparticles oral exposure to pregnant rats and its distribution.

BACKGROUND: Titanium dioxide (TiO2) nanoparticles are among the most manufactured nanomaterials in the industry, and are used in food products, toothpastes, cosmetics and paints. Pregnant women as well as their conceptuses may be exposed to TiO2 nanoparticles; however, the potential effects of these nanoparticles during pregnancy are controversial, and their internal distribution has not been investigated. Therefore, in this study, we investigated the potential effects of oral exposure to TiO2 nanoparticles and their distribution during pregnancy. TiO2 nanoparticles were orally administered to pregnant Sprague-Dawley rats (12 females per group) from gestation days (GDs) 6 to 19 at dosage levels of 0, 100, 300 and 1000 mg/kg/day, and then cesarean sections were conducted on GD 20. RESULTS: In the maternal and embryo-fetal examinations, there were no marked toxicities in terms of general clinical signs, body weight, food consumption, organ weights, macroscopic findings, cesarean section parameters and fetal morphological examinations. In the distribution analysis, titanium contents were increased in the maternal liver, maternal brain and placenta after exposure to high doses of TiO2 nanoparticles. CONCLUSION: Oral exposure to TiO2 during pregnancy increased the titanium concentrations in the maternal liver, maternal brain and placenta, but these levels did not induce marked toxicities in maternal animals or affect embryo-fetal development. These results could be used to evaluate the human risk assessment of TiO2 nanoparticle oral exposure during pregnancy, and additional comprehensive toxicity studies are deemed necessary considering the possibility of complex exposure scenarios and the various sizes of TiO2 nanoparticles.

Reproductive and developmental toxicity screening of polyhexamethylene guanidine phosphate by oral gavage in rats.

Polyhexamethylene guanidine phosphate (PHMG-P) has effective antimicrobial activity against various microorganisms and has been widely used as a biocide in commercial products. However, its use as a humidifier disinfectant has provoked fatal idiopathic lung disease in South Korea, especially in pregnant or postpartum women and their young children. PHMG-P-related toxicological studies of reproduction and development in experimental animals have not been identified, and thus, we investigated the potential effects of early-stage oral exposure to PHMG-P by assessing its toxicological properties. PHMG-P was repeatedly administered by oral gavage at dose levels of 0, 13, 40 and 120 mg/kg to Sprague-Dawley rats during the pre-mating, mating, gestation and early lactation periods, and then general systemic and reproductive/developmental toxicities were investigated. At 120 mg/kg, PHMG-P-related toxicities including subdued behavior, thin appearance, decreased body weight, decreased food consumption and decreased F1 pup body weight were observed. Based on the results of this study, the no-observed-adverse-effect levels (NOAELs) of PHMG-P for both general systemic effects and development are considered to be 40 mg/kg/day.

Prediction of cognitive impairment via deep learning trained with multi-center neuropsychological test data.

BACKGROUND: Neuropsychological tests (NPTs) are important tools for informing diagnoses of cognitive impairment (CI). However, interpreting NPTs requires specialists and is thus time-consuming. To streamline the application of NPTs in clinical settings, we developed and evaluated the accuracy of a machine learning algorithm using multi-center NPT data. METHODS: Multi-center data were obtained from 14,926 formal neuropsychological assessments (Seoul Neuropsychological Screening Battery), which were classified into normal cognition (NC), mild cognitive impairment (MCI) and Alzheimer's disease dementia (ADD). We trained a machine learning model with artificial neural network algorithm using TensorFlow (https://www.tensorflow.org) to distinguish cognitive state with the 46-variable data and measured prediction accuracies from 10 randomly selected datasets. The features of the NPT were listed in order of their contribution to the outcome using Recursive Feature Elimination. RESULTS: The ten times mean accuracies of identifying CI (MCI and ADD) achieved by 96.66 ± 0.52% of the balanced dataset and 97.23 ± 0.32% of the clinic-based dataset, and the accuracies for predicting cognitive states (NC, MCI or ADD) were 95.49 ± 0.53 and 96.34 ± 1.03%. The sensitivity to the detection CI and MCI in the balanced dataset were 96.0 and 96.0%, and the specificity were 96.8 and 97.4%, respectively. The 'time orientation' and '3-word recall' score of MMSE were highly ranked features in predicting CI and cognitive state. The twelve features reduced from 46 variable of NPTs with age and education had contributed to more than 90% accuracy in predicting cognitive impairment. CONCLUSIONS: The machine learning algorithm for NPTs has suggested potential use as a reference in differentiating cognitive impairment in the clinical setting.

Design of a 900 MHz Dual-Mode SWIPT for Low-Power IoT Devices.

This paper presents a duty cycle-based, dual-mode simultaneous wireless information and power transceiver (SWIPT) for Internet of Things (IoT) devices in which a sensor node monitors the received power and adaptively controls the single-tone or multitone communication mode. An adaptive power-splitting (PS) ratio control scheme distributes the received radio frequency (RF) energy between the energy harvesting (EH) path and the information decoding (ID) path. The proposed SWIPT enables the self-powering of an ID transceiver above 20 dBm input power, leading to a battery-free network. The optimized PS ratio of 0.44 enables it to provide sufficient harvested energy for self-powering and energy-neutral operation of the ID transceiver. The ID transceiver can demodulate the amplitude-shift keying (ASK) and the binary phase-shift keying (BPSK) signals. Moreover, for low-input power level, a peak-to-average power ratio (PAPR) scheme based on multitone is also proposed for demodulation of the information-carrying RF signals. Due to the limited power, information is transmitted in uplink by backscatter modulation instead of RF signaling. To validate our proposed SWIPT architecture, a SWIPT printed circuit board (PCB) was designed with a multitone SWIPT board at 900 MHz. The demodulation of multitone by PAPR was verified separately on the PCB. Results showed the measured sensitivity of the SWIPT to be -7 dBm, and the measured peak power efficiency of the RF energy harvester was 69% at 20 dBm input power level. The power consumption of the injection-locked oscillator (ILO)-based phase detection path was 13.6 mW, and it could be supplied from the EH path when the input power level was high. The ID path could demodulate 4-ASK- and BPSK-modulated signals at the same time, thus receiving 3 bits from the demodulation process. Maximum data rate of 4 Mbps was achieved in the measurement.

Genetic Factors of Cerebral Small Vessel Disease and Their Potential Clinical Outcome.

Cerebral small vessel diseases (SVD) have been causally correlated with ischemic strokes, leading to cognitive decline and vascular dementia. Neuroimaging and molecular genetic tests could improve diagnostic accuracy in patients with potential SVD. Several types of monogenic, hereditary cerebral SVD have been identified: cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL), cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), cathepsin A-related arteriopathy with strokes and leukoencephalopathy (CARASAL), hereditary diffuse leukoencephalopathy with spheroids (HDLS), COL4A1/2-related disorders, and Fabry disease. These disorders can be distinguished based on their genetics, pathological and imaging findings, clinical manifestation, and diagnosis. Genetic studies of sporadic cerebral SVD have demonstrated a high degree of heritability, particularly among patients with young-onset stroke. Common genetic variants in monogenic disease may contribute to pathological progress in several cerebral SVD subtypes, revealing distinct genetic mechanisms in different subtype of SVD. Hence, genetic molecular analysis should be used as the final gold standard of diagnosis. The purpose of this review was to summarize the recent discoveries made surrounding the genetics of cerebral SVD and their clinical significance, to provide new insights into the pathogenesis of cerebral SVD, and to highlight the possible convergence of disease mechanisms in monogenic and sporadic cerebral SVD.

Selective Production of p-Xylene from Dimethylfuran and Ethylene Over Tungstated Zirconia Catalysts.

p-Xylene (PX) is an important large-volume commodity chemical in the petrochemical industry. Therefore, research on producing PX from bio-mass-derived resources is a considerable interest in relation to future alternative technologies. Recently, a new potential route for the direct and selective production of bio-based PX was reported, referred to as the Diels-Alder cycloaddition of biomassderived 2,5-dimethylfuran (DMF) and ethylene followed by the dehydration of an intermediate. Here, we prepared tungstated zirconia (WOx-ZrO2) materials at different calcination temperatures and times as solid acid catalysts for PX production. From structural analyses and measurements of the surface acidity, the WOx-ZrO2 was found to be composed of mesopores with high surface acidity within the optimum calcination temperature and time range. This WOx-ZrO2 catalyst exhibited high catalytic activity upon the cycloaddition of DMF with ethylene as compared to commercial beta zeolite and previously reported silica-alumina catalysts.

A Sigma-Delta ADC for Signal Conditioning IC of Automotive Piezo-Resistive Pressure Sensors with over 80 dB SNR.

This paper presents a second-order discrete-time Sigma-Delta (SD) Analog-to-Digital Converter (ADC) with over 80 dB Signal to Noise Ratio (SNR), which is applied in a signal conditioning IC for automotive piezo-resistive pressure sensors. To reduce the flicker noise of the structure, choppers are used in every stage of the high gain amplifiers. Besides, to reduce the required area and power, only the CIC filter structure is adopted as a decimation filter. This filter has a configurable structure that can be applied to different data rates and input signal bandwidths. The proposed ADC was fabricated and measured in a 0.18-µm CMOS process. Due to the application of only a CIC filter, the total active area of the SD-ADC and reference generator is 0.49 mm² where the area of the decimation filter is only 0.075 mm². For the input signal bandwidth of 1.22 kHz, it achieved over 80 dB SNR in a 2.5 MHz sampling frequency while consuming 646 µW power.

Effect of Silica Content on Production of p-Xylene from Dimethylfuran/Ethylene Over Mesoporous SiO2­Al2O3 Catalysts.

Mesoporous SiO2­Al2O3 (SA) catalysts with different SiO2 contents were prepared, for the selective production of p-xylene from dimethylfuran/ethylene through the combination of cycloaddition and dehydrative aromatization reactions, by a co-precipitation method. For comparison, commercial SiO2­Al2O3 and ZSM-5 zeolites (Si/Al2 = 30, Si/Al2 = 80) were also employed as catalysts in the same reaction. The pore size of the catalysts played an important role in determining the catalytic performance in the production of p-xylene. Among the catalysts tested, the order of the yield and production rate of p-xylene was as follows: mesoporous SA > commercial SiO2­Al2O3 > commercial ZSM-5. In the mesoporous SA catalysts in particular, p-xylene yields showed a volcano-shaped trend with respect to the catalyst's SiO2 content. The SA-60 catalyst, with SiO2 = 52.3, showed the highest yield (75%) and production rate (57.7 mmol/g-cat · h) because of a catalyst structure with moderate pore size, which prevented side reactions.

Extrapyramidal Signs and Cognitive Subdomains in Alzheimer Disease.

OBJECTIVE: Extrapyramidal signs (EPS), commonly observed in Alzheimer disease (AD), predict cognitive impairment and functional decline. This study investigated the association between EPS and five cognitive subdomains in a large number of participants with AD. DESIGN: Cross-sectional analyses of the nationwide Clinical Research of Dementia of South Korea (CREDOS) study, 2005-2012. SETTING: Multicenter clinical settings. PARTICIPANTS: 1,737 participants with AD drawn from the CREDOS study. MEASUREMENTS: The EPS group was defined by the presence of at least one EPS based on neurologic examination. We assessed five cognitive subdomains: attention, language, visuospatial function, memory, and frontal/executive function using the Seoul Neuropsychological Screening Battery-Dementia version. The associations of EPS with each cognitive subdomain were analyzed with a multiple linear regression model after controlling for confounding factors: sex, age, years of education, severity of dementia (Clinical Dementia Rating Sum of Boxes), and white matter hyperintensities. RESULTS: 164 AD participants (9.4%) had EPS. AD participants with EPS showed lower performance compared with those without EPS in two cognitive subdomains: attention and visuospatial function. The language, memory, and frontal/executive subdomains did not differ between the EPS-positive and the EPS-negative groups. In addition, we found a significant moderating relationship between EPS and deep white matter hyperintensities on visuospatial function score. CONCLUSIONS: EPS in AD are associated with severe cognitive impairment in attention and visuospatial function. Careful screening for EPS in patients with AD may assist in prediction of cognitive profile.

Impact of Alzheimer's Disease in Nine Asian Countries.

BACKGROUND: Asia will soon have the majority of demented patients in the world. OBJECTIVE: To assess dementia using a uniform data system to update the current status of dementia in Asia. METHODS: A uniformed data set was administered in Taiwan, China, Hong Kong, Korea, Japan, Philippines, Thailand, Singapore, and Indonesia to gather data with regard to Alzheimer's disease (AD) and its related issues for these countries. RESULTS: In total, 2,370 AD patients and their caregivers were recruited from 2011 to 2014. The demographic characteristics of these patients and the relationships between patients and caregivers were different among individuals in these countries (p < 0.001). Of note, the family history for having dementia was 8.2% for females in contrast to 3.2% for males. CONCLUSION: Our study highlighted the differences in dementia assessment and care in developing versus developed countries. Greater effort with regard to studying dementia, especially in developing countries, is necessary.

Gender differences in risk factors for transition from mild cognitive impairment to Alzheimer's disease: A CREDOS study.

BACKGROUND: Women are subject to a disproportionate burden from Alzheimer's disease (AD) and sex differences exist in treatment response and prognosis of the disease. Yet gender-specific risk factors have not been widely studied. We aimed to investigate gender-specific risk factors for AD in subjects with mild cognitive impairment (MCI). METHODS: Participants (n=294) with MCI were recruited from a nationwide, prospective cohort study of dementia and were followed for a median (range) of 13.8 (6.0-36.0) months. Sex-stratified associations of progression to AD with baseline characteristics were explored. RESULTS: Seventy-four individuals (25.2%) developed incident dementia (67 AD) during follow-up. Significant risk factors for probable AD differed by sex. In men, the significant risk factors were severe periventricular white matter hyperintensities, and poorer global cognitive function. In women, older age, clinically significant depressive symptoms at baseline, and positive APOE ε4 alleles were the significant risk factors. CONCLUSIONS: Risk factors for progression from MCI to probable AD differed in men and women. These results may translate to gender-specific preventative or therapeutic strategies for patients with MCI.

Periventricular white matter hyperintensities and the risk of dementia: a CREDOS study.

BACKGROUND: Cerebral white matter hyperintensities (WMH) are prevalent incident findings on brain MRI scans among elderly people and have been consistently implicated in cognitive dysfunction. However, differential roles of WMH by region in cognitive function are still unclear. The aim of this study was to ascertain the differential role of regional WMH in predicting progression from mild cognitive impairment (MCI) to different subtypes of dementia. METHODS: Participants were recruited from the Clinical Research Center for Dementia of South Korea (CREDOS) study. A total of 622 participants with MCI diagnoses at baseline and follow-up evaluations were included for the analysis. Initial MRI scans were rated for WMH on a visual rating scale developed for the CREDOS. Differential effects of regional WMH in predicting incident dementia were evaluated using the Cox proportional hazards model. RESULTS: Of the 622 participants with MCI at baseline, 139 patients (22.3%) converted to all-cause dementia over a median of 14.3 (range 6.0-36.5) months. Severe periventricular WMH (PWMH) predicted incident all-cause dementia (Hazard ratio (HR) 2.22; 95% confidence interval (CI) 1.43-3.43) and Alzheimer's disease (AD) (HR 1.86; 95% CI 1.12-3.07). Subcortical vascular dementia (SVD) was predicted by both PWMH (HR 16.14; 95% CI 1.97-132.06) and DWMH (HR 8.77; 95% CI 1.77-43.49) in more severe form (≥ 10 mm). CONCLUSIONS: WMH differentially predict dementia by region and severity. Our findings suggest that PWMH may play an independent role in the pathogenesis of dementia, especially in AD.

A new classification system for ischemia using a combination of deep and periventricular white matter hyperintensities.

The Clinical Research Center for Dementia of South Korea (CREDOS) group developed a new classification system for ischemia using a combination of deep and periventricular white matter hyperintensities (WMHs). In this study, we aimed to evaluate the validity of the CREDOS ischemia classification system. A total of 352 patients with cognitive impairments were included. Their WMH scores were rated using the CREDOS WMH visual rating scale. These patients were divided into 3 groups according to the CREDOS ischemia classification system. The volume of WMH was also automatically measured. The number of lacunes and microbleeds (MBs) were counted. The CREDOS ischemia classification system was revised with factor analysis using vascular risk factors and cerebrovascular disease (CVD) markers (WMH volume, lacunes, and MBs). External validation was performed in another group of patients with cognitive impairment using multinomial logistic regression analysis. The CREDOS WMH visual rating scale showed excellent correlation with the automatically measured volume of WMH. The factor analysis showed that the severe group was expanded to D3P1 and D3P2 in the revised CREDOS ischemia classification system. In the validation group, the presence of vascular risk factors and the severity of CVD markers could be distinguished according to the revised CREDOS ischemia classification. We validated a newly developed classification system for ischemia. This simple visual classification system was capable of providing information on vascular risk factors and CVD markers by simply rating WMH on magnetic resonance imaging.