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The desiccant dehumidification system can separate the latent heat and sensible heat in the air-conditioning system and achieve energy savings by removing latent heat. Industrial waste heat and renewable energy could be utilized in desiccant dehumidification systems, where the desorption process can be performed below 70 °C. The vapor pressure and temperature of the regenerating air dictate the desorption process corresponding to the isotherm properties. This study has focused on the effects of various temperatures and humidity ratios of regeneration air on the performance of a desiccant dehumidifier using a polymer as an adsorbent. Experiments were performed using the regeneration air with the humidity ratios of 0.005 kg kg−1, 0.010 kg kg−1, 0.015 kg kg−1, and 0.020 kg kg−1, while the air temperatures were varied from 40 °C to 70 °C. The evaluation of this study employs the adsorption/desorption amount, average moisture removal capacity, and latent energy ratio (LER) of the regeneration process as key performance indexes. At the regeneration temperature of 68 °C, the peak desorption amount at the humidity ratio of 0.005 kg kg−1 and 0.010 kg kg−1 both reached 0.011 kg kg−1. The results indicated that the higher desorption temperature led to a higher desorption amount. Besides, with the increased desorption temperature, the average moisture removal capacity increases. In contrast, the high humidity ratio of regeneration air resulted in a weak dehumidification ability. Lower regeneration temperature was difficult to apply to regenerate the polymer-based desiccant under a high-humidity-ratio atmosphere. To attain a high LER, a lower humidity ratio of dry air and regeneration temperature was preferred. The regeneration air with a humidity ratio of 0.020 kg kg−1 is not suitable to apply in the dehumidification system in the temperature range of 40–70 °C. [ABSTRACT FROM AUTHOR]

In this paper, we present an electric field analysis for the optimal structural design of lightning rods for high performance with a charge transfer system (CTS). In the case of a conventional rod that is produced with an empirical design and structure without quantitative data because the design is structurally very simple, only the materials and radius of curvature of the lightning rod to concentrate the electric field at the tip part of the rod are considered. Recently, the development of new types of lightning rods, such as early streamer emission (ESE) and charge transfer system (CTS), has been introduced through simulation analysis and experiments, but detailed specifications and information about the optimal design and structure have not been fully reported. In this paper, we performed an electric field analysis of the structures and materials for the optimal structural design of lightning rods with a function of CTS through computer software analysis with consideration for the radius of curvature, the size of corona ring, and optimal position (X-axis and Y-axis) of the floating electrode. For optimal structural design of lightning rods based on electric field analysis, we used a source of lightning voltage with 1.2/50 µs based on a double exponential equation. The results revealed that the electric field on the relaxation part decreases as the radius of curvature and corona ring increases. For the radius of curvature, the electric field first decreases and then increases with increasing radius of curvature and reaches a minimum at 7 mm and a maximum above 8 mm. For the case of the corona ring, the electric field decreases with increasing corona ring, and the optimal size of the corona ring was selected as 4 mm; the size of the 4 mm corona ring uniformly formed the electric field both at the tip part of the ground current collector and the corona ring. For the electric field concentration part, we found that the optimal X-axis position of the floating electrode and the Y-axis position between the ionizer conductor and floating electrode are 7 mm and 0.1 mm, respectively. These simulation results in this paper are expected to provide useful information for the design of optimized CTS-type lightning rods. [ABSTRACT FROM AUTHOR]

Background: Postoperative delirium (POD) in older adults is a very serious complication. Due to the complexity of too many risk factors (RFs), an overall assessment of RFs may be needed. The aim of this study was to evaluate comprehensively the RFs of POD regardless of the organ undergoing operation, efficiently incorporating the concept of comprehensive big data using a smart clinical data warehouse (CDW).Methods: We reviewed the electronic medical data of inpatients aged 65 years or older who underwent major surgery between January 2010 and June 2016 at Hallym University Sacred Heart Hospital. The following six major operation types were selected: cardiac, stomach, colorectal, hip, knee, and spine. Clinical features, laboratory findings, perioperative variables, and medication history were compared between patients without POD and with POD.Results: Six hundred eighty-six of 3634 patients (18.9%) developed POD. In multivariate logistic regression analysis, common, independent RFs of POD were as follows (descending order of odds ratio): operation type ([hip] OR 8.858, 95%CI 3.432-22.863; p = 0.000; [knee] OR 7.492, 95%CI 2.739-20.487; p = 0.000; [spine] OR 6.919, 95%CI 2.687-17.815; p = 0.000; [colorectal] OR 2.037, 95%CI 0.784-5.291; p = 0.144; [stomach] OR 1.500, 95%CI 0.532-4.230; p = 0.443; [cardiac] reference), parkinsonism (OR 2.945, 95%CI 1.564-5.547; p = 0.001), intensive care unit stay (OR 1.675, 95%CI 1.354-2.072; p = 0.000), stroke history (OR 1.591, 95%CI 1.112-2.276; p = 0.011), use of hypnotics and sedatives (OR 1.307, 95%CI 1.072-1.594; p = 0.008), higher creatinine (OR 1.107, 95%CI 1.004-1.219; p = 0.040), lower hematocrit (OR 0.910, 95%CI 0.836-0.991; p = 0.031), older age (OR 1.053, 95%CI 1.037-1.069; p = 0.000), and lower body mass index (OR 0.967, 95%CI 0.942-0.993; p = 0.013). The use of analgesics (OR 0.644, 95%CI 0.467-0.887; p = 0.007) and antihistamines/antiallergics (OR 0.764, 95%CI 0.622-0.937; p = 0.010) were risk-reducing factors. Operation type with the highest odds ratio for POD was orthopedic surgery.Conclusions: Big data analytics could be applied to evaluate RFs in electronic medical records. We identified common RFs of POD, regardless of operation type. Big data analytics may be helpful for the comprehensive understanding of POD RFs, which can help physicians develop a general plan to prevent POD. [ABSTRACT FROM AUTHOR]

Behavioral variant frontotemporal dementia (bvFTD) is the most common form of frontotemporal dementia, and tau pathology can be found in 40%–50% of bvFTD patients. In this study, we sought to investigate 18 F-flortaucipir-binding patterns and their correlates in clinically diagnosed bvFTD patients by comparing with results for Alzheimer's disease (AD) patients. We enrolled 20 bvFTD, 20 AD, and 20 age-matched healthy subjects who underwent neuropsychological tests, magnetic resonance imaging, and tau positron emission tomography scans with 18 F-flortaucipir. Regional standardized uptake value ratios for the cerebral cortex and underlying white matter were compared between the 2 groups. The bvFTD patients showed increased 18 F-flortaucipir binding in the putamen and globus pallidus when compared to the healthy controls. In addition, bvFTD was associated with increased binding in the white matter regions underlying the frontal, anterior cingulate, and insula cortices. The bvFTD patients may exhibit predominantly subcortical 18 F-flortaucipir-binding pattern that is distinct from the patterns seen in AD patients. We hypothesize that the clinical characteristics of bvFTD patients may be attributable to the dysfunctional frontal-subcortical networks. However, concerns remain regarding unknown “off-target” binding in the white matter and the basal ganglia. [ABSTRACT FROM AUTHOR]

We aimed to categorize subjective memory impairment (SMI) individuals based on their patterns of cortical thickness and to propose simple models that can classify each subtype. We recruited 613 SMI individuals and 613 age- and gender-matched normal controls. Using hierarchical agglomerative cluster analysis, SMI individuals were divided into 3 subtypes: temporal atrophy (12.9%), minimal atrophy (52.4%), and diffuse atrophy (34.6%). Individuals in the temporal atrophy (Alzheimer's disease–like atrophy) subtype were older, had more vascular risk factors, and scored the lowest on neuropsychological tests. Combination of these factors classified the temporal atrophy subtype with 73.2% accuracy. On the other hand, individuals with the minimal atrophy (non-neurodegenerative) subtype were younger, were more likely to be female, and had depression. Combination of these factors discriminated the minimal atrophy subtype with 76.0% accuracy. We suggest that SMI can be largely categorized into 3 anatomical subtypes that have distinct clinical features. Our models may help physicians decide next steps when encountering SMI patients and may also be used in clinical trials. [ABSTRACT FROM AUTHOR]

Although several recent studies have found that type 1 porcine reproductive and respiratory syndrome virus (PRRSV) modified live virus (MLV) vaccine showed appreciable levels of cross-protection against type 2 PRRSV infection, the possibility of cross-protection between two genotype of PRRSV is still controversial. To determine potential protective efficacy against hetero-genotype field strain of PRRSV and to improve understandings of the mechanisms underlying performance improvement after infection in vaccinated animals, piglets were vaccinated with type 1 PRRSV MLV vaccine and challenged with type 2 field strain of PRRSV. As a result, vaccinated animals gained on average 8.45 kg in comparison to 4.77 kg measured in non-vaccinated animals during a 3-week period after viral challenge, which shows using a certain PRRSV vaccine could be clinically effective against heterologous genotypic virus challenge. In vaccinated animals, viremia was reduced and cleared rapidly, whilst viral load was much higher and reduced more slowly, indicating rebound viremia in non-vaccinated animals. The titers of neutralizing antibody against the type 2 PRRSV did not exceed the protective level in any animal from both vaccinated and control groups. Instead, antibody avidity of vaccinated animals was much higher than in the control group clearly. Furthermore, a strong negative correlation between antibody avidity and viremia was noted in 80% of vaccinated animals. Through those results from tests evaluating degree of antibody maturation and its relevance with clearing viremia, it could be suggested that non-neutralizing antibodies induced by vaccination prior to challenge might play a key role in protection against PRRSV infection, especially in early time course. [ABSTRACT FROM AUTHOR]

Previous preclinical studies have suggested a close relationship between cerebrovascular disease (CVD) and Alzheimer's disease. However, a direct correlation between CVD and amyloid burden has not yet been shown in humans. If there is a relationship between CVD and amyloid burden, it is possible that the apolipoprotein E4 (APOE4) genotype may have an effect on this relationship because APOE4 is a risk factor for the development of AD. We therefore evaluated the effects of APOE4 on the relationship between white matter hyperintensities (WMH), a marker of CVD, and amyloid burden, measured by 11C-Pittsburgh compound B (PiB) PET. We recruited 53 patients with subcortical vascular cognitive impairments, who had both WMH on MRI and amyloid deposition assessed by PiB PET. Twenty-two of these patients were APOE4 carriers (41.5%). In the APOE4 non-carriers, a significant positive correlation was shown between the volume of WMH and PiB retention (β = 7.0 × 10-3, p = 0.034) while no significant correlation was found in APOE4 carriers (β = -9.0 × 10-3, p = 0.085). Statistical parametric mapping analyses in APOE4 non-carriers showed that WMH were associated with PiB retention in the bilateral medial occipitotemporal gyrus, cuneus, and superior cerebellum. Our results suggested that WMH are correlated with amyloid burden especially in the posterior brain regions in APOE4 non-carriers. However, this correlation was not observed in APOE4 carriers, perhaps because in these subjects the influence of APOE4 overrides the effect of CVD. [ABSTRACT FROM AUTHOR]

Abstract: Although patients with amnestic mild cognitive impairment (aMCI) are at higher risk of developing Alzheimer's disease (AD), their pathologies could be heterogeneous. We aimed to evaluate structural changes in amyloid-negative and amyloid-positive aMCI patients. Forty-eight aMCI patients who underwent Pittsburgh compound B (PiB) positron emission tomography were recruited. They were classified as PiB (−) aMCI (N = 16) and PiB (+) (N = 32). Hippocampal shape and regional cortical thickness were compared with 41 subjects with normal cognition (NC). Relative to NC, PiB(−) aMCI exhibited hippocampal deformity in the right cornu ammonis 1, whereas PiB(+) aMCI exhibited hippocampal deformity in bilateral subiculum and cornu ammonis 1 subregions. Relative to NC, PiB(−) aMCI showed cortical thinning in the left medial prefrontal and right anterior temporal regions, whereas PiB(+) aMCI exhibited cortical thinning in bilateral medial temporal regions, temporoparietal junctions and precuneus, and prefrontal cortices. Our findings suggest that structural changes in PiB(−) aMCI might be due to several possible pathologic changes, whereas structural changes in PiB(+) aMCI reflect AD-like structural changes. [Copyright &y& Elsevier]

Previous preclinical studies have suggested a close relationship between cerebrovascular disease (CVD) and Alzheimer's disease. However, a direct correlation between CVD and amyloid burden has not yet been shown in humans. If there is a relationship between CVD and amyloid burden, it is possible that the apolipoprotein E4 (APOE4) genotype may have an effect on this relationship because APOE4 is a risk factor for the development of AD. We therefore evaluated the effects of APOE4 on the relationship between white matter hyperintensities (WMH), a marker of CVD, and amyloid burden, measured by 11C-Pittsburgh compound B (PiB) PET. We recruited 53 patients with subcortical vascular cognitive impairments, who had both WMH on MRI and amyloid deposition assessed by PiB PET. Twenty-two of these patients were APOE4 carriers (41.5%). In the APOE4 non-carriers, a significant positive correlation was shown between the volume of WMH and PiB retention (β = 7.0 × 10-3, p = 0.034) while no significant correlation was found in APOE4 carriers (β = -9.0 × 10-3, p = 0.085). Statistical parametric mapping analyses in APOE4 non-carriers showed that WMH were associated with PiB retention in the bilateral medial occipitotemporal gyrus, cuneus, and superior cerebellum. Our results suggested that WMH are correlated with amyloid burden especially in the posterior brain regions in APOE4 non-carriers. However, this correlation was not observed in APOE4 carriers, perhaps because in these subjects the influence of APOE4 overrides the effect of CVD. [ABSTRACT FROM AUTHOR]

Abstract: Cerebrovascular disease (CVD) and amyloid burden are the most frequent pathologies in subjects with cognitive impairment. However, the relationship between CVD, amyloid burden, and cognition are largely unknown. We aimed to evaluate whether CVD (lacunes, white matter hyperintensities, and microbleeds) and amyloid burden (Pittsburgh compound B [PiB] retention ratio) contribute to cognitive impairment independently or interactively. We recruited 136 patients with subcortical vascular cognitive impairment who underwent magnetic resonance imaging, PiB–positron emission tomography, and neuropsychological testing. The number of lacunes was associated with memory, frontal dysfunctions, and disease severity. The volume of white matter hyperintensities and the PiB retention ratio were associated only with memory dysfunction. There was no direct correlation between CVD markers and PiB retention ratio except that the number of lacunes was negatively correlated with the PiB retention ratio. In addition, there were no interactive effects of CVD and PiB retention ratio on cognition. Our findings suggest that CVD and amyloid burden contribute independently and not interactively to specific patterns of cognitive dysfunction in patients with subcortical vascular cognitive impairment. [Copyright &y& Elsevier]

Abstract: Although individuals with subjective memory impairment (SMI) tend to be at an increased risk for dementia and the majority of them have depressive symptoms, it remains unclear whether SMI with depression is associated with an increased or decreased risk of dementia. The purpose of this study was to investigate the relationship between depressive symptoms and hippocampal/amygdalar volume, a reliable biomarker in the prediction of progression to dementia in SMI. Ninety subjects with SMI participated in the study, and 28 healthy participants without memory complaints served as a normal control (NC) group. 3-D T1-weighted structural MRI scans were completed in all subjects. When the volumes of hippocampus and amygdala were compared among the groups, the SMI group showed significantly smaller volumes than the NC group. When multiple regression analysis was conducted in all subjects, neither hippocampal nor amygdalar volume showed significant interaction effect between group and Geriatric Depression Scale (GDS). However, when the analysis was conducted within each group, lower GDS score was associated with smaller hippocampal volume in the SMI group, and higher GDS score was associated with smaller amygdalar volume in the NC group. Thus, individuals with SMI and less depressive symptoms tend to have smaller hippocampus, which could be associated with more risk of dementia, than normal individuals. [Copyright &y& Elsevier]

Abstract: Patients with early-onset Alzheimer''s disease (EOAD) are reported to be different from those with late-onset Alzheimer''s disease (LOAD) in terms of neuropsychological and neuroimaging findings. In this study, we aimed to compare the longitudinal volume changes of 6 subcortical structures (the amygdala, hippocampus, thalamus, putamen, globus pallidus, and caudate nucleus) between patients with EOAD and LOAD for 3 years. We prospectively recruited 36 patients with probable Alzheimer''s disease (14 EOAD, 22 LOAD) and 14 normal control subjects. We analyzed the volume of subcortical structures using an automatic surface-based method. At baseline, there were no differences in the volumes of subcortical structures between patients with EOAD and LOAD. However, over 3 years of longitudinal follow-up, patients with EOAD showed more rapid volumetric decline in the caudate, putamen, and thalamus than patients with LOAD, which is consistent with neuropsychological results. Our findings suggested that the cognitive reserve theory might be applicable to explain different decline rates of the volumes of the basal ganglia and thalamus according to onset age. [Copyright &y& Elsevier]

Background: Patients with early-onset Alzheimer's disease (EOAD) may differ from those with late-onset Alzheimer's disease (LOAD) in cognitive impairment profiles and clinical course. Postmortem studies also reported that EOAD has a greater pathologic burden than LOAD. We examined the effects of age at onset on the burden and distribution of amyloid plaques in patients with AD, using a statistical parametric mapping (SPM) and regions of interest (ROIs) analyses of the Pittsburgh compound B (PiB)-PET. Methods: We initially recruited 72 patients with AD who had completed the [11C] PiB-PET scan, but four patients were excluded due to familial AD or incomplete MRI data. Of the 68 patients, 61 were classified as PiB-positive (PiB+) and seven as PiB-negative (PiB-) using the measured global PiB uptake ratio values. Of the 61 patients with PiB+ AD, in order to maximize the effect of onset age, we excluded 20 patients in their 60 s. Thus among the remaining 41 patients, the amyloid deposition of only 17 patients with EOAD (age onset <60 years) and 24 patients with LOAD (onset age &nvge;70 years) were compared. Results: There were no significant differences in the global mean PiB index between EOAD and LOAD patients, whereas SPM and ROIs analyses showed that those with EOAD retained higher levels of PiB in the bilateral basal ganglia, bilateral thalamus, left superior temporal cortex, and left cuneus compared to those with LOAD. Conclusion: Our findings demonstrated that EOAD patients differed from those with LOAD in the topography of amyloid deposition, which may partly account for the findings from previous studies that extrapyramidal symptoms and frontal dysfunction are more common in EOAD than in LOAD patients. [ABSTRACT FROM AUTHOR]

Objective Cerebral microbleeds (CMBs) are a neuroimaging marker of small vessel disease (SVD) with relevance for understanding disease mechanisms in cerebrovascular disease, cognitive impairment, and normal aging. It is hypothesized that lobar CMBs are due to cerebral amyloid angiopathy (CAA) and deep CMBs are due to subcortical ischemic SVD. We tested this hypothesis using structural magnetic resonance imaging (MRI) markers of subcortical SVD and in vivo imaging of amyloid in patients with cognitive impairment. Methods We included 226 patients: 89 with Alzheimer disease-related cognitive impairment (ADCI) and 137 with subcortical vascular cognitive impairment (SVCI). All subjects underwent amyloid imaging with [11C] Pittsburgh compound B (PiB) positron emission tomography, and MRI to detect CMBs and markers of subcortical SVD, including the volume of white matter hyperintensities (WMH) and the number of lacunes. Results Parietal and occipital lobar CMBs counts were higher in PiB+ ADCI with moderate WMH than PiB+ ADCI with minimal WMH, whereas PiB− patients with SVCI (ie, 'pure' SVCI) showed both lobar and deep CMBs. In multivariate analyses of the whole cohort, WMH volume and lacuna counts were positively associated with both lobar and deep CMBs, whereas amyloid burden (PiB) was only associated with lobar CMBs. There was an interaction between lacuna burden and PiB retention on lobar (but not deep) CMBs ( p<0.001). Interpretation Our findings suggest that although deep CMBs are mainly linked to subcortical SVD, both subcortical SVD and amyloid-related pathologies (eg, CAA) contribute to the pathogenesis of lobar CMBs, at least in subjects with mixed lobar and deep CMBs. Furthermore, subcortical SVD and amyloid-related pathologies interact to increase the risk of lobar CMBs. Ann Neurol 2013;73:584-593 [ABSTRACT FROM AUTHOR]

There are some studies identifying the association between kidney dysfunction and cognitive impairment through various mechanisms including small vessel disease. However, results concerning the relationship between kidney dysfunction and cortical atrophy have been inconsistent. Thus, we aimed to evaluate the relationship among kidney dysfunction, small vessel disease, and cortical thinning in probable Alzheimer's disease (AD) dementia patients. Patients consisted of 162 subjects with probable AD dementia who underwent high-resolution T1-weighted volumetric magnetic resonance imaging (MRI) scans using the same scanner. The estimated glomerular filtration rate (GFR) was calculated and divided into the quartiles of patients for comparison. Volume of white matter hyperintensities (WMH) was automatically measured. Two neurologists counted the number of lacunes. Cortical thickness was measured using a surface-based method. GFR was not associated with WMH and the number of lacunes. However, the lowest quartile group of GFR (GFR 1) had cortical thinning in each lobe, compared to the highest quartile group of GFR (GFR 4). The topography of cortical thinning in the GFR 1 group was distributed predominantly in temporoparietal regions, compared to GFR 4. After further adjustment of small vessel disease MRI markers, the association between GFR and the cortical thinning remained. Our findings suggested that kidney dysfunction, represented by GFR, was related to temporoparietal thinning independent of small vessel disease in probable AD dementia patients. [ABSTRACT FROM AUTHOR]

Background: Patients with early-onset Alzheimer's disease (EOAD) may differ from those with late-onset Alzheimer's disease (LOAD) in cognitive impairment profiles and clinical course. Postmortem studies also reported that EOAD has a greater pathologic burden than LOAD. We examined the effects of age at onset on the burden and distribution of amyloid plaques in patients with AD, using a statistical parametric mapping (SPM) and regions of interest (ROIs) analyses of the Pittsburgh compound B (PiB)-PET. Methods: We initially recruited 72 patients with AD who had completed the [11C] PiB-PET scan, but four patients were excluded due to familial AD or incomplete MRI data. Of the 68 patients, 61 were classified as PiB-positive (PiB+) and seven as PiB-negative (PiB-) using the measured global PiB uptake ratio values. Of the 61 patients with PiB+ AD, in order to maximize the effect of onset age, we excluded 20 patients in their 60 s. Thus among the remaining 41 patients, the amyloid deposition of only 17 patients with EOAD (age onset <60 years) and 24 patients with LOAD (onset age ≥70 years) were compared. Results: There were no significant differences in the global mean PiB index between EOAD and LOAD patients, whereas SPM and ROIs analyses showed that those with EOAD retained higher levels of PiB in the bilateral basal ganglia, bilateral thalamus, left superior temporal cortex, and left cuneus compared to those with LOAD. Conclusion: Our findings demonstrated that EOAD patients differed from those with LOAD in the topography of amyloid deposition, which may partly account for the findings from previous studies that extrapyramidal symptoms and frontal dysfunction are more common in EOAD than in LOAD patients. [ABSTRACT FROM AUTHOR]

Abstract: Classical swine fever (CSF) is a contagious viral disease that affects pigs. Wild boars can play an important epidemiological role in CSF outbreaks. In the past decades, studies conducted in many countries have reported that the CSF virus (CSFV) may persist in wild boar populations. The existence of CSFV in the free-ranging wild boar populations was indirectly confirmed by determining the prevalence of antibodies against CSFV in the serum of hunted wild boars. However, analyzing sero-prevalence in hunted wild boars to study the risk of CSF outbreaks is difficult due to insufficient number of samples, limitation of hunting area and biased age distribution of hunted wild boars. To improve this survey method, we collected feces of wild boars from their habitat and tested them using CSFV antibody enzyme-linked immunosorbent assay (ELISA) and CSF virus neutralization (VN) test. In this study, ELISA was found to be highly sensitive for detecting antibodies against CSFV in fecal samples. Most of doubtful or positive results obtained in CSFV ELISA were confirmed by VN tests. Despite the high coincidence rate of antibody-positive samples between CSFV ELISA and VN test, the possibility of false positive reaction should be considered. In the regional distribution, a fact that antibody-positive fecal and serum samples were found in geographically close area was shown. Hence, presence of antibodies in fecal samples may provide vital information regarding the risk of CSF outbreaks in wild boar groups in geographical proximity. [Copyright &y& Elsevier]

To determine the existence of cortical thinning in subcortical vascular dementia (SVaD) with a negative 11C-Pittsburgh compound B (PiB) positron emission tomography scan and to compare the topography of cortical thinning between PiB-negative SVaD and Alzheimer's disease (AD), we enrolled 24 patients with PiB(-) SVaD, 81 clinically probable AD individuals, and 72 normal cognitive controls. Compared with controls, cortical thinning in PiB(-) SVaD was most profound in the perisylvian area, medial prefrontal area, and posterior cingulate gyri, while the precuneus and medial temporal lobes were relatively spared. When the cortical thickness of AD and PiB(-) SVaD were directly compared, PiB(-) SVaD demonstrated significant cortical thinning in the bilateral inferior frontal, superior temporal gyri, and right medial frontal and orbitofrontal lobes, while AD showed significant cortical thinning in the right medial temporal region. SVaD without amyloid burden may lead to substantial cortical atrophy. Moreover, characteristic topography of cortical thinning in PiB(-) SVaD suggests different mechanisms of cortical thinning in PiB(-) SVaD and AD. [ABSTRACT FROM AUTHOR]

Abstract: Recent studies have demonstrated that ultra-high resolution MRA imaging using 7 Tessla (T) MRI can be employed to noninvasively visualize the lenticulostriate arteries (LSA) that supply the basal ganglia and internal capsule. Subcortical vascular dementia (SVaD) is believed to involve these regions from an early stage. We investigated whether LSA abnormalities measured by 7T MRA correlate with MRI ischemia markers and neuropsychological/motor deficits. A total of 24 subjects (12 with SVaD, 12 normal controls (NC)) were imaged with 3T and 7T MRIs. We assessed the severity of white matter hyperintensities (WMH) and the number of lacunes and microbleeds (MB) by visually inspecting images obtained from conventional 3T MRI. We also analyzed three-dimensional models of the measured LSAs obtained from 7T MRI. Compared to the NC, the SVaD subjects had fewer branches of LSAs and greater radii of LSAs. The number of branches was correlated with the number of lacunes. The number of branches was correlated with the delayed recall scores on Rey''s Complex Figure Test (RCFT). While not quite reaching statistical significance, the immediate recall, recognition scores on the RCFT, recognition scores on the Seoul Verbal Learning Test, and the word and color readings of Stroop trended in the direction of correlation with the number of branches, as well as with the extrapyramidal scores. Our findings suggest that LSA imaging using 7T MRI might be a potent candidate for the detection of SVaD. [Copyright &y& Elsevier]

Background: Amnestic mild cognitive impairment (aMCI) is regarded as a prodromal stage of Alzheimer's disease (AD). Given that patients with early-onset AD (EOAD) and with late-onset AD (LOAD) are known to have different clinical courses, symptoms and neuroimaging findings, early-onset (EOMCI) and late-onset aMCI (LOMCI) might be expected to have similar differences as EOAD versus LOAD. Methods: Our study involving 425 patients with aMCI (124 EOMCI, 301 LOMCI), who were followed for around 1.5 years, and 958 normal control subjects (NC) investigated neuropsychological characteristics and prediction of progression to AD in patients with EOMCI versus LOMCI. Neuropsychological scores were compared between EOMCI, LOMCI and NC with analyses of covariance controlling age, gender, education and disease duration. The risk of AD conversion was evaluated by Cox proportional hazard analyses. Results: The baseline neuropsychological performances were comparable between EOMCI and LOMCI. Visuospatial memory for EOMCI and verbal memory scores for LOMCI were significant predictors of AD conversion. Conclusion: Our study indicates that EOMCI with visuospatial memory impairment, which implies underlying right predominant pathology, and LOMCI with poor verbal memory, which suggests underlying left predominant pathology, are individual conditions at an increased risk of conversion to AD. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background A previous study described the outcomes of a treatment protocol using a prospective design and identified three clinical risk factors for recurrent keloids. Objective To introduce a novel classification of earlobe keloids through a retrospective study and describe the appropriate surgical methods according to this new classification. Methods One thousand twenty-seven earlobe keloids were treated at Kangbuk Samsung Hospital from March 2001 to February 2011. All cases were studied retrospectively and classified. Results The earlobe keloids were classified into five groups. The frequency of earlobe keloids in descending order were a sessile type, single nodular pattern; pedunculated type; sessile type, multinodular pattern; buried type; and mixed type. Different surgical methods were used based on the Chang-Park classification according to gross morphology, including core extirpation using a penetrating technique, standard keloidectomy, radical keloidectomy, keloidectomy with core extirpation, and a combination of these. All cases were closed primarily without skin grafting or sacrifice of the surrounding tissue. Conclusions This novel classification for earlobe keloids can lead to a better understanding of the different types of earlobe keloids and inform decisions regarding surgical methods. [ABSTRACT FROM AUTHOR]

Amnestic mild cognitive impairment (MCI) is considered to be a prodromal stage of Alzheimer's disease. Likewise, subcortical vascular MCI (svMCI) is considered as a prodromal stage of subcortical vascular dementia (SVaD). The objective of this study was to investigate neuropsychiatric features in patients with svMCI compared to healthy controls and patients with SVaD. We evaluated 31 patients with svMCI, 42 with SVaD, and 28 healthy controls who underwent neuropsychiatric assessments using the Neuropsychiatric Inventory (NPI) and the Frontal Behavioral Inventory (FBI). On both the NPI and FBI, SVaD patients had the most severe neuropsychiatric symptoms, followed by svMCI patients and then healthy controls, suggesting that svMCI might be a prodromal stage of SVaD in terms of neuropsychiatric abnormalities. When we compared the differences of mean scores between negative and positive symptoms in FBI, negative symptoms tended to be more predominant than positive symptoms in both svMCI and SVaD patients, but the tendency was stronger in SVaD patients than in svMCI patients. These results suggest that vascular cognitive impairment with small vessel disease would start with both negative and positive neuropsychiatric symptoms and progress to present more severe negative symptoms. These behavioral ratings may be useful for early detection of vascular cognitive impairment associated with small vessel disease. [ABSTRACT FROM AUTHOR]

Abstract: The neurochemical alterations in the entorhinal cortex have not yet been measured, even though the entorhinal cortex is the earliest involved brain region in aMCI. In this study, we investigated whether brain regions including the entorhinal cortex would show early involvement of neurochemical abnormalities in aMCI, and whether magnetic resonance spectroscopy (MRS) abnormalities might be a predictive marker of conversion of aMCI to Alzheimer''s disease (AD). MRS was performed on 13 aMCI patients and 11 patients with no cognitive impairment (NCI). Localizing voxels were placed within the entorhinal cortex, hippocampus, posterior cingulate gyrus, and occipital white matter in the dominant hemisphere. N-acetyl aspartate/creatinine (NAA/Cr) ratios in the entorhinal cortex were significantly lower in aMCI patients than in NCI subjects. After a three-year follow-up, seven aMCI patients converted to AD and six remained stable. Baseline NAA/Cr ratios of entorhinal cortex were decreased in converters, compared to NCI. Our study suggested the entorhinal cortex is the earliest site that is subject to neurochemical alteration in aMCI patients, and baseline MRS metabolite ratios in the entorhinal cortex can be a marker for predicting conversion of aMCI to AD. [Copyright &y& Elsevier]

Abstract: Patients with probable Alzheimer''s disease (AD) and the amnesic form of mild cognitive impairment (aMCI) often demonstrate several types of neuropsychological deficits. These deficits are often related to cortical atrophy, induced by neuronal degradation. The purpose of this study is to investigate whether different anatomic patterns of cortical atrophy are associated with specific neuropsychological deficits. The participants were 170 patients with AD and 99 patients with aMCI. All participants underwent the Seoul Neuropsychological Screening Battery (SNSB), which includes tests that assess attention, language, visuospatial functions, verbal and visual memory, and frontal/executive functions. Cortical atrophy (thinning) was quantified by measuring the thickness of the cortical mantle across the entire brain using automated, three-dimensional magnetic resonance imaging. The relationship between cortical thickness and neuropsychological performance was analysed using stepwise multiple linear regression analyses. These analyses (corrected P <.001) showed that several specific brain regions with cortical thinning were associated with cognitive dysfunction including: digit span backward, verbal and picture recall, naming and fluency, drawing–copying, response inhibition and selective attention. Some of the other functions, however, were not associated with specific foci of cortical atrophy (digit span forward, the word reading portion of the Stroop test, word and picture recognition). Our study, involving a large sample of participants with aMCI and AD, provides support for the postulate that cortical thinning-atrophy in specific anatomic loci are pathological markers for specific forms of cognitive dysfunction. [Copyright &y& Elsevier]

Dye-sensitized solar cells (DSSCs) were fabricated using graphene-coated Al2O3 (GCA)-TiO2 nanocomposite electrodes. The GCA-TiO2 pastes were prepared by simply blending the GCA particles with TiO2 particles without any complex treatments. The DSSC with 1 wt.% GCA-TiO2 exhibited much better overall energy conversion efficiency, when compared to the DSSCs with TiO2 alone and with carbon nanotube-TiO2. It can be attributed to efficient electron transport through the GCA-TiO2 to the transparent conducting oxide, resulting in significantly enhanced electron lifetime. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Vascular cognitive impairment associated with small vessel disease (sVCI) may manifest as both cognitive and motor dysfunctions. However, few instruments exist for systematically assessing motor symptoms in sVCI, even though many neuropsychological tests exist to evaluate cognitive function. We developed a new scale for assessing motor impairments and evaluated the reliability and validity of the scale in patients with sVCI. Methods: A new motor scale, called the PEPS (Pyramidal and Extra Pyramidal Scale for sVCI), consisted of 34 items (for 60 total points) with 5 subdomains: corticospinal, corticobulbar, extrapyramidal signs, gait abnormalities, and gait severity. The PEPS was compared between 75 patients with sVCI and 73 control patients who had dementia or mild cognitive impairment (MCI) without ischemia. Results: The PEPS had good interrater and test–retest reliability, and it was moderately to highly correlated with the UPDRS, NIHSS, MMSE, CDR, and ADL scales. An optimal cut-off score of PEPS to discriminate dementia or MCI patients with ischemia from those without ischemia was 6.5 with a sensitivity of 88% and a specificity of 100%. Conclusion: The PEPS is a reliable and valid scale that can be used to assess and monitor motor impairment in patients with vascular cognitive impairment due to small vessel disease. [Copyright &y& Elsevier]

Abstract: The aim of this study was to investigate the effect of demographic factors (age of onset, sex and years of education) on the distribution of cortical thickness in a large sample of patients with Alzheimer''s disease (AD). The study participants consisted of 193 AD patients and 142 controls with no cognitive impairment (NCI) that were measured with cortical thickness across the entire brain. The effects of demographic factors on cortical thickness were analyzed by applying linear regression after controlling confounding factors. Older individuals in NCI group showed more cortical thinning in frontal, temporal association cortices and insula than younger participants. Early onset AD was associated with cortical thinning in the parietal lobe, whereas late onset AD was associated with cortical thinning in the medial temporal region. The NCI group demonstrated sex-related differences in cortical thickness, although those differences were not present in the AD group. While the education effect was absent in NCI individuals, high levels of education in the AD group correlated with cortical thinning in the frontal and temporoparietal association cortices. Our results show that AD with earlier onset and higher education had suffered more pronounced cortical atrophy in specific parts of the brain than their counterparts, which may be related to cognitive reserve theory. [Copyright &y& Elsevier]

Abstract: Mental confusion or delirium can occur after application of scopolamine patch. However, predisposing factors for scopolamine-induced delirium are not known. It is expected that undetected incipient dementia or mild cognitive impairment (MCI) may be prone to develop mental confusion after applying the scopolamine patch. For the past 5 years, we found seven elderly women who had experienced transdermal scopolamine-induced mental confusion. They underwent neuropsychological tests after recovery from mental confusion (mean duration from onset to the test: 66 days). The results showed that all the patients were impaired in at least one of cognitive domains, fulfilling the criteria of MCI. These findings suggest that scopolamine patch-induced mental confusion should be included in the differential diagnoses of mental confusion in elderly, especially in travel situation, and that older people with undetected MCI are prone to develop scopolamine patch-induced mental confusion. [Copyright &y& Elsevier]

Abstract: Amnestic mild cognitive impairment (aMCI) can be classified into single domain (S-aMCI) and multiple domain (M-aMCI) subtypes. However, there have been no studies that specifically investigate the structural differences that support this classification. In an attempt to compare regional cortical thickness in two subtypes of aMCI, we aimed to map the distribution of cortical thinning using a surface based cortical analysis of magnetic resonance imaging. The cortical thickness across the entire brain was measured in 9 patients with S-aMCI, 22 patients with M-aMCI, and 61 normal healthy subjects. Differences in the patterns of cortical thinning between S-aMCI and M-aMCI were assessed using ANCOVA on a vertex-by-vertex basis, and statistical maps of differences in cortical thickness between the groups were constructed using a surface model. Relative to controls, S-aMCI patients showed cortical thinning in the left medial temporal lobe, and M-aMCI patients showed cortical thinning in the left medial temporal lobe, precuneus, and anterior and inferior basal temporal, insular, and temporal association cortices. When the two MCI groups were directly compared, M-aMCI patients showed cortical thinning in left precuneus. Our studies suggest that M-aMCI is a transitional state between S-aMCI and Alzheimer''s disease, and that the cortical thinning is evidence that the precuneus is responsible for the multiple cognitive impairments in M-aMCI. [Copyright &y& Elsevier]

Background: Risk factors for cardiovascular disease, including elevated blood pressure, are known to increase risk of Alzheimer's disease. There has been increasing awareness of the relationship between long-term blood pressure (BP) patterns and their effects on the brain. We aimed to investigate the association of repeated BP measurements with Alzheimer's and vascular disease markers. Methods: We recruited 1,952 participants without dementia between August 2015 and February 2022. During serial clinic visits, we assessed both systolic BP (SBP) and diastolic BP (DBP), and visit-to-visit BP variability (BPV) was quantified from repeated measurements. In order to investigate the relationship of mean SBP (or DBP) with Alzheimer's and vascular markers and cognition, we performed multiple linear and logistic regression analyses after controlling for potential confounders (Model 1). Next, we investigated the relationship of with variation of SBP (or DBP) with the aforementioned variables by adding it into Model 1 (Model 2). In addition, mediation analyses were conducted to determine mediation effects of Alzheimer's and vascular makers on the relationship between BP parameters and cognitive impairment. Results: High Aβ uptake was associated with greater mean SBP (β = 1.049, 95% confidence interval 1.016–1.083). High vascular burden was positively associated with mean SBP (odds ratio = 1.293, 95% CI 1.015–1.647) and mean DBP (1.390, 1.098–1.757). High tau uptake was related to greater systolic BPV (0.094, 0.001–0.187) and diastolic BPV (0.096, 0.007–0.184). High Aβ uptake partially mediated the relationship between mean SBP and the Mini-Mental State Examination (MMSE) scores. Hippocampal atrophy mediated the relationship between diastolic BPV and MMSE scores. Conclusions: Each BP parameter affects Alzheimer's and vascular disease markers differently, which in turn leads to cognitive impairment. Therefore, it is necessary to appropriately control specific BP parameters to prevent the development of dementia. Furthermore, a better understanding of pathways from specific BP parameters to cognitive impairments might enable us to select the managements targeting the specific BP parameters to prevent dementia effectively. [ABSTRACT FROM AUTHOR]

Background: Amyloid-β (Aβ) commonly coexists and impacts prognosis in subcortical vascular cognitive impairment (SVCI). Objective: This study aimed to examine the differences in clinical and neuroimaging variables between Aβ-positive and Aβ-negative SVCI and to propose a prediction model for Aβ positivity in clinically diagnosed SVCI patients. Methods: A total of 130 patients with SVCI were included in model development, and a separate cohort of 70 SVCI patients was used in external validation. The variables for the prediction model were selected by comparing the characteristics of the Aβ-negative and Aβ-positive SVCI groups. The final model was determined using a stepwise method. The model performance was evaluated using the receiver operating characteristic (ROC) curve and a calibration curve. A nomogram was used for visualization. Results: Among 130 SVCI patients, 70 (53.8%) were Aβ-positive. The Aβ-positive SVCI group was characterized by older age, tendency to be in the dementia stage, a higher prevalence of APOEɛ4, a lower prevalence of lacune, and more severe medial temporal atrophy (MTA). The final prediction model, which excluded MTA grade following the stepwise method for variable selection, demonstrated good accuracy in distinguishing between Aβ-positive and Aβ-negative SVCI, with an area under the curve (AUC) of 0.80. The external validation demonstrated an AUC of 0.71. Conclusions: The findings suggest that older age, dementia stage, APOEɛ4 carrier, and absence of lacunes may be predictive of Aβ positivity in clinically diagnosed SVCI patients. [ABSTRACT FROM AUTHOR]

We investigated the survival time of each clinical syndrome of frontotemporal dementia (FTD) and the impacts of behavioral and motor features on survival of FTD. A total of 216 patients with FTD [82 behavioral variant FTD (bvFTD), 78 semantic variant primary progressive aphasia (svPPA), 43 non-fluent/agrammatic variant PPA (nfvPPA), 13 FTD-motor neuron disease (MND)] were enrolled from 16 centers across Korea. Behaviors and parkinsonism were assessed using the Frontal Behavioral Inventory and Unified Parkinson's Disease Rating Scale Part III, respectively. The Kaplan–Meier method was used for the survival analysis and the Cox proportional hazards model was applied for analysis of the effect of behavioral and motor symptoms on survival, after controlling vascular risk factors and cancer. An overall median survival of FTD was 12.1 years. The survival time from onset was shortest for FTD-MND and longest for svPPA. The median survival time of patients with bvFTD was unavailable but likely comparable to that of patients with nfvPPA. In the bvFTD group, negative behavioral symptoms and akinetic rigidity were significantly associated with survival. In the nfvPPA group, the presence of dysarthria had a negative impact on survival. These findings provide useful information to clinicians planning for care. [ABSTRACT FROM AUTHOR]

Previous studies on Alzheimer's disease-type cognitive impairment (ADCI) and subcortical vascular cognitive impairment (SVCI) has rarely explored spatiotemporal heterogeneity. This study aims to identify distinct spatiotemporal cortical atrophy patterns in ADCI and SVCI. 1,338 participants (713 ADCI, 208 SVCI, and 417 cognitively unimpaired elders) underwent brain magnetic resonance imaging (MRI), amyloid positron emission tomography, and neuropsychological tests. Using MRI, this study measures cortical thickness in five brain regions (medial temporal, inferior temporal, posterior medial parietal, lateral parietal, and frontal areas) and utilizes the Subtype and Stage Inference (SuStaIn) model to predict the most probable subtype and stage for each participant. SuStaIn identifies two distinct cortical thinning patterns in ADCI (medial temporal: 65.8%, diffuse: 34.2%) and SVCI (frontotemporal: 47.1%, parietal: 52.9%) patients. The medial temporal subtype of ADCI shows a faster decline in attention, visuospatial, visual memory, and frontal/executive domains than the diffuse subtype (p-value < 0.01). However, there are no significant differences in longitudinal cognitive outcomes between the two subtypes of SVCI. Our study provides valuable insights into the distinct spatiotemporal patterns of cortical thinning in patients with ADCI and SVCI, suggesting the potential for individualized therapeutic and preventive strategies to improve clinical outcomes. Using the SuStaIn model on 1,338 individuals, this study reveals distinct cortical atrophy in Alzheimer's disease-type cognitive impairment and subcortical vascular cognitive impairment, revealing varying cognitive decline trajectories. [ABSTRACT FROM AUTHOR]

We investigated the effect of education on the edge efficiency in resting state functional networks (RSFNs) in amnestic mild cognitive impairment (aMCI) and Alzheimer's disease dementia (ADD). We collected the data of 57 early aMCI, 141 late aMCI, 173 mild ADD, and 39 moderate-to-severe ADD patients. We used years of education as a proxy for cognitive reserve. We measured edge efficiency for each edge in RSFNs, and performed simple slope analyses to discover their associations with education level among the four groups. In the late aMCI, a sub-network that had hub nodes in the right middle frontal gyrus and the right posterior cingulate gyrus, showed a positive association between RSFN edge efficiency and education (threshold = 2.5, p = 0.0478). There was no negative effect of education on the RSFN edge efficiency. In the early aMCI, mild ADD, and moderate-to-severe ADD, there were no sub-networks showing positive or negative correlation between education and RSFN edge efficiency. There was a positive effect of higher education on RSFN edge efficiency in the late aMCI, but not in the early aMCI or ADD. This indicates that in late aMCI, those who have higher education level have greater ability to resist collapsed functional network. [ABSTRACT FROM AUTHOR]

Background: Cholesterol plays important roles in β-amyloid (Aβ) metabolism and atherosclerosis. However, the relationships of plasma cholesterol levels with Aβ and cerebral small vessel disease (CSVD) burdens are not fully understood in Asians. Herein, we investigated the relationships between plasma cholesterol profile components and Aβ and CSVD burdens in a large, non-demented Korean cohort. Methods: We enrolled 1,175 non-demented participants (456 with unimpaired cognition [CU] and 719 with mild cognitive impairment [MCI]) aged ≥ 45 years who underwent Aβ PET at the Samsung Medical Center in Korea. We performed linear regression analyses with each cholesterol (low-density lipoprotein cholesterol [LDL-c], high-density lipoprotein cholesterol [HDL-c], and triglyceride) level as a predictor and each image marker (Aβ uptake on PET, white matter hyperintensity [WMH] volume, and hippocampal volume) as an outcome after controlling for potential confounders. Results: Increased LDL-c levels (β = 0.014 to 0.115, p = 0.013) were associated with greater Aβ uptake, independent of the APOE e4 allele genotype and lipid-lowering medication. Decreased HDL-c levels (β = − 0.133 to − 0.006, p = 0.032) were predictive of higher WMH volumes. Increased LDL-c levels were also associated with decreased hippocampal volume (direct effect β = − 0.053, p = 0.040), which was partially mediated by Aβ uptake (indirect effect β = − 0.018, p = 0.006). Conclusions: Our findings highlight that increased LDL-c and decreased HDL-c levels are important risk factors for Aβ and CSVD burdens, respectively. Furthermore, considering that plasma cholesterol profile components are potentially modified by diet, exercise, and pharmacological agents, our results provide evidence that regulating LDL-c and HDL-c levels is a potential strategy to prevent dementia. [ABSTRACT FROM AUTHOR]

Background: An advanced age and the female sex are widely recognized risk factors for both cataract and dementia. We investigated the effect of cataract surgery on the incidence of dementia in a Korean population aged ≥ 45 years with a previous diagnosis of cataract. Methods: This nationwide cohort study was performed using Korean National Health Insurance Service data collected from 2006 to 2017. A total of 300,327 subjects aged ≥ 45 years with a history of cataract diagnosis but no previous diagnosis of dementia were analyzed. The relationship between cataract surgery and dementia was evaluated, applying a time-varying analysis to evaluate the hazard ratio (HR) and 95% confidence interval (CI) values according to dementia. It was calculated via a multivariable Cox regression model, with adjustments for age, sex, visual acuity (VA), ocular and systemic comorbidities, and social factors (including body mass index, income, smoking, and drinking). Results: In the multivariate analysis, the cataract surgery group showed a marginal difference in dementia development (HR 1.10 [95% CI 1.02–1.19]) because both cataract and dementia share common risk factors. However, in the subgroup analysis, men (HR 0.49 [95% CI 0.26–0.90]) and patients under 65 years of age (HR 0.88 [95% CI 0.79–0.99]) in the group with cataract surgery and good VA showed a significantly lower incidence of dementia. Conclusion: Through visual improvement, together with timely surgical intervention, the procedure can alleviate the risk of dementia in visually impaired patients, especially in younger and male patients. [ABSTRACT FROM AUTHOR]

Abstract The concept of cognitive reserve (CR) originated from discrepancies between the degree of brain pathology and the severity of clinical manifestations. CR has been characterized through CR proxies, such as education and occupation complexity; however, such approaches have inherent limitations. Although several methods have been developed to overcome these limitations, they fail to reflect the entire Alzheimer's disease (AD) pathology. Meanwhile, graph theory analysis, one of most powerful and flexible approaches, have established remarkable network properties of the brain. The functional and structural brain networks are damaged in neurodegenerative diseases. Therefore, network analysis has been applied to clarify the characteristics of the disease or give insight. Here, using multimodal neuroimaging, we propose an intuitive model to estimate CR based on its original definition, and explore the neural substrates of CR from the perspective of networks and functional connectivity. A total of 87 subjects (21 AD, 32 mild cognitive impairment, and 34 normal aging) underwent tau and amyloid PET, 3D T1-weighted MR, and resting-state fMRI. We hypothesized CR as a residual of actual cognitive performance and expected performance to be related to quantitative factors, such as AD pathology, demographics, and a genetic factor. Then, we correlated this marker using education and occupation complexity as conventional CR proxies. We validated this marker by testing whether it would modulate the effect of brain pathology on memory function. To examine the neural substrates associated with CR, we performed graph analysis to investigate the association between the CR marker and network measures at different granularities in total subjects, AD spectrum and normal aging, respectively. The CR marker from our model was well associated with education and occupation complexity. More directly, the CR marker was revealed to modify the relationship between brain pathology and memory function among AD spectrum. The CR marker was correlated with the global efficiency of the entire network, nodal clustering coefficient, and local efficiency of the right middle-temporal pole. In connectivity analysis, one cluster of edges centered on right middle-temporal pole was significantly correlated with the CR marker. In subgroup analysis, the network measures of right middle-temporal pole still correlated with the CR marker among AD spectrum. However, right precentral gyrus was revealed to be associated with the CR marker in normal aging. This study demonstrates that our intuitive model using multimodal neuroimaging and network perspective adequately and comprehensively captures CR. From a network perspective, CR is associated with the capacity to process information efficiently in the brain. The right middle-temporal pole was revealed to be a pivotal neural substrate of CR in AD spectrum. These findings foster understanding of AD and will be useful to help identify individuals with vulnerability or resistance to AD pathology, and characterize patients for intervention or drug trials. Highlights • We generated an equation to quantify cognitive reserve (CR) reflecting overall AD neuropathology using multimodal neuroimaging techniques. • CR was proved to modify the relationship between brain pathology and memory function in AD spectrum. • CR was associated with global network efficiency and nodal clustering coefficient and local efficiency of the right middle-temporal pole. • Graph parameters of right middle-temporal pole was revealed to modulate the effect of brain atrophy on cognition in AD spectrum. [ABSTRACT FROM AUTHOR]

Abstract We categorized patients with amnestic mild cognitive impairment (aMCI) based on cortical atrophy patterns and evaluated whether the prognosis differed across the subtypes. Furthermore, we developed a classifier that learns the cortical atrophy pattern and predicts subtypes at an individual level. A total of 662 patients with aMCI were clustered into 3 subtypes based on cortical atrophy patterns. Of these, 467 patients were followed up for more than 12 months, and the median follow-up duration was 43 months. To predict individual-level subtype, we used a machine learning–based classifier with a 10-fold cross-validation scheme. Patients with aMCI were clustered into 3 subtypes: medial temporal atrophy, minimal atrophy (Min), and parietotemporal atrophy (PT) subtypes. The PT subtype had higher prevalence of APOE ε4 carriers, amyloid PET positivity, and greater risk of dementia conversion than the Min subtype. The accuracy for binary classification was 89.3% (MT vs. Rest), 92.6% (PT vs. Rest), and 86.6% (Min vs. Rest). When we used ensemble model of 3 binary classifiers, the accuracy for predicting the aMCI subtype at an individual level was 89.6%. Patients with aMCI with the PT subtype were more likely to have underlying Alzheimer's disease pathology and showed the worst prognosis. Our classifier may be useful for predicting the prognosis of individual aMCI patients. Highlights 1. Amnestic MCI patients were clustered into medial temporal, minimal, and parietotemporal atrophy subtypes. 2. Patients with parietotemporal atrophy subtype showed the worst prognosis. 3. The accuracy for predicting the aMCI subtype at an individual level was 89.6%. [ABSTRACT FROM AUTHOR]

Objective: Lateral temporal lobe epilepsy (LTLE) has been diagnosed in only a small number of patients; therefore, its surgical outcome is not as well-known as that of mesial temporal lobe epilepsy. We aimed to evaluate the long-term (5 years) and short-term (2 years) surgical outcomes and identify possible prognostic factors in patients with LTLE. Methods: This retrospective cohort study was conducted between January 1995 and December 2018 among patients who underwent resective surgery in a university-affiliated hospital. Patients were classified as LTLE if ictal onset zone was in lateral temporal area. Surgical outcomes were evaluated at 2 and 5 years. We subdivided based on outcomes and compared clinical and neuroimaging data including cortical thickness between two groups. Results: Sixty-four patients were included in the study. The mean follow-up duration after the surgery was 8.4 years. Five years after surgery, 45 of the 63 (71.4%) patients achieved seizure freedom. Clinically and statistically significant prognostic factors for postsurgical outcomes were the duration of epilepsy before surgery and focal cortical dysplasia on postoperative histopathology at the 5-year follow-up. Optimal cut-off point for epilepsy duration was eight years after the seizure onset (odds ratio 4.375, p-value = 0.0214). Furthermore, we propose a model for predicting seizure outcomes 5 years after surgery using the receiver operating characteristic curve and nomogram (area under the curve = 0.733; 95% confidence interval, 0.588–0.879). Cortical thinning was observed in ipsilateral cingulate gyrus and contralateral parietal lobe in poor surgical group compared to good surgical group (p-value < 0.01, uncorrected). Conclusions: The identified predictors of unfavorable surgical outcomes may help in selecting optimal candidates and identifying the optimal timing for surgery among patients with LTLE. Additionally, cortical thinning was more extensive in the poor surgical group. [ABSTRACT FROM AUTHOR]

Several programs are widely used for clinical and research purposes to automatically quantify the degree of amyloid deposition in the brain using positron emission tomography (PET) images. Given that very few studies have investigated the use of Heuron, a PET image quantification software approved for clinical use, this study aimed to compare amyloid deposition values quantified from 18F-flutemetamol PET images using PMOD and Heuron. Amyloid PET data obtained from 408 patients were analysed using each quantitative program; moreover, the standardized uptake value ratios (SUVRs) of target areas were obtained by dividing the standardized uptake value (SUV) of the target region by the SUV of cerebellar grey matter as a reference. Compared with PMOD, Heuron yielded significantly higher SUVRs for all target areas (paired sample t-test, p < 0.001), except for the PC/PCC (p = 0.986). However, the Bland–Altman plot analysis indicated that the two quantitative methods may be used interchangeably. Moreover, receiver operating characteristic curve analysis revealed no significant between-method difference in the performance of the SUVRs in evaluating the visual positivity of amyloid deposits (p = 0.948). In conclusion, Heuron and PMOD have comparable performance in quantifying the degree of amyloid deposits in PET images. [ABSTRACT FROM AUTHOR]

DNA methylation is a key epigenetic marker, and its alternations may be involved in Alzheimer's disease (AD). CpGs sharing similar biological functions or pathways tend to be co-methylated. We performed an integrative network-based DNA methylation analysis on 2 independent cohorts (N = 941) using brain DNA methylation profiles and RNA-sequencing as well as AD pathology data. Weighted co-methylation network analysis identified 6 modules as significantly associated with neuritic plaque burden. In total, 15 hub CpGs including 3 novel CpGs were identified and replicated as being significantly associated with AD pathology. Furthermore, we identified and replicated 4 target genes (ATP6V1G2 , VCP , RAD52 , and LST1) as significantly regulated by DNA methylation at hub CpGs. In particular, VCP gene expression was also associated with AD pathology in both cohorts. This integrative network-based multiomics study provides compelling evidence for a potential role of DNA methylation alternations and their target genes in AD. [ABSTRACT FROM AUTHOR]

Background: A growing body of evidence shows differences in the prevalence of cardiometabolic syndrome (CMS) and dementia based on gender and ethnicity. However, there is a paucity of information about ethnic- and gender-specific CMS effects on brain age. We investigated the different effects of CMS on brain age by gender in Korean and British cognitively unimpaired (CU) populations. We also determined whether the gender-specific difference in the effects of CMS on brain age changes depending on ethnicity. Methods: These analyses used de-identified, cross-sectional data on CU populations from Korea and United Kingdom (UK) that underwent brain MRI. After propensity score matching to balance the age and gender between the Korean and UK populations, 5759 Korean individuals (3042 males and 2717 females) and 9903 individuals from the UK (4736 males and 5167 females) were included in this study. Brain age index (BAI), calculated by the difference between the predicted brain age by the algorithm and the chronological age, was considered as main outcome and presence of CMS, including type 2 diabetes mellitus (T2DM), hypertension, obesity, and underweight was considered as a predictor. Gender (males and females) and ethnicity (Korean and UK) were considered as effect modifiers. Results: The presence of T2DM and hypertension was associated with a higher BAI regardless of gender and ethnicity (p < 0.001), except for hypertension in Korean males (p = 0.309). Among Koreans, there were interaction effects of gender and the presence of T2DM (p for T2DM*gender = 0.035) and hypertension (p for hypertension*gender = 0.046) on BAI in Koreans, suggesting that T2DM and hypertension are each associated with a higher BAI in females than in males. In contrast, among individuals from the UK, there were no differences in the effects of T2DM (p for T2DM*gender = 0.098) and hypertension (p for hypertension*gender = 0.203) on BAI between males and females. Conclusions: Our results highlight gender and ethnic differences as important factors in mediating the effects of CMS on brain age. Furthermore, these results suggest that ethnic- and gender-specific prevention strategies may be needed to protect against accelerated brain aging. [ABSTRACT FROM AUTHOR]

Background: Accessible and cost-effective diagnostic tools are urgently needed to accurately quantify blood biomarkers to support early diagnosis of Alzheimer's disease (AD). In this study, we investigated the ability of plasma amyloid-beta (Aβ)42/Aβ40 ratio measured by an antibody-free mass-spectrometric (MS) method, ABtest-MS, to detect early pathological changes of AD. Methods: This cohort study included data from the baseline and 2-year follow-up visits from the Fundació ACE Healthy Brain Initiative (FACEHBI) study. Plasma Aβ42/Aβ40 was measured with ABtest-MS and compared to 18F-Florbetaben PET as the reference standard (cutoff for early amyloid deposition of 13.5 centiloids). Cross-validation was performed in an independent DPUK-Korean cohort. Additionally, associations of plasma Aβ42/Aβ40 with episodic memory performance and brain atrophy were assessed. Results: The FACEHBI cohort at baseline included 200 healthy individuals with subjective cognitive decline (SCD), of which 36 (18%) were Aβ-PET positive. Plasma Aβ42/Aβ40 levels were significantly lower in Aβ-PET positive individuals (median [interquartile range, IQR], 0.215 [0.203–0.236]) versus Aβ-PET negative subjects (median [IQR], 0.261 [0.244–0.279]) (P <.001). Plasma Aβ42/Aβ40 was significantly correlated with Aβ-PET levels (rho = −0.390; P <.001) and identified Aβ-PET status with an area under the receiver operating characteristic curve (AUC) of 0.87 (95% confidence interval [CI], 0.80–0.93). A cutoff for the Aβ42/Aβ40 ratio of 0.241 (maximum Youden index) yielded a sensitivity of 86.1% and a specificity of 80.5%. These findings were cross-validated in an independent DPUK-Korean cohort (AUC 0.86 [95% CI 0.77–0.95]). Lower plasma Aβ42/Aβ40 ratio was associated with worse episodic memory performance and increased brain atrophy. Plasma Aβ42/Aβ40 at baseline predicted clinical conversion to mild cognitive impairment and longitudinal changes in amyloid deposition and brain atrophy at 2-year follow-up. Conclusions: This study suggests that plasma Aβ42/Aβ40, as determined by this MS-based assay, has potential value as an accurate and cost-effective tool to identify individuals in the earliest stages of AD, supporting its implementation in clinical trials, preventative strategies and clinical practice. [ABSTRACT FROM AUTHOR]

Background: Age at onset was suggested as one possible risk factor for motor dysfunction in Alzheimer's disease (AD). Objective: We investigated the association of motor symptoms with cognition or neurodegeneration in patients with AD, and whether this association differs by the age at onset. Methods: We included 113 amyloid positive AD patients and divided them into early-onset AD (EOAD) and late-onset AD (LOAD), who underwent the Unified Parkinson's Disease Rating Scale (UPDRS)-Part III (=UPDRS) scoring, Mini-Mental State Examination (MMSE)/Clinical Deterioration Rating Sum-of-Boxes (CDR-SOB), and magnetic resonance image (MRI). Multiple linear regression was used to evaluate the association of UPDRS and MMSE/CDR-SOB or MRI neurodegeneration measures, and whether the association differs according to the group. Results: The prevalence of motor symptoms and their severity did not differ between the groups. Lower MMSE (β= –1.1, p < 0.001) and higher CDR-SOB (β= 2.0, p < 0.001) were significantly associated with higher UPDRS. There was no interaction effect between MMSE/CDR-SOB and AD group on UPDRS. Global or all regional cortical thickness and putaminal volume were negatively associated with UPDRS score, but the interaction effect of neurodegeneration and AD group on UPDRS score was significant only in parietal lobe (p for interaction = 0.035), which showed EOAD to have a more pronounced association between parietal thinning and motor symptoms. Conclusion: Our study suggested that the severity of motor deterioration in AD is related to the severity of cognitive impairment itself rather than age at onset, and motor symptoms might occur through multiple mechanisms including cortical and subcortical atrophy. [ABSTRACT FROM AUTHOR]

Abstract: Previous studies showed that white matter hyperintensities (WMH) are related to cognitive decline in patients with mild cognitive impairment (MCI) or dementia. Moreover, periventricular WMH (periventricular white matter hyperintensities (PWMH)) and deep WMH (deep white matter hyperintensities (DWMH)) may have different effects on cognition. The purpose of this study is to investigate the contributions of PWMH and DWMH to the topography of cortical thinning and to investigate the relationship among WMH, cortical thinning, and cognitive impairments. Participants included 226 patients with Alzheimer''s disease or subcortical vascular dementia, and 135 patients with amnestic MCI or subcortical vascular MCI. Cortical thickness was measured using the surface based method. The topography of cortical thinning related to WMH was distributed in the frontal and perisylvian regions, which was similar to that of PWMH. In contrast, there were only small areas of cortical thinning inversely associated with DWMH, which were distributed in medial frontal and lingual gyrus. PWMH, but not DWMH, were associated with the frontal thinning and executive dysfunction; where both PWMH and frontal thinning were independently associated with executive dysfunction. Our results suggest that PWMH are associated with frontal thinning, which is further associated with frontal executive dysfunction. [Copyright &y& Elsevier]

Background. This study was conducted to comprehensively examine the central auditory processing (CAP) abilities of patients with amnestic mild cognitive impairment (aMCI) as well as to compare the results with cognitively normal elderly controls. Methods. A total of 78 participants were screened through pure-tone audiometry and word recognition score in order to exclude peripheral auditory dysfunction. Forty-five people passed screening tests, and 33 people failed. Finally, 25 aMCI (mean age = 71.52 ± 4.8 ; male : female = 24 : 76) and 20 controls (mean age = 73.45 ± 4.32 ; male : female = 45 : 55) were enrolled in the study. Seven CAP tests (frequency pattern test, duration pattern test, Gap-In-Noise© test, dichotic digits test, low-pass filtered word test, speech perception in noise test, and binaural fusion test) were conducted only after the two groups passed the screening. A linear mixed model was applied to analyze CAP tests except for the binaural fusion test. For the binaural fusion test, the independent t-test was used to compare the means of test score between two groups. Results. The aMCI group had a decrease in the mean score of the frequency pattern test, duration pattern test, Gaps-In-Noise© test, dichotic digits test, and speech perception in noise test compared with the control group. Conclusion. The aMCI group's CAP abilities were significantly lower than those of the control group. Thus, if the cognitive assessment and hearing evaluation are conducted in combination, the sensitivity of the diagnostic process for aMCI will be increased. [ABSTRACT FROM AUTHOR]

Background: The standard Centiloid (CL) method was proposed to harmonize and quantify global 18F-labeled amyloid beta (Aβ) PET ligands using MRI as an anatomical reference. However, there is need for harmonizing and quantifying regional Aβ uptakes between ligands using CT as an anatomical reference. In the present study, we developed and validated a CT-based regional direct comparison of 18F-florbetaben (FBB) and 18F-flutemetamol (FMM) Centiloid (rdcCL). Methods: For development of MRI-based or CT-based rdcCLs, the cohort consisted of 63 subjects (20 young controls (YC) and 18 old controls (OC), and 25 participants with Alzheimer's disease dementia (ADD)). We performed a direct comparison of the FMM-FBB rdcCL method using MRI and CT images to define a common target region and the six regional VOIs of frontal, temporal, parietal, posterior cingulate, occipital, and striatal regions. Global and regional rdcCL scales were compared between MRI-based and CT-based methods. For clinical validation, the cohort consisted of 2245 subjects (627 CN, 933 MCI, and 685 ADD). Results: Both MRI-based and CT-based rdcCL scales showed that FMM and FBB were highly correlated with each other, globally and regionally (R2 = 0.96~0.99). Both FMM and FBB showed that CT-based rdcCL scales were highly correlated with MRI-based rdcCL scales (R2 = 0.97~0.99). Regarding the absolute difference of rdcCLs between FMM and FBB, the CT-based method was not different from the MRI-based method, globally or regionally (p value = 0.07~0.95). In our clinical validation study, the global negative group showed that the regional positive subgroup had worse neuropsychological performance than the regional negative subgroup (p < 0.05). The global positive group also showed that the striatal positive subgroup had worse neuropsychological performance than the striatal negative subgroup (p < 0.05). Conclusions: Our findings suggest that it is feasible to convert regional FMM or FBB rdcSUVR values into rdcCL scales without additional MRI scans. This allows a more easily accessible method for researchers that can be applicable to a variety of different conditions. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is characterized by the presence of β-amyloid (Aβ) and tau, and subcortical vascular cognitive impairment (SVCI) is characterized by cerebral small vessel disease (CSVD). They are the most common causes of cognitive impairment in the elderly population. Concurrent CSVD burden is more commonly observed in AD-type dementia than in other neurodegenerative diseases. Recent developments in Aβ and tau positron emission tomography (PET) have enabled the investigation of the relationship between AD biomarkers and CSVD in vivo. In this review, we focus on the interaction between AD and CSVD markers and the clinical effects of these two markers based on molecular imaging studies. First, we cover the frequency of AD imaging markers, including Aβ and tau, in patients with SVCI. Second, we discuss the relationship between AD and CSVD markers and the potential distinct pathobiology of AD markers in SVCI compared to AD-type dementia. Next, we discuss the clinical effects of AD and CSVD markers in SVCI, and hemorrhagic markers in cerebral amyloid angiopathy. Finally, this review provides both the current challenges and future perspectives for SVCI. [ABSTRACT FROM AUTHOR]

Synergistic effects of amyloid deposition and cerebral small vessel disease (CSVD) on the systematic disruption of large-scale brain anatomical organization are not well known. We investigated the brain structural covariance network (SCN) in 245 cognitively impaired older adults with the information of amyloid deposition and CSVD represented by white matter hyperintensities (WMH). We stratified the participants into 4 groups based on amyloid burden (A+/A -) and WMH severity (W+/W-). Using source-based morphometry analysis, we selected 13 independent components (ICs) in functional brain networks. SCNs between ICs were defined using Pearson correlations between individual weights; SCNs of the A+W+ group were compared with those of other groups using Fisher's r-to-z transformation. Our results revealed that SCN characteristics related to amyloid burden with CSVD could be represented by decreased intra- and increased cortico-subcortical inter-network connectivity in the salience (SN) and default mode networks (DMN), decreased cortico-subcortical internetwork connectivity in the central executive network (CEN), and altered internetwork connectivity among DMN-SN-CEN. Amyloid deposition and CSVD maybe associated with altered connectivity in structural networks in the brain and should be considered when assessing network disruption. [ABSTRACT FROM AUTHOR]

Cortical atrophy is measured clinically according to established visual rating scales based on magnetic resonance imaging (MRI). Although brain MRI is the primary imaging marker for neurodegeneration, computed tomography (CT) is also widely used for the early detection and diagnosis of dementia. However, they are seldom investigated. Therefore, we developed a machine learning algorithm for the automatic estimation of cortical atrophy on brain CT. Brain CT images (259 Alzheimer's dementia and 55 cognitively normal subjects) were visually rated by three neurologists and used for training. We constructed an algorithm by combining the convolutional neural network and regularized logistic regression (RLR). Model performance was then compared with that of neurologists, and feature importance was measured. RLR provided fast and reliable automatic estimations of frontal atrophy (75.2% accuracy, 93.6% sensitivity, 67.2% specificity, and 0.87 area under the curve [AUC]), posterior atrophy (79.6% accuracy, 87.2% sensitivity, 75.9% specificity, and 0.88 AUC), right medial temporal atrophy (81.2% accuracy, 84.7% sensitivity, 79.6% specificity, and 0.88 AUC), and left medial temporal atrophy (77.7% accuracy, 91.1% sensitivity, 72.3% specificity, and 0.90 AUC). We concluded that RLR-based automatic estimation of brain CT provided a comprehensive rating of atrophy that can potentially support physicians in real clinical settings. [ABSTRACT FROM AUTHOR]