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Reevaluating the composition of the double metal cyanide catalyst (DMC) as a salt of (NC)6Co3- anions with 1:1 Zn2+/(X)Zn+ cations (X = Cl, RO, AcO), we prepared a series of well-defined DMCs, [ClZn+][Zn2+][(NC)6Co3-][ROH], [(RO)Zn+][Zn2+][(NC)6Co3-], [(AcO)Zn+][Zn2+][(NC)6Co3-], [(RO)Zn+]p[ClZn+](1-p)[Zn2+][(NC)6Co3-], [(AcO)Zn+]p[(tBuO)Zn+]q[Zn2+][(NC)6Co3-], and [(AcO)Zn+]p[(tBuO)Zn+]q[ClZn+]r[Zn2+][(NC)6Co3-]. The structure of [(MeOC3H6O)Zn+][Zn2+][(NC)6Co3-] was precisely determined at the atomic level through Rietveld refinement of the synchrotron X-ray powder diffraction data. By evaluating the catalyst's performance in both propylene oxide (PO) polymerization and PO/CO2 copolymerization, a correlation between structure and performance was established on various aspects including activity, dispersity, unsaturation level, and carbonate fraction in the resulting polyols. Ultimately, our study identified highly efficient catalysts that outperformed the state-of-the-art benchmark DMC not only in PO polymerization [DMC-(OAc/OtBu/Cl)(0.59/0.38/0.15)] but also in PO/CO2 copolymerization [DMC-(OAc/OtBu)(0.95/0.08)].
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Melanogenesis, the intricate process of melanin synthesis, is central to skin pigmentation and photoprotection and is regulated by various signaling pathways and transcription factors. To develop potential skin-whitening agents, we used B16F1 melanoma cells to investigate the inhibitory effects of anhydrous alum on melanogenesis and its underlying molecular mechanisms. Anhydrous alum (KAl(SO4)2) with high purity (>99%), which is generated through the heat-treatment of hydrated alum (KAl(SO4)2·12H2O) at 400 °C, potentiates a significant reduction in melanin content without cytotoxicity. Anhydrous alum downregulates the master regulator of melanogenesis, microphthalmia-associated transcription factor (MITF), which targets key genes involved in melanogenesis, thereby inhibiting α-melanocyte-stimulating hormone (α-MSH)-induced melanogenesis. Phosphorylation of the cAMP response element-binding protein, which acts as a co-activator of MITF gene expression, is attenuated by anhydrous alum, resulting in compromised MITF transcription. Notably, anhydrous alum promoted extracellular signal-regulated kinase phosphorylation, leading to the impaired nuclear localization of MITF. Overall, these results demonstrated the generation and mode of action of anhydrous alum in B16F1 cells, which constitutes a promising option for cosmetic or therapeutic use.
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Melaninas , alfa-MSH , Melaninas/metabolismo , alfa-MSH/metabolismo , Monofenol Monooxigenasa/metabolismo , Factor de Transcripción Asociado a Microftalmía/genética , Factor de Transcripción Asociado a Microftalmía/metabolismo , Línea Celular TumoralRESUMEN
The efficiency of plasma surface modifications depends on the operating conditions. This study investigated the effect of chamber pressure and plasma exposure time on the surface properties of 3Y-TZP with N2/Ar gas. Plate-shaped zirconia specimens were randomly divided into two categories: vacuum plasma and atmospheric plasma. Each group was subdivided into five subgroups according to the treatment time: 1, 5, 10, 15, and 20 min. Following the plasma treatments, we characterized the surface properties, including wettability, chemical composition, crystal structure, surface morphology, and zeta potential. These were analyzed through various techniques, such as contact angle measurement, XPS, XRD, SEM, FIB, CLSM, and electrokinetic measurements. The atmospheric plasma treatments increased zirconia's electron donation (γ-) capacity, while the vacuum plasma treatments decreased γ- parameter with increasing times. The highest concentration of the basic hydroxyl OH(b) groups was identified after a 5 min exposure to atmospheric plasmas. With longer exposure times, the vacuum plasmas induce electrical damage. Both plasma systems increased the zeta potential of 3Y-TZP, showing positive values in a vacuum. In the atmosphere, the zeta potential rapidly increased after 1 min. Atmospheric plasma treatments would be beneficial for the adsorption of oxygen and nitrogen from ambient air and the generation of various active species on the zirconia surface.
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Presión Atmosférica , Circonio , Cerámica/química , Ensayo de Materiales , Propiedades de Superficie , Humectabilidad , Itrio , Circonio/químicaRESUMEN
To evaluate whether an impaired anterior visual pathway (retinal structures with microvasculature) is associated with underlying beta-amyloid (Aß) pathologies in patients with Alzheimer's disease dementia (ADD) and mild cognitive impairment (MCI), we compared retinal structural and vascular factors in each subgroup with positive or negative amyloid biomarkers. Twenty-seven patients with dementia, thirty-five with MCI, and nine with cognitively unimpaired (CU) controls were consecutively recruited. All participants were divided into positive Aß (A+) or negative Aß (A-) pathology based on amyloid positron emission tomography or cerebrospinal fluid Aß. The retinal circumpapillary retinal nerve fiber layer thickness (cpRNFLT), macular ganglion cell/inner plexiform layer thickness (mGC/IPLT), and microcirculation of the macular superficial capillary plexus were measured using optical coherence tomography (OCT) and OCT angiography. One eye of each participant was included in the analysis. Retinal structural and vascular factors significantly decreased in the following order: dementia < MCI < CU controls. The A+ group had significantly lower microcirculation in the para- and peri-foveal temporal regions than did the A-. However, the structural and vascular parameters did not differ between the A+ and A- with dementia. The cpRNFLT was unexpectedly greater in the A+ than in the A- with MCI. mGC/IPLT was lower in the A+ CU than in the A- CU. Our findings suggest that retinal structural changes may occur in the preclinical and early stages of dementia but are not highly specific to AD pathophysiology. In contrast, decreased temporal macula microcirculation may be used as a biomarker for the underlying Aß pathology.
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INTRODUCTION: A one-way valve lesion plays an important role in the formation of Baker's cysts and serves as an important landmark for accessing these cysts during arthroscopic surgery. This study aimed to investigate the incidence of one-way valve lesions and their effect on clinical outcomes in patients who underwent arthroscopic cystectomy for Baker's cysts. MATERIALS AND METHODS: Patients who underwent arthroscopic cystectomy for Baker's cysts between June 2005 and November 2017 were retrospectively reviewed. Patient demographic characteristics, radiologic/arthroscopic findings (presence of one-way valve lesions, concurrent chondral and meniscal lesions, and cyst wall thickness), and clinical outcomes (clinical recurrence rate, Lysholm score, and complications) at the 2-year follow-up were evaluated. Subgroup analysis was performed to compare clinical outcomes between patients with and without one-way valve lesions. RESULTS: Thirty patients (mean age, 57.4 ± 9.4 years) were included in this study. One-way valve lesions were surgically documented in 11 patients (36.7%). Ten patients (33.3%) had chondral lesions with an International Cartilage Repair Society grade ≥ 3, and 23 patients (76.7%) had concurrent chondral and meniscal lesions. At the 2-year follow-up, none of the patients had experienced clinical recurrence; the mean Lysholm score was 76.3 ± 17.5 (48-100). Three patients reported persistent pain, while two reported numbness or paresthesia. Subgroup analysis showed no significant differences in clinical recurrence rates, Lysholm scores, and complication rates between the groups. CONCLUSIONS: The incidence of one-way valve lesions during arthroscopic cystectomy for Baker's cysts was lower than that previously reported. Arthroscopic cystectomy showed good clinical results in patients with and without these lesions.
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Cistectomía , Quiste Poplíteo , Humanos , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Incidencia , Cistectomía/efectos adversos , Quiste Poplíteo/epidemiología , Quiste Poplíteo/cirugía , Quiste Poplíteo/complicaciones , Artroscopía/métodosRESUMEN
PURPOSE: Local steroid injection is an effective treatment modality for carpal tunnel syndrome. This study aimed to investigate the success rate of ultrasonography-guided local steroid injection and determine the prognostic value of the cross-sectional area (CSA) of the median nerve for steroid injection. METHODS: We retrospectively evaluated 40 patients with carpal tunnel syndrome whose median nerve CSA was >15 mm2 (large-CSA group; n = 16) or ≤15 mm2 (small-CSA group; n = 24). The CSA was measured using ultrasonography, and all the patients were treated with ultrasonography-guided corticosteroid injection. Demographic characteristics, symptoms, initial QuickDASH score, Boston Carpal Tunnel Questionnaires, and results of the nerve conduction study were assessed at baseline. Treatment success was defined in this study as the absence of symptom recurrence within the entire follow-up period. RESULTS: The treatment success rate was 45% (n = 18) after an average follow-up of 16 months. Overall, 11 patients (28%) underwent carpal tunnel release on an average of 11 months after steroid injection. The large-CSA group showed a significantly worse grade of electrodiagnostic testing at baseline than did the small-CSA group; however, there was no significant difference in final Boston Carpal Tunnel Questionnaires symptom score (1.7 vs 1.8, respectively) and the rate of continued treatment success at the last follow-up (42% vs 50%, respectively). The proportions of patients who required carpal tunnel decompression were 29% and 25% in the small-CSA and large-CSA groups, respectively. CONCLUSIONS: Local steroid injection for carpal tunnel syndrome has an overall success rate of 45% after a mean follow-up of 16 months. Preinjection CSA was not associated with whether the steroid injection was considered successful. This indicates that increased median nerve CSA does not preclude the possibility of symptomatic relief after a local steroid injection. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.
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Síndrome del Túnel Carpiano , Nervio Mediano , Humanos , Nervio Mediano/diagnóstico por imagen , Nervio Mediano/cirugía , Síndrome del Túnel Carpiano/diagnóstico por imagen , Síndrome del Túnel Carpiano/tratamiento farmacológico , Síndrome del Túnel Carpiano/cirugía , Pronóstico , Estudios Retrospectivos , Ultrasonografía , Esteroides/uso terapéuticoRESUMEN
Importance: Polygenic risk scores (PRSs), which aggregate the genetic effects of single-nucleotide variants identified in genome-wide association studies (GWASs), can help distinguish individuals at a high genetic risk for Alzheimer disease (AD). However, genetic studies have predominantly focused on populations of European ancestry. Objective: To evaluate the transferability of a PRS for AD in the Korean population using summary statistics from a prior GWAS of European populations. Design, Setting, and Participants: This cohort study developed a PRS based on the summary statistics of a large-scale GWAS of a European population (the International Genomics of Alzheimer Project; 21â¯982 AD cases and 41â¯944 controls). This PRS was tested for an association with AD dementia and its related phenotypes in 1634 Korean individuals, who were recruited from 2013 to 2019. The association of a PRS based on a GWAS of a Japanese population (the National Center for Geriatrics and Gerontology; 3962 AD cases and 4074 controls) and a transancestry meta-analysis of European and Japanese GWASs was also evaluated. Data were analyzed from December 2020 to June 2021. Main Outcomes and Measures: Risk of AD dementia, amnestic mild cognitive impairment (aMCI), earlier symptom onset, and amyloid ß deposition (Aß). Results: A total of 1634 Korean patients (969 women [59.3%]), including 716 individuals (43.6%) with AD dementia, 222 (13.6%) with aMCI, and 699 (42.8%) cognitively unimpaired controls, were analyzed in this study. The mean (SD) age of the participants was 71.6 (9.0) years. Higher PRS was associated with a higher risk of AD dementia independent of APOE É4 status in the Korean population (OR, 1.95; 95% CI, 1.40-2.72; P < .001). Furthermore, PRS was associated with aMCI, earlier symptom onset, and Aß deposition independent of APOE É4 status. The PRS based on a transancestry meta-analysis of data sets comprising 2 distinct ancestries showed a slightly improved accuracy. Conclusions and Relevance: In this cohort study, a PRS derived from a European GWAS identified individuals at a high risk for AD dementia in the Korean population. These findings emphasize the transancestry transferability and clinical value of PRSs and suggest the importance of enriching diversity in genetic studies of AD.
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Enfermedad de Alzheimer , Humanos , Femenino , Enfermedad de Alzheimer/diagnóstico , Péptidos beta-Amiloides , Estudio de Asociación del Genoma Completo , Estudios de Cohortes , Factores de Riesgo , Fenotipo , Apolipoproteínas E/genéticaRESUMEN
Residual oxygen in wurtzite-type aluminum nitride (AlN) crystal, which significantly affects phonon transport and crystal growth, is crucial to thermal conductivity and the crystal quality of AlN ceramics. In this study, the effect of residual oxygen on the lattice of AlN was examined for as-synthesized and sintered samples. By controlling reaction time in the carbothermal reduction nitridation (CRN) procedure, AlN powder was successfully synthesized, and the amount of residual oxygen was systematically controlled. The evolution of lattice parameters of AlN with respect to oxygen conc. was carefully investigated via X-ray diffraction analysis. With increasing amounts of residual oxygen in the as-synthesized AlN, lattice expansion in the ab plane was induced without a significant change in the c-axis lattice parameter. The lattice expansion in the ab plane owing to the residual oxygen was also confirmed with high-resolution transmission electron microscopy, in contrast to the invariant lattice parameter of the sintered AlN phase. Micro-strain values from XRD peak broadening confirm that stress, induced by residual oxygen, expands the AlN lattice. In this work, the lattice expansion of AlN with increasing residual oxygen was elucidated via X-ray diffraction and HR-TEM, which is useful to estimate and control the lattice oxygen in AlN ceramics.
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STUDY DESIGN: Retrospective case-control study. PURPOSE: To reduce unnecessary absolute bed rest (ABR), this study sought to determine the optimal aimed length of ABR in older patients getting conservative treatment for osteoporotic vertebral fractures (OVFs). OVERVIEW OF LITERATURE: OVFs are quite common in elderly patients. ABR is a vital part of conservative treatment for OVFs, although the length of ABR may increase patient. No recommendations regarding how long ABR should last. METHODS: This study was conducted in 134 patients with OVFs initially treated conservatively. The patients were split into two groups: 3-day and 7-day ABR. From the time of injury to 1, 4, and 12 weeks after injury, compression rate (CR) and local kyphotic angle (LKA) were assessed and compared between the two groups. Any complications such as pneumonia, deep vein thrombosis, delirium, and urinary tract infection known to be related to ABR were examined based on the electronic medical record. RESULTS: Forty-four patients underwent ABR for 3 days and 90 underwent ABR for 7 days. There was no significant difference in CR and LKA between the two groups at the time of injury versus 1, 4, and 12 weeks after injury. The patients were divided into two groups: those who received a 3-day ABR and those who received a 7-day ABR. CR and LKA were measured and compared between the two groups from the time of damage to 1, 4, and 12 weeks after injury. The ABR-related complication rate was 43.4% in the 7-day ABR group and 22.7% in 3-day ABR group (p=0.02). The duration of hospital stay was significantly shorter in the 3-day ABR group (12.8 days) than in the 7-day group (16 days) (p=0.01). CONCLUSIONS: Considering radiological outcomes, prognosis, complications, patient convenience, and economic impact, a 3-day ABR period is appropriate for the conservative treatment of OVFs.
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Plasma surface treatment can be an attractive strategy for modifying the chemically inert nature of zirconia to improve its clinical performance. This study aimed to clarify the effect of plasma gas compositions on the physicochemical surface modifications of 3 mol% yttria-stabilized zirconia (3Y-TZP). The cold, atmospheric plasma discharges were carried out by using four different plasma gases, which are He/O2, N2/Ar, N2, and Ar from an application distance of 10 mm for 60 s. Static contact angles were measured to define the surface free energy. Changes in elemental composition, surface crystallinity, and surface topography were assessed with X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), confocal laser scanning microscopy (CLSM), and scanning electron microscopy (SEM), respectively. A significant decrease in water contact angle was observed in all plasma groups with the lowest value of 69° in the N2/Ar group. CLSM and SEM investigations exhibited no morphological changes in all plasma groups. XPS revealed that a reduction in the surface C content along with an increase in O content was pronounced in the case of N2/Ar compared to others, which was responsible for high hydrophilicity of the surface. XRD showed that the changes in crystallite size and microstrain due to oxygen atom displacements were observed in the N2/Ar group. The N2/Ar plasma treatment may contribute to enhancing the bioactivity as well as the bonding performance of 3Y-TZP by controlling the plasma-generated nitrogen functionalities.
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Gases em Plasma , Itrio , Cerámica/química , Ensayo de Materiales , Microscopía Electrónica de Rastreo , Propiedades de Superficie , Difracción de Rayos X , Itrio/química , Circonio/químicaRESUMEN
The clinical outcomes of patients with amyloid beta-positive (Aß+) mild cognitive impairment (MCI) are heterogeneous. We therefore developed prediction models for distinguishable cognitive trajectories in Aß+ participants with MCI. We included 238 Aß+ participants with MCI from the Alzheimer's Disease Neuroimaging Initiative to develop a group-based trajectory model and 63 Aß+ participants with MCI from the Samsung Medical Center for external validation. Three distinguishable classes, slow decliners (18.5%), intermediate decliners (42.9%), and fast decliners (38.7%), were identified. Intermediate decliners were associated with older age, higher AV45 standardized uptake value ratios (SUVR) and lower fluorodeoxyglucose (FDG) SUVR than slow decliners. Fast decliners were associated with older age, presence of APOE ε4, higher AV45 SUVR and lower FDG SUVR than slow decliners. Prediction models of cognitive decline showed good discrimination and calibration capabilities in the development and validation data sets. Our analysis yields novel insights into the cognitive trajectories of Aß+ patients with MCI, which will facilitate their effective stratification in Aß-targeted clinical trials.
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Enfermedad de Alzheimer , Amiloidosis , Disfunción Cognitiva , Enfermedad de Alzheimer/diagnóstico por imagen , Péptidos beta-Amiloides , Cognición , Disfunción Cognitiva/diagnóstico por imagen , Fluorodesoxiglucosa F18 , Humanos , Tomografía de Emisión de Positrones/métodosRESUMEN
OBJECTIVE: This study aimed to pilot PAX ("Play, Act & Interact"), an activity-based emotional support intervention for caregivers of child with cancer, which focuses on addressing their psychological distress and post-traumatic stress symptoms (PTSSs). METHOD: Sixteen mothers whose children were child with cancer participated in this 4-week intervention. Their children (n = 16; 14 males; median age at diagnosis = 10.3 years; the median amount of time from diagnosis = 9 months) were at different treatment stages for a range of different diagnoses. Caregivers completed self-report instruments assessing their psychological distress including PTSSs and family functioning before and after the intervention and a brief open-response exit survey. Paired sample t-tests were computed to compare the pre-and post-intervention scores. RESULTS: The Post-traumatic Stress Disorder Checklist scores significantly decreased from pre- (M = 37.00, SD = 14.75) to post-intervention (M = 32.56, SD = 15.52), t(15) = 4.25, p < .001. There was also a significant difference between pre- (M = 33.5, SD = 3.18) and post-intervention (M = 35.7, SD = 3.14) scores on the Family Adherence subscale of the Family Adaptability and Cohesion Evaluation Scales III, t(15) = -2.58, p = .02. CONCLUSIONS: PAX was a promising intervention for supporting caregivers' PTSSs and family adaptability. Future studies investigating the long-term effects and replicating the current study with more participants and a control group are needed.
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Cuidadores/psicología , Neoplasias , Apoyo Social , Estrés Psicológico/terapia , Niño , Femenino , Humanos , Masculino , Madres , Neoplasias/terapia , Encuestas y CuestionariosRESUMEN
Objective: We investigated the mediation effects of subcortical volume change in the relationship of amyloid beta (Aß) and lacune with cognitive function in patients with mild cognitive impairment (MCI). Methods: We prospectively recruited 101 patients with MCI who were followed up with neuropsychological tests, MRI, or Pittsburgh compound B (PiB) PET for 3 years. The mediation effect of subcortical structure on the association of PiB or lacunes with cognitive function was analyzed using mixed effects models. Results: Volume changes in the amygdala and hippocampus partially mediated the effect of PiB changes on memory function (direct effect = -0.168/-0.175, indirect effect = -0.081/-0.077 for amygdala/hippocampus) and completely mediated the effect of PiB changes on clinical dementia rating scale sum of the box (CDR-SOB) (indirect effect = 0.082/0.116 for amygdala/hippocampus). Volume changes in the thalamus completely mediated the effect of lacune on memory, frontal executive functions, and CDR-SOB (indirect effect = -0.037, -0.056, and 0.047, respectively). Conclusions: Our findings provide a better understanding of the distinct role of subcortical structures in the mediation of the relationships of amyloid or vascular changes with a decline in specific cognitive domains.
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Although sandblasting is mainly used to improve bonding between dental zirconia and resin cement, the details on the in-depth damages are limited. The aim of this study was to evaluate phase transformations and subsurface changes after sandblasting in three different dental zirconia (3, 4, and 5 mol% yttria-stabilized zirconia; 3Y-TZP, 4Y-PSZ, and 5Y-PSZ). Zirconia specimens (14.0 × 14.0 × 1.0 mm3) were sandblasted using different alumina particle sizes (25, 50, 90, 110, and 125 µm) under 0.2 MPa for 10 s/cm2. Phase transformations and residual stresses were investigated using X-ray diffraction and the Williamson-Hall method. Subsurface damages were evaluated with cross-sections by a focused ion beam. Stress field during sandblasting was simulated by the finite element method. The subsurface changes after sandblasting were the emergence of a rhombohedral phase, micro/macro cracks, and compressive/tensile stresses depending on the interactions between blasting particles and zirconia substrates. 3Y-TZP blasted with 110-µm particles induced the deepest transformed layer with the largest compressive stress. The cracks propagated parallel to the surface with larger particles, being located up to 4.5 µm under the surface in 4Y- or 5Y-PSZ subgroups. The recommended sandblasting particles were 110 µm for 3Y-TZP and 50 µm for 4Y-PSZ or 5Y-PSZ for compressive stress-induced phase transformations without significant subsurface damages.
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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.
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Enfermedad de Alzheimer/fisiopatología , Disfunción Cognitiva/fisiopatología , Demencia/fisiopatología , Escolaridad , Red Nerviosa/fisiopatología , Anciano , Anciano de 80 o más Años , Algoritmos , Cognición/fisiología , Femenino , Giro del Cíngulo/diagnóstico por imagen , Giro del Cíngulo/fisiopatología , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Memoria/fisiología , Persona de Mediana Edad , Modelos Neurológicos , Pruebas Neuropsicológicas/estadística & datos numéricosRESUMEN
To characterize the course of Alzheimer's disease (AD) over a longer time interval, we aimed to construct a disease course model for the entire span of the disease using two separate cohorts ranging from preclinical AD to AD dementia. We modelled the progression course of 436 patients with AD continuum and investigated the effects of apolipoprotein E ε4 (APOE ε4) and sex on disease progression. To develop a model of progression from preclinical AD to AD dementia, we estimated Alzheimer's Disease Assessment Scale-Cognitive Subscale 13 (ADAS-cog 13) scores. When calculated as the median of ADAS-cog 13 scores for each cohort, the estimated time from preclinical AD to MCI due to AD was 7.8 years and preclinical AD to AD dementia was 15.2 years. ADAS-cog 13 scores deteriorated most rapidly in women APOE ε4 carriers and most slowly in men APOE ε4 non-carriers (p < 0.001). Our results suggest that disease progression modelling from preclinical AD to AD dementia may help clinicians to estimate where patients are in the disease course and provide information on variation in the disease course by sex and APOE ε4 status.
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Enfermedad de Alzheimer/patología , Demencia/patología , Anciano , Enfermedad de Alzheimer/metabolismo , Apolipoproteína E4/metabolismo , Disfunción Cognitiva/metabolismo , Disfunción Cognitiva/patología , Estudios de Cohortes , Demencia/metabolismo , Progresión de la Enfermedad , Femenino , Heterocigoto , Humanos , Masculino , Pruebas NeuropsicológicasRESUMEN
To develop a disease progression model of Alzheimer's disease (AD) that shows cognitive decline from subjective cognitive impairments (SCI) to the end stage of AD dementia (ADD) and to investigate the effect of education level on the whole disease spectrum, we enrolled 565 patients who were followed up more than three times and had a clinical dementia rating sum of boxes (CDR-SB). Three cohorts, SCI (n = 85), amnestic mild cognitive impairment (AMCI, n = 240), and ADD (n = 240), were overlapped in two consecutive cohorts (SCI and AMCI, AMCI and ADD) to construct a model of disease course, and a model with multiple single-cohorts was estimated using a mixed-effect model. To examine the effect of education level on disease progression, the disease progression model was developed with data from lower (≤ 12) and higher (> 12) education groups. Disease progression takes 274.3 months (22.9 years) to advance from 0 to 18 points using the CDR-SB. Based on our predictive equation, it takes 116.5 months to progress from SCI to AMCI and 56.2 months to progress from AMCI to ADD. The rate of CDR-SB progression was different according to education level. The lower-education group showed faster CDR-SB progression from SCI to AMCI compared to the higher-education group, and this trend disappeared from AMCI to ADD. In the present study, we developed a disease progression model of AD spectrum from SCI to the end stage of ADD. Our disease modeling provides us with more understanding of the effect of education on cognitive trajectories.
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Enfermedad de Alzheimer/patología , Escolaridad , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/psicología , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/patología , Disfunción Cognitiva/psicología , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos Biológicos , Pruebas Neuropsicológicas , República de Corea , Factores de TiempoRESUMEN
OBJECTIVE: To investigate the association between APOE genotype and ß-amyloid (Aß) burden, as measured by PET in patients with subcortical vascular cognitive impairment (SVCI) and those with Alzheimer disease-related cognitive impairment (ADCI). METHODS: This was a cross-sectional study of 310 patients with SVCI and 999 with ADCI. To evaluate the effects of APOE genotype or diagnostic group on Aß positivity, we performed multivariate logistic regression analyses. Further distinctive underlying features of latent subgroups were examined by employing a latent class cluster analysis approach. RESULTS: In comparison with ε3 homozygotes, in the ADCI group, ε2 carriers showed a lower frequency of Aß positivity (odds ratio [OR] 0.43, 95% confidence interval [CI] 0.23-0.79), while in the SVCI group, ε2 carriers showed a higher frequency of Aß positivity (OR 2.26, 95% CI 1.02-5.01). In particular, we observed an interaction effect of ε2 carrier status and diagnostic group on Aß positivity (OR 5.12, 95% CI 1.93-13.56), in that relative to ε3 homozygotes, there were more Aß-positive ε2 carriers in the SVCI group than in the ADCI group. We also identified latent subgroups of Aß-positive APOE ε2 carriers with SVCI and Aß-positive APOE ε4 carriers with ADCI. CONCLUSIONS: Our findings suggest that APOE ε2 is distinctly associated with Aß deposition in patients with SVCI and those with ADCI. Our findings further suggest that there is a distinctive subgroup of Aß-positive APOE ε2 carriers with SVCI among patients with cognitive impairment.