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The Korean Dementia Association (KDA) has been organizing biennial international academic conferences since 2019, with the International Conference of the KDA (IC-KDA) 2023 held in Busan under the theme ‘Beyond Boundaries: Advancing Global Dementia Solutions.’ The conference comprised 6 scientific sessions, 3 plenary lectures, and 4luncheon symposiums, drawing 804 participants from 35 countries. Notably, a Korea– Taiwan Joint Symposium addressed insights into Alzheimer’s disease (AD). Plenary lectures by renowned scholars explored topics such as microbiome-related AD pathogenesis, social cognition in neurodegenerative diseases, and genetic frontotemporal dementia (FTD). On the first day, specific presentations covered subjects like the gut–brain axis and neuroinflammation in dementia, blood-based biomarkers in AD, and updates in AD therapeutics. The second day’s presentations addressed recent issues in clinical neuropsychology, FTD cohort studies, and the pathogenesis of non-AD dementia. The Academic Committee of the KDA compiles lecture summaries to provide comprehensive understanding of the advanced dementia knowledge presented at IC-KDA 2023.
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Background@#and Purpose: Dementia subtypes, including Alzheimer’s dementia (AD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD), pose diagnostic challenges. This review examines the effectiveness of 18 F-Fluorodeoxyglucose Positron Emission Tomography ( 18 F-FDG PET) in differentiating these subtypes for precise treatment and management. @*Methods@#A systematic review following Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines was conducted using databases like PubMed and Embase to identify studies on the diagnostic utility of 18 F-FDG PET in dementia. The search included studies up to November 16, 2022, focusing on peer-reviewed journals and applying the goldstandard clinical diagnosis for dementia subtypes. @*Results@#From 12,815 articles, 14 were selected for final analysis. For AD versus FTD, the sensitivity was 0.96 (95% confidence interval [CI], 0.88–0.98) and specificity was 0.84 (95% CI, 0.70–0.92). In the case of AD versus DLB, 18F-FDG PET showed a sensitivity of 0.93 (95% CI 0.88-0.98) and specificity of 0.92 (95% CI, 0.70–0.92). Lastly, when differentiating AD from non-AD dementias, the sensitivity was 0.86 (95% CI, 0.80–0.91) and the specificity was 0.88 (95% CI, 0.80–0.91). The studies mostly used case-control designs with visual and quantitative assessments. @*Conclusions@#18 F-FDG PET exhibits high sensitivity and specificity in differentiating dementia subtypes, particularly AD, FTD, and DLB. This method, while not a standalone diagnostic tool, significantly enhances diagnostic accuracy in uncertain cases, complementing clinical assessments and structural imaging.
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Background@#and Purpose: We investigated the correlation between the deep distribution of white matter hyperintensity (WMH) (dWMH: WMH in deep and corticomedullary areas, with minimal periventricular WMH) and a positive agitated saline contrast echocardiography result. @*Methods@#We retrospectively recruited participants with comprehensive dementia evaluations, an agitated saline study, and brain imaging. The participants were classified into two groups according to WMH-distributions: dWMH and dpWMH (mainly periventricular WMH with or without deep WMH.) We hypothesized that dWMH is more likely associated with embolism, whereas dpWMH is associated with small-vessel diseases. We compared the clinical characteristics, WMH-distributions, and positive rate of agitated saline studies between the two groups. @*Results@#Among 90 participants, 27 and 12 met the dWMH and dpWMH criteria, respectively. The dWMH-group was younger (62.2±7.5 vs. 78.9±7.3, p<0.001) and had a lower prevalence of hypertension (29.6% vs. 75%, p=0.008), diabetes mellitus (3.7% vs.25%, p=0.043), and hyperlipidemia (33.3% vs. 83.3%, p=0.043) than the dpWMH-group. Regarding deep white matter lesions, the number of small lesions (<3 mm) was higher in the dWMH-group(10.9±9.7) than in the dpWMH-group (3.1±6.4) (p=0.008), and WMH was predominantly distributed in the border-zones and corticomedullary areas. Most importantly, the positive agitated saline study rate was higher in the dWMH-group than in the dpWMH-group (81.5% vs. 33.3%, p=0.003). @*Conclusions@#The dWMH-group with younger participants had fewer cardiovascular risk factors, showed more border-zone-distributions, and had a higher agitated saline test positivity rate than the dpWMH-group, indicating that corticomedullary or deep WMHdistribution with minimal periventricular WMH suggests embolic etiologies.
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Purpose@#Neuroinflammation is considered an important pathway associated with several diseases that result in cognitive decline. 18F-THK5351 positron emission tomography (PET) signals might indicate the presence of neuroinflammation, as well as Alzheimer’s disease-type tau aggregates. β-amyloid (Aβ)-negative (Aβ–) amnestic mild cognitive impairment (aMCI) may be associated with non-Alzheimer’s disease pathophysiology. Accordingly, we investigated associations between 18F-THK5351 PET positivity and cognitive decline among Aβ– aMCI patients. @*Materials and Methods@#The present study included 25 amyloid PET negative aMCI patients who underwent a minimum of two follow-up neuropsychological evaluations, including clinical dementia rating-sum of boxes (CDR-SOB). The patients were classified into two groups: 18F-THK5351-positive and -negative groups. The present study used a linear mixed effects model to estimate the effects of 18F-THK5351 PET positivity on cognitive prognosis among Aβ– aMCI patients. @*Results@#Among the 25 Aβ– aMCI patients, 10 (40.0%) were 18F-THK5351 positive. The patients in the 18F-THK5351-positive group were older than those in the 18F-THK5351-negative group (77.4±2.2 years vs. 70.0±5.5 years; p<0.001). There was no difference between the two groups with regard to the proportion of apolipoprotein E ε4 carriers. Interestingly, however, the CDR-SOB scores of the 18F-THK5351-positive group deteriorated at a faster rate than those of the 18F-THK5351-negative group (B=0.003, p=0.033). @*Conclusion@#The results of the present study suggest that increased 18F-THK5351 uptake might be a useful predictor of poor prognosis among Aβ– aMCI patients, which might be associated with increased neuroinflammation (ClinicalTrials.gov NCT02656498).
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Background@#To deliver therapeutics into the brain, it is imperative to overcome the issue of the blood-brain-barrier (BBB). One of the ways to circumvent the BBB is to administer therapeutics directly into the brain parenchyma. To enhance the treatment efficacy for chronic neurodegenerative disorders, repeated administration to the target location is required. However, this increases the number of operations that must be performed. In this study, we developed the IntraBrain Injector (IBI), a new implantable device to repeatedly deliver therapeutics into the brain parenchyma. @*Methods@#We designed and fabricated IBI with medical grade materials, and evaluated the efficacy and safety of IBI in 9 beagles. The trajectory of IBI to the hippocampus was simulated prior to surgery and the device was implanted using 3D-printed adaptor and surgical guides. Ferumoxytol-labeled mesenchymal stem cells (MSCs) were injected into the hippocampus via IBI, and magnetic resonance images were taken before and after the administration to analyze the accuracy of repeated injection. @*Results@#We compared the planned vs. insertion trajectory of IBI to the hippocampus.With a similarity of 0.990 ± 0.001 (mean ± standard deviation), precise targeting of IBI was confirmed by comparing planned vs. insertion trajectories of IBI. Multiple administrations of ferumoxytol-labeled MSCs into the hippocampus using IBI were both feasible and successful (success rate of 76.7%). Safety of initial IBI implantation, repeated administration of therapeutics, and long-term implantation have all been evaluated in this study. @*Conclusion@#Precise and repeated delivery of therapeutics into the brain parenchyma can be done without performing additional surgeries via IBI implantation.
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Purpose@#This study was performed To investigate the use of hydrophilic guidewires for facilitating catheter advancement during varicose vein treatment using radiofrequency ablation (RFA) or cyanoacrylate closure (CAC). @*Methods@#From March 2016 to April 2019, 463 limbs of 285 with incompetent great saphenous veins were subjected to RFA (321 limbs of 197 patients) or CAC (142 limbs of 88 patients). Procedure records were reviewed for the use of a hydrophilic guidewire, reason for the guidewire usage, and diameter of the guidewire. @*Results@#A hydrophilic guidewire was used to facilitate catheter advancement to treat 92 of 463 limbs (19.9%). For RFA, a guidewire was used to treat 53 of 321 limbs (16.5%). Among them, 15 limbs (28.3%) had vasospasm, and 38 limbs (71.7%) had venous tortuosity. For CAC, guidewire was used for 39 of 142 limbs (27.5%). Among them, 10 limbs (25.6%) had vasospasm, 23 limbs (59.0%) had venous tortuosity, and 6 limbs (15.4%) had repeated engagement of a J-tip guidewire into the varicose tributaries. In CAC, the frequency of hydrophilic guidewire usage was higher than that in RFA (P = 0.006). All varicose vein treatment sessions were technically successful. @*Conclusion@#Hydrophilic guidewire usage could facilitate catheter advancement when hindered by vasospasm, tortuosity of the saphenous vein, or repeated engagement into the varicose tributaries.
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PURPOSE: Pim kinases are highly conserved serine/threonine kinases, and different expression patterns of each isoform (Pim-1, Pim-2, and Pim-3) have been observed in various types of human cancers, including gastric cancer. AZD1208 is a potent and selective inhibitor that affects all three isoforms of Pim. We investigated the effects of AZD1208 as a single agent and in combination with an Akt inhibitor in gastric cancer cells. MATERIALS AND METHODS: The antitumor activity of AZD1208 with/without an Akt inhibitor was evaluated in a large panel of gastric cancer cell lines through growth inhibition assays. The underlying mechanism was also examined by western blotting, immunofluorescence assay, and cell cycle analysis. RESULTS: AZD1208 treatment decreased gastric cancer cell proliferation rates and induced autophagy only in long-term culture systems. Light chain 3B (LC3B), a marker of autophagy, was increased in sensitive cells in a dose-dependent manner with AZD1208 treatment, which suggested that the growth inhibition effect of AZD1208 was achieved through autophagy, not apoptosis. Moreover, we found that cells damaged by Pim inhibition were repaired by activation of the DNA damage repair pathway, which promoted cell survival and led the cells to become resistant to AZD1208. We also confirmed that the combination of an Akt inhibitor with AZD1208 produced a highly synergistic effect in gastric cancer cell lines. CONCLUSION: Treatment with AZD1208 alone induced considerable cell death through autophagy in gastric cancer cells. Moreover, the combination of AZD1208 with an Akt inhibitor showed synergistic antitumor effects through regulation of the DNA damage repair pathway.
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Humans , Apoptosis , Autophagy , Blotting, Western , Cell Cycle , Cell Death , Cell Line , Cell Proliferation , Cell Survival , DNA Damage , Fluorescent Antibody Technique , Phosphotransferases , Protein Isoforms , Stomach NeoplasmsABSTRACT
BACKGROUND AND PURPOSE: In Alzheimer's continuum (a comprehensive of preclinical Alzheimer's disease [AD], mild cognitive impairment [MCI] due to AD, and AD dementia), cognitive dysfunctions are often related to cortical atrophy in specific brain regions. The purpose of this study was to investigate the association between anatomical pattern of cortical atrophy and specific neuropsychological deficits. METHODS: A total of 249 participants with Alzheimer's continuum (125 AD dementia, 103 MCI due to AD, and 21 preclinical AD) who were confirmed to be positive for amyloid deposits were collected from the memory disorder clinic in the department of neurology at Samsung Medical Center in Korea between September 2013 and March 2018. To analyze neuropsychological test-specific neural correlates representing the relationship between cortical atrophy measured by cortical thickness and performance in specific neuropsychological tests, a linear regression analysis was performed. Two neural correlates acquired by 2 different standardized scores in neuropsychological tests were also compared. RESULTS: Cortical atrophy in several specific brain regions was associated with most neuropsychological deficits, including digit span backward, naming, drawing-copying, verbal and visual recall, semantic fluency, phonemic fluency, and response inhibition. There were a few differences between 2 neural correlates obtained by different z-scores. CONCLUSIONS: The poor performance of most neuropsychological tests is closely related to cortical thinning in specific brain areas in Alzheimer's continuum. Therefore, the brain atrophy pattern in patients with Alzheimer's continuum can be predict by an accurate analysis of neuropsychological tests in clinical practice.
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Humans , Alzheimer Disease , Atrophy , Brain , Cognition , Dementia , Korea , Linear Models , Memory Disorders , Cognitive Dysfunction , Neuroanatomy , Neurology , Neuropsychological Tests , Plaque, Amyloid , SemanticsABSTRACT
BACKGROUND: The food and food service influence the quality of life and the general health condition of older persons living in long-term care (LTC) facilities. Purchasing good food materials is a ground of good food service. In Korea, the residents in LTC facilities should pay for the cost of food materials and ingredients out of their pocket because it is not covered by LTC insurance. This study explored what factors affect the cost of food materials paid by LTC facility residents and which factor affects most. METHODS: We used data from the study on out-of-pocket payment on national LTC insurance, which surveyed 1,552 family caregivers of older residents in LTC facilities. We applied conditional multi-level model, of which the first level represents the characteristics of care receivers and caregivers and its second level reflects those of LTC facilities. RESULTS: We found that the facility residents with college-graduated family caregivers paid 11,545 Korean won more than those with less than elementary-graduated ones. However, the income level of family caregivers did not significantly affect the amount of the food material cost of the residents. The residents in privately owned, large, metropolitan-located facilities were likely to pay more than those in other types of facilities. The amount of the food material cost of the residents was mainly decided by the facility level factors rather than the characteristics of care recipients and their family caregivers (intra-class correlation=82%). CONCLUSION: These findings suggest that it might be effective to design a policy targeting facilities rather than residents in order to manage the cost of food materials of residents in LTC facilities. Setting a standard price for food materials in LTC facilities, like Japan, could be suggested as a feasible policy option. It needs to inform the choice of LTC users by providing comparable food material cost information. The staffing requirement of nutritionist also needs to be reviewed.
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Humans , Caregivers , Food Services , Health Expenditures , Insurance , Insurance, Long-Term Care , Japan , Korea , Long-Term Care , Nutritionists , Quality of LifeABSTRACT
PURPOSE@#To compare the MRI findings of anterior talofibular ligament (ATFL) and calcaneofibular ligament (CFL) injuries in chronic lateral ankle instability (CLAI) between surgical treatment groups.@*MATERIALS AND METHODS@#Fifty-two patients with CLAI were divided into the modified Broström procedure (MBP) (n = 31) and lateral ankle ligament reconstruction (LAR) (n = 21) groups. T2-weighted MRI findings between the groups were compared for caliber change, slope, signal intensity, and thickness measurements of the ligaments. Additionally, the talar tilt angles were measured on stress radiographs.@*RESULTS@#The injured ATFL (p = 0.002 vs. p = 0.001) and CFL (p = 0.008 vs. p = 0.039) were more commonly scarce or thin and had decreased slopes in the LAR group. The mean thickness of ATFL (P = 0.002) and CFL (p = 0.002) was 1.1 ± 0.9 mm and 1.3 ± 0.8 mm, respectively, in the LAR group and 2.2 ± 1.3 mm and 2.1 ± 0.9 mm, respectively, in the MBP group. The mean talar tilt angle was greater in the LAR group (13.4 ± 3.9°) than in the MBP group (9.5 ± 3.8°) (p = 0.001).@*CONCLUSION@#A qualitative analysis of the ligaments on MRI is valuable in selecting the surgical method.