Authors: Jeon, Hyeong-Min | Lee, Ki-Kwang | Lee, Jun-Young | Shin, Ju-Hwan | Eom, Gwang-Moon
Article Type: Research Article
Abstract: BACKGROUND: Joint loads in different walking strategies during stair descent have been investigated in terms of the joint moment in association with the risk of osteoarthritis. However, the absorption mechanisms of the potential energy loss are not known. OBJECTIVE: This study aims to compare the mechanical energy absorptions in lower limb joints in different initial foot contact strategies. METHODS: Nineteen young subjects walked down on instrumented stairs with two different strategies, i.e., forefoot and rearfoot strike. Power and energy at lower limb joints during stance phase were compared between strategies. RESULTS: Lower limb joints absorbed 73 ± 11% of the …potential energy released by descending stairs and there was no difference between strategies. Rearfoot strategy absorbed less energy than forefoot strategy at the ankle joint in the 1st phase, which was compensated mainly by more energy absorption at the knee in the 2nd phase and less energy generation at the hip joints in the 3rd phase. CONCLUSION: The results suggest that a leg absorbs most of the potential energy while descending stairs irrespective of the walking strategies and that any reduction of energy absorption at one joint is compensated by other joints. Greater energy absorption at the knee joint compared to the other joints suggests high burden of knee joint muscles and connective tissues during stair-descent, which is even more significant for the rearfoot strike strategy. Show more
Keywords: Energy absorption, mechanism, stair descent, foot strike strategy, osteoarthritis
DOI: 10.3233/THC-218041
Citation: Technology and Health Care, vol. 29, no. S1, pp. 433-440, 2021
Authors: Yoo, Yongjoon | Shin, Seong A. | Park, Soowon | Lee, Ji-Hye | Youn, Jung-Hae | Kim, Yu Kyeong | Lee, Jun-Young
Article Type: Research Article
Abstract: Background: A standardized tool for evaluating semantic knowledge of the Korean population is needed. Objective: The purpose of this study was to develop a neuropsychological test for the evaluation of semantic knowledge in the Korean elderly population. Methods: The Korean version of the Size/Weight Attribute Test (SWAT-K) was developed in reference to the original version. The diagnostic validity of SWAT-K was evaluated with 95 elderly outpatients [67 normal controls; 18 with Alzheimer’s disease (AD); 10 with semantic-variant progressive aphasia (SV-PPA)]. Voxel-based morphometry (VBM) was employed to examine associations between SWAT-K scores and morphological changes of the brain. Results: SWAT-K could …discriminate the three subject groups (normal >AD, p < 0.001; AD >SV-PPA, p = 0.040), whereas Boston Naming Test could not distinguish SV-PPA from AD. ROC curve analysis confirmed high levels of sensitivity (0.90) and specificity (0.93) for SWAT-K. The test’s inter-rater reliability (ICC = 0.827) and test-retest reliability (ICC = 0.666) were assessed as well. VBM found a significant positive correlation (uncorrected p < 0.005, k > 100) between SWAT-K scores and gray matter volume in right inferior frontal cortex (T = 4.08, k = 191) and bilateral temporal cortices (left, T = 4.42, k = 135; right, T = 3.55, k = 253), the areas the most affected in SV-PPA. Conclusions: SWAT-K is a sensitive and reliable test for evaluating semantic knowledge in the Korean elderly population. Strong positive correlations between SWAT-K scores and the brain areas responsible for semantic processing further corroborate the validity of SWAT-K. Show more
Keywords: Aged, aphasia, primary progressive, cognition, frontotemporal dementia, imaging, three-dimensional, language, neuropsychological tests, semantics
DOI: 10.3233/JAD-150492
Citation: Journal of Alzheimer's Disease, vol. 49, no. 2, pp. 377-386, 2016
Authors: Kwak, Seyul | Oh, Dae Jong | Jeon, Yeong-Ju | Oh, Da Young | Park, Su Mi | Kim, Hairin | Lee, Jun-Young
Article Type: Research Article
Abstract: Background: In assessing the levels of clinical impairment in dementia, a summary index of neuropsychological batteries has been widely used in describing the overall functional status. Objective: It remains unexamined how complex patterns of the test performances can be utilized to have specific predictive meaning when the machine learning approach is applied. Methods: In this study, the neuropsychological battery (CERAD-K) and assessment of functioning level (Clinical Dementia Rating scale and Instrumental Activities of Daily Living) were administered to 2,642 older adults with no impairment (n = 285), mild cognitive impairment (n = 1,057), and Alzheimer’s disease (n = 1,300). Predictive accuracy on functional …impairment level with the linear models of the single total score or multiple subtest scores (Model 1, 2) and support vector regression with low or high complexity (Model 3, 4) were compared across different sample sizes. Results: The linear models (Model 1, 2) showed superior performance with relatively smaller sample size, while nonlinear models with low and high complexity (Model 3, 4) showed an improved accuracy with a larger dataset. Unlike linear models, the nonlinear models showed a gradual increase in the predictive accuracy with a larger sample size (n > 500), especially when the model training is allowed to exploit complex patterns of the dataset. Conclusion: Our finding suggests that nonlinear models can predict levels of functional impairment with a sufficient dataset. The summary index of the neuropsychological battery can be augmented for specific purposes, especially in estimating the functional status of dementia. Show more
Keywords: Dementia, functional status, machine learning, neuropsychological tests
DOI: 10.3233/JAD-215244
Citation: Journal of Alzheimer's Disease, vol. 85, no. 3, pp. 1357-1372, 2022
Authors: Choe, Yeong Sim | Kim, Regina E.Y. | Kim, Hye Weon | Kim, JeeYoung | Lee, Hyunji | Lee, Min Kyoung | Lee, Minho | Kim, Keun You | Kim, Se-Hong | Kim, Ji-hoon | Lee, Jun-Young | Kim, Eosu | Kim, Donghyeon | Lim, Hyun Kook
Article Type: Research Article
Abstract: Background: Application of visual scoring scales for regional atrophy in Alzheimer’s disease (AD) in clinical settings is limited by their high time cost and low intra/inter-rater agreement. Objective: To provide automated atrophy scoring using objective volume driven from deep-learning segmentation methods for AD subtype classification using magnetic resonance imaging (MRI). Methods: We enrolled 3,959 participants (1,732 cognitively normal [CN], 1594 with mild cognitive impairment [MCI], and 633 with AD). The occupancy indices for each regional volume were calculated by dividing each volume by the size of the lateral and inferior ventricular volumes. MR images from 355 participants (119 CN, 119 …MCI, and 117 AD) from three different centers were used for validation. Two neuroradiologists performed visual assessments of the medial temporal, posterior, and global cortical atrophy scores in the frontal lobe using T1-weighted MR images. Images were also analyzed using the deep learning-based segmentation software, Neurophet AQUA. Cutoff values for the three scores were determined using the data distribution according to age. The scoring results were compared for consistency and reliability. Results: Four volumetric-driven scoring results showed a high correlation with the visual scoring results for AD, MCI, and CN. The overall agreement with human raters was weak-to-moderate for atrophy scoring in CN participants, and good-to-almost perfect in AD and MCI participants. AD subtyping by automated scores also showed usefulness as a research tool. Conclusions: Determining AD subtypes using automated atrophy scoring for late-MCI and AD could be useful in clinical settings or multicenter studies with large datasets. Show more
Keywords: Alzheimer’s disease, atrophy, cognitive dysfunction, magnetic resonance imaging, visual scoring
DOI: 10.3233/ADR-230105
Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 863-876, 2024
Authors: Lee, Seung Hoon | Byun, Min Soo | Lee, Jun Ho | Yi, Dahyun | Sohn, Bo Kyung | Lee, Jun-Young | Kim, Yu Kyeong | Shin, Seong A. | Sohn, Chul-Ho | Lee, Dong Young | for the KBASE ResearchGroup
Article Type: Research Article
Abstract: Background: Although recent studies indicate that the relationship between body mass index (BMI) and Alzheimer’s disease (AD) may differ by both sex and age of BMI measurement, little information is available on sex- or age-specific associations between BMI and AD neuropathologies. Objective: To examined whether sex-specific BMIs measured at different life-stages (in early adulthood, midlife, and late life) were associated with cerebral amyloid-β (Aβ) deposition and AD-signature region cortical thickness (AD-CT) in cognitively normal (CN) older adults. Methods: A total of 212 CN subjects aged 60–90 years (females 108, males 104), who participated in the Korean Brain Aging Study for …Early Diagnosis and Prediction of Alzheimer’s Disease (KBASE), an ongoing prospective cohort study, were included. All participants underwent comprehensive clinical and neuropsychological assessments, [11 C] Pittsburgh Compound B positron emission tomography, and brain magnetic resonance imaging. BMIs at different life stages were calculated. Multiple regression analyses were performed separately for either sex. Results: In males, lower early adulthood or midlife BMI was associated with greater cerebral Aβ deposition, but late life BMI was not. Lower midlife BMI was associated with reduced AD-CT, but the BMI in early adulthood and late life was not. In females, no significant association was observed between any lifetime BMI and Aβ deposition or AD-CT. Conclusion: Our results support a male-specific association between BMI prior to late life, and in vivo AD pathologies. Avoiding underweight status early in life may be important to prevent AD dementia in males, but not females. Show more
Keywords: Alzheimer’s disease, cerebral amyloid, lifetime body mass index, neurodegeneration, sex
DOI: 10.3233/JAD-191216
Citation: Journal of Alzheimer's Disease, vol. 75, no. 3, pp. 767-777, 2020
Authors: Byeon, Gihwan | Byun, Min Soo | Yi, Dahyun | Lee, Jun Ho | Jeon, So Yeon | Ko, Kang | Jung, Gijung | Lee, Jun-Young | Kim, Yu Kyeong | Lee, Yun-Sang | Kang, Koung Mi | Sohn, Chul-Ho | Lee, Dong Young | for the KBASE research group
Article Type: Research Article
Abstract: Background: Both elevated blood homocysteine and diabetes mellitus (DM) are related to cognitive impairments or dementia. A previous study also demonstrated that the association between homocysteine and cognitive decline was much stronger in individuals with DM than in those without DM. Objective: This study aimed to examine the interactive effect of blood homocysteine and DM on brain pathological changes including brain atrophy, amyloid-β and tau deposition, and small vessel disease (SVD) related to cognitive impairments. Methods: A total of 430 non-demented older adults underwent comprehensive clinical assessment, measurement of serum homocysteine level, [11 C] Pittsburgh Compound B (PiB) PET, [18 …F] AV-1451 PET, and brain MRI. Results: The interactive effect of homocysteine with the presence of DM on brain atrophy, especially in aging-related brain regions, was significant. Higher homocysteine concentration was associated with more prominent brain atrophy in individuals with DM, but not in those without DM. In contrast, interaction effect of homocysteine and DM was found neither on Alzheimer’s disease (AD) pathologies, including amyloid-β and tau deposition, nor white matter hyperintensity volume as a measure of SVD. Conclusion: The present findings suggest that high blood homocysteine level and DM synergistically aggravate brain damage independently of AD and cerebrovascular disease. With regard to preventing dementia or cognitive decline in older adults, these results support the importance of strictly controlling blood glucose in individuals with hyperhomocysteinemia and lowering blood homocysteine level in those with DM. Show more
Keywords: Brain atrophy, diabetes mellitus, homocysteine, magnetic resonance imaging, positron emission tomography
DOI: 10.3233/JAD-210036
Citation: Journal of Alzheimer's Disease, vol. 81, no. 1, pp. 287-295, 2021
Authors: Sohn, Bo Kyung | Byun, Min Soo | Yi, Dahyun | Jeon, So Yeon | Lee, Jun Ho | Choe, Young Min | Lee, Dong Woo | Lee, Jun-Young | Kim, Yu Kyeong | Sohn, Chul-Ho | Lee, Dong Young | for the KBASE Research Group
Article Type: Research Article
Abstract: Background: Physical activities (PA) have been suggested to reduce the risk of Alzheimer‘s disease (AD) dementia. However, information on the neuropathological links underlying the relationship is limited. Objective: We investigated the role of midlife and late-life PA with in vivo AD neuropathologies in old adults without dementia. Methods: This study included participants from the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer’s disease (KBASE). The participants underwent comprehensive clinical and neuropsychological assessment, [11 C] Pittsburgh Compound B positron emission tomography (PET), [18 F] fluorodeoxyglucose PET, and magnetic resonance imaging. Using the multi-modal brain imaging data, in vivo …AD pathologies including global amyloid deposition, AD-signature region cerebral glucose metabolism (AD-CM), and AD-signature region cortical thickness (AD-CT) were quantified. Both midlife and late-life PA of participants were measured using the Lifetime Total Physical Activity Questionnaire. Results: This study was performed on 260 participants without dementia (195 with normal cognitive function and 65 with mild cognitive impairment). PA of neither midlife nor late-life showed direct correspondence with any neuroimaging biomarker. However, late-life PA moderated the relationship of brain amyloid-β (Aβ) deposition with AD-CM and AD-CT. Aβ positivity had a significant negative effect on both AD-CM and AD-CT in individuals with lower late-life PA, but those with higher late-life PA did not show such results. Midlife PA did not have such a moderation effect. Conclusion: The findings suggest that physically active lifestyle in late-life, rather than that in midlife, may delay AD-associated cognitive decline by decreasing Aβ-induced neurodegenerative changes in old adults. Show more
Keywords: Amyloid, cortical thickness, neurodegeneration, physical activity
DOI: 10.3233/JAD-215258
Citation: Journal of Alzheimer's Disease, vol. 86, no. 1, pp. 441-450, 2022
Authors: Moon, Seok Woo | Byun, Min Soo | Yi, Dahyun | Kim, Min Jung | Jung, Joon Hyung | Kong, Nayeong | Jung, Gijung | Ahn, Hyejin | Lee, Jun-Young | Kang, Koung Mi | Sohn, Chul-Ho | Kim, Yu Kyeong | Lee, Dong Young
Article Type: Research Article
Abstract: Background: Ankle-brachial index (ABI), an indicator of atherosclerosis or arterial stiffness, has been associated with Alzheimer’s disease (AD) dementia and related cognitive impairment. Nevertheless, only limited information is available regarding its contribution to brain alterations leading to cognitive decline in late-life. Objective: We aimed to investigate the relationship of ABI with in vivo AD pathologies and cerebrovascular injury in cognitively impaired older adults. Methods: Total 127 cognitively impaired (70 mild cognitive impairment and 57 AD dementia) individuals, who participated in an ongoing prospective cohort study, were included. All participants underwent comprehensive clinical and neuropsychological assessment, ABI measurement, apolipoprotein E (APOE …) ɛ4 genotyping, and multi-modal brain imaging including [11 C] Pittsburgh Compound B (PiB)-positron emission tomography (PET) and [18 F] fludeoxyglucose (FDG)-PET, and MRI. Results: General linear model analysis showed significant relationship between ABI strata (low ABI: <1.00, normal ABI: 1.00–1.29, and high ABI: ≥1.30) and AD-signature region cerebral glucose metabolism (AD-CM), even after controlling age, sex, clinical dementia rating–sum of box, and APOE ɛ4 positivity (p = 0.029). Post hoc comparison revealed that low ABI had significantly lower AD-CM than middle and high ABI, while no difference of AD-CM was found between middle and high ABI. There was no significant difference of global Aβ deposition, AD-signature region cortical thickness, and white matter hyperintensity volume between the three ABI strata. Conclusion: Our findings suggest that lower ABI, likely related to atherosclerosis, may contribute to the aggravation of AD-related regional neurodegeneration in cognitively impaired older adults. Show more
Keywords: Alzheimer’s disease, ankle-brachial index, cerebral Aβ deposition, mild cognitive impairment, neurodegeneration
DOI: 10.3233/JAD-220911
Citation: Journal of Alzheimer's Disease, vol. 93, no. 1, pp. 87-95, 2023
Authors: Yun, Yejin | Lee, Sang-Yeon | Choi, Won Hoon | Park, Jong-Chan | Lee, Dong Han | Kim, Yun Kyung | Lee, Jung Hoon | Lee, Jun-Young | Lee, Min Jae | Kim, Young Ho
Article Type: Research Article
Abstract: Background: Although the existence of proteasomes in human blood, termed circulating proteasomes (c-proteasomes), has been reported previously, their origin and pathophysiological functions remain largely unknown. Objective: Given that c-proteasome activity was significantly reduced in Alzheimer’s disease model mice and relatively high frequency of mild cognitive impairment (MCI) is accompanied by chronic tinnitus in aged patients, we examined whether c-proteasome activity in human plasma was associated with cognitive function in patients with chronic tinnitus. Methods: c-Proteasome activity in the plasma of tinnitus patients (N = 55) was measured with fluorogenic reporter substrate, suc-LLVY-AMC. To assess MCI, the Montreal Cognitive Assessment was conducted with …a cut-off score of 22/23. All patients underwent audiological and psychoacoustic analyses. Levels of c-proteasomes, Aβ42 , and Aβ40 were measured using ELISA, and their association with c-proteasome activity was evaluated. Results: The activity of circulating proteasomes was significantly lower in patients with chronic tinnitus and MCI (p = 0.042), whereas activities of other plasma enzymes showed little correlation. In addition, c-proteasome activity was negatively associated with the level of plasma Aβ and was directly dependent on its own concentration in the plasma of patients with chronic tinnitus. Conclusion: Our current work provides a new perspective for understanding the potential relationship between circulating proteasomes in the plasma and cognitive dysfunction, suggesting a novel, non-invasive biomarker in the context of MCI diagnosis. Show more
Keywords: Amyloid-β, biomarker, mild cognitive impairment, plasma, proteasome, tinnitus
DOI: 10.3233/JAD-200728
Citation: Journal of Alzheimer's Disease, vol. 78, no. 1, pp. 195-205, 2020
Authors: Lee, Jun Ho | Byun, Min Soo | Yi, Dahyun | Ko, Kang | Jeon, So Yeon | Sohn, Bo Kyung | Lee, Jun-Young | Lee, Younghwa | Joung, Haejung | Lee, Dong Young | for the KBASE Research Group
Article Type: Research Article
Abstract: Background: Previous studies indicated an association between Alzheimer’s disease (AD) dementia and air particulate matter (PM) with aerodynamic diameter <10μ m (PM10), as well as smaller PM. Limited information, however, is available for the neuropathological links underlying such association. Objective: This study aimed to investigate the relationship between long-term PM10 exposure and in vivo pathologies of AD using multimodal neuroimaging. Methods: The study population consisted of 309 older adults without dementia (191 cognitively normal and 118 mild cognitive impairment individuals), who lived in Republic of Korea. Participants underwent comprehensive clinical assessments, 11 C-Pittsburg compound B (PiB) positron emission tomography (PET), …and magnetic resonance imaging scans. A subset of 78 participants also underwent 18 F-AV-1451 tau PET evaluation. The mean concentration of PM with aerodynamic diameter <10μ m over the past 5 years (PM10mean ) collected from air pollution surveillance stations were matched to each participant’s residence. Results: In this non-demented study population, of which 62% were cognitively normal and 38% were in mild cognitive impairment state, exposure to the highest tertile of PM10mean was associated with increased risk of amyloid-β (Aβ) positivity (odds ratio 2.19, 95% confidence interval 1.13 to 4.26) even after controlling all potential confounders. In contrast, there was no significant associations between PM10mean exposure and tau accumulation. AD signature cortical thickness and white matter hyperintensity volume were also not associated with PM10mean exposure. Conclusion: The findings suggest that long-term exposure to PM10 may contribute to pathological Aβ deposition. Show more
Keywords: Amyloid-β, cognitively normal, mild cognitive impairment, neurodegeneration, PM10, tau
DOI: 10.3233/JAD-200694
Citation: Journal of Alzheimer's Disease, vol. 78, no. 2, pp. 745-756, 2020