Browsing by Author "Yun, Jihwan"

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    Cerebral Amyloid Angiopathy and Downstream Alzheimer Disease Plasma Biomarkers
    (American Medical Association, 2025-05-01) Kang, Sung Hoon; Lee, Eun Hye; Kim, Young Ju; Jang, Hyemin; Shin, Daeun; Zetterberg, Henrik; Blennow, Kaj; Gonzalez-Ortiz, Fernando; Ashton, Nicholas J.; Yun, Jihwan; Kim, Hee Jin; Na, Duk L.; Kim, Jun Pyo; Seo, Sang Won; Radiology and Imaging Sciences, School of Medicine
    Importance: As amyloid-targeted therapies have become commercially available, the monitoring of cerebral amyloid angiopathy (CAA), which is an important risk factor for amyloid-related imaging abnormalities, has received increasing attention. However, comprehensive evidence on the association between Alzheimer disease (AD) plasma biomarkers and various CAA imaging markers is still lacking. Objective: To examine the association of CAA imaging markers with downstream AD plasma biomarkers in relation to amyloid-β (Aβ) uptake on positron emission tomography (PET) and whether their interplay is associated with cognitive changes. Design, setting, and participants: This registry-based cohort study in 25 hospitals across South Korea recruited participants aged 45 years or older who were registered between January 1, 2016, and December 31, 2023. Participants were categorized as having no cognitive impairment, mild cognitive impairment, or dementia of the Alzheimer type. Exposures: Cerebral amyloid angiopathy imaging markers assessed by magnetic resonance imaging, including cerebral microbleeds (CMBs), cortical superficial siderosis, white matter hyperintensities, lacunes, and enlarged perivascular spaces. Main outcomes and measures: Plasma phosphorylated tau-217 (p-tau217) was measured using a commercial assay. Glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) were measured using a single-molecule assay on a single platform. All participants underwent amyloid PET imaging. Associations of CAA and vascular imaging markers with downstream AD plasma biomarkers were investigated using linear regression. Results: A total of 1708 participants were included (mean [SD] age, 71.2 [8.4] years; 1044 female [61.1%]). The mean (SD) follow-up period was 4.3 (3.1) years. Lobar CMB counts and the presence of CAA were associated with downstream AD plasma biomarkers, including p-tau217 (β = 0.12 [95% CI, 0.05-0.18] and 0.29 [95% CI, 0.12-0.47], respectively), GFAP (β = 0.07 [95% CI, 0.03-0.12] and 0.20 [95% CI, 0.09-0.31], respectively), and NfL (β = 0.07 [95% CI, 0.03-0.11] and 0.16 [95% CI, 0.06-0.25], respectively) with and without the mediation of Aβ uptake on PET (indirect effect: lobar CMBs-p-tau217, 59.8% [β = 0.07 (95% CI, 0.03-0.11)]; lobar CMBs-GFAP, 49.3% [β = 0.04 (95% CI, 0.01-0.06)]; lobar CMBs-NfL, 20.9% [β = 0.01 (95% CI, 0.01-0.03)]; CAA-p-tau217, 50.9% [β = 0.15 (95% CI, 0.06-0.24)]; CAA-GFAP, 39.2% [β = 0.08 (95% CI, 0.03-0.13)]; CAA-NfL, 19.2% [β = 0.03 (95% CI, 0.01-0.05)]). Amyloid-β uptake fully mediated the associations between cortical superficial siderosis and downstream AD plasma markers. In contrast, hypertensive arteriosclerotic vascular imaging markers, including lacunes, deep CMBs, and enlarged perivascular spaces in basal ganglia, were associated with only NfL levels (β = 0.07 [95% CI, 0.01-0.13], 0.20 [95% CI, 0.08-0.32], and 0.14 [95% CI, 0.06-0.23], respectively), regardless of Aβ uptake on PET. Finally, there were interactive associations of lobar CMBs in conjunction with p-tau217 levels (β = -0.56 [95% CI, -0.79 to -0.34]) and GFAP levels (β = -0.44 [95% CI, -0.70 to -0.17]) with annual Mini-Mental State Examination changes. Conclusions and relevance: In this cohort study of participants with no cognitive impairment, mild cognitive impairment, or dementia of the Alzheimer type, a novel association was found among CAA imaging markers, downstream AD plasma biomarkers, and cognitive declines in relation to brain Aβ burdens. The findings emphasize the importance of understanding the clinical effects of amyloid-related imaging abnormality-like CAA imaging markers in light of upcoming amyloid-targeted therapies.
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    Effects of risk factors on the development and mortality of early- and late-onset dementia: an 11-year longitudinal nationwide population-based cohort study in South Korea
    (Springer Nature, 2024-04-25) Chun, Min Young; Chae, Wonjeong; Seo, Sang Won; Jang, Hyemin; Yun, Jihwan; Na, Duk L.; Kang, Dongwoo; Lee, Jungkuk; Hammers, Dustin B.; Apostolova, Liana G.; Jang, Sung-In; Kim, Hee Jin; Neurology, School of Medicine
    Background: Early-onset dementia (EOD, onset age < 65) and late-onset dementia (LOD, onset age ≥ 65) exhibit distinct features. Understanding the risk factors for dementia development and mortality in EOD and LOD respectively is crucial for personalized care. While risk factors are known for LOD development and mortality, their impact on EOD remains unclear. We aimed to investigate how hypertension, diabetes mellitus, hyperlipidemia, atrial fibrillation, and osteoporosis influence the development and mortality of EOD and LOD, respectively. Methods: Using the Korean National Health Insurance Service (NHIS) database, we collected 546,709 dementia-free individuals and followed up for 11 years. In the two study groups, the Younger group (< 65 years old) and the Older group (≥ 65 years old), we applied Cox proportional hazard models to assess risk factors for development of EOD and LOD, respectively. Then, we assessed risk factors for mortality among EOD and LOD. Results: Diabetes mellitus and osteoporosis increased the risk of EOD and LOD development. Hypertension increased the risk of EOD, while atrial fibrillation increased the risk of LOD. Conversely, hyperlipidemia exhibited a protective effect against LOD development. Additionally, diabetes mellitus increased mortality in EOD and LOD. Hypertension and atrial fibrillation increased mortality in LOD, while hyperlipidemia decreased mortality in EOD and LOD. Conclusions: Risk factors influencing dementia development and mortality differed in EOD and LOD. Targeted public health interventions addressing age-related risk factors may reduce dementia incidence and mortality.
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    Emerging role of vascular burden in AT(N) classification in individuals with Alzheimer's and concomitant cerebrovascular burdens
    (BMJ, 2023-12-14) Chun, Min Young; Jang, Hyemin; Kim, Soo-Jong; Park, Yu Hyun; Yun, Jihwan; Lockhart, Samuel N.; Weiner, Michael; De Carli, Charles; Moon, Seung Hwan; Choi, Jae Yong; Nam, Kyung Rok; Byun, Byung-Hyun; Lim, Sang-Moo; Kim, Jun Pyo; Choe, Yeong Sim; Kim, Young Ju; Na, Duk L.; Kim, Hee Jin; Seo, Sang Won; Radiology and Imaging Sciences, School of Medicine
    Objectives: Alzheimer's disease (AD) is characterised by amyloid-beta accumulation (A), tau aggregation (T) and neurodegeneration (N). Vascular (V) burden has been found concomitantly with AD pathology and has synergistic effects on cognitive decline with AD biomarkers. We determined whether cognitive trajectories of AT(N) categories differed according to vascular (V) burden. Methods: We prospectively recruited 205 participants and classified them into groups based on the AT(N) system using neuroimaging markers. Abnormal V markers were identified based on the presence of severe white matter hyperintensities. Results: In A+ category, compared with the frequency of Alzheimer's pathological change category (A+T-), the frequency of AD category (A+T+) was significantly lower in V+ group (31.8%) than in V- group (64.4%) (p=0.004). Each AT(N) biomarker was predictive of cognitive decline in the V+ group as well as in the V- group (p<0.001). Additionally, the V+ group showed more severe cognitive trajectories than the V- group in the non-Alzheimer's pathological changes (A-T+, A-N+; p=0.002) and Alzheimer's pathological changes (p<0.001) categories. Conclusion: The distribution and longitudinal outcomes of AT(N) system differed according to vascular burdens, suggesting the importance of incorporating a V biomarker into the AT(N) system.