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4. Impact of amyloid and cardiometabolic risk factors on prognostic capacity of plasma neurofilament light chain for neurodegeneration

Author

Kim, Keun You, Kim, Eosu, and Lee, Jun-Young

Subjects
Health Services and Systems, Health Sciences, Dementia, Neurodegenerative, Prevention, Behavioral and Social Science, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Alzheimer's Disease, Brain Disorders, Clinical Research, Neurosciences, Aging, Acquired Cognitive Impairment, 2.1 Biological and endogenous factors, Neurological, Humans, Female, Male, Aged, Neurofilament Proteins, Longitudinal Studies, Amyloid beta-Peptides, Prognosis, Biomarkers, Cardiometabolic Risk Factors, Positron-Emission Tomography, Aged, 80 and over, Cognitive Dysfunction, Alzheimer Disease, Hippocampus, Magnetic Resonance Imaging, Neurofilament light chain, Alzheimer's disease, Blood-based biomarker, Cardiovascular disease, Metabolic syndrome, Kidney disease, Alzheimer’s Disease Neuroimaging Initiative, Alzheimer’s disease, Medical and Health Sciences, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundPlasma neurofilament light chain (NfL) is a blood biomarker of neurodegeneration, including Alzheimer's disease. However, its usefulness may be influenced by common conditions in older adults, including amyloid-β (Aβ) deposition and cardiometabolic risk factors like hypertension, diabetes mellitus (DM), impaired kidney function, and obesity. This longitudinal observational study using the Alzheimer's Disease Neuroimaging Initiative cohort investigated how these conditions influence the prognostic capacity of plasma NfL.MethodsNon-demented participants (cognitively unimpaired or mild cognitive impairment) underwent repeated assessments including the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) scores, hippocampal volumes, and white matter hyperintensity (WMH) volumes at 6- or 12-month intervals. Linear mixed-effect models were employed to examine the interaction between plasma NfL and various variables of interest, such as Aβ (evaluated using Florbetapir positron emission tomography), hypertension, DM, impaired kidney function, or obesity.ResultsOver a mean follow-up period of 62.5 months, participants with a mean age of 72.1 years (n = 720, 48.8% female) at baseline were observed. Higher plasma NfL levels at baseline were associated with steeper increases in ADAS-Cog scores and WMH volumes, and steeper decreases in hippocampal volumes over time (all p-values

Published
2024

5. Developmental origin of oligodendrocytes determines their function in the adult brain

Author

Foerster, Sarah, Floriddia, Elisa M., van Bruggen, David, Kukanja, Petra, Hervé, Bastien, Cheng, Shangli, Kim, Eosu, Phillips, Benjamin U., Heath, Christopher J., Tripathi, Richa B., Call, Cody, Bartels, Theresa, Ridley, Katherine, Neumann, Björn, López-Cruz, Laura, Crawford, Abbe H., Lynch, Cian J., Serrano, Manuel, Saksida, Lisa, Rowitch, David H., Möbius, Wiebke, Nave, Klaus-Armin, Rasband, Matthew N., Bergles, Dwight E., Kessaris, Nicoletta, Richardson, William D., Bussey, Timothy J., Zhao, Chao, Castelo-Branco, Gonçalo, and Franklin, Robin J. M.

Published
2024
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19. Automated Scoring of Alzheimer’s Disease Atrophy Scale with Subtype Classification Using Deep Learning-Based T1-Weighted Magnetic Resonance Image Segmentation

Author

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, and Lim, Hyun Kook

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.

Published
2024
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20. In patients with late-life depression and cognitive decline, adding tDCS to cognitive training does not significantly affect depressive symptoms but shows potential benefits on cognition as measured by fMRI

Author

Ha, Junghee, primary, Fang, Yu, additional, Cron, Greg O., additional, Heo, Jaeseok, additional, Jung, Eunjin, additional, Lee, Deokjong, additional, Kim, Hyunjeong, additional, Kim, Eosu, additional, Park, Jin Young, additional, and Lee, Jin Hyung, additional

Published
2024
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21. Cholesterol profiling reveals 7β‐hydroxycholesterol as a pathologically relevant peripheral biomarker of Alzheimer's disease.

Author

Ha, Junghee, Kwon, Go Eun, Son, Yumi, Jang, Soo Ah, Cho, So Yeon, Park, Soo Jin, Kim, Hyunjeong, Lee, Jimin, Lee, Juseok, Seo, Dongryul, Lee, Myeongjee, Lee, Do Yup, Choi, Man Ho, and Kim, Eosu

Subjects
EXECUTIVE function, RECOGNITION (Psychology), ALZHEIMER'S disease, MILD cognitive impairment, INDIVIDUALIZED medicine, COMPULSIVE hair pulling
Abstract

Aim: Cholesterol homeostasis is associated with Alzheimer's disease (AD). Despite the multitude of cholesterol metabolites, little is known about which metabolites are directly involved in AD pathogenesis and can serve as its potential biomarkers. Methods: To identify "hit" metabolites, steroid profiling was conducted in mice with different age, diet, and genotype and also in humans with normal cognition, mild cognitive impairment, and AD using gas chromatography–mass spectrometry. Then, using one of the "hit" molecules (7β‐hydroxycholesterol; OHC), molecular and histopathological experiment and behavioral testing were conducted in normal mice following its intracranial stereotaxic injection to see whether this molecule drives AD pathogenesis and causes cognitive impairment. Results: The serum levels of several metabolites, including 7β‐OHC, were increased by aging in the 3xTg‐AD unlike normal mice. Consistently, the levels of 7β‐OHC were increased in the hairs of patients with AD and were correlated with clinical severity. We found that 7β‐OHC directly affects AD‐related pathophysiology; intrahippocampal injection of 7β‐OHC induced astrocyte and microglial cell activation, increased the levels of pro‐inflammatory cytokines (TNF‐alpha, IL‐1β, IL‐6), and enhanced amyloidogenic pathway. Mice treated with 7β‐OHC also exhibited deficits in memory and frontal/executive functions assessed by object recognition and 5‐choice serial reaction time task, respectively. Conclusions: Our results suggest that 7β‐OHC could serve as a convenient, peripheral biomarker of AD. As directly involved in AD pathogenesis, 7β‐OHC assay may help actualize personalized medicine in a way to identify an at‐risk subgroup as a candidate population for statin‐based AD treatment. [ABSTRACT FROM AUTHOR]

Published
2024
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22. Neural Effects of One's Own Voice on Self-Talk for Emotion Regulation.

Author

Jo, Hye-jeong, Park, Chanmi, Lee, Eunyoung, Lee, Jee Hang, Kim, Jinwoo, Han, Sujin, Kim, Joohan, Kim, Eun Joo, Kim, Eosu, and Kim, Jae-Jin

Subjects
RECOLLECTION (Psychology), TEMPORAL lobe, AFFIRMATIONS (Self-help), EMOTION regulation, FUNCTIONAL magnetic resonance imaging, SELF-talk
Abstract

One's own voice undergoes unique processing that distinguishes it from others' voices, and thus listening to it may have a special neural basis for self-talk as an emotion regulation strategy. This study aimed to elucidate how neural effects of one's own voice differ from those of others' voices on the implementation of emotion regulation strategies. Twenty-one healthy adults were scanned using fMRI while listening to sentences synthesized in their own or others' voices for self-affirmation and cognitive defusion, which were based on mental commitments to strengthen one's positive aspects and imagining metaphoric actions to shake off negative aspects, respectively. The interaction effect between voice identity and strategy was observed in the superior temporal sulcus, middle temporal gyrus, and parahippocampal cortex, and activity in these regions showed that the uniqueness of one's own voice is reflected more strongly for cognitive defusion than for self-affirmation. This interaction was also seen in the precuneus, suggesting intertwining of self-referential processing and episodic memory retrieval in self-affirmation with one's own voice. These results imply that unique effects of one's own voice may be expressed differently due to the degree of engagement of neural sharpening-related regions and self-referential networks depending on the type of emotion regulation. [ABSTRACT FROM AUTHOR]

Published
2024
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28. TDP-43 gains function due to perturbed autoregulation in a Tardbp knock-in mouse model of ALS-FTD

Author

White, Matthew A., Kim, Eosu, Duffy, Amanda, Adalbert, Robert, Phillips, Benjamin U., Peters, Owen M., Stephenson, Jodie, Yang, Sujeong, Massenzio, Francesca, Lin, Ziqiang, Andrews, Simon, Segonds-Pichon, Anne, Metterville, Jake, Saksida, Lisa M., Mead, Richard, Ribchester, Richard R, Barhomi, Youssef, Serre, Thomas, Coleman, Michael P., Fallon, Justin R., Bussey, Timothy J., Brown, Jr, Robert H., and Sreedharan, Jemeen

Published
2018
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39. Weight loss and risk of dementia in individuals with versus without obesity.

Author

Kim, Keun You, Ha, Junghee, Lee, Jun‐Young, and Kim, Eosu

Abstract

INTRODUCTION: Using nationwide cohort data, we aimed to elucidate whether baseline obesity altered the relationship between loss in body mass index (BMI) or waist circumference (WC) and risk of dementia. METHODS: Among 9689 participants whose BMIs and WCs were repeatedly measured over 1 year, 1:1 propensity score matching was conducted between participants with and without obesity (n = 2976 per group, mean age 70.9). For each group, we explored the association between loss in BMI, or WC, and incidence of dementia during an approximately 4‐year follow‐up period. RESULTS: BMI loss was associated with an increased risk of all‐cause dementia and Alzheimer's disease in participants without obesity; however, this association was absent in participants with obesity. WC loss was associated with decreased Alzheimer's disease risk only in participants with obesity. DISCUSSION: Only unfavorable loss (loss from non‐obese state) in BMI, not WC, can be a metabolic biomarker of prodromal dementia. [ABSTRACT FROM AUTHOR]

Published
2023
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