Browsing by Author "Li, Zhiyuan"

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    Sex and APOE ε4 allele differences in longitudinal white matter microstructure in multiple cohorts of aging and Alzheimer's disease
    (Wiley, 2025) Peterson, Amalia; Sathe, Aditi; Zaras, Dimitrios; Yang, Yisu; Durant, Alaina; Deters, Kacie D.; Shashikumar, Niranjana; Pechman, Kimberly R.; Kim, Michael E.; Gao, Chenyu; Khairi, Nazirah Mohd; Li, Zhiyuan; Yao, Tianyuan; Huo, Yuankai; Dumitrescu, Logan; Gifford, Katherine A.; Wilson, Jo Ellen; Cambronero, Francis E.; Risacher, Shannon L.; Beason-Held, Lori L.; An, Yang; Arfanakis, Konstantinos; Erus, Guray; Davatzikos, Christos; Tosun, Duygu; Toga, Arthur W.; Thompson, Paul M.; Mormino, Elizabeth C.; Habes, Mohamad; Wang, Di; Zhang, Panpan; Schilling, Kurt; Alzheimer's Disease Neuroimaging Initiative (ADNI); BIOCARD Study Team; Alzheimer's Disease Sequencing Project (ADSP); Albert, Marilyn; Kukull, Walter; Biber, Sarah A.; Landman, Bennett A.; Johnson, Sterling C.; Schneider, Julie; Barnes, Lisa L.; Bennett, David A.; Jefferson, Angela L.; Resnick, Susan M.; Saykin, Andrew J.; Hohman, Timothy J.; Archer, Derek B.; Radiology and Imaging Sciences, School of Medicine
    Introduction: The effects of sex and apolipoprotein E (APOE)-Alzheimer's disease (AD) risk factors-on white matter microstructure are not well characterized. Methods: Diffusion magnetic resonance imaging data from nine well-established longitudinal cohorts of aging were free water (FW)-corrected and harmonized. This dataset included 4741 participants (age = 73.06 ± 9.75) with 9671 imaging sessions over time. FW and FW-corrected fractional anisotropy (FAFWcorr) were used to assess differences in white matter microstructure by sex and APOE ε4 carrier status. Results: Sex differences in FAFWcorr in projection tracts and APOE ε4 differences in FW limbic and occipital transcallosal tracts were most pronounced. Discussion: There are prominent differences in white matter microstructure by sex and APOE ε4 carrier status. This work adds to our understanding of disparities in AD. Additional work to understand the etiology of these differences is warranted. Highlights: Sex and apolipoprotein E (APOE) ε4 carrier status relate to white matter microstructural integrity. Females generally have lower free water-corrected fractional anisotropy compared to males. APOE ε4 carriers tended to have higher free water than non-carriers.
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    Sex, racial, and APOE-ε4 allele differences in longitudinal white matter microstructure in multiple cohorts of aging and Alzheimer’s disease
    (bioRxiv, 2024-06-12) Peterson, Amalia; Sathe, Aditi; Zaras, Dimitrios; Yang, Yisu; Durant, Alaina; Deters, Kacie D.; Shashikumar, Niranjana; Pechman, Kimberly R.; Kim, Michael E.; Gao, Chenyu; Khairi, Nazirah Mohd; Li, Zhiyuan; Yao, Tianyuan; Huo, Yuankai; Dumitrescu, Logan; Gifford, Katherine A.; Wilson, Jo Ellen; Cambronero, Francis; Risacher, Shannon L.; Beason-Held, Lori L.; An, Yang; Arfanakis, Konstantinos; Erus, Guray; Davatzikos, Christos; Tosun, Duygu; Toga, Arthur W.; Thompson, Paul M.; Mormino, Elizabeth C.; Zhang, Panpan; Schilling, Kurt; Alzheimer’s Disease Neuroimaging Initiative (ADNI); BIOCARD Study Team; Alzheimer’s Disease Sequencing Project (ADSP); Albert, Marilyn; Kukull, Walter; Biber, Sarah A.; Landman, Bennett A.; Johnson, Sterling C.; Schneider, Julie; Barnes, Lisa L.; Bennett, David A.; Jefferson, Angela L.; Resnick, Susan M.; Saykin, Andrew J.; Hohman, Timothy J.; Archer, Derek B.; Radiology and Imaging Sciences, School of Medicine
    Introduction: The effects of sex, race, and Apolipoprotein E (APOE) - Alzheimer's disease (AD) risk factors - on white matter integrity are not well characterized. Methods: Diffusion MRI data from nine well-established longitudinal cohorts of aging were free-water (FW)-corrected and harmonized. This dataset included 4,702 participants (age=73.06 ± 9.75) with 9,671 imaging sessions over time. FW and FW-corrected fractional anisotropy (FAFWcorr) were used to assess differences in white matter microstructure by sex, race, and APOE-ε4 carrier status. Results: Sex differences in FAFWcorr in association and projection tracts, racial differences in FAFWcorr in projection tracts, and APOE-ε4 differences in FW limbic and occipital transcallosal tracts were most pronounced. Discussion: There are prominent differences in white matter microstructure by sex, race, and APOE-ε4 carrier status. This work adds to our understanding of disparities in AD. Additional work to understand the etiology of these differences is warranted.
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    The effect of Alzheimer's disease genetic factors on limbic white matter microstructure
    (Wiley, 2025) Lorenz, Anna; Sathe, Aditi; Zaras, Dimitrios; Yang, Yisu; Durant, Alaina; Kim, Michael E.; Gao, Chenyu; Newlin, Nancy R.; Ramadass, Karthik; Kanakaraj, Praitayini; Khairi, Nazirah Mohd; Li, Zhiyuan; Yao, Tianyuan; Huo, Yuankai; Dumitrescu, Logan; Shashikumar, Niranjana; Pechman, Kimberly R.; Jackson, Trevor Bryan; Workmeister, Abigail W.; Risacher, Shannon L.; Beason-Held, Lori L.; An, Yang; Arfanakis, Konstantinos; Erus, Guray; Davatzikos, Christos; Habes, Mohamad; Wang, Di; Tosun, Duygu; Toga, Arthur W.; Thompson, Paul M.; Mormino, Elizabeth C.; Zhang, Panpan; Schilling, Kurt; Alzheimer's Disease Neuroimaging Initiative (ADNI)The BIOCARD Study Team; The Alzheimer's Disease Sequencing Project (ADSP); Albert, Marilyn; Kukull, Walter; Biber, Sarah A.; Landman, Bennett A.; Johnson, Sterling C.; Bendlin, Barbara; Schneider, Julie; Barnes, Lisa L.; Bennett, David A.; Jefferson, Angela L.; Resnick, Susan M.; Saykin, Andrew J.; Hohman, Timothy J.; Archer, Derek B.; Radiology and Imaging Sciences, School of Medicine
    Introduction: White matter (WM) microstructure is essential for brain function but deteriorates with age and in neurodegenerative conditions such as Alzheimer's disease (AD). Diffusion MRI, enhanced by advanced bi-tensor models accounting for free water (FW), enables in vivo quantification of WM microstructural differences. Methods: To evaluate how AD genetic risk factors affect limbic WM microstructure - crucial for memory and early impacted in disease - we conducted linear regression analyses in a cohort of 2,614 non-Hispanic White aging adults (aged 50.12 to 100.85 years). The study evaluated 36 AD risk variants across 26 genes, the association between AD polygenic scores (PGSs) and WM metrics, and interactions with cognitive status. Results: AD PGSs, variants in TMEM106B, PTK2B, WNT3, and apolipoprotein E (APOE), and interactions involving MS4A6A were significantly linked to WM microstructure. Discussion: These findings implicate AD-related genetic factors related to neurodevelopment (WNT3), lipid metabolism (APOE), and inflammation (TMEM106B, PTK2B, MS4A6A) that contribute to alternations in WM microstructure in older adults. Highlights: AD risk variants in TMEM106B, PTK2B, WNT3, and APOE genes showed distinct associations with limbic FW-corrected WM microstructure metrics. Interaction effects were observed between MS4A6A variants and cognitive status. PGS for AD was associated with higher FW content in the limbic system.
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    White Matter Abnormalities and Cognition in Aging and Alzheimer Disease
    (American Medical Association, 2025-06-09) Peter, Christopher; Sathe, Aditi; Shashikumar, Niranjana; Pechman, Kimberly R.; Workmeister, Abigail W.; Jackson, T. Bryan; Huo, Yuankai; Mukherjee, Shubhabrata; Mez, Jesse; Dumitrescu, Logan C.; Gifford, Katherine A.; Bolton, Corey J.; Gaynor, Leslie S.; Risacher, Shannon L.; Beason-Held, Lori L.; An, Yang; Arfanakis, Konstantinos; Erus, Guray; Davatzikos, Christos; Tosun-Turgut, Duygu; Habes, Mohamad; Wang, Di; Toga, Arthur W.; Thompson, Paul M.; Zhang, Panpan; Schilling, Kurt G.; Albert, Marilyn; Kukull, Walter; Biber, Sarah A.; Landman, Bennett A.; Bendlin, Barbara B.; Johnson, Sterling C.; Schneider, Julie; Barnes, Lisa L.; Bennett, David A.; Jefferson, Angela L.; Resnick, Susan M.; Saykin, Andrew J.; Crane, Paul K.; Cuccaro, Michael L.; Hohman, Timothy J.; Archer, Derek B.; Alzheimer’s Disease Sequencing Project Phenotype Harmonization Consortium (ADSP-PHC) Analyst Team; Alzheimer’s Disease Neuroimaging Initiative (ADNI); Biomarkers of Cognitive Decline Among Normal Adults (BIOCARD) Study Team; Alzheimer’s Disease Sequencing Project (ADSP); Zaras, Dimitrios; Yang, Yisu; Durant, Alaina; Kanakaraj, Praitayini; Kim, Michael E.; Gao, Chenyu; Newlin, Nancy R.; Ramadass, Karthik; Khairi, Nazirah Mohd; Li, Zhiyuan; Yao, Tianyuan; Choi, Seo-Eun; Klinedinst, Brandon; Lee, Michael L.; Scollard, Phoebe; Trittschuh, Emily H.; Sanders, Elizabeth A.; Radiology and Imaging Sciences, School of Medicine
    Importance: There has yet to be a large-scale study quantifying the association between white matter microstructure and cognitive performance and decline in aging and Alzheimer disease (AD). Objective: To investigate the associations between tract-specific white matter microstructure and cognitive performance and decline in aging and AD-related cognitive impairment. Design, setting, and participants: This prognostic study of aging and AD, a secondary data analysis of multisite cohort studies, acquired data from 9 cohorts between September 2002 and November 2022. Participants were eligible if they had diffusion-weighted magnetic resonance imaging (dMRI) data, domain-specific cognitive composite z scores, demographic and clinical data, were aged 50 years or older, and passed neuroimaging quality control. Demographic and clinical covariates included age, sex, education, race and ethnicity, APOE haplotype status (ε2, ε3, ε4), and clinical status. The present study was conducted from June 2024 to February 2025. Exposures: White matter microstructure and cognitive performance and decline. Main outcomes and measures: Clinical diagnosis, imaging measures (dMRI, T1-weighted MRI, and amyloid and tau positron emission tomography), and cognitive tests. Results: Of 4467 participants who underwent 9208 longitudinal cognitive sessions, 2698 (60.4%) were female, and the mean age (SD) was 74.3 (9.2) years; 3213 were cognitively unimpaired, 972 had mild cognitive impairment, and 282 had AD dementia. White matter free water (FW) showed the strongest associations with cross-sectional cognitive performance and longitudinal cognitive decline across all domains, particularly memory. FW in limbic tracts, such as the cingulum, presented the strongest associations with both memory performance (cingulum: β = -0.718; P < .001; fornix: β = -1.069; P < .001) and decline (cingulum: β = -0.115; P < .001; fornix: β = -0.153; P < .001). White matter FW measures interacted with baseline diagnosis, gray matter atrophy, APOE ε4 status, and amyloid positivity to predict poorer cognitive performance and accelerated cognitive decline. Noteworthy interactions include fornix FW and hippocampal volume (β = 10.598; P < .001), cingulum FW and SPARE-AD index (β = -0.532; P < .001), and inferior temporal gyrus transcallosal tract FW and baseline diagnosis (β = -0.537; P < .001), all predicting poorer memory performance. Conclusions and relevance: White matter microstructural changes, particularly FW, play a critical role in cognitive decline in aging and AD-related cognitive impairment. These findings highlight the importance of FW correction in dMRI studies and highlight the limbic system, especially the cingulum and fornix, as key regions associated with cognitive decline; the interaction models highlight that integrating FW-corrected metrics with other AD biomarkers may further elucidate the biological mechanisms of neurodegeneration in aging.