White Matter Abnormalities and Cognition in Aging and Alzheimer Disease.
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
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, and the Alzheimer’s Disease Sequencing Project Phenotype Harmonization Consortium (ADSP-PHC) Analyst Team, 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
Аннотация
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.