Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
Amyloid-related default mode network hyperconnectivity and longitudinal decline in network distinctiveness in preclinical Alzheimer's disease.
СтатьяПоддержка исследования: вне правительства СШАПоддержка NIH: внешняя программаНазвание и аннотация: Перевод пока не подготовлен
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Cha Woo-Jin, Chumin Evgeny J, Yi Dahyun, Byun Min Soo, Jung Joon Hyung, Ahn Hyejin, Jung Gijung, Kim Yu Kyeong, Lee Yun-Sang, Kang Koung Mi, Sohn Chul-Ho, Risacher Shannon L, Sporns Olaf, Nho Kwangsik, Saykin Andrew J, Lee Dong Young, KBASE Research Group
Аннотация
INTRODUCTION: We investigated stage-specific alterations in functional connectivity (FC) of the default mode network (DMN) across the Alzheimer's disease (AD) continuum and tested whether early amyloid beta (Aβ)-related changes in within-DMN FC (DMN-FCwithin) predicted longitudinal alterations in DMN between-network connectivity (DMN-FCbetween).
METHODS: Resting-state functional magnetic resonance imaging (fMRI) data were analyzed from 396 older adults: Aβ-negative cognitively normal (CN-, n = 213), Aβ-positive CN (CN+, n = 37), Aβ-positive mild cognitive impairment (MCI+, n = 72), and Aβ-positive dementia (dementia+, n = 74). Cross-sectional analyses compared DMN-FC across groups and examined associations with continuous Aβ burden at baseline. Longitudinal analyses in 171 CN participants with 2-year follow-up (CN-, n = 147; CN+, n = 24) tested whether baseline DMN-FCwithin predicted changes in DMN-FCbetween.
RESULTS: CN+ individuals showed elevated DMN-FCwithin and reduced DMN-FCbetween relative to other groups. In CN, Aβ burden was associated with FC, and baseline DMN-FCwithin predicted longitudinal increases in DMN-FCbetween only in CN+.
DISCUSSION: Aβ-related hyperconnectivity characterizes preclinical AD and may drive progressive network-level vulnerability.
HIGHLIGHTS: Cognitively normal amyloid beta (Aβ)-positive (CN+) individuals showed stronger connectivity within the default mode network (DMN). CN+ individuals also showed weaker links between the DMN and other brain networks. Amyloid was not linked to connectivity changes in cognitively impaired adults. Higher DMN connectivity predicted broader network changes in CN+ individuals.
METHODS: Resting-state functional magnetic resonance imaging (fMRI) data were analyzed from 396 older adults: Aβ-negative cognitively normal (CN-, n = 213), Aβ-positive CN (CN+, n = 37), Aβ-positive mild cognitive impairment (MCI+, n = 72), and Aβ-positive dementia (dementia+, n = 74). Cross-sectional analyses compared DMN-FC across groups and examined associations with continuous Aβ burden at baseline. Longitudinal analyses in 171 CN participants with 2-year follow-up (CN-, n = 147; CN+, n = 24) tested whether baseline DMN-FCwithin predicted changes in DMN-FCbetween.
RESULTS: CN+ individuals showed elevated DMN-FCwithin and reduced DMN-FCbetween relative to other groups. In CN, Aβ burden was associated with FC, and baseline DMN-FCwithin predicted longitudinal increases in DMN-FCbetween only in CN+.
DISCUSSION: Aβ-related hyperconnectivity characterizes preclinical AD and may drive progressive network-level vulnerability.
HIGHLIGHTS: Cognitively normal amyloid beta (Aβ)-positive (CN+) individuals showed stronger connectivity within the default mode network (DMN). CN+ individuals also showed weaker links between the DMN and other brain networks. Amyloid was not linked to connectivity changes in cognitively impaired adults. Higher DMN connectivity predicted broader network changes in CN+ individuals.