Left Frontoparietal Control Network Connectivity Moderates the Effect of Amyloid on Cognitive Decline in Preclinical Alzheimer's Disease: The A4 Study

作者：Rory Boyle, Hannah M Klinger, Zahra Shirzadi, Gillian Coughlan, Mabel Seto, Michael Properzi, Diana L. Townsend, Zengqiang Yuan, Catherine E Scanlon, Roos J. Jutten, Kathryn V. Papp, Rebecca E. Amariglio, Dorene M. Rentz, Jasmeer P. Chhatwal, Michael Donohue, R A Sperling, A.P. Schultz, Rachel F. Buckley · 发表于：The Journal of Prevention of Alzheimer s Disease · 年份：2024 · DOI：10.14283/jpad.2024.140 · 被引用次数：15 · 研究领域：Functional Brain Connectivity Studies、Dementia and Cognitive Impairment Research、Alzheimer's disease research and treatments

BACKGROUND: Stronger resting-state functional connectivity of the default mode and frontoparietal control networks has been associated with cognitive resilience to Alzheimer's disease related pathology and neurodegeneration in smaller cohort studies. OBJECTIVES: We investigated whether these networks are associated with longitudinal CR to AD biomarkers of beta-amyloid (Aβ). DESIGN: Longitudinal mixed. SETTING: The Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) study and its natural history observation arm, the Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) study. PARTICIPANTS: A sample of 1,021 cognitively unimpaired older adults (mean age = 71.2 years [SD = 4.7 years], 61% women, 42% APOEε4 carriers, 52% Aβ positive). MEASUREMENTS: Global cognitive performance (Preclinical Alzheimer's Cognitive Composite) was assessed over an average 5.4 year follow-up period (SD = 2 years). Cortical Aβ and functional connectivity (left and right frontoparietal control and default mode networks) were estimated from fMRI and PET, respectively, at baseline. Covariates included baseline age, APOEε4 carrier status, years of education, adjusted gray matter volume, head motion, study group, cumulative treatment exposure, and cognitive test version. RESULTS: Mixed effects models revealed that functional connectivity of the left frontoparietal control network moderated the negative effect of Aβ on cognitive change (p = .025) such that stronger connectivity was...