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

• Published in: The journal of prevention of Alzheimer's disease Vol. 11; no. 4; pp. 881 - 888
• Main Authors: Boyle, R., Klinger, H. M., Shirzadi, Z., Coughlan, G. T., Seto, M., Properzi, M. J., Townsend, D. L., Yuan, Z., Scanlon, C., Jutten, R. J., Papp, K. V., Amariglio, R. E., Rentz, D. M., Chhatwal, J. P., Donohue, M. C., Sperling, R. A., Schultz, A. P., Buckley, Rachel F.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 2024
• Subjects: Geriatrics/Gerontology; Medicine; Medicine & Public Health; Neurology; Original Research; functional connectivity; functional magnetic resonance imaging positron emission tomography (PET); Cognitive resilience; β-amyloid
• ISSN: 2426-0266
• DOI: 10.14283/jpad.2024.140

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 associated with reduced Aβ-related cognitive decline. Conclusions Our results demonstrate a potential protective effect of functional connectivity in preclinical AD, such that stronger connectivity in this network is associated with slower Aβ-related cognitive decline.