Resting State Functional Connectivity Signature Differentiates Cognitively Normal from Individuals Who Convert to Symptomatic Alzheimer’s Disease
Julie K. Wisch, Catherine M. Roe, Ganesh M. Babulal, Suzanne E. Schindler, Anne M. Fagan, Tammie L.S. Benzinger, John C. Morris, Beau M. Ances
Abstract
BACKGROUND: Changes in resting state functional connectivity (rs-fc) occur in Alzheimer's disease (AD), but few longitudinal rs-fc studies have been performed. Most studies focus on single networks and not a global measure of rs-fc. Although the amyloid tau neurodegeneration (AT(N)) framework is increasingly utilized by the AD community, few studies investigated when global rs-fc signature changes occur within this model. OBJECTIVE: 1) Identify a global rs-fc signature that differentiates cognitively normal (CN) individuals from symptomatic AD. 2) Assess when longitudinal changes in rs-fc occur relative to conversion to symptomatic AD. 3) Compare rs-fc with amyloid, tau, and neurodegeneration biomarkers. METHODS: A global rs-fc signature composed of intra-network connections was longitudinally evaluated in a cohort of cognitively normal participants at baseline (n = 335). Biomarkers, including cerebrospinal fluid (Aβ42 and tau), structural magnetic resonance imaging, and positron emission tomography were obtained. RESULTS: Global rs-fc signature distinguished CN individuals from individuals who developed symptomatic AD. Changes occurred nearly four years before conversion to symptomatic AD. The global rs-fc signature most strongly correlated with markers of neurodegeneration. CONCLUSION: The global rs-fc signature changes near symptomatic onset and is likely a neurodegenerative biomarker. Rs-fc changes could serve as a biomarker for evaluating potential therapies for symptomatic conversion to AD.