Predicting brain age from functional connectivity in symptomatic and preclinical Alzheimer disease

Abstract

"Brain-predicted age" quantifies apparent brain age compared to normative neuroimaging trajectories. Advanced brain-predicted age has been well established in symptomatic Alzheimer disease (AD), but is underexplored in preclinical AD. Prior brain-predicted age studies have typically used structural MRI, but resting-state functional connectivity (FC) remains underexplored. Our model predicted age from FC in 391 cognitively normal, amyloid-negative controls (ages 18-89). We applied the trained model to 145 amyloid-negative, 151 preclinical AD, and 156 symptomatic AD participants to test group differences. The model accurately predicted age in the training set. FC-predicted brain age gaps (FC-BAG) were significantly older in symptomatic AD and significantly younger in preclinical AD compared to controls. There was minimal correspondence between networks predictive of age and AD. Elevated FC-BAG may reflect network disruption during symptomatic AD. Reduced FC-BAG in preclinical AD was opposite to the expected direction, and may reflect a biphasic response to preclinical AD pathology or may be driven by inconsistency between age-related vs. AD-related networks. Overall, FC-predicted brain age may be a sensitive AD biomarker.Fil: Allegri, Ricardo Francisco. Fleni. Departamento de Neurología. Servicio de Neurología Cognitiva, Neuropsicología y Neuropsiquiatría; Argentina.Fil: Millar, Peter R. Washington University. Department of Neurology; Estados Unidos.Fil: Luckett, Patrick H. Washington University. Department of Neurology; Estados Unidos.Fil: Gordon, Brian A. Washington University. Department of Radiology; Estados Unidos.Fil: Benzinger, Tammie L.S. Washington University. Department of Radiology; Estados Unidos.Fil: Schindler, Suzanne E. Washington University. Department of Neurology; Estados Unidos.Fil: Fagan, Anne M. Washington University. Department of Neurology; Estados Unidos.Fil: Cruchaga, Carlos. Washington University. Department of Psychiatry; Estados Unidos.Fil: Bateman, Randall J. Washington University. Department of Neurology; Estados Unidos.Fil: Jucker, Mathias. German Center for Neurodegenerative Diseases (DZNE); Alemania. University of Tübingen. Hertie Institute for Clinical Brain Research; Alemania.Fil: Lee, Jae-Hong. University of Ulsan College of Medicine. Department of Neurology, Asan Medical Center; Corea.Fil: Mori, Hiroshi. Nagaoka Sutoku University; Japón. Osaka City University Medical School. Department of Clinical Neuroscience; Japón.Fil: Ances, Beau M. Washington University. Department of Neurology; Estados Unidos.Fil: Salloway, Stephen P. Brown University. Department of Neurology; Estados Unidos.Fil: Igor, Yakushev. Technical University of Munich. Department of Nuclear Medicine; Alemania.Fil: Morris, John C. Washington University. Department of Neurology; Estados Unidos