A Longitudinal Study of Functional Brain Complexity in Progressive Alzheimer's Diseases

Motivation: Complexity is generally reduced in mild cognitive impairment (MCI) and Alzheimer's disease (AD) than cognitive normal (CN) in cross-sectional cohorts. However, the trajectory of complexity in AD progression remains unknown. Goal(s): To investigate longitudinal changes in resting-state fMRI (rsfMRI)-complexity in AD progression. Approach: A linear mixed-effects model was implemented to investigate the main effects of Group and Group-by-time interactions. Results: rsfMRI-complexity was reduced in the MCItoAD group (those converted from MCI to AD) relative to the CN group. The CNtoMCI group (those converted from CN to MCI) showed the most pronounced rsfMRI-complexity decline over time. Impact: fMRI-complexity as a novel marker for Alzheimer's disease (AD) progression remains poorly understood although cross-sectional studies indicated reduced complexity relative to healthy aging. Our study demonstrates longitudinal changes in AD-related fMRI-complexity, indicating its potential as an early AD biomarker.