Abstract

Abstract Aging is widely acknowledged as the primary risk factor for brain degeneration, with Parkinson's disease (PD) tending to follow accelerated aging trajectories. We aim to investigate the impact of structural brain aging on the temporal dynamics of a large‐scale functional network in PD. We enrolled 62 PD patients and 32 healthy controls (HCs). The level of brain aging was determined by calculating global and local brain age gap estimates (G‐brainAGE and L‐brainAGE) from structural images. The neural network activity of the whole brain was captured by identifying coactivation patterns (CAPs) from resting‐state functional images. Intergroup differences were assessed using the general linear model. Subsequently, a spatial correlation analysis between the L‐brainAGE difference map and CAPs was conducted to uncover the anatomical underpinnings of functional alterations. Compared to HCs (−3.73 years), G‐brainAGE was significantly higher in PD patients (+1.93 years), who also exhibited widespread elevation in L‐brainAGE. G‐brainAGE was correlated with disease severity and duration. PD patients spent less time in CAPs involving activated default mode and the fronto‐parietal network (DMN‐FPN), as well as the sensorimotor and salience network (SMN‐SN), and had a reduced transition frequency from other CAPs to the DMN‐FPN and SMN‐SN CAPs. Furthermore, the pattern of localized brain age acceleration showed spatial similarities with the SMN‐SN CAP. Accelerated structural brain aging in PD adversely affects brain function, manifesting as dysregulated brain network dynamics. These findings provide insights into the neuropathological mechanisms underlying neurodegenerative diseases and imply the possibility of interventions for modifying PD progression by slowing the brain aging process.