BRAIN FUNCTIONAL NETWORK CHANGES IN AGEING AND ALZHEIMER'S DISEASE

Abstract

Understanding the brain mechanisms underlying ageing and Alzheimer’s disease (AD) is a major research goal in the 21st century. Functional magnetic resonance imaging has been widely used to characterize age-related and AD-related disruptions in large-scale functional brain networks that may underlie cognitive deterioration. However, little remains known about functional network disruptions in AD patients with concomitant cerebrovascular disease (CeVD). Moreover, few studies have examined longitudinal functional connectivity changes in ageing and AD. To address these gaps, we examined cross-sectional and longitudinal functional connectivity changes in healthy elderly, as well as prodromal and clinical AD patients with and without CeVD. We revealed divergent effects of AD and CeVD pathology on cross-sectional and longitudinal functional connectivity changes, with AD burden associated with default mode network connectivity disruptions and CeVD burden associated with executive control network connectivity disruptions. Further, using a Singaporean healthy elderly dataset, we demonstrated age-related cross-sectional and longitudinal functional network segregation loss particularly in higher-order cognitive networks, and higher cross-sectional age-related frequency of dynamic connectivity states characterized by low network segregation. Together, these findings advance knowledge on the trajectory of brain functional network changes underlying ageing and AD, and highlight the utility of using functional connectivity to track disease progression.