Default mode network dissociation linking cerebral beta amyloid retention and depression in cognitively normal older adults

Abstract

AbstractBackgroundTo date, cerebral beta amyloid (Aß) deposition and late‐life depression (LLD) are known to be associated with trajectory of Alzheimer’s disease (AD). However, their neurobiological link is not clear. Although previous studies showed aberrant functional connectivity (FC) change of default mode network (DMN) in early Aß deposition and LLD respectively, its mediating role is not elucidated. The aim of this study is to investigate distinctive association pattern of DMN FC linking LLD and Aß retention in the cognitively normal older adults.MethodTwo hundred thirty‐five cognitively normal older adults with (N=118) and without depression (N=117) underwent resting state functional magnetic resonance image and 18F‐Flutemetamol positron emission tomography. We investigated associations among Aß burden, depression, and DMN FC.ResultIndependent component analysis showed increased anterior DMN FC and decreased posterior DMN FC in depression group compared with no depression group. Global cerebral Aß retention correlated positively with anterior and negatively with posterior DMN FC. Anterior DMN FCs were positively correlated with depression severity whereas posterior DMN FCs were negatively correlated with cognitive function. In addition, effect of global cerebral Aß retention on depression severity was mediated by subgenual anterior cingulate FC.ConclusionOur results of anterior and posterior DMN FC dissociation pattern might play pivotal role in linking cerebral Aß pathology and LLD in the course of AD progression. Further longitudinal studies would be needed to confirm causal relationships between cerebral Aß retention and LLD.