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


Cerebral beta amyloid (Aβ) deposition and late-life depression (LLD) are known to be associated with the trajectory of Alzheimer’s disease (AD). However, their neurobiological link is not clear. Previous studies showed aberrant functional connectivity (FC) changes in the default mode network (DMN) in early Aβ deposition and LLD, but its mediating role has not been elucidated. This study was performed to investigate the distinctive association pattern of DMN FC linking LLD and Aβ retention in cognitively normal older adults. A total of 235 cognitively normal older adults with (n = 118) and without depression (n = 117) underwent resting-state functional magnetic resonance imaging and 18F-flutemetamol positron emission tomography to investigate the associations between Aβ burden, depression, and DMN FC. Independent component analysis showed increased anterior DMN FC and decreased posterior DMN FC in the depression group compared with the no depression group. Global cerebral Aβ retention was positively correlated with anterior and negatively correlated with posterior DMN FC. Anterior DMN FC was positively correlated with severity of depression, whereas posterior DMN FC was negatively correlated with cognitive function. In addition, the effects of global cerebral Aβ retention on severity of depression were mediated by subgenual anterior cingulate FC. Our results of anterior and posterior DMN FC dissociation pattern may be pivotal in linking cerebral Aβ pathology and LLD in the course of AD progression. Further longitudinal studies are needed to confirm the causal relationships between cerebral Aβ retention and LLD.

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Fig. 1: Group difference of functional connectivity.
Fig. 2: Effect of depression on the relationships between Aß retention and FC.
Fig. 3: Direction of the association between FC and Aß retention.
Fig. 4: Mediation analysis.


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Author information




S-MW and HKL drafted the manuscript and contributed to project design, data collection, management, analysis, and interpretation. N-YK and DWK contributed to project design, data collection, and management. YHU, H-RN, and CUL contributed to data management and revision of the manuscript.

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Correspondence to Hyun Kook Lim.

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Wang, SM., Kim, NY., Um, Y.H. et al. Default mode network dissociation linking cerebral beta amyloid retention and depression in cognitively normal older adults. Neuropsychopharmacol. 46, 2180–2187 (2021).

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