AUTHOR=Li Binyin , Zhang Miao , Jang Ikbeom , Ye Guanyu , Zhou Liche , He Guiying , Lin Xiaozhu , Meng Hongping , Huang Xinyun , Hai Wangxi , Chen Shengdi , Li Biao , Liu Jun 

TITLE=Amyloid-Beta Influences Memory via Functional Connectivity During Memory Retrieval in Alzheimer's Disease

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=13

YEAR=2021

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2021.721171

DOI=10.3389/fnagi.2021.721171

ISSN=1663-4365

ABSTRACT=<p><bold>Objective:</bold> Amnesia in Alzheimer's disease (AD) appears early and could be caused by encoding deficiency, consolidation dysfunction, and/or impairment in the retrieval of stored memory information. The relationship between AD pathology biomarker β-amyloid and memory dysfunction is unclear.</p><p><bold>Method:</bold> The memory task functional MRI and amyloid PET were simultaneously performed to investigate the relationship between memory performance, memory phase-related functional connectivity, and cortical β-amyloid deposition. We clustered functional networks during memory maintenance and compared network connectivity between groups in each memory phase. Mediation analysis was performed to investigate the mediator between β-amyloid and related cognitive performance.</p><p><bold>Results:</bold> Alzheimer's disease was primarily characterized by decreased functional connectivity in a data-driven network composed of an <italic>a priori</italic> default mode network, limbic network, and frontoparietal network during the memory maintenance (0.205 vs. 0.236, <italic>p</italic> = 0.04) and retrieval phase (0.159 vs. 0.183, <italic>p</italic> = 0.017). Within the network, AD had more regions with reduced connectivity during the retrieval than the maintenance and encoding phases (chi-square <italic>p</italic> = 0.01 and &lt; 0.001). Furthermore, the global cortical β-amyloid negatively correlated with network connectivity during the memory retrieval phase (<italic>R</italic> = – 0.247, <italic>p</italic> = 0.032), with this relationship mediating the effect of cortical β-amyloid on memory performance (average causal mediation effect = – 0.05, <italic>p</italic> = 0.035).</p><p><bold>Conclusion:</bold> We demonstrated that AD had decreased connectivity in specific networks during the memory retrieval phase. Impaired functional connectivity during memory retrieval mediated the adverse effect of β-amyloid on memory. These findings help to elucidate the involvement of cortical β-amyloid (Aβ) in the memory performance in the early stages of AD.</p>