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

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

doi:10.3389/fnagi.2021.721171

Abstract

Objective: 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.Method: 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.Results: Alzheimer's disease was primarily characterized by decreased functional connectivity in a data-driven network composed of an a priori default mode network, limbic network, and frontoparietal network during the memory maintenance (0.205 vs. 0.236, p = 0.04) and retrieval phase (0.159 vs. 0.183, p = 0.017). Within the network, AD had more regions with reduced connectivity during the retrieval than the maintenance and encoding phases (chi-square p = 0.01 and < 0.001). Furthermore, the global cortical β-amyloid negatively correlated with network connectivity during the memory retrieval phase (R = – 0.247, p = 0.032), with this relationship mediating the effect of cortical β-amyloid on memory performance (average causal mediation effect = – 0.05, p = 0.035).Conclusion: 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.

Highlights

Alzheimer’s disease is marked by prominent memory deficiency in the early stage
Neuro psychologic test performance, and Aβ positivity determined by an agreement between one nuclear medicine specialist and one memorydisorder specialist, 36 Aβ positive (Aβ+) Alzheimer’s disease (AD) participants and 36 Aβ negative (Aβ-) normal controls were included in this study
The two groups were matched in age, education, and sex (Table 1), and AD had worse cognitive performance in all cognitive domains assessed by the MMSE, Montreal Cognitive Assessment (MoCA), and Addenbrooke’s Cognitive Examination-Revised (ACER), as expected

Summary

Introduction

Alzheimer’s disease is marked by prominent memory deficiency in the early stage. It is controversial whether the observed amnesia is due to disrupted encoding, the consolidation of episodic information, or an impairment in the retrieval of stored memory information. Several studies have suggested that the ineffective encoding of new information in the brain triggers episodic memory deficits (Pasquier et al, 2001; Weintraub et al, 2012), while more evidence supported a retrieval deficit in early Alzheimer’s disease (AD) (Grober and Kawas, 1997; Albert et al, 2001; Li et al, 2016). Many studies have been conducted to show that memory is retrieved by neural networks (Palm, 2013). Episodic memory processingrelated medial temporal lobe activation was negatively associated with higher global Aβ levels (Mormino et al, 2012; Vannini et al, 2012)

Methods

Results

Discussion

Conclusion