Abstract

BackgroundIndividuals with subjective memory complaints (SMC) feature a higher risk of cognitive decline and clinical progression of Alzheimer’s disease (AD). However, the pathological mechanism underlying SMC remains unclear. We aimed to assess the intrinsic connectivity network and its relationship with AD-related pathologies in SMC individuals.MethodsWe included 44 SMC individuals and 40 normal controls who underwent both resting-state functional MRI and positron emission tomography (PET). Based on graph theory approaches, we detected local and global functional connectivity across the whole brain by using degree centrality (DC) and eigenvector centrality (EC) respectively. Additionally, we analyzed amyloid deposition and tauopathy via florbetapir-PET imaging and cerebrospinal fluid (CSF) data. The voxel-wise two-sample T-test analysis was used to examine between-group differences in the intrinsic functional network and cerebral amyloid deposition. Then, we correlated these network metrics with pathological results.ResultsThe SMC individuals showed higher DC in the bilateral hippocampus (HP) and left fusiform gyrus and lower DC in the inferior parietal region than controls. Across all subjects, the DC of the bilateral HP and left fusiform gyrus was positively associated with total tau and phosphorylated tau181. However, no significant between-group difference existed in EC and cerebral amyloid deposition.ConclusionWe found impaired local, but not global, intrinsic connectivity networks in SMC individuals. Given the relationships between DC value and tau level, we hypothesized that functional changes in SMC individuals might relate to pathological biomarkers.

Highlights

  • Individuals with subjective memory complaints (SMC) feature a higher risk of cognitive decline and clinical progression of Alzheimer’s disease (AD)

  • Given the relationships between degree centrality (DC) value and tau level, we hypothesized that functional changes in SMC individuals might relate to pathological biomarkers

  • The links between the DC value and cerebrospinal fluid (CSF) tau level in the temporal regions suggested that the functional alternation in SMC individuals may result from tau-related pathologies

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Summary

Introduction

Individuals with subjective memory complaints (SMC) feature a higher risk of cognitive decline and clinical progression of Alzheimer’s disease (AD). SMC individuals feature both functional connectivity and metabolic alterations in the medial temporal and occipitoparietal regions [11,12,13,14,15] These results jointly suggested SMC as the middle stage between MCI and normal controls (NC) and (2018) 7:27 demonstrated that SMC might be among the earliest AD clinical symptoms. PET study found increased entorhinal cortical tauopathy in SMC individuals and noted that tauopathy might be the most suggestive sign of SMC [17] Despite these findings, the link between AD-related biomarkers and functional changes in SMC individuals is unclear

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