Abstract
The aim of our study was to explore the dynamic functional alterations in the brain in patients with subjective cognitive decline (SCD) and their relationship to apolipoprotein E (APOE) €4 alleles. In total, 95 SCD patients and 49 healthy controls (HC) underwent resting-state functional magnetic resonance imaging (rs-fMRI). Then, the mean time series of 90 cortical or subcortical regions were extracted based on anatomical automatic labeling (AAL) atlas from the preprocessed rs-fMRI data. The static functional connectome (SFC) and dynamic functional connectome (DFC) were constructed and compared using graph theory methods and leading eigenvector dynamics analysis (LEiDA), respectively. The SCD group displayed a shorter lifetime (p = 0.003, false discovery rate corrected) and lower probability (p = 0.009, false discovery rate corrected) than the HC group in a characteristic dynamic functional network mainly involving the bilateral insular and temporal neocortex. No significant differences in the SFC were detected between the two groups. Moreover, the lower probability in the SCD group was found to be negatively correlated with the number of APOE ε4 alleles (r = −0.225, p = 0.041) in a partial correlation analysis with years of education as a covariate. Our results suggest that the DFC may be a more sensitive parameter than the SFC and can be used as a potential biomarker for the early detection of SCD.
Highlights
Alzheimer’s disease (AD) is the most common neurodegenerative cause of dementia and is associated with significant morbidity and mortality
In the dynamic functional analysis, a significant difference was detected only in PL state 3 when the dynamic functional connectome (DFC) was divided into four PL states (Figure 1)
The probability of PL state 3 was negatively correlated with the number of apolipoprotein E (APOE) ε4 alleles (r = −0.225, p = 0.041), while the LT of PL state 3 was not significantly correlated with the number of APOE ε4 alleles (r = −0.057, p = 0.607) (Figure 3). We evaluated both static and dynamic alterations in the brain functional network in the Subjective cognitive decline (SCD) group compared with the healthy controls (HCs) group
Summary
Alzheimer’s disease (AD) is the most common neurodegenerative cause of dementia and is associated with significant morbidity and mortality. Subjective cognitive decline (SCD), known as significant memory concern (SMC), has been suggested to be the preclinical stage of AD, which is characterized by a subjective decline in cognitive function without any notable alterations in neuropsychological. Dynamics of Brain Functional Network test results (Sperling et al, 2011; Viviano and Damoiseaux, 2020). Exploring biomarkers of SCD will contribute to the early diagnosis of AD. As a non-invasive neuroimaging technique, resting-state functional magnetic resonance imaging (rs-fMRI) has been widely applied to explore the neural mechanisms underlying SCD based on various neuroimaging measures, such as regional homogeneity (Li et al, 2021), amplitude of low-frequency fluctuations (Sun et al, 2016), functional connectivity (Hafkemeijer et al, 2013; Dillen et al, 2016) and complex network measures (Chen et al, 2020; Xue et al, 2020)
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