Abstract
Objective: To investigate variation in the characteristics of regional cerebral blood flow (rCBF), brain activity, and intrinsic functional connectivity (FC) across the Alzheimer's disease spectrum (ADS).Methods: The study recruited 20 individuals in each of the following categories: Alzheimer's disease (AD), mild cognitive impairment (MCI), subjective cognitive decline (SCD), and healthy control (HC). All participants completed the 3.0T resting-state functional MRI (rs-fMRI) and arterial spin labeling scans in addition to neuropsychological tests. Additionally, the normalized CBF, regional homogeneity (ReHo), and amplitude of low-frequency fluctuation (ALFF) of individual subjects were compared in the ADS. Moreover, the changes in intrinsic FC were investigated across the ADS using the abnormal rCBF regions as seeds and behavioral correlations. Finally, a support-vector classifier model of machine learning was used to distinguish individuals with ADS from HC.Results: Compared to the HC subjects, patients with AD showed the poorest level of rCBF in the left precuneus (LPCUN) and right middle frontal gyrus (RMFG) among all participants. In addition, there was a significant decrease in the ALFF in the bilateral posterior cingulate cortex (PCC) and ReHo in the right PCC. Moreover, RMFG- and LPCUN-based FC analysis revealed that the altered FCs were primarily located in the posterior brain regions. Finally, a combination of altered rCBF, ALFF, and ReHo in posterior cingulate cortex/precuneus (PCC/PCUN) showed a better ability to differentiate ADS from HC, AD from SCD and MCI, but not MCI from SCD.Conclusions: The study demonstrated the significance of an altered rCBF and brain activity in the early stages of ADS. These findings, therefore, present a potential diagnostic neuroimaging-based biomarker in ADS. Additionally, the study provides a better understanding of the pathophysiology of AD.
Highlights
Alzheimer’s disease (AD) is one of the most important public health burdens worldwide
More importantly, the four groups showed significant differences with each other in the episodic memory scores which decreased with disease severity (i.e., health control (HC) > subjective cognitive decline (SCD) > mild cognitive impairment (MCI) > AD)
The partial correlation analysis revealed that there was a negative association between amplitude of low-frequency fluctuations (ALFF) in the LPCL and the Mini-Mental State Examination (MMSE) scores, while regional homogeneity (ReHo) in LPCC and LMTG had a positive association with most of the behavioral tests
Summary
Alzheimer’s disease (AD) is one of the most important public health burdens worldwide. The obvious brain structure atrophy might imply the appearance of irreversible neuronal damage in the process of AD pathophysiology. The resting-state functional MRI (rs-fMRI) can detect early functional changes in the brain reflected by the intrinsic blood-oxygen-level-dependent (BOLD) signals before the appearance of cognitive decline and brain structural atrophy (Galvin et al, 2011; Habib et al, 2017; Kawagoe et al, 2019). Functional changes in the brain are independent of and even more sensitive than brain structure atrophy during the early stages of AD (Galvin et al, 2011; Xie et al, 2015; Kawagoe et al, 2019)
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