Altered Regional Cerebral Blood Flow and Brain Function Across the Alzheimer's Disease Spectrum: A Potential Biomarker

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.

Early Warning Value of ASL-MRI to Estimate Premorbid Variations in Patients With Early Postoperative Cognitive Dysfunctions

“…In contrast with the above, our results also showed that, compared with the NPOCD group, preoperative MRI in the POCD group indicated increased CBF in the frontal gyrus. Previous studies have demonstrated hypoperfusion in the frontal gyrus in patients with impaired cognitive function (Bangen et al, 2014;Ding et al, 2014;Zou et al, 2014;Zhang et al, 2021). There have also been some studies about hyperperfusion in the frontal gyrus in patients with impaired cognitive function which is consistent with our results (Duan et al, 2020).…”

Altered Patterns of Amplitude of Low-Frequency Fluctuations and Fractional Amplitude of Low-Frequency Fluctuations Between Amnestic and Vascular Mild Cognitive Impairment: An ALE-Based Comparative Meta-Analysis

“…We also found a meta-analysis based on brain 18F-fluorodeoxyglucose positron emission tomography (FDG-PET), which found that the left PCC/PCUN was the most robust and reliable metabolic altered brain region for metabolic alterations in aMCI converted to AD. The hypometabolism in the left PCC/PCNU and altered fMRI may serve as a potential biomarker for AD and other forms of cognitive impairment (Ma et al, 2018 ; Zhang Q. et al, 2021 ). These findings support our meta-analysis results that found that these aberrant regions may be regarded as early neuroimaging biomarkers for aMCI (Lau et al, 2016 ).…”

Modulation of Brain Activity and Functional Connectivity by Acupuncture Combined With Donepezil on Mild-to-Moderate Alzheimer's Disease: A Neuroimaging Pilot Study

“…Recently, functional brain imaging changes have been proven as potential targets in early-stage AD ( 4 ), among which fractional amplitude of low-frequency fluctuation (fALFF) and functional connectivity (FC) are the most commonly used imaging indexes. Both fALFF, directly reflecting spontaneous brain activity, and FC decreased as early as in the preclinical AD stage of subjective cognitive decline ( 5 ). A study has carried out combined analysis of fALFF with FC, seeking precisely-significant seed point through the former method and applying it in the latter analysis, to investigate the pathological mechanisms of AD as rigorously as possible ( 5 ).…”

“…Both fALFF, directly reflecting spontaneous brain activity, and FC decreased as early as in the preclinical AD stage of subjective cognitive decline ( 5 ). A study has carried out combined analysis of fALFF with FC, seeking precisely-significant seed point through the former method and applying it in the latter analysis, to investigate the pathological mechanisms of AD as rigorously as possible ( 5 ). Several brain regions, including the hippocampus, posterior cingulate cortex, precuneus, pre-frontal cortex, temporal lobe, and angular gyrus, have been reported and well known as the core brain regions involved in the pathophysiology of AD ( 6 – 8 ).…”