A Comparative Study on the Predictive Value of Different Resting-State Functional Magnetic Resonance Imaging Parameters in Preclinical Alzheimer's Disease

Abstract

Objective: Diverse resting-state functional magnetic resonance imaging (rs-fMRI) studies showed that rs-fMRI might be able to reflect the earliest detrimental effect of cerebral beta-amyloid (Aβ) pathology. However, no previous studies specifically compared the predictive value of different rs-fMRI parameters in preclinical AD.Methods: A total of 106 cognitively normal adults (Aβ+ group = 66 and Aβ− group = 40) were included. Three different rs-fMRI parameter maps including functional connectivity (FC), fractional amplitude of low-frequency fluctuations (fALFF), and regional homogeneity (ReHo) were calculated. Receiver operating characteristic (ROC) curve analyses were utilized to compare classification performance of the three rs-fMRI parameters.Results: FC maps showed the best classifying performance in ROC curve analysis (AUC, 0.915, p < 0.001). Good but weaker performance was achieved by using ReHo maps (AUC, 0.836, p < 0.001) and fALFF maps (AUC, 0.804, p < 0.001). The brain regions showing the greatest discriminative power included the left angular gyrus for FC, left anterior cingulate for ReHo, and left middle frontal gyrus for fALFF. However, among the three measurements, ROI-based FC was the only measure showing group difference in voxel-wise analysis.Conclusion: Our results strengthen the idea that rs-fMRI might be sensitive to earlier changes in spontaneous brain activity and FC in response to cerebral Aβ retention. However, further longitudinal studies with larger sample sizes are needed to confirm their utility in predicting the risk of AD.

Associating brain imaging phenotypes and genetic risk factors via a hypergraph based netNMF method

“…Maeno (2019) found that Aβ deposition in the anterior cuneiform of AD patients was associated with atrophy of the right occipitotemporal region. The left medial orbital age has a strong negative correlation, which is valid in the age adjustment of AD subjects (Wang et al, 2021).…”

“…The left angular gyrus is associated with increased brain metabolism in AD patients (Weissberger et al, 2017). Studies on rs-fMRI have shown that the left angular gyrus is the brain functional connectivity region showing the most significant discrimination (Wang et al, 2021). The left inferior frontal gyrus is associated with genetic variants of cortical atrophy in AD, contributing to further understanding AD's genetic basis (Kim et al, 2021).…”

Basal forebrain activity predicts functional degeneration in the entorhinal cortex and decreases with Alzheimer’s Disease progression

“…It showed, for instance, decreased fALFF signals in the bilateral middle frontal and left precuneus in participants with positive Aβ 14 . In preclinical AD, increases and decreases in fALFF were reported in the right inferior frontal gyrus 14,45 , and in prodromal AD lower fALFF signals could be shown in the bilateral precuneus, right middle frontal gyrus, right precentral gyrus, and postcentral gyrus. Finally, in AD fALFF was increased in the right fusiform gyrus, medial temporal lobe and inferior temporal gyrus, but decreased in the bilateral precuneus, left posterior cingulate cortex, left cuneus and superior occipital gyrus 45 .…”

“…Importantly, previous work did not specifically focus on the NbM and EC but other, typically larger brain regions. It showed, for instance, decreased fALFF signals in the bilateral middle frontal and left precuneus in participants with positive Ab 14 . In preclinical AD, increases and decreases in fALFF were reported in the right inferior frontal gyrus 14,45 , and in prodromal AD lower fALFF signals could be shown in the bilateral precuneus, right middle frontal gyrus, right precentral gyrus, and postcentral gyrus.…”

“…In detail, we analyzed (a) the fractional amplitude of low-frequency fluctuations (fALFF) to quantify spontaneous neuronal activity [10][11][12] , (b) regional homogeneity (ReHo) reflecting the synchronicity of neural activity between a voxel and its neighboring voxels 13 , and finally (c) the functional connectivity between NbM and EC. While all three measures may help to gain new insights into AD progression, we initially focused on fALFF given its established role [14][15][16] , and report ReHo and functional connectivity analyses in the supplementary material.…”