Reduced Dynamic Complexity of BOLD Signals Differentiates Mild Cognitive Impairment From Normal Aging

Abstract

Mild cognitive impairment (MCI) is characterized as a transitional phase between cognitive decline associated with normal aging and Alzheimer's disease (AD). Restingstate functional magnetic resonance imaging (fMRI) measuring blood oxygenation leveldependent (BOLD) signals provides complementary information considered essential for understanding disease progression. Previous studies suggested that multi-scale entropy (MSE) analysis quantifying the complexity of BOLD signals is a novel and promising method for investigating neurodegeneration associated with cognitive decline in different stages of MCI. Therefore, the current study used MSE to explore the changes in the complexity of resting-state brain BOLD signals in patients with early MCI (EMCI) and late MCI (LMCI). We recruited 345 participants' data from the Alzheimer's Disease Neuroimaging Initiative database, including 176 normal control (NC) subjects, 87 patients with EMCI and 82 patients with LMCI. We observed a significant reduction of brain signal complexity toward regularity in the left fusiform gyrus region in the EMCI group and in the rostral anterior cingulate cortex in the LMCI group. Our results extend prior work by revealing that significant reductions of brain BOLD signal complexity can be detected in different stages of MCI independent of age, sex and regional atrophy. Notably, the reduction of BOLD signal complexity in the rostral anterior cingulate cortex was significantly associated with greater risk of progression to AD. The present study thus identified MSE as a potential imaging biomarker for the early diagnosis of preclinical Alzheimer's disease and provides further insights into the neuropathology of cognitive decline in prodromal AD.

Complexity changes in functional state dynamics suggest focal connectivity reductions

“…Several authors have attempted to compare the functional complexity of groups and subjects by other means (Ostwald and Bagshaw, 2011;Liu et al, 2013;McIntosh et al, 2014;Grieder et al, 2018;Zheng et al, 2020;Xin et al, 2021), but they may overlook interregional statistical dependencies and thus risk erroneous estimates of region-specific complexity. A rigorous means of quantifying the functional complexity alterations which characterize psychiatric disorders remains elusive.…”

Reduced Inter-Voxel White Matter Integrity in Subjective Cognitive Decline: Diffusion Tensor Imaging With Tract-Based Spatial Statistics Analysis

“…Previous resting-state functional MRI studies have exhibited reduced functional connectivity of ACC in patients with MCI/AD compared with the HC group ( Cao et al, 2020 ; Ibrahim et al, 2021 ). A recent study, which used sample entropy (SE) in measuring the complexity of dynamic BOLD signal, has further indicated that individuals with lower SE were associated with a 3.4-fold increased risk of progression to AD in comparison with those with high SE ( Zheng et al, 2020 ). Our results further showed reduced DA of right ACC in the SCD vs. HC groups.…”

Alzheimer's disease: Potential pathogenesis and imaging findings

“…93 It has also been shown that reduced BOLD signal complexity (quantified by multiscale entropy analysis) can be detected at the MCI stage and that reduced BOLD signal complexity in the anterior cingulate corrostrum is associated with the risk of progression to AD. 94 The causes of BOLD signal low-frequency fluctuation are complex, not only include neuronal activity itself but also being influenced by some interference factors, some of which can be filtered, such as breathing and heartbeat pulsation. 95 Tong et al 95 found that there was also a kind of fluctuation spreading along with bloodstream and had a frequency similar to neural activity fluctuations, which affected the recognition of simple neural activity, and thus affected the quantification of brain networks.…”

“…Some studies have shown that BOLD variation is increased in AD patients, which needs to be further explored by expanding the sample size 93 . It has also been shown that reduced BOLD signal complexity (quantified by multiscale entropy analysis) can be detected at the MCI stage and that reduced BOLD signal complexity in the anterior cingulate corrostrum is associated with the risk of progression to AD 94 . The causes of BOLD signal low‐frequency fluctuation are complex, not only include neuronal activity itself but also being influenced by some interference factors, some of which can be filtered, such as breathing and heartbeat pulsation 95 .…”