Abstract
Mild cognitive impairment (MCI) is characterized as a transitional phase between cognitive decline associated with normal aging and Alzheimer’s disease (AD). Resting-state functional magnetic resonance imaging (fMRI) measuring blood oxygenation level-dependent (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 pre-clinical Alzheimer’s disease and provides further insights into the neuropathology of cognitive decline in prodromal AD.
Highlights
Mild cognitive impairment (MCI) is a condition in which individuals exhibit cognitive decline exceeding that expected with normal aging that does not notably interfere with activities of daily life (Petersen, 2004)
The results of the current analyses reveal that people with early MCI (EMCI) or late MCI (LMCI) exhibit reduced resting-state functional magnetic resonance imaging (fMRI) blood oxygenation leveldependent (BOLD) signal complexity toward the regular pattern compared with the normal control (NC) group
In the EMCI group, reduced complexity was observed in the fusiform gyrus (FG), whereas in the LMCI group, this reduction was found in the rostral anterior cingulate cortex (rACC)
Summary
Mild cognitive impairment (MCI) is a condition in which individuals exhibit cognitive decline exceeding that expected with normal aging that does not notably interfere with activities of daily life (Petersen, 2004). Resting-state functional magnetic resonance imaging (fMRI) studies based on blood oxygen level-dependent (BOLD) signal, which indirectly measures neural activity by detecting changes in blood oxygenation, have revealed the potential of BOLD signals as a biomarker for early detection of the neurophysiological alterations associated with MCI. This is attributable to its non-invasive and task-free nature (Ogawa et al, 1990; Deyoe et al, 1994), as well as because functional changes appear well before structural changes (Pievani et al, 2011; Teipel et al, 2015) and detectable cerebrospinal fluid amyloid-β and phosphorylated tau abnormalities (Chen et al, 2016). It is critical to consider this issue while analyzing spontaneous fluctuations of resting-state BOLD signals
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