Abstract
Distinguishing progressive supranuclear palsy (PSP) from multiple system atrophy (MSA) in the early clinical stages is challenging; few sensitive and specific biomarkers are available for their differential diagnosis. Resting-state functional magnetic resonance imaging (rs-fMRI) is used to study the fluctuations in blood oxygen level-dependent (BOLD) signals at rest, which provides evidence for aberrant brain functional networks in neurodegenerative diseases. We aimed to examine whether rs-fMRI data could differentiate between PSP and MSA via a multiscale entropy (MSE) analysis of BOLD signals, which estimates the complexity of temporal fluctuations in brain activity. We recruited 14 and 18 patients with PSP and MSA, respectively, who underwent neuropsychological tests and rs-fMRI. PSP patients demonstrated greater cognitive function impairments, particularly in the frontal executive function. The bilateral prefrontal cortex revealed lower entropy BOLD signal values in multiple time scales for PSP, compared to the values observed in MSA patients; however, the functional connectivity of the representative brain networks was comparable between the diseases. The reduced complexity of BOLD signals in the prefrontal cortex was associated with frontal dysfunction. Thus, an MSE analysis of rs-fMRI could differentiate between PSP and MSA, and the reduced complexity of BOLD signals could be associated with cognitive impairment.
Highlights
Progressive supranuclear palsy (PSP) and multiple system atrophy (MSA) are neurodegenerative diseases with diverse brain pathologies: progressive supranuclear palsy (PSP) is characterized by tau filaments with four repeats, globular neurofibrillary changes, and glial fiber changes in the astrocytes and oligodendrocytes; MSA is characterized by fibrillar inclusions of α-synuclein in the oligodendrocytes [1,2]
There were no significant differences in age and sex between the PSP and MSA groups
frontal assessment battery (FAB)-measured cognitive functions were lower in the PSP than those in the MSA group; only FAB exhibited statistical significance (MMSE: p = 0.051, FAB: p = 0.004)
Summary
Progressive supranuclear palsy (PSP) and multiple system atrophy (MSA) are neurodegenerative diseases with diverse brain pathologies: PSP is characterized by tau filaments with four repeats, globular neurofibrillary changes, and glial fiber changes in the astrocytes and oligodendrocytes; MSA is characterized by fibrillar inclusions of α-synuclein (termed glial cytoplasmic inclusions) in the oligodendrocytes [1,2]. Both of their gross pathological features display atrophy in common regions, such as the brain stem, cerebellum, basal ganglia, and frontal lobe, which represent the structural basis for clinical magnetic resonance imaging (MRI) examination [3]. A definitive clinical diagnosis between PSP and MSA is occasionally difficult [5,6]
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