Whole-Brain Structure-Function Coupling Abnormalities in Mild Cognitive Impairment: A Study Combining ALFF and VBM

Abstract

Background Alzheimer's disease, one of the most leading nervous system diseases, is accompanied by symptoms including loss of memory, thinking, and language ability. Both mild cognitive impairment (MCI) and very MCI (VMCI) are the transitional pathological stage between normal ageing and AD. While the changes to whole-brain structural and functional information have been extensively investigated in AD, the impaired structure-function coupling within whole brain remains unknown. Methods Current study employed the OASIS-3 dataset including 53 MCI, 90 VMCI and 100 age-, gender- and education-matched normal controls (NC). Several structural and functional parameters including amplitude of low frequency fluctuations (ALFF), voxel-based morphometry and ALFF/VBM ratio analysis were used to estimate the whole-brain abnormalities among MCI, VMCI and NC. Results As the disease symptoms became more severe, these regions distributing in the cerebellum and putamen within gray matter exhibited progressively increasing ALFF (ALFFNC < ALFFVMCI < ALFFMCI). Similar results were also found in the frontal-inf-orb, putamen, and paracentral-lobule within white matter. More importantly, as the symptoms of disease got worse, parahippocampal gyrus and hippocampus within gray matter showed progressively decreasing structure-function coupling, and was also applicable to the cuneus and frontal lobe within WM. In addition, the structure-function coupling values in the parahippocampal gyrus and hippocampus were positive relationship with severity of cognitive impairment, suggesting the important applications of the structure-function coupling index in brain disorders. Conclusion Our findings provided a novel information for discovering the pathophysiological mechanisms and indicated that WM lesions were also an important cause of cognitive decline in AD.