Decoupling of Regional Cerebral Blood Flow and Brain Function Along the Alzheimer's Disease Continuum

Background: Alzheimer's disease (AD) is accompanied with impaired neurovascular coupling. However, its early alteration remains elusive along the AD continuum. Objective: This study aimed to investigate the early disruption of neurovascular coupling in cognitively normal (CN) and mild cognitive impairment (MCI) elderly and its association with cognition and AD pathologies. Methods: We included 43 amyloid-beta-negative CN participants and 38 amyloid-beta-positive individuals (18 CN and 20 MCI) from the Alzheimer's Disease Neuroimaging Initiative dataset. Regional homogeneity (ReHo) map was used to represent neuronal activity and cerebral blood flow (CBF) map was used to represent cerebral blood perfusion. Neurovascular coupling was assessed by CBF/ReHo ratio at the voxel level. Analyses of covariance to detect the between-group differences and to further investigate the relations between CBF/ReHo ratio and AD biomarkers or cognition. In addition, the correlation of cerebral small vessel disease (SVD) burden and neurovascular coupling was assessed as well. Results: Related to amyloid-beta-negative CN group, amyloid-beta-positive groups showed decreased CBF/ReHo ratio mainly in the left medial and inferior temporal gyrus. Furthermore, lower CBF/ReHo ratio was associated with a lower Mini-Mental State Examination score as well as higher AD pathological burden. No association between CBF/ReHo ratio and SVD burden was observed. Conclusion: AD pathology is a major correlate of the disturbed neurovascular coupling along the AD continuum, independent of SVD pathology. The CBF/ReHo ratio may be an index for detecting neurovascular coupling abnormalities, which could be used for early diagnosis in the future.