Resting-State Cerebral Blood Flow and Its Disconnect From Functional Connectivity in Alzheimer's Disease Spectrum

Disruption of neurovascular coupling is implicated in the pathogenesis of Alzheimer's disease (AD). However, the early changes in symptomatic AD patients remain inconclusive.

We enrolled 50 amyloid-positive AD patients, 38 amyloid-positive mild cognitive impairment (MCI) patients, and 50 cognitively unimpaired (CU) individuals from Tianjin Medical University General Hospital. The whole-brain functional connectivity strength (FCS) map was utilized to represent neuronal activity, while the cerebral blood flow (CBF) map was employed to indicate cerebral perfusion. Global neurovascular coupling was assessed through cross-voxel CBF-FCS correlation across global regions. In specific localized areas, regional neurovascular coupling was evaluated by calculating the CBF/FCS ratio.

Compared to the CU group, the overall neurovascular coupling (CBF-FCS) exhibited a gradual decline in symptomatic AD patients. A significantly reduced CBF/FCS ratio was primarily observed in the bilateral middle and inferior temporal gyri as well as the angular gyrus among symptomatic AD patients. Furthermore, regional CBF/FCS ratios in inferior temporal were found to be positively correlated with visuospatial function in patients with AD dementia.

Neurovascular decoupling is evident in the early stages of AD and worsens with disease progression. The CBF/FCS ratio, serving as an indirect indicator of neurovascular coupling, shows promise as a potential biomarker for the early diagnosis and clinical evaluation of AD.