Neurovascular coupling and functional connectivity changes through the Alzheimer's disease spectrum: Effects of simvastatin treatment.

Abstract

INTRODUCTION: Alzheimer's disease (AD) is a leading cause of dementia, with vascular dysfunction being an early pathogenic event. Cardiovascular interventions show therapeutic promise, hence may improve neurovascular coupling (NVC) and resting-state functional connectivity (RSFC) hemodynamic responses. METHODS: NVC and RSFC were recorded longitudinally in control and AD transgenic mice treated or not with simvastatin (SV) using optical imaging of intrinsic signals (OIS), together with memory testing. RESULTS: AD mice showed early decreases in NVC and bilateral connectivity (BC) in motor and cingulate cortex, and hypoconnectivity within the sensory-motor network. Early default-mode network (DMN) hyperconnectivity was followed by hypoconnectivity, together with a decreased BC in somatosensory (S) cortex. SV restored NVC, prevented aberrant DMN hyperconnectivity, improved BC of S, and preserved memory. DISCUSSION: Our results indicate that OIS can detect early AD-related changes in NVC and RSFC, and that a preventive cardiovascular strategy may bear therapeutic promise in at-risk individuals. HIGHLIGHTS: Optical imaging of intrinsic signals captures Alzheimer's disease (AD) progression and response to therapy. Neurovascular coupling (NVC) and resting-state functional connectivity (RSFC) disruptions precede memory decline in AD transgenic mice. Simvastatin prevented NVC and AD-specific RSFC disruptions and protected memory. This study supports translational value of hemodynamic signal in early AD detection.