Evidence for direct control of neurovascular function by circulating platelets in healthy older adults

Platelets prevent bleeding through haemostasis, but inappropriate activation leads to pathophysiology such as athero-thrombosis. Elevated haemostatic markers are linked to dementia but the mechanism linking haemostasis with brain pathophysiology remains unclear. To address this we combined magnetic resonance imaging (MRI) of neurovascular function, peripheral vascular physiology, and platelet function analysis in 52 healthy mid- to older-age adults. We show that platelet reactivity and neurovascular function are directly linked independent of vascular reactivity. This link is mechanistically specific: Distinct platelet signalling mechanisms were associated with specific components of the hemodynamic response to neural activation, not mediated by peripheral vascular effects. This discovery challenges the belief that vessel health alone determines the vascular component of neurovascular function, representing a significant advancement in understanding dementia pathophysiology.