Fig. 1.

Mechanisms of cardiovascular cognitive injury. Direct structural routes (solid) and indirect mediated routes (dashed) converge on the cumulative vascular substrate, which erodes cognition in its own right. Vessel caliber is not a third route; it determines lesion topography. Impaired perivascular clearance is shown as a mechanism upstream of the substrate rather than a component of it. The substrate and Alzheimer pathology may reinforce one another biologically, with asymmetric confidence in the two directions and cerebral amyloid angiopathy as the physical interface; separately, and on firmer evidence, accumulated vascular injury gates the clinical expression of a given Alzheimer burden