Fig. 10.

Schematization of the putative cellular and molecular events linking risk factors for cardiovascular diseases, cerebral microcirculation, and the development of cognitive decline in middle-age mice. Cerebrovascular cells, astrocytes, and perivascular neurons constitute the interconnected neurovascular unit (NVU) that maintains proper brain functions. Vascular risk factors accelerate the rate of cognitive decline, but their impact on the NVU is not clear. We show that hypertensive, atherosclerotic (LDLr^−/−;hApoB100^+/+) mice prematurely develop cognitive decline associated with cerebral micro-bleeds, reduced microvessel density, and endothelial dysfunction. These alterations were associated with blood-brain barrier leakage, brain hypoperfusion, senescence and inflammation, and brain atrophy. Induction of severe systolic hypertension in wild-type mice altered both vascular and neuronal functions. Thus, vascular risk factors disrupt the NVU and contribute to premature cognitive failure