Taken together, a cognitive profile characterized by deficits of the frontal-lobe functions and relatively preserved episodic memory, only among APOE-ε4 noncarriers, as well as the exacerbating role of cardiovascular comorbidities (heart disease and claudication), point toward the existence of vascular brain pathology as a potential driver of cognitive dysfunction related to MetS—at least in the initial stage of cognitive deterioration. Here, APOE is linked to metabolic syndrome.