Linking cardiometabolic disorders to sporadic Alzheimer’s disease: a perspective on potential mechanisms and mediators

There is increasing evidence that the incidence of Alzheimer's disease (AD) is significantly influenced by cardiovascular risk factors in association with a cluster of metabolic diseases including diabetes and atherosclerosis. The shared risk is also reflected in the dietary and lifestyle links to both metabolic disorders and AD-type cognitive dysfunction. Recent studies with genetic and diet-induced animal models have begun to illuminate convergent mechanisms and mediators between these two categories of disease conditions with distinct tissue-specific pathologies. Although it is clear that peripheral inflammation and insulin resistance are central to the pathogenesis of the disorders of metabolic syndrome, it seems that the same mechanisms are also in play across the blood-brain barrier that lead to AD-like molecular and cognitive changes. This review highlights these convergent mechanisms and discusses the role of cerebrovascular dysfunction as a conduit to brain emergence of these pathogenic processes that might also represent future therapeutic targets in AD in common with metabolic disorders.