Insulin resistance as a key link for the increased risk of cognitive impairment in the metabolic syndrome

Metabolic syndrome (MetS) is a cluster of cardiovascular risk factors that includes obesity, diabetes, and dyslipidemia. Accumulating evidence implies that MetS contributes to the development and progression of Alzheimer’s disease (AD); however, the factors connecting this association have not been determined. Insulin resistance (IR) is at the core of MetS and likely represent the key link between MetS and AD. In the central nervous system, insulin plays key roles in learning and memory, and AD patients exhibit impaired insulin signaling that is similar to that observed in MetS. As we face an alarming increase in obesity and T2D in all age groups, understanding the relationship between MetS and AD is vital for the identification of potential therapeutic targets. Recently, several diabetes therapies that enhance insulin signaling are being tested for a potential therapeutic benefit in AD and dementia. In this review, we will discuss MetS as a risk factor for AD, focusing on IR and the recent progress and future directions of insulin-based therapies. Mounting evidences suggest a strong link between Alzheimer's disease and insulin resistance associated with the metabolic syndrome. The hormone insulin is best known for managing blood sugar levels but it also regulates numerous brain functions. The review by Bhumsoo Kim and Eva Feldman at the University of Michigan in the USA suggets that abnormalities in insulin signaling is intimately connected with the neurodegeneration and dementia seen in Alzheimer's disease. Individuals with type 2 diabetes, or exhibiting obesity and abnormal blood lipid levels that precede diabetes, are at a considerably greater risk of Alzheimer's disease. Disrupted insulin signaling appears to actively promote the accumulation of the toxic protein clumps that are primary hallmarks of this neurological disorder. The authors suggest that interventions that target insulin pathways will slow the progression of Alzheimer's disease.