Figure 1.

Obesity and metabolic syndrome are precursor disorders to type 2 diabetes. All three conditions independently and interactively activate a range of metabolic, inflammatory, and oxidative changes that contribute to deleterious effects on the brain. The damaging effects of metabolic disorders are influenced by several modifying factors, including endocrine changes such as low testosterone and genetic factors such as the apolipoprotein E (Apo E) ε4 allele. In response to these damaging pathways, the brain exhibits cognitive decline and increased risk to Alzheimer’s and vascular dementias.