Table 1. Effects of the primary mediators of chronic stress and their similarity with the mechanisms that trigger Alzheimer's disease.

Primary mediators	Mechanisms	Effects	Relationship with
Cortisol and glucose	↑Cortisol induces hyperglycemia and insulin resistance	• Increased Ab peptide formation • Neuroinflammation, oxidative stress and cellular damage • Hyperphosphorylation of tau protein • Decreased neuroplasticity • Hippocampal atrophy and memory loss	• In individuals with MCI or AD, there is a change in the HPA axis and cortisol concentration • DM2 is associated with higher risk of AD
DHEA-S	↓DHEA-S is associated with immunological dysfunction	• Lower brain protection against Ab toxicity • Lower antioxidant defenses and vascular protection • Increased atherogenesis • Memory decline	• DHEA-S decreased in AD patients
Proinflammatory cytokines	↑IL-6 and IL-1	• Change in APP metabolism, facilitating the amyloidogenic pathway • Increased Ab deposition • Demyelination • Synaptic dysregulation and neurodegeneration	• IL-6 increased in AD patients

Ab: beta-amyloid; MCI: mild cognitive impairment; AD: Alzheimer's disease; HPA: hypothalamic-pituitary-adrenal; DM2: type 2 diabetes mellitus; DHEA-S: Dehydroepiandrosterone sulfate; IL-6: interleukin 6; IL-1: interleukin 1; APP: amyloid precursor protein.