Depression, diabetes and dementia

Abstract

Depression, diabetes and dementia are three disorders associated with staggering morbidity and mortality worldwide. The association between depression and diabetes has been well established. Furthermore, both depression and diabetes have been shown to increase the incidence of dementia individually and synergistically. The metabolic-brain axis appears to be a key mediator connecting depression, diabetes and dementia. Brain regions important for cognition and emotional regulation may be damaged by the effects of hyperglycemia and insulin resistance. Indeed, insulin resistance and decreased insulin in the central nervous system (CNS) results in decreased intracellular glucose levels in frontal and subcortical regions, neurotoxicity, decreased neuroplasticity, decreased signaling, decreased synaptic connectivity and disturbances in neural circuitry. The aforementioned changes may be attributable to brain bioenergetics wherein there is a bias toward energy conservation. The insulin pathway also has a bidirectional interaction with amyloid-β oligomer formation, one of the hallmarks of Alzheimer's disease. As well, depression may further facilitate neural circuit damage through the inflammatory pathway, hypothalamic-pituitary-adrenal axis dysregulation, monoamine changes and lowering of neurotrophic support to the CNS. Stress and psychosocial determinants of health may also be key mediators in how these systems interact. The involvement of several pathways may present new potential drug targets for the treatment and prevention of dementia using a lifetime approach. Systemic and intranasal insulin, oral diabetic medications, exercise, dietary changes, bariatric surgery and improved screening practices with early treatment of depression and diabetes all show promise in the treatment and prevention of comorbid depression, diabetes and dementia.