Insulin resistance, affective disorders, and Alzheimer's disease: review and hypothesis

Affective disorders (ad) and Alzheimer's disease (AD) have been associated for almost a century, and various neurophysiologic factors have been implicated as common biologic markers. Yet, links between ad and AD still await elucidation. We propose that insulin resistance (IR) is one of the missing links between ad and AD. IR with hyperinsulinemia and subsequent impairment of glucose metabolism especially in ad patients may promote neurodegeneration and facilitate the onset of AD. According to our hypothesis, IR may persist even into ad remission in some patients. Persistent regional hypometabolism and vascular changes resulting from long-standing IR may lead to currently irreversible structural changes. Evidence in support of the hypothesis is reviewed and clinical implications suggested.