Insulin resistance in the brain precedes and contributes to cognitive decline above and beyond other causes of Alzheimer's disease, according to a new study from the University of Pennsylvania. Insulin is an important hormone in many bodily functions, including the health of brain cells. The team identified extensive abnormalities in the activity of two major signaling pathways for insulin and insulin-like growth factor in non-diabetic people with Alzheimer's disease. These pathways could be targeted with treatments to help resensitize the brain to insulin and possibly slow down or even improve cognitive decline. The investigators used samples of postmortem brain tissue from non-diabetics who had died with Alzheimer's disease, stimulated the tissue with insulin and measured how much the insulin activated various proteins in the insulin-signaling pathways. There was less insulin activation in Alzheimer's cases than in tissue from people who had died without brain disease.