Metabolic links between diabetes and Alzheimer's disease.

There is a cluster of risk factors for Type 2 diabetes and vascular disease that include high blood glucose, obesity, high blood pressure, increased blood triacylglycerols and insulin resistance. All of these factors, both individually and collectively, increase the risk of Alzheimer's disease (AD) and vascular dementia. Alterations in insulin signaling, glucose and fatty acid metabolism, as well as the accumulation of oxidatively modified and glycated proteins, are associated with both diabetes and the dementias. Data from animal and cell culture models have shown that there is a synergistic interaction between most of these stresses in both AD and diabetes, and with the elevated beta-amyloid peptide levels that are also linked to AD. Some of these parameters can be modified by diet and others may require novel drugs. However, because of the multiplicity of physiological pathways involved, conventional drug therapies directed against a single target are not going to be effective in treating AD or the complications of diabetes. It is therefore likely that the only successful therapy will involve the use of drugs with multiple targets in concert with changes in diet and lifestyle.