By Dr. Mitchell Kahn, M.D.

A link between the two diseases raise concerns – and hopes
Understanding insulin’s role
Mice studies

A link between the two diseases raise concerns – and hopes
Mounting evidence linking diabetes and Alzheimer’s disease may be particularly sobering to diabetes sufferers. But there could be a silver lining. The recent findings offer an important new clue to researchers hot on the trail of treatments for Alzheimer’s.

A recent Swedish study of 1,173 people over age 75 concluded that those with even borderline diabetes were about 70% likelier to develop Alzheimer’s than those with normal sugar levels. The findings confirmed a landmark study two years ago at Chicago’s Rush University, where diabetic participants were 65% more likely to develop Alzheimer’s than those without diabetes.

The past several years have seen an evolving body of thought linking Alzheimer’s to a variety of diseases with certain things in common: high levels of lipids, atherosclerosis risk and high cholesterol. It is known that diabetes increases the risk for atherosclerosis, but it has been more difficult to link diabetes itself to Alzheimer’s disease.

We can’t do much about many of the risk factors for Alzheimer’s, such as genetics and age. Doctors and patients need to know what they can do. The diabetes-Alzheimer’s connection points toward such a “modifiable” Alzheimer’s risk.

Understanding insulin’s role
It’s not yet clear why diabetes would promote Alzheimer’s, but there are several theories:

• Insulin helps control the deposits that occur on the brain of people with Alzheimer’s. These deposits are the key ingredients in the plaque that clogs the brains of Alzheimer’s patients.
• As diabetes develops, a person becomes increasingly resistant to insulin. In response, the body makes more insulin, and therefore needs more of an enzyme that breaks it down. That same enzyme is needed to remove amyloid from the brain but since it is also tackling the excess insulin, less is available to prevent the amyloid buildup that can lead to Alzheimer’s.
• Another study at Brown University shows that there are reduced insulin levels in the brains of patients with progressing Alzheimer’s disease, and that the insulin loses its ability to attach to cells, leading to cell dysfunction and death — similar to what happens in other organs of diabetics.

Insulin resistance is a major contributor to type 2 diabetes and is part of the ”metabolic syndrome” which affects 50 million Americans and is a major risk for diseases related to plaque buildup in artery walls, such as coronary artery disease and stroke. In these insulin-resistant states, body tissues such as muscle, liver and fat fail to respond normally to insulin produced by the pancreas, leading to metabolic abnormalities. Scientists have recently realized there are insulin receptors on all body tissues including the brain, that may affect the tissues’ function.

Various research findings also suggest that disruption of the insulin signaling system may occur in such disorders as Alzheimer’s and Parkinson’s diseases. These recent studies confirm that the insulin resistance in brain cells can affect how they function, causing some of the biochemical changes typically seen in Alzheimer’s.

Mice studies
Some recent experiments in mice lacking insulin receptors on their brain cells showed that nerve-specific insulin resistance could contribute to type 2 diabetes, loss of normal appetite control, obesity and even infertility. These mice had markedly reduced activity of insulin signaling proteins in the brain. This led to overactivity of an enzyme called GSK3 beta, which in turn, led to excess phosphorylation of a protein called tau.

The excess phosphorylation of tau is a hallmark of brain lesions seen in Alzheimer’s and has been suggested to be an early marker of this disease. On the other hand, these mice showed no changes in the survival of brain cells, memory or basal brain glucose metabolism, suggesting that insulin resistance may interact with other risk factors to promote full-blown Alzheimer’s.

Whatever the mechanism, the link between diabetes and Alzheimer’s gives people one more reason to try to get their diabetes under control. With the newer oral medications and insulin pumps and the ability to monitor blood sugar relatively painlessly, people can do more than ever before to manage their diabetes. Sure, it is a lot of trouble. But this link to Alzheimer’s gives extra impetus to the idea that those efforts are worth it.

Mitchell Kahn, M.D. is Assistant Clinical Professor of Medicine at Columbia Medical School and is Director of the Miller Health Care Institute at New York’s St. Luke’s-Roosevelt Hospital.

©Longevity Alliance, Inc. 2006