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Monday, Oct. 17, 2011

Worrisome link between diabetes, Alzheimer's


NEW YORK — In 1999, the Rotterdam Study uncovered the strong association between diabetes and Alzheimer's disease. In this landmark study carried out in the Netherlands, 6,370 elderly men and women were followed for an average of two years. In what was perhaps one of the first reports on this issue, they found that having diabetes almost doubled the risk of dementia. Since then, several studies have confirmed these findings, and threw light on the probable mechanism for this connection.

A nine-year study published in 2004 followed 842 older Catholic nuns, priests and brothers. Although none of them had any signs of Alzheimer's at the beginning of the study, at the end of it, 151 of them had developed Alzheimer's. A statistical analysis found that those who had type 2 diabetes had a 65 percent increased risk of getting Alzheimer's. Later, it was also found that this increased risk applies to both type 1 and type 2 diabetes.

Type 1 diabetes frequently occurs before the age of 20. It is caused by antibodies destroying the pancreas, the organ that produces insulin. This type of diabetes occurs in 10 to 15 percent of diabetics. In type 2 diabetes, which occurs in 85 to 90 percent of diabetics, the cause is primarily a condition called "insulin resistance" where insulin just doesn't work as it is supposed to do. Type 2 diabetes has a strong genetic component but, initially at least, can be prevented with changes in diet and lifestyle.

In the United States, Alzheimer's disease affects one in 10 Americans over 65 years of age, and almost 50 percent of those over 85. Almost 26 million Americans have diabetes and close to 80 million are pre-diabetic, meaning they haven't developed all the symptoms of the disease. While care for diabetics represents $174 billion in health care costs, the cost for the estimated 5.4 million Americans who have Alzheimer's is over $180 billion.

A Swedish study published in 2008 found that men with low insulin production at age 50 were nearly one-and-a-half times more likely to develop Alzheimer's disease than people without insulin problems. That study also found that the strongest association between diabetes and risk of Alzheimer's was strongest in people who did not have the APOE4 gene. That gene has been found to increase the risk for Alzheimer's disease.

Diabetes may also lead to people developing mild cognitive impairment, which is a transitional stage between the cognitive characteristics of normal aging and the more serious problems resulting from Alzheimer's or other kinds of dementia. For example, because diabetes damages the blood vessels, it has long been known as a serious risk factor for vascular dementia, manifested by cognitive and memory problems.

What explains the association between these two serious diseases? Studies carried out over the last several years show that both diabetes and Alzheimer's share some very damaging molecules known as advanced glycation end products (AGEs). Once produced, these substances affect the structure and functions of important proteins in the body.

The connection between diabetes and Alzheimer's begs the obvious question. Is it possible to affect Alzheimer's by altering insulin levels? By mimicking high insulin levels in healthy adults ranging in age from 55 to 81, researchers were able to elevate some markers of Alzheimer's in the brain.

But, how about lowering insulin levels? Would that also have an effect? Researchers from the Boston University School of Public Health reported that individuals who used thiazolidenedione (TZD) drugs to lower their blood sugar levels had lower rates of Alzheimer's disease. In 142,328 patients who received a first prescription for TZDs or insulin without previous prescription for either medication had up to 20 percent fewer cases of Alzheimer's than patients who hadn't received them.

These important studies suggest that preventing or effectively treating diabetes may lower the risks for Alzheimer's disease. The positive effects on diabetes of dietary changes, exercise, nutrients and drugs are well known. Now there is an additional reason to put them to use.

Cesar Chelala, M.D., Ph.D, carried out research in biochemistry, molecular genetics and pharmacology.


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