What's the Connection Between Diabetes and Alzheimer's? New Discoveries Shed Light on the Disease

Clinical trials are examining a hypothesis once considered revolutionary: that the causes of Alzheimer's are linked to diabetes. The origin of the beta cells in the pancreas, whose loss causes diabetes, is the same embryonic source as the nerve cells in the brain. So what is the link between diabetes and Alzheimer's, and can a diabetes medication alleviate Alzheimer's symptoms?

According to Dr. Shmuel Gevaon, a family medicine specialist at Clalit, a study first published in April 2006 suggests that the diabetes drug Avandia (rosiglitazone) may slow or halt the uncontrolled progression of Alzheimer's disease. Early research found this drug could do so, at least in patients who do not carry the ApoE4 gene, associated with a rapidly progressing form of early-onset Alzheimer's. 

Is this good news?

Dr. Shmuel Gevaon says, "Given the urgent need for new treatments and prevention methods for the disease, this is good news. However, the hypothesis behind this treatment posits that the same processes characterizing diabetes are also at the core of Alzheimer's disease."  

Is the diabetes epidemic in the United States linked to the obesity epidemic? Does obesity predict an increase in the prevalence of Alzheimer's?

"This aligns perfectly with our hypothesis," says Dr. Allen Roses. "Some researchers find a similarity in the metabolism of diabetes and Alzheimer's. The origin of beta cells in the pancreas, whose loss leads to diabetes, is the same embryonic source as the nerve cells in the brain."

"People with diabetes are at a higher risk of developing Alzheimer's," says Dr. Bill Thies, vice president for medical and scientific affairs at the Alzheimer's Association in Chicago. Thies notes that at least among women, obesity also increases the risk of Alzheimer's. "We have studies indicating that people who are obese in middle age are at greater risk of developing Alzheimer's. There's some masking because if you're a man and very overweight, you typically don't live long enough to develop the severe disease, but this tendency is clear in women."

Exploring New Medications: Hoping to Find a Treasure

Dr. Roses, now senior vice president for genetic research at the pharmaceutical company GSK, and Dr. Anne Saunders, his wife and research associate, detailed the hypothesis in the Alzheimer's & Dementia Association's bulletin in April.

In the early 1990s, Dr. Roses and his colleagues were the first to find the link between the ApoE4 gene and early-onset Alzheimer's. "We discovered that the ApoE4 gene is significantly associated with the most common form of the disease," says Dr. Roses. "What wasn't known was how the gene acts in the brain. Over the years, we've conducted experiments to see how different forms of the gene metabolize sugars in animals. We found a change in sugar utilization."

The body has complex, interrelated systems for regulating the burning of its primary fuel - sugar (glucose). This system is completely disrupted in both diabetes and Alzheimer's. Dr. Roses points to studies using imaging that have shown lower regulation of sugar burning in the brains of people carrying the ApoE4 gene.

(Photo: shutterstock)

Is the diabetes medication effective for Alzheimer's? 

Roses' company, GSK, manufactures Avandia, one of a group of diabetes drugs that improve sugar uptake by cells. Small clinical trials show that Avandia slightly improves cognitive function in people with mild to moderate Alzheimer's. However, it seems effective only in individuals who do not carry the ApoE4 gene. "If you have Alzheimer's and don't carry the ApoE4 gene, you may see quicker and better results with Avandia," says Dr. Roses. "But if you carry the ApoE4 gene, the drug doesn't seem to work, or you may need higher doses."  

The U.S. Food and Drug Administration has already approved a large-scale clinical trial with Avandia in Alzheimer's patients who have undergone genetic screening. Until the study results are known, which will take years, caution is advised against using Avandia to treat Alzheimer's, warns Dr. Roses. Dr. Thies also says it's too early to trial Avandia or any other diabetes medication to treat Alzheimer's. However, the findings give Thies hope. "It's another opening that might lead to the next generation of treatments for the disease," he says. "The more doors we open, the closer we'll get to finding a treasure behind one of them."

Physical and Mental Activity: A Protective Wall Against the Disease

Alzheimer's disease is severe, affecting nerve cells in patients' brains. Initially, it primarily impacts memory, but as it progresses, it can affect orientation, thinking, and motor skills. Currently, there are several drugs meant to slow the disease's progression, but their benefits are limited and short-term. If researchers can gain a deeper understanding of the causes of this degenerative disease, more effective drugs and other preventive measures could be identified. It is known that people with diabetes are more frequently affected by this disease, and the aforementioned researchers are trying to find the connection between the two diseases.

"According to research published in early June on the webmed site, adults who maintained physical activity in middle age reduced the risk of developing dementia 21 years later by 52 percent compared to those who did not engage in any activity. Their risk of developing Alzheimer's was even lower: 62 percent. This trend was even more pronounced among people carrying the ApoE e4 gene, which is associated with a higher risk of Alzheimer's," says Dr. Shmuel Gevaon.

The study conducted in Finland involved 1,449 men and women who completed questionnaires on their dietary habits and physical activity at work and leisure. Analyzing the questionnaires revealed that job-related physical activity, like heavy lifting, did not protect health to the same extent as leisure physical activity. According to the researchers, there was a slight reduction in dementia risk among those with physically demanding jobs, "but it's quite possible the findings were merely coincidental."

"Through physical activity in middle age, people carrying the ApoE e4 gene may reduce their Alzheimer's risk to the same level as those who do not carry it," says researcher Suvi Raurama from the Karolinska Institute in Stockholm, Sweden. The researcher emphasized that this involves vigorous physical activity for 20 to 30 minutes, twice to three times per week, "making you sweat and feel short of breath and not just a casual stroll around the neighborhood."

Conversely, Dr. Maria Carrillo, director of scientific and medical relations at the Alzheimer's Association, states that there is growing evidence that physical activity "does not have to be strenuous and doesn't even need special time allocation. It is most effective when done routinely and in combination with a brain-healthy diet, mental activity, and social interactions. Physical activity that combines mental activities - like planning the route and paying attention to traffic and signals - adds extra value to brain health. Performing this activity with another person offers the bonus of social connection."

"We know that physical activity is essential for maintaining blood flow to the brain and encouraging the development of new brain cells," added Dr. Carrillo. "Physical activity may also significantly reduce the risk of heart attacks, strokes, and diabetes, thereby protecting against risk factors for Alzheimer's and other dementias."

The Chicken and Egg: Function and Health

Intellectual activity and challenging employment may serve as a protective wall against memory loss from Alzheimer's disease and other dementias, Italian researchers led by Dr. Valentina Garibotto from the National Institute of Neuroscience in Milan at San Raffaele University claim.

The study adds to similar research that found a link between mental activity and Alzheimer's risk. Medical experts estimate that approximately 30 million people worldwide suffer from dementia, with Alzheimer's being the leading cause.

The research was published in the medical journal Neurology on October 21, 2008. It involved 242 Alzheimer's patients, 72 men and women with mild memory impairments, and 144 volunteers without memory impairment.

Dr. Shmuel Gevaon: "Researchers examined memory and brain function and used imaging devices for brain mapping (CT). They found that intellectually active individuals who suffered brain damage due to changes in the brain could preserve their memory and cognitive abilities better than intellectually inactive individuals with similar brain damage. These findings were consistent among people diagnosed with Alzheimer's and those with mild memory impairments where the disease was in its early developmental stages and confirmed in further study."

"The assumption is that education and work create a shield against the effects of dementia on the brain or on its functional reserves," said Dr. Garibotto. "In such people, the brain can compensate for the damage, allowing them to maintain functioning despite the brain damage."

"As with the chicken and egg question, researchers are still unsure where the ability to defend originates: do genetic factors allowing for higher education and work achievements determine the size of brain reserve, or is it the education itself that causes the brain to deal more successfully with Alzheimer's disease?" concludes Dr. Shmuel Gevaon.​