Diabetes: A Modifiable Risk Factor for Alzheimer’s Disease

Learn more about the connections between Alzheimer's disease and diabetes.

In the United States population, nearly 1 in 10 of us has diabetes mellitus, a disorder of glucose metabolism that harms multiple body systems. When we refer to diabetes mellitus, we are grouping together two distinct disorders: Type 1 diabetes reflects degeneration of insulin-producing pancreatic cells, requiring treatment with insulin. In type 2 diabetes, which may or may not require insulin treatment, insulin deficiency and resistance develop more slowly, typically a decade or longer, and result in high blood sugar (hyperglycemia). This article describes some recent findings about the relationship between diabetes and Alzheimer’s disease and reviews some of the recommendations for prevention, as well as detection and treatment. Diabetes, for the purpose of this article, refers here to type 2 diabetes.

The Impact of Diabetes on the Body

Diabetes, particularly if untreated or poorly treated, is known to damage the eyes, the heart and blood vessels, and the kidneys. It can increase the medical risks associated with pregnancy, predispose to depression, and induce pain from damaged nerves (peripheral neuropathy). For those of us exploring risk factors for dementia, the effects of diabetes on the brain are of special interest. Among people with diabetes, the risk of developing Alzheimer’s has been found to be 65 percent higher than among non-diabetic controls. In people with Alzheimer’s, the rate of diabetes is very high, measured in one large community study to be 35 percent. An even higher number of people with Alzheimer’s (46 percent) have glucose intolerance, which can be a precursor to diabetes.  Even without overt diabetes, impaired regulation of glucose levels has been associated with cognitive impairment.

Further, even established cases of diabetes are quite treatable, so detection allows for interventions that can lessen diabetic complications such as heart disease or dementia One of the compelling questions raised by the established association between diabetes and Alzheimer’s is how these disorders influence each other. A variety of mechanisms have been suggested, some direct and others indirect. Diabetes is known to damage the arteries that bring blood, with its supply of glucose and oxygen, to the brain. Interference with this source of nourishment is thought to increase the likelihood of brain deterioration. Vascular dementia, in fact, is even more common than Alzheimer’s among people with diabetes. The formation of Advanced glycation end products (AGEs), which are tissue-damaging molecules derived from sugars and proteins, is facilitated in the presence of high blood glucose and elevated beta-amyloid levels. Beta-amyloid plaques are one of the hallmark signs of Alzheimer’s disease. Diabetes, too, is linked with an increase in systemic inflammation, an observation of increasing interest to AD researchers who note the link between inflammatory processes and dementia. Increased blood pressure and elevated blood fats (hyperlipidemia), often associated with diabetes, are known to increase dementia risk. Elevated blood sugar, called hyperglycemia, is a hallmark of diabetes and has also been correlated with cognitive decline. Not only glucose but also insulin levels are elevated in people with diabetes, and this may be an important factor in the brain-damaging effects of diabetes. Although normal levels of insulin contribute to brain health, higher levels have been shown to be harmful. The reasons for this are not fully understood yet, but one proposal is that high levels of insulin in the brain result in competition for Insulin Degrading Enzyme (IDE), a protein that helps regulate insulin levels but also contributes to the removal of beta-amyloid, an important component of Alzheimer’s plaques.

It is not yet clear which of these effects best explains diabetes’ contribution to the development of Alzheimer’s, but it is likely that they work together to increase risk.

Detection and Treatment of Diabetes Can Be Improved

Cost-benefit analyses have not provided support for widespread diabetes screening in the general population, but evidence does support the value of screening individuals at risk. A recent United States Preventive Services Task Force screening guideline, which recommended annual screening of individuals at risk for abnormal glucose metabolism or diabetes, identified the following risk factors:

• age of 45 years or older,
• overweight or obesity,
• presence of a first degree relative with diabetes,
• women with a history of gestational diabetes or polycystic ovarian syndrome, and
• African American, American Indian/Alaska Native, Asian American, Hispanic/Latino, or Native Hawaiian/Pacific Islander ancestry.

Individuals found to have abnormal results on fasting blood glucose, glucose tolerance test, or the HgbA1C test can be counseled to adopt health-promoting lifestyle changes, including:

• a weight loss program targeting loss of 7 percent of body weight
• a program of physical activity with the goal of at least 150 minutes per week of moderate activity, and
• consideration of medication prevention of type 2 diabetes using metformin.

Through prevention of onset, delay of progression, and treatment of established cases of diabetes, many medical complications of diabetes can be reduced, including the risk for cognitive decline. Established cases of dementia in diabetic individuals, whether primarily Alzheimer’s or other causes, are currently treated according to standards for care of dementia added to concurrent treatment approaches for diabetes. In the future, the connection between diabetes and dementia may promote further exploration of dementia treatments that exploit insulin’s effects on the brain. Insulin itself is currently being investigated as a treatment for Alzheimer’s, which some investigators regard as a sort of “diabetes of the brain,” and preliminary trials have measured the beneficial cognitive effects of intranasal (nasal) insulin. Intranasal insulin is not yet available as an Alzheimer’s treatment, as it is currently in clinical trials.

Conclusion

There is little doubt that diabetes, among its other devastating effects, increases the risk and severity of dementia in general and Alzheimer’s in particular. A brain-healthy lifestyle includes modifications of diet and physical activity that will decrease the risk for diabetes. Not all cases of diabetes can be prevented, but treatment offers many benefits, including the likelihood of reduced risk for dementia. Early detection and aggressive treatment of diabetes will help reduce the many burdens that this disease imposes on our population, including the burden imposed by diabetes’ damaging partnership with Alzheimer’s.