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Can optimal glucose management reduce risk for dementia in diabetes?
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In adults with diabetes, failure to control glucose levels for both the short term and the long term may lead to impaired cognitive function.
Glycemic control is most likely a contributor to risk for future dementia. People with diabetes can develop cognitive decline for several potential reasons, most of them vascular. Those with type 2 diabetes, in particular, can develop vascular disease unrelated to glucose levels since they often have high blood pressure and hyperlipidemia. However, in the DCCT study, a younger population without a lot of other health risks at baseline was followed for 18 years, and researchers found that HbA1c correlated with declining cognitive function. Similarly, other studies looking at large populations have shown that people with diabetes, particularly type 2, have higher rates of dementia and cognitive decline vs. people without diabetes. Although the findings do not necessarily show that glycemic control is a risk factor, it is presumed that glycemic control is probably contributing.
We take a multitiered approach to improving glucose levels that involves healthier eating, regular physical activity and medications as needed. We are fortunate these days that we have a much wider range of medications to treat people with type 1 and type 2 diabetes, so we can more safely get to glucose levels that are in the more normal range without the higher risk for hypoglycemia that we had with previous medications.
However, we must walk a fine line. Hypoglycemia can be a limiting factor in all people with type 1 diabetes and in many with type 2 diabetes, especially those with longer disease duration. We must balance improving HbA1c levels with the risk for hypoglycemia. The major guidelines call for variable HbA1c targets, depending on a person’s risk for hypoglycemia. As people with diabetes age, we relax control, because older adults are at increased risk for a more severe reaction.
Acute changes in blood sugar levels also impair memory and attention. Studies have found impairment in memory and attention in patients whose blood glucose levels rise above 300 mg/dL. This tells us that it is not just long-term glucose control, but also short-term that are key to improving cognition and reducing the risk for further decline.
Thomas W. Donner, MD, is associate professor of medicine at Johns Hopkins University School of Medicine and director of the Johns Hopkins Diabetes Center in Baltimore. Disclosure: Donner reports no relevant financial disclosures.
Glucose targets cannot yet be implemented universally in people with diabetes as a strategy for dementia prevention since the mechanisms by which diabetes impairs brain function and cognition are not fully understood.
In general, if you look at the literature, glycemic control is associated with brain function, structure and cognition. My colleagues and I have worked with HMO data in Israel on HbA1c levels for the last 20 years in our participants. Not surprisingly, those with HbA1c trajectories that are relatively stable and around 7% or below have the best cognitive function. Those with diabetes and an HbA1c trending upward, or declining but beginning very high, tend to have poorer cognitive function. Based on those data, you could theoretically say, yes, if we control glucose well, we will decrease the risk for Alzheimer’s disease or dementia, in general, in diabetes.
However, strict diabetes control has been demonstrated to carry risk for certain populations.
Recently the American Diabetes Association has made some changes, calling for softer HbA1c targets in some cases. For people with diabetes and MCI, the HbA1c cutoff is 8%, and that is because they believe that hypoglycemia has the most adverse effect on brain function. For people who already have some cognitive impairment, even without substantive complications of other kinds, the guidelines allow for higher cutoffs just to prevent this major hypoglycemic episode. There is consistent literature showing people with diabetes who were hospitalized for hypoglycemic episodes were at an increased risk for developing dementia. This is very similar to what we see in other diabetes complications, but with an additional twist — that when your cognition is declining, you might be entering a dangerous cycle of not being as compliant or getting confused with the medication, thereby doing some damage to your brain that is led, or is caused, by cognitive impairment.
Theoretically speaking, the answer is it is not good to have a high HbA1c, because the higher HbA1c, the poorer your cognition. However, we do not have long-term data on cognitive status in people with diabetes and a sustained, higher HbA1c, since by definition, if someone has sustained high blood glucose levels, the physician is going to try to lower them. Additionally, new research suggests that specific genetic variants — and not HbA1c — may better predict cognitive decline in people with diabetes, and advances in precision medicine may be able to better target at-risk patients. Until more is known, it is not clear which of the diabetes-related factors is crucial predict cognitive decline.
Michal Schnaider Beeri, PhD, is professor of psychiatry at the Icahn School of Medicine at Mount Sinai, New York, and director of the Joseph Sagol Neuroscience Center at Sheba Medical Center, Israel. Disclosure: Beeri reports no relevant financial disclosures.