Cognitive Function in Diabetes: How to Protect Our Patients

People with diabetes pose a particular challenge when trying to assess cognitive function longitudinally. Population data suggest that the risk of developing dementia, both vascular and neurodegenerative, among people with diabetes followed for 20 years is roughly double that of those without diabetes. It may be even greater because the increased mortality from diabetes may create a survivor bias that eliminates those with diabetes prematurely.

Diabetes incidence increases with age, and cognitive impairment may predate the diabetes. Comorbidity with cardiovascular disease, hypertension, lipid disorders, and effects of multiple medicines adds to the difficulty of assessing changes over time. What's worse is that the changes are usually insidious. The patient may pass through physicians every few years with their diabetes-related mental capacity evolving over a much longer time frame.

In the exam room, our electronic health records have facilitated some longitudinal assessments of easily measurable numerical data — weight, A1c, blood pressure, and LDL-C — that can be graphed with a few clicks. Parameters that lack numbers, such as sensory or autonomic neuropathies, can be more elusive but are not hard to identify. Cognitive function, however, which may turn out to be a patient's greatest source of disability or barrier to certain therapeutic interventions, is notoriously difficult to recognize.

As we chat with our patients, we can get a sense of their self-care and capacity — although sometimes, the accompanying family member does the talking, and it is not always apparent if this reflects usual family dynamics or limitations on the part of the patient.

So, what can we do? Recently, a few studies have added insight into how clinicians might help protect or even reverse cognitive decline among those with diabetes.

Better Glycemic Control, Better Cognitive Performance?

A retrospective analysis assessed how supervised intensive lifestyle changes affected cognitive function in older patients with diabetes. A number of parameters were measured. One test of note was the Rey Auditory Verbal Learning Test. Participants were asked to repeat a series of words after hearing them, and then repeat them again later after being distracted with another task. They were also asked to duplicate a digital symbol scale where numbers are given a nonnumerical symbol.

The most consistent correlation showed that those who achieved the lowest fasting glucose levels on the day of the test showed better auditory learning. People classified as overweight had better performance than those noted to have overt obesity, and digital symbol performance correlated with improved A1c levels. Of particular importance, those with preexisting cardiovascular disease derived the most benefit mentally from regular participation in an exercise program. However, there was enormous variation in the raw data that precludes firm conclusions applicable to large populations.

Improving Brain Glucose Metabolism

Imaging studies suggest that brain glucose metabolism is impaired in dementia, but it remains unclear if glucose metabolism in the central nervous system runs parallel to factors we can improve using systemic targets of glucose control. Among the research efforts have been a number of experiments to see if one medication option offers a better cognitive result than other options, including intranasal insulin, liraglutide, metformin, and a ketogenic diet — all of these trials in progress — along with an unsuccessful trial using pioglitazone. One recently published metformin analysis suggests favorable results.

Another significant clue about selecting diabetic treatment options comes from a recent study involving community-living seniors with diabetes and nondiabetic participants as control subjects.

None of the people had dementia at baseline, and extensive cognitive testing was performed at 2-year intervals for 6 years. About half of those with diabetes took metformin, either alone or in combination; the other half received a controlled diet or were treated with other hypoglycemic agents. At 6 years, those receiving metformin maintained their executive functions at the level of the control subjects, whereas those treated in other ways developed significantly more measurable cognitive impairment. In addition, there seemed to be no confounding by other risk factors such as blood pressure or even the APOE genotype associated with dementia.

Awaiting Consensus

There is a lot of uncertainty in protecting cognitive function in aging patients with diabetes. Even whether to screen for cognitive dysfunction in patients with diabetes has brought some controversy, although a consensus in favor of screening is emerging.

The magnitude and importance of this challenge to the people affected and its public economic consequences remain immense, so we await expert consensus on best practices. For now, we have a few glimpses of what our best office options might be, but more conclusive studies would be of immeasurable value.

Richard M. Plotzker, MD, is a retired endocrinologist with 40 years of experience treating patients in both private practice and hospital settings. He has been a Medscape contributor since 2012.

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