Study Suggests Association Between Hypoglycemia, Dementia in Older Adults With Diabetes

A study of older adults with diabetes mellitus (DM) suggests a bidirectional association between hypoglycemic (low blood glucose) events and dementia, according to a report published Online First by JAMA Internal Medicine, a JAMA Network publication.1

There is a growing body of evidence that DM may increase the risk for developing cognitive impairment, including Alzheimer disease and vascular dementia, and there is research interest in whether DM treatment can prevent cognitive decline. When blood glucose declines to low levels, cognitive function is impaired and severe hypoglycemia may cause neuronal damage. Previous research on the potential association between hypoglycemia and cognitive impairment has produced conflicting results, the authors write in the study background.

Kristine Yaffe, M.D., of the University of California, San Francisco, and colleagues studied 783 older adults with DM (average age 74 years). During a 12-year follow-up, 61 patients (7.8 percent) had a reported hypoglycemic event and 148 (18.9 percent) developed dementia.

“Hypoglycemia commonly occurs in patients with diabetes mellitus (DM) and may negatively influence cognitive performance. Cognitive impairment in turn can compromise DM management and lead to hypoglycemia,” according to the study.

Patients who experienced a hypoglycemic event had a two-fold increased risk for developing dementia compared with those who did not have a hypoglycemic event (34.4 percent vs. 17.6 percent). Older adults with DM who developed dementia had a greater risk for having a subsequent hypoglycemic event compared with patients who did not develop dementia (14.2 percent vs. 6.3 percent), according to the study results.

“Among older adults with DM who were without evidence of cognitive impairment at study baseline, we found that clinically significant hypoglycemia was associated with a two-fold increased risk for developing dementia … Similarly, participants with dementia were more likely to experience a severe hypoglycemic event,” the authors conclude. “The association remained even after adjustment for age, sex, educational level, race/ethnicity, comorbidities and other covariates. These results provide evidence for a reciprocal association between hypoglycemia and dementia among older adults with DM.”

In an invited commentary2, Kasia J. Lipska, M.D., M.H.S. of the Yale University School of Medicine, New Haven, Conn., and Victor M. Montori, M.D., of the Mayo Clinic, Rochester, Minn., write: “Hypoglycemia is a major adverse consequence of glucose-lowering therapy in patients with type 2 diabetes mellitus (DM). … Older patients are at higher risk of hypoglycemia. Aging-related changes in renal function and drug clearance may contribute to this vulnerability.”

“Efforts to mitigate the risk of hypoglycemia are clearly warranted to improve quality of life and potentially prevent the associated adverse events,” they continue.

“Hypoglycemia in the course of type 2 DM treatment is both common and associated with poor outcomes. Therefore, decisions about the intensity and type of antihyperglycemic therapy must take into account the harms of hypoglycemia. Involving patients in these treatment decisions may favorably shift the current glucose-centric paradigm to a more holistic patient-centered one,” they conclude.


1. JAMA Intern Med. Published online June 10, 2013. doi:10.1001/jamainternmed.2013.6176.
2. JAMA Intern Med. Published online June 10, 2013. doi:10.1001/jamainternmed.2013.6189.