Older diabetics who’d had an episode of hypoglycemia had a twofold increased risk of dementia, and those who developed dementia over the 12 years of the study had a threefold greater risk of having a hypoglycemic event, Kristine Yaffe, MD, of the University of California San Francisco, and colleagues reported online in JAMA Internal Medicine.
“Our results provide evidence for a bidirectional association between severe hypoglycemia and dementia,” they wrote. “Hypoglycemia may impair cognitive health, and reduced cognitive function may increase the risk for a hypoglycemic event that could further compromise cognition, resulting in a detrimental cycle.”
The direction of the association between hypoglycemia and cognitive impairment has been debated, and some work has suggested that it may be reciprocal, but little prospective work has been done.
To gain insight into the relationship, Yaffe and colleagues assessed data from the 3,075-patient Health, Aging, and Body Composition (Health ABC) Study, in which about a quarter of the patients (783) had diabetes but no cognitive impairment at baseline. The study did not specify whether patients had type 1 or type 2 disease.
Mean patient age was 74, 47% of patients were African American, and 47.6% were female. Patients were followed for a mean of 12 years.
The researchers determined dementia diagnoses and hypoglycemic events via hospital records. During those 12 years of follow-up, 61 patients (7.8%) had a reported hypoglycemic event, and 18.9% developed dementia.
Yaffe and colleagues found that significantly more patients who had a hypoglycemic event developed dementia than did those who did not have a hypoglycemic event (34.4% versus 17.6%, P<0.001). After adjustment for age, sex, education, insulin use, race/ethnicity, and other confounders, these patients had twice the risk of developing dementia, they found (HR 2.1, 95% CI 1.0 to 4.4), adding that the number needed to harm was 5.9. Similarly, more older adults with diabetes who developed dementia had a subsequent hypoglycemic event compared with those who didn't develop dementia (14.2% versus 6.3%, P<0.001). In adjusted analyses, the risk of hypoglycemia was about three times higher for patients who'd developed dementia (HR 3.1, 95% CI 1.5 to 6.6), and the number needed to harm was 12.7, they reported. Yaffe and colleagues explained that hypoglycemia may contribute to the pathogenesis of dementia through several mechanisms, including the fact that recurrent severe hypoglycemia has been shown to result in brain damage. It can also lead to ionic homeostasis and increases in reactive oxygen species that can lead to neuronal death, they wrote. At the same time, dementia contributes to hypoglycemia risk because it may make it more difficult for patients to manage their diabetes treatment regimens. Cognitive dysfunction may also delay the recognition of symptoms of hypoglycemia, they wrote. "More studies are needed to reduce the incidence of hypoglycemia among older persons with dementia as well as in those with less severe forms of cognitive impairment," they wrote. Yaffe and colleagues concluded that clinicians should consider cognitive function in the clinical management of older patients with diabetes. In an accompanying editorial, Kasia Lipska, MD, of Yale, and Victor Montori, MD, of the Mayo Clinic in Rochester, Minn., wrote that clinicians' understanding "of the interplay between cognitive dysfunction and hypoglycemia continues to evolve." Minimizing the risk of hypoglycemia in this population is important, they wrote, but they noted that the "right choice for a patient at a given point in time requires a careful balance of the circumstances of the patient, his or her goals and preferences, and the research evidence about the alternatives."