The risk for dementia associated with hypoglycemia was consistently more than doubled in both mid-life and late-life cohorts.

The association between severe hypoglycemic episodes and dementia has been assessed and established by several studies using different data sources, design elements, and analysis methods, explains Wajd Alkabbani, MSc, PhD-candidate.

“While some of these studies assessed the link between the number of severe hypoglycemic episodes and dementia, none focused on the age when the hypoglycemic episode occurred,” Alkabbani says. “For example, studies looking at other dementia risk factors, such as depression, stroke, menopause, or even diabetes itself, have considered the potential impact of age at occurrence. This, however, was never explored for hypoglycemia. Therefore, this was an important gap to address to further our understanding of the relationship between hypoglycemia and dementia.”

Mid-Life and Late-Life Cohorts Compared for Dementia Link

For a study published in Diabetes Care, Alkabbani and colleagues examined if the correlation between severe hypoglycemia and dementia risk is consistently present if hypoglycemia occurs in mid-life or late-life. The researchers used administrative healthcare claims data from the province of British Columbia. They had access to anonymized data on hospital admissions, physician visits, drug dispensations, and several demographic characteristics of almost all residents from 1996 to 2018. After linking these databases, they created a base cohort of patients with T2D and then created two sub cohorts, a mid-life (aged 45-64) sub cohort and a late-life (aged 65-84) sub cohort.

“In each sub cohort, we assessed if the first-ever severe hypoglycemia event (hospitalization or physician visit) occurred, and we went on to assess the association with dementia later on using established epidemiologic methods that take into account a patient’s history and other risk factors for both hypoglycemia and dementia,” Alkabbani says.

“We anticipated an increased risk for dementia if hypoglycemia occurs later in life, as the brain is potentially more vulnerable,” she continues. “However, it was surprising to see that the association was consistent whether hypoglycemia occurred in mid- or late-life. I think physicians, especially endocrinologists but also all healthcare professionals who provide care for patients with diabetes, should be aware of the association between hypoglycemia and cognitive impairment, regardless of age.”

Physicians Can Identify Those Patients at Risk

The main takeaway of this study, according to the authors, is that the risk for dementia associated with hypoglycemia was consistently more than doubled in both the mid-life and late-life cohorts. This was robust even after the study team employed several subgroup and sensitivity analyses and used various methodologies.

Alkabbani and colleagues observed that the overall findings of the primary and secondary analyses were consistent across a range of sensitivity analyses (Figure). This included changing the age cutoff, lag period, and hypoglycemia definition used to define the cohorts. They note that some estimates had wider confidence intervals due to a smaller sample size.

“Our research highlights the need to prevent and protect patients receiving insulin and insulin-secreting agents from severe hypoglycemic episodes throughout their life,” Alkabbani notes. “Physicians can identify those at high risk for hypoglycemia and discuss potential tradeoffs between the intensity of diabetes therapy and avoidance of severe hypoglycemic events. Discussions on the importance of recognizing signs and symptoms of hypoglycemia, how to manage them, and when to seek care are also critical for patients with diabetes.”

The study team would like to see research focused on further elucidating the exact mechanisms by which hypoglycemia can cause this long-lasting damage. “From an epidemiology perspective, I hope to see future studies assess how hypoglycemia interacts with other cardiometabolic risk factors for dementia, such as stroke,” Alkabbani says.