Associations of mid- and late-life severe hypoglycemic episodes with incident dementia among patients with type 2 diabetes: A population-based cohort study

Objective: Severe hypoglycemia is associated with an increased risk of dementia. We examined if the association is consistently present for mid-life and late-life hypoglycemia. 

Methods: Using healthcare data from Population Data BC, we created a base cohort of patients with incident type-2 diabetes aged ≥40 years. Exposure was the first occurrence of severe hypoglycemia (hospitalization or physician visit). We assessed exposure vs no exposure in mid-life (age 45-64) and late-life (age 65-84) cohorts. Index date was the later of the 45th birthday (mid-life cohort), 65th birthday (late-life cohort) or diabetes diagnosis. Those with hypoglycemia or dementia before index date were excluded. Patients were followed from index date until dementia diagnosis, death, emigration or December 31, 2018. Exposure was modeled as time-dependent. We adjusted for confounding using propensity score weighting. Dementia risk was estimated using cause-specific hazards models with death as a competing risk. 

Results: Of 221,683 patients in the mid-life cohort, 1,793 experienced their first severe hypoglycemic event. Over a median of 9.14 years, 3,117 dementia outcomes occurred (32 among exposed). Of 223,940 patients in the late-life cohort, 2,466 experienced their first severe hypoglycemic event. Over a median of 6.7 years, 15,997 dementia outcomes occurred (158 among exposed). The rate of dementia was higher for those with (vs. without) hypoglycemia in both the mid-life (hazard ratio, 95% confidence interval=2.85, 1.72-4.72) and late-life (2.38, 1.83-3.11) cohorts.

Conclusion: Both mid-life and late-life hypoglycemia were associated with approximately double the risk of dementia, indicating the need for prevention throughout the life-course of diabetes.