Association between hypoglycemia and dementia in patients with type 2 diabetes

- Both T2DM and hypoglycemia are considered as risk factors of dementia.
- Acute, severe hypoglycemic episodes induce brain damage and subsequent dementia.
- The effect of recurrent moderate hypoglycemia on dementia remains uncertain.
- Possible pathophysiological links between hypoglycemia and dementia were proposed.
- Appropriate diabetes management strategies are needed to minimize the risks of hypoglycemia.

In addition to increased risks of macrovascular and microvascular complications, patients with type 2 diabetes mellitus (T2DM) usually also are at increased risk for cognitive impairment and dementia. Hypoglycemia, a common consequence of diabetes treatment, is considered an independent risk factor for dementia in patients with T2DM. Hypoglycemia and dementia are clinically underestimated and are related to poor outcomes; thus, they may compromise the life expectancy of patients with T2DM. Epidemiological evidence of hypoglycemia-associated cognitive decline and dementia is highly varied. Acute, severe hypoglycemic episodes induce chronic subclinical brain damage, cognitive decline, and subsequent dementia. However, the effects of recurrent moderate hypoglycemia on cognitive decline and dementia remain largely uninvestigated. Poor glycemic control (including fluctuation of hemoglobin A1C [HbA1c] and glucose values) and the viscous circle of bidirectional associations between dementia and hypoglycemia may be clinically relevant. The possible pathophysiological hypotheses include post-hypoglycemic neuronal damage, inflammatory processes, coagulation defects, endothelial abnormalities, and synaptic dysfunction of hippocampal neurons during hypoglycemia episodes. This article reviews previous findings, provides insight into the detection of groups at high risk of hypoglycemia-associated dementia, and proposes specific strategies to minimize the potential burdens associated with hypoglycemia-related neurocognitive disorders in patients with T2DM.