Hypoglycemia is a frequent and often serious complication of diabetes management. While its acute effects on cognition are well documented, growing evidence suggests that recurrent or severe hypoglycemia exposure may also contribute to long-term cognitive decline and increased risk of dementia in patients with diabetes. In fact, clinical and epidemiological data suggest that repeated hypoglycemic events are associated with lower performance in multiple cognitive domains, especially in pediatric and elderly populations. Moreover, meta-analyses and cohort studies highlight a significant association between severe hypoglycemia and increased risk of dementia while cognitive impairment has been shown to also increase the risk of hypoglycemia. This suggests a potential bidirectional relationship between hypoglycemia and cognitive decline. On the molecular level, both animal and human studies reveal that recurrent hypoglycemia induces oxidative stress, impairs mitochondrial dynamics, and leads to synaptic injury, particularly in vulnerable brain regions such as the hippocampus and cortex. These findings underscore the need for personalized glucose management strategies that minimize hypoglycemia risk while maintaining glycemic targets, particularly in populations vulnerable to cognitive impairment. This review summarizes the current understanding of the impact of hypoglycemia on brain function, including its structural, cellular, metabolic, and cognitive consequences.
Ancona et al. (Mon,) studied this question.