Recurrent Hypoglycemia and Dementia Risk in Older Adults with Type 2 Diabetes: A Systematic Review

Background Type 2 diabetes mellitus (T2DM) affects over 25% of adults aged 65 and older. While tight glycemic control is often indicated to reduce the risk of complications, it also elevates the risk of hypoglycemic episodes, particularly in older adults with reduced regulatory responses. Increasing evidence suggests that the recurrence of hypoglycemia may be linked to long-term cognitive decline and dementia. However, the strength of this association continues to be unclear. This systematic review analyzes current literature to assess how repeated hypoglycemic episodes can negatively impact cognitive function in older adults with T2DM.

Methods A literature search was conducted in Ovid MEDLINE on May 11, 2025. The search terms included combinations of “type 2 diabetes,” “recurrent hypoglycemia,” “cognitive impairment,” “dementia,” and “older adults.” MeSH keywords were used for sensitivity. The inclusion criteria were: (1) studies involving human subjects older than 60 years of age, (2) a documented association between recurrent hypoglycemia episodes and cognitive outcomes, and (3) English-language publications. Study screening, reviewing, and data extraction were done by two reviewers using the Catchii platform. The final inclusion was determined with consensus, and PRISMA guidelines were followed.

Results Eighteen studies met the inclusion criteria, including large-scale cohort studies, case-control studies, and meta-analyses. Across these studies, recurrent hypoglycemia was consistently associated with increased risk of dementia, Alzheimer’s disease, and vascular dementia. Several studies demonstrated a dose-response relationship, emphasizing the frequency of these events on the cognitive outcome in patients. Several biological mechanisms have been proposed throughout the studies, including neuronal glucose deprivation, cerebral microvascular damage, and accumulation of amyloid-beta and tau proteins. However, inconsistencies were noted in the definitions of hypoglycemia, cognitive assessment tools, and population characteristics. Most of the studies focused on severe hypoglycemia that required hospitalization, which limits generalizability to outpatient-managed patients.

Conclusion Recurrent hypoglycemia is a significant risk factor for cognitive decline in older adults with T2DM. Increasing frequencies of hypoglycemic episodes, whether secondary to tight glycemic control or age-related diminished regulatory responses, predict even higher dementia risks. Data suggests a strong association, but limitations remain in the generalizability of the results due to differences in study = design and outcome measures. Future research should aim to standardize the definitions of hypoglycemia and measure specific cognitive functions. Additionally, we should investigate whether preventing hypoglycemia in elderly patients can decrease the risk of cognitive deterioration. These findings highlight the importance of individualized glycemic regimen in elderly diabetic patients to preserve long-term cognitive function.