Increased Risk of Alzheimer's Disease With Glycemic Variability: A Systematic Review and Meta-Analysis.

There is increasing evidence that establishes a connection between fluctuations in glucose metabolism and the onset of Alzheimer's disease (AD). Current research supports the notion that this metabolic imbalance significantly affects cognitive health. However, the specific mechanisms through which these fluctuations influence neurodegeneration, eventually leading to AD, require further exploration. This study aims to determine the risk of AD among individuals with fluctuations in blood glucose levels, with or without type 2 diabetes mellitus (T2DM), further providing the most recent and thorough overview of the evidence in this area. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, a thorough search was carried out utilizing particular phrases in the PubMed, Elsevier, Research Gate, and Cochrane databases: ("glucose variability" or "glycemic variability" or "glucose fluctuation" or "glucose instability" or "glycemic fluctuation") and ("Alzheimer's disease" or "Alzheimer disease" or "Alzheimer dementia" or "Alzheimer"). Studies published between January 2014 to January 2024, written in English, and examining the relationship between glucose variability and AD, were included. The outcomes measured were risk of cognitive impairment and AD, cognitive performance, and risk of AD. The results of the literature search produced 142 records, with six studies meeting the eligibility criteria. Parameters for glycemic variability included fasting plasma glucose (FPG) variability, glycated hemoglobin (HbA1c) variability, FPG variability independent of the mean (VIM), FPG coefficient of variation (CV), and FPG standard deviation (SD). The studies revealed a positive correlation between glycemic variability and the risk of AD over time, and the findings indicated that maintaining stable glycemic levels may reduce the risk of cognitive decline among individuals with or without T2DM. Due to the small number of studies that are currently available, despite a calculated relative risk of 2.65 indicating a higher risk of AD among subjects with glycemic variability, the inclusion of the null value in the confidence interval (0.61-11.45) renders these findings not statistically significant. This comprehensive review demonstrated that, in people with or without diabetes, glycemic variability influences cognitive decline and the risk of AD. The studies demonstrated a correlation between higher fluctuations in glucose levels and an increased risk of AD, highlighting the importance of managing blood sugar levels to mitigate dementia risks. Despite these strong associations, the actual incidence rates of AD in the studied populations remained relatively low. Overall, the results were not statistically significant. Further research is recommended to explore the risk of AD among individuals with fluctuations in blood glucose levels.