Association of glycosylated hemoglobin concentrations with structural and functional brain changes in the normoglycemic population: A systematic review

Abstract Optimal glucose control is crucial for maintaining brain health and preventing metabolic and cognitive disorders in the general population. Glycosylated hemoglobin (HbA1c) serves as a key marker for assessing glucose intolerance and its impact on brain structure and function in healthy individuals. However, existing literature presents conflicting findings, necessitating a systematic review to consolidate current knowledge in this domain. This systematic review examines 26 English‐language studies involving participants aged 15 years and above, investigating the relationship between HbA1c levels and brain health. Studies focusing on normal/general populations and utilizing magnetic resonance imaging (MRI) as the imaging modality were included. Exclusion criteria encompassed review articles, abstracts, letters, animal studies, and research involving neuropsychiatric or metabolic diseases. Data were gathered from PubMed, Scopus, and Web of Science databases up to November 2023. Analysis reveals significant associations between HbA1c levels and various brain metrics, including volume, cortical thickness, fractional anisotropy, mean diffusivity, activity, and connectivity. However, findings exhibit inconsistency, likely attributed to disparities in sample characteristics and study sizes. Notably, hippocampal volume, white matter hyperintensity, and ventral attention network connectivity emerge as frequently affected structures and functions, mirroring trends observed in diabetic populations. Despite inconclusive evidence, glucose intolerance appears to exert considerable influence on select brain structures and functions in individuals without diagnosed metabolic disorders. Understanding these associations is critical for mitigating the risk of cognitive decline and dementia in healthy populations. Future investigations should aim to elucidate the intricate relationship between HbA1c concentrations and brain health parameters in normoglycemic individuals.