Relationships Between Brain Glucose Metabolism Patterns and Impaired Glycemic Status: A Systematic Review of FDG-PET Studies With a Focus on Alzheimer's Disease

It is well-established that individuals with type 2 diabetes have an increased risk of developing cognitive impairment and Alzheimer's disease (AD). However, it is not fully determined how insulin resistance and type 2 diabetes are related to AD-related brain glucose metabolism abnormalities. For this aim, we performed a systematic review of the studies investigating the association between cerebral glucose metabolism and glycemic status, including diabetes, insulin resistance, or hyperglycemia. Medline, Embase, and Cochrane databases were searched (till February 2, 2025). All English full-text papers studying 18F-FDG-PET that investigated the association between cerebral FDG uptake or cerebral metabolism rate and glycemic status were included. These studies were reviewed for quality assessment, data extraction, and qualitative synthesis. After screening titles and abstracts of 718 unique records identified from our search, 23 studies (5308 participants) addressing the association between brain glucose metabolism alterations, as assessed by FDG-PET scan, and glycemic status were included for qualitative analysis. Of these 23 studies, 22 studies suggested that hyperglycemia or insulin resistance is related to global or regional cerebral glucose hypometabolism. The regional brain metabolism reductions were mostly in the frontal cortex, parietotemporal cortex, posterior cingulate cortex, and precuneus cortex, known as AD-signature areas. Hyperglycemia, diabetes, and insulin resistance are associated with cerebral glucose hypometabolism in similar regions compared to AD. This can suggest that even in cognitively normal individuals, insulin resistance can potentially increase the predisposition to abnormal AD-like glucose metabolism.