Higher Blood Glucose Levels Linked to Faster Brain Aging
Ingrid Fadelli
July 5, 2026 (MedicalXpress) — The human brain is known to naturally change with age, shrinking in size and volume after people reach their 30s or 40s. In some cases, however, it can age faster than expected, which can increase the risk of early memory loss, cognitive decline and some brain-related disorders.
Faster brain aging has been linked to various neurological and psychiatric disorders, as well as some neurodegenerative diseases. The factors that influence the speed at which the brain ages, however, have not yet been clearly and comprehensively elucidated.
Researchers at Jilin University and China Medical University recently analyzed available neuroimaging, genomic and biological data to better understand the contribution of metabolic processes (i.e., the chemical reactions that transform food into energy) to brain aging. Their findings, published in Molecular Psychiatry, suggest that higher levels of glucose in the blood are associated with accelerated brain aging.
Uncovering metabolic signatures of brain aging with AI
To explore the biological underpinnings of brain aging, the researchers analyzed data from the UK Biobank, a large biomedical database that contains health-related, genetic and imaging data collected from thousands of people living in the U.K. By analyzing these people’s brain scans, they derived measurable brain features, such as the size of specific brain regions, tissue characteristics and structural changes.
Subsequently, they trained machine learning algorithms to predict the age of people based on the brain features they identified. They found that a specific statistical method, known as a least absolute shrinkage and selection operator (LASSO) regression model, was best at predicting the age of people’s brains, with an average error rate of 3.26 years.
“We integrated multimodal neuroimaging (MRI), plasma metabolomics, and genomic data from the UK Biobank to identify metabolic markers of brain aging and evaluate their causal relevance,” wrote Zhirong Li, Yating Miao and their colleagues in their paper. “Using 1,079 imaging-derived phenotypes (IDPs) from 4,333 healthy participants, we trained and validated machine learning models for brain age prediction, with a LASSO regression model achieving the best performance. Brain age gap (BAG) was then estimated in 37,458 participants.”
Using the best-performing LASSO model, the researchers calculated a value called BAG for thousands of people included in the UK Biobank database. This is essentially a value indicating whether a person’s predicted brain age is higher or lower than their actual age, and by how many years.
Li, Miao and their colleagues then analyzed metabolomics data derived from the same people’s blood samples. This allowed them to identify nine molecules in the blood that appeared to be significantly associated with BAG values.
Notably, glucose appeared to have the strongest association with BAG values. Specifically, higher blood glucose levels were linked to brains that showed more signs of aging in imaging scans and thus appeared older than their actual age.
“Association analyses in 21,780 individuals identified nine plasma metabolites significantly linked to BAG after Bonferroni correction, with glucose showing the strongest effect (β = 0.32, P = 9.90 × 10⁻¹²),” wrote Li, Miao and their colleagues. “Genome-wide association studies (GWAS) identified 392 BAG-associated single-nucleotide polymorphisms (SNPs) (P < 5 × 10⁻⁸), and two-sample Mendelian randomization (MR) provided evidence supporting a potential causal role of glucose in accelerating brain aging.”
Informing the prevention of some brain-related conditions
This study offers evidence suggesting that glucose in the blood may contribute to processes linked to accelerated brain aging. Interestingly, the researchers found that higher levels of blood glucose were also linked to an increased risk of developing seven different conditions known to affect brain function.
“Clinically, elevated plasma glucose was positively associated with seven brain disorders, including all-cause dementia, Alzheimer’s disease, vascular dementia, Parkinson’s disease, stroke, depression, and anxiety, and negatively associated with cognitive performance, movement function, and mental health outcomes,” wrote the authors.
“Higher glucose concentrations were also associated with reduced regional brain volumes across 80 cortical, subcortical, and cerebellar regions. These findings implicate glucose metabolism as a modifiable pathway in brain aging, with implications for early intervention strategies aimed at preserving brain health across the lifespan.”
Future studies could draw inspiration from the team’s findings and further explore the association between higher glucose levels and brain aging, perhaps focusing on specific neurodegenerative or neuropsychiatric conditions. Eventually, the recent work by Li, Miao and their colleagues may contribute to the development of strategies for monitoring and preserving brain health.
Written by Ingrid Fadelli, edited by Lisa Lock, and fact-checked and reviewed by Andrew Zinin.
Publication details
Zhirong Li et al, Metabolomic signatures of brain aging: A multimodal and genetic study, Molecular Psychiatry (2026). DOI: 10.1038/s41380-026-03703-3
Journal information: Molecular Psychiatry