Routine Test Reveals Risk of Fast-Progressing Alzheimer’s
At the European Academy of Neurology (EAN) Congress 2025, researchers from the University of Brescia presented a breakthrough study linking insulin resistance to rapid cognitive decline in Alzheimer’s disease. Using a simple blood test known as the triglyceride-glucose (TyG) index, the team found that patients with high TyG scores were up to four times more likely to experience rapid mental deterioration.
The study reviewed records of 315 non-diabetic individuals with cognitive impairments, including 200 with confirmed Alzheimer’s disease.. Over a three-year follow-up period, patients were grouped based on their TyG levels. Those in the highest third of the TyG index in the Mild Cognitive Impairment (MCI) Alzheimer’s subgroup declined significantly faster, losing more than 2.5 points per year on the Mini-Mental State Examination. This pattern did not appear in patients without Alzheimer’s. According to Dr. Bianca Gumina, the lead investigator, the findings offer a practical tool to identify high-risk patients early using a test available in most hospital laboratories.
Understanding the Metabolic Link in Alzheimer’s disease. Progression
While insulin resistance has long been suspected to contribute to Alzheimer’s onset, this study sheds new light on its influence over disease progression, particularly during the MCI stage—a period marked by wide variation in patient outcomes. The TyG index, a low-cost marker of insulin resistance calculated from routine blood tests, served as the key metric in the study.
In Alzheimer’s disease, insulin resistance may hinder the brain’s ability to absorb glucose, promote amyloid plaque build-up, disrupt the blood–brain barrier, and trigger inflammation. These biological mechanisms seem especially relevant in Alzheimer’s, but not in other forms of neurodegenerative diseases. Dr. Gumina noted the surprising specificity of the results. “It suggests a disease-specific vulnerability to metabolic stress during the prodromal window, when interventions may still change the trajectory,” she explained.
Implications for Early Intervention and Future Research
The findings open new avenues for early treatment strategies and clinical trials. Patients identified with high TyG levels could be ideal candidates for targeted therapies such as anti-amyloid or anti-tau treatments. Furthermore, lifestyle or pharmacological interventions aimed at improving insulin sensitivity could become part of early management strategies for Alzheimer’s.
The research team, led by Professors Padovani and Pilotto, also found links between high TyG scores, blood–brain barrier disruption, and cardiovascular risks, though notably, these did not overlap with the well-known APOE ε4 genetic risk factor. This indicates that genetic and metabolic risks may affect Alzheimer’s progression through different biological pathways.
The team is now exploring whether TyG levels correspond with neuroimaging biomarkers to further improve early detection and patient stratification. As Dr. Gumina concluded, “If targeting metabolism can delay progression, we will have a readily modifiable target that works alongside emerging disease-modifying drugs.”
This discovery underscores the potential of routine metabolic tests in transforming Alzheimer’s care.
