Insulin Resistance Test Predicts Cognitive Decline in Alzheimer's Patients

Recent research presented at the European Academy of Neurology (EAN) Congress 2025 indicates that insulin resistance, as measured by the triglyceride-glucose (TyG) index, can serve as a predictive marker for rapid cognitive decline in early Alzheimer's disease patients. This study, conducted by neurologists at the University of Brescia, reviewed the records of 315 non-diabetic individuals diagnosed with cognitive deficits, including 200 with confirmed Alzheimer's disease.

The findings suggest that individuals in the highest third of the TyG index were associated with a significantly faster cognitive decline, losing over 2.5 points annually on the Mini Mental State Examination. The hazard ratio for rapid decline among those with high TyG levels was calculated at 4.08, indicating a fourfold increase in risk compared to their lower-TyG counterparts. Notably, this correlation did not extend to patients with other forms of neurodegenerative diseases, highlighting a unique vulnerability associated with Alzheimer's.

Dr. Bianca Gumina, the lead investigator, emphasized the importance of these findings, stating, "Families often inquire about the rate of progression once mild cognitive impairment is diagnosed. Our data indicates that a simple metabolic marker, readily available in hospital laboratories, can help identify patients who may benefit from targeted therapeutic strategies."

The study underscores the relationship between insulin resistance and Alzheimer’s disease progression, focusing on the prodromal mild cognitive impairment (MCI) stage. Insulin resistance is known to impair neuronal glucose uptake and promote amyloid accumulation, processes that are critical in the pathophysiology of Alzheimer's.

While insulin resistance has been previously linked to the onset of Alzheimer’s disease, its role in the rate of progression has been less explored. This research aims to fill that gap, suggesting that metabolic dysfunction may serve as a significant predictor of cognitive decline. Professor Alessandro Padovani, a co-author of the study, noted that identifying patients with high TyG levels could enhance enrollment criteria for clinical trials targeting amyloid or tau pathways and encourage earlier lifestyle interventions to improve insulin sensitivity.

Furthermore, the study revealed that high TyG levels correlated with disruptions in the blood-brain barrier and cardiovascular risk factors, yet showed no interaction with the APOE ε4 genotype, indicating that metabolic and genetic risks may operate through different mechanisms. "Our findings emphasize that targeting metabolism could be a promising approach to delay cognitive decline in Alzheimer's disease," Dr. Gumina concluded.

The researchers are now investigating whether TyG levels correlate with neuroimaging biomarkers to facilitate earlier detection and stratification of patients at risk.

In summary, this research marks a pivotal stride in understanding the potential of metabolic markers in predicting cognitive decline, presenting new avenues for targeted therapies in Alzheimer's disease management. As the global prevalence of Alzheimer's continues to rise, identifying modifiable risk factors through routine assessments could significantly influence clinical outcomes and patient quality of life.