Simple Blood Test Predicts Cognitive Decline in Alzheimer's Patients

Rapid progression in Alzheimer’s disease (AD) is difficult to predict, especially during the mild cognitive impairment (MCI) stage, when patient outcomes vary widely. While insulin resistance is known to contribute to the development of AD, its impact on how quickly cognitive decline progresses has been underexplored. Now, a new study presented at the European Academy of Neurology (EAN) Congress 2025 shows that insulin resistance, measured by a routine triglyceride-glucose (TyG) index, can identify early-stage Alzheimer’s patients who are four times more likely to experience rapid cognitive deterioration.

This study by neurologists at the University of Brescia (Brescia, Italy) focused on understanding whether insulin resistance could serve as a predictive marker for disease progression in people with early AD. Their focus was on the prodromal MCI stage, where clinical trajectories can differ significantly. The researchers used the TyG index—a low-cost and widely available surrogate for insulin resistance—to assess metabolic dysfunction in 315 non-diabetic patients with cognitive deficits. Among these, 200 had biologically confirmed AD. Each participant underwent TyG assessment and a three-year clinical follow-up to monitor cognitive outcomes.

The study's findings revealed that in the MCI-AD subgroup, patients in the highest third of TyG index values showed markedly faster cognitive decline, losing more than 2.5 points per year on the Mini Mental State Examination. This group had a hazard ratio of 4.08 (95% CI 1.06–15.73) for rapid decline compared to those with lower TyG scores. No similar association was found in patients with non-AD neurodegenerative conditions, indicating a disease-specific sensitivity to metabolic dysfunction in Alzheimer’s.

Further analysis showed that high TyG levels were also associated with blood–brain barrier disruption and cardiovascular risk factors. However, there was no interaction with the APOE ε4 genotype, suggesting that genetic and metabolic risk factors may influence AD progression through separate pathways. In practical terms, the TyG index could help clinicians identify high-risk patients early in the disease course, offering an opportunity to tailor interventions that improve insulin sensitivity. It also holds promise for refining patient selection in anti-amyloid or anti-tau clinical trials. The team is now exploring how TyG correlates with neuroimaging biomarkers to aid in early detection and patient stratification.

“Once mild cognitive impairment is diagnosed, families always ask how fast it will progress”, said lead investigator Dr. Bianca Gumina. “Our data show that a simple metabolic marker available in every hospital laboratory can help identify more vulnerable subjects who may be suitable candidates for targeted therapy or specific intervention strategies.”

Related Links:
University of Brescia