The Common Blood Test that Predicts How Quickly Alzheimer’s Will Develop

A simple blood test could reveal which Alzheimer’s patients in the early stages are at greatest risk of rapid decline. Researchers found that people with high insulin resistance—measured using the TyG index—were four times more likely to experience faster cognitive decline. The study points to a great opportunity: a common laboratory value that is already available in hospitals could help develop personalized treatment strategies. This discovery also reveals a unique vulnerability of Alzheimer’s disease to metabolic stress and opens up new possibilities for intervention while the disease is still in its early stages.

A Simple Metabolic Marker can Help Identify People Who are Particularly at Risk

Insulin resistance, as determined by the routinely measured triglyceride-glucose index (TyG), can identify people with early-stage Alzheimer’s who are four times more likely to experience rapid cognitive decline, according to a new study presented at the 2025 Congress of the European Academy of Neurology (EAN). Neurologists at the University of Brescia examined the records of 315 non-diabetic patients with cognitive deficits, including 200 with biologically confirmed Alzheimer’s disease. All subjects underwent an assessment of insulin resistance using the TyG index and were clinically followed up over a period of three years. When the patients were classified according to the TyG index, the condition of those in the top third of the subgroup with mild cognitive impairment and Alzheimer’s dementia deteriorated much more rapidly than that of their peers with lower TyG indices. They lost more than 2.5 points per year on the Mini-Mental Status Test (hazard ratio 4.08, 95% CI 1.06–15.73). No such association was found in the cohort without Alzheimer’s dementia. “Once mild cognitive impairment is diagnosed, families always ask how quickly it will progress,” said lead researcher Dr. Bianca Gumina. “Our data show that a simple metabolic marker available in any hospital laboratory can help identify particularly vulnerable individuals who may be candidates for targeted therapy or specific intervention strategies.”

Although insulin resistance is associated with the onset of Alzheimer’s disease, its role in the progression of the disease is less well understood. This study aimed to fill this gap by focusing on its effects during the prodromal phase of mild cognitive impairment (MCI), when patients follow very different trajectories. The researchers used the TyG index, a low-cost, routinely available surrogate measure of insulin resistance, to investigate whether metabolic abnormalities could help predict the rate of cognitive decline after diagnosis. In AD in particular, insulin resistance is thought to impair glucose uptake by nerve cells, promote amyloid accumulation, disrupt the blood-brain barrier, and promote inflammation—processes that are less relevant or regulated differently in other neurodegenerative diseases. The researchers were surprised that this effect occurred only in the Alzheimer’s spectrum and not in other neurodegenerative diseases. This suggests a disease-specific susceptibility to metabolic stress during the prodromal window, when interventions can still influence the course of the disease.

Improving Insulin Sensitivity

The researchers at the University of Brescia, led by Professor Padovani and Professor Pilotto, found that a high TyG score was also associated with blood-brain barrier dysfunction and cardiovascular risk factors, but did not interact with the APOE ε4 genotype, suggesting that metabolic and genetic risks may act through different pathways. Identifying patients with high TyG scores could refine recruitment for anti-amyloid or anti-tau studies and enable earlier lifestyle or pharmacological interventions to improve insulin sensitivity. The researchers are currently investigating whether TyG scores also correlate with neuroimaging biomarkers to enable earlier detection and stratification.