The common blood test that predicts how fast Alzheimer’s hits
Insulin resistance detected by routine triglyceride-glucose (TyG) index can flag people with early Alzheimer's who are four times more likely to present rapid cognitive decline.
- Date:
- June 22, 2025
- Source:
- Beyond
- Summary:
- A simple blood test could reveal which early Alzheimer’s patients are most at risk for rapid decline. Researchers found that people with high insulin resistance—measured by the TyG index—were four times more likely to experience faster cognitive deterioration. The study highlights a major opportunity: a common lab value already available in hospitals could help guide personalized treatment strategies. This discovery also uncovers a unique vulnerability in Alzheimer’s disease to metabolic stress, offering new possibilities for intervention while the disease is still in its early stages.
- Share:
Insulin resistance detected by routine triglyceride-glucose (TyG) index can flag people with early Alzheimer's who are four times more likely to present rapid cognitive decline, according to new research presented at the European Academy of Neurology (EAN) Congress 2025.1
Neurologists at the University of Brescia reviewed records for 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 a clinical follow-up of 3 years. When patients were divided according to TyG index, those in the highest third of the Mild Cognitive Impairment AD subgroup deteriorated far more quickly than their lower-TyG peers, losing >2.5 points on the Mini Mental State Examination per year (hazard ratio 4.08, 95% CI 1.06-15.73). No such link appeared in the non-AD cohort.
"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."
While insulin resistance has been linked to the onset of Alzheimer's disease, its role in how quickly the condition progresses has received less attention. This study aimed to fill that gap by focusing on its impact during the prodromal mild cognitive impairment (MCI) stage, when patients follow highly variable trajectories. The researchers used the TyG index, which offers a low-cost, routinely available surrogate for insulin resistance, to explore whether metabolic dysfunction could help predict the pace of cognitive decline after diagnosis.
In AD specifically, insulin resistance is believed to impair neuronal glucose uptake, promote amyloid accumulation, disrupt the blood-brain barrier, and fuel inflammation - pathways that are less relevant or differently regulated in other neurodegenerative diseases.
"We were surprised to see the effect only in the Alzheimer's spectrum and not in other neurodegenerative diseases," Dr. Gumina noted. "It suggests a disease-specific vulnerability to metabolic stress during the prodromal window, when interventions may still change the trajectory."
The researchers at University of Brescia, led by Professor Padovani and Professor Pilotto, found that high TyG was also associated with blood-brain barrier disruption and cardiovascular risk factors, yet it showed no interaction with the APOE ε4 genotype, indicating that metabolic and genetic risks may act through distinct pathways.2
Identifying high-TyG patients could refine enrolment for anti-amyloid or anti-tau trials and prompt earlier lifestyle or pharmacological measures to improve insulin sensitivity. The researchers are currently investigating whether TyG levels also track with neuroimaging biomarkers to aid earlier detection and stratification.
"If targeting metabolism can delay progression, we will have a readily modifiable target that works alongside emerging disease-modifying drugs," concluded Dr. Gumina.
References:
- Gumina B., Galli A., Tolassi C. et al. The Triglyceride-Glucose Index as Predictor of Cognitive Decline in Alzheimer's Spectrum Disorders. Presented at the European Academy of Neurology (EAN) Congress 2025; 23 June 2025; Helsinki, Finland.
- Padovani A., Galli A., Bazzoli E., et al. (2025). The role of insulin resistance and APOE genotype on blood-brain barrier integrity in Alzheimer's disease. Alzheimer's & Dementia. Advance online publication. https://doi.org/10.1002/alz.14556
Cite This Page: