(Helsinki, Finland, Monday, 23 June 2025) 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.
ENDS
Notes to Editors:
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A reference to the EAN Congress 2025 must be included when communicating the information within this press release.
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About the Expert:
Dr Bianca Gumina, MD, is a neurology resident at the University of Brescia’s Brain Health Centre, Italy (ASST Spedali Civili, Brescia). Her research explores how systemic metabolic factors, blood-brain barrier integrity, and genetic risk interact to drive Alzheimer’s progression.
About the EAN:
EAN is a non-profit, independent organisation representing more than 45,000 members, as well as 48 European national societies. As a medical society we promote excellence in the practice of general neurology throughout Europe, leading to improved patient care.
We also aim to keep Europe at the forefront of neurological research and maintain its position as one of the world’s leading scientific hotspots in neurology.
Learn more: ean.org
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