People with early Alzheimer’s disease and insulin resistance, as detected by a routine triglyceride-glucose (TyG) index, are four times more likely too experience rapid cognitive decline, according to research presented at the European Academy of Neurology (EAN) Congress 2025¹.

Neurologists at the University of Brescia analyzed data from 315 non-diabetic patients with cognitive issues, including 200 individuals with confirmed Alzheimer’s disease. All participants were evaluated for insulin resistance using the TyG index and followed clinically for three years. Patients in the highest third of the Mild Cognitive Impairment AD subgroup, based on their TyG index, showed significantly faster deterioration, losing more than 2.5 points per year on the Mini Mental State examination (hazard ratio 4.08, 95% CI 1.06-15.73). This correlation was not observed in the non-AD group.

Lead investigator Dr.Bianca Gumina stated, “Once mild cognitive impairment is diagnosed, families always ask how fast it will progress. 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.”

The study highlights the potential of the tyg index, a readily available and inexpensive measure of insulin resistance, to predict the rate of cognitive decline in individuals with mild cognitive impairment. Researchers aimed to investigate the impact of insulin resistance during the prodromal mild cognitive impairment (MCI) stage, a period characterized by diverse patient trajectories.

Specifically in Alzheimer’s disease, insulin resistance is thought to disrupt neuronal glucose uptake, encourage amyloid accumulation, compromise the blood-brain barrier, and stimulate inflammation.These mechanisms may be less relevant or regulated differently in other neurodegenerative conditions.

“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 research team,led by Professor Padovani and Professor Pilotto,also discovered that elevated TyG levels were linked to blood-brain barrier disruption and cardiovascular risk factors,but showed no interaction with the APOE ε4 genotype. this suggests that metabolic and genetic risks may operate through separate pathways².

Identifying patients with high TyG could improve the selection process for clinical trials involving anti-amyloid or anti-tau therapies. It may also encourage earlier implementation of lifestyle changes or medications aimed at improving insulin sensitivity.The researchers are currently exploring whether TyG levels correlate with neuroimaging biomarkers to facilitate 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.