In a new study tracking memory and metabolism, researchers have found that a simple blood marker may hold powerful clues about the pace of cognitive decline in Alzheimer’s disease.
The study, presented at the 11th Congress of the European Academy of Neurology, showed the triglyceride-glucose (TyG) index—a surrogate marker of insulin resistance—was linked to significantly faster cognitive decline in patients with early-stage Alzheimer’s. Those with higher TyG levels experienced more rapid memory loss over time compared with those with lower levels, according to data presented at a leading neurology conference.
Researchers analyzed data from 315 non-diabetic patients with neurodegenerative diseases, including 210 with Alzheimer’s disease and 115 with other conditions. The TyG index, based on blood triglyceride and glucose levels, was used to assess insulin resistance. Patients were categorized into low, medium, and high TyG groups.
Among those with Alzheimer’s, high TyG levels were associated with over four times the risk of rapid cognitive decline compared with lower TyG levels. Rapid decline was defined as a drop of more than 2.5 points per year on the Mini-Mental State Examination (MMSE), a standard measure of cognitive function.
In the subgroup with mild cognitive impairment due to Alzheimer’s (MCI-AD), the association was particularly strong. Patients with high TyG levels had a hazard ratio of 4.08 (95% confidence interval [CI], 1.06–15.73) for faster cognitive decline over three years.
The study included data collected from 2014 to 2024. Diagnoses were confirmed using cerebrospinal fluid (CSF) biomarkers, and all patients had at least six months of clinical follow-up. Baseline characteristics—including sex, education, apolipoprotein E (APOE) genotype, and Alzheimer’s-related CSF biomarkers—were comparable across TyG groups.
No significant association between TyG and cognitive progression was found in patients with other neurodegenerative diseases, such as Parkinson’s disease or frontotemporal dementia. The observed effect appeared specific to Alzheimer’s, particularly in its early stages.
Researchers also noted that Alzheimer’s patients with high TyG levels had more cardiovascular risk factors and showed alterations in blood-brain barrier markers. An interaction between TyG and the APOE ε4ε4 genotype was observed for these biological markers, but not for disease progression.
While the study also examined conversion from MCI to dementia, the trend toward faster progression in high TyG patients did not reach statistical significance (P = .086).
The findings suggest that insulin resistance plays a role in the progression of Alzheimer’s disease and that the TyG index may be a useful biomarker for identifying patients at greater risk of decline. This could help guide earlier or more targeted interventions in clinical practice.
The study adds to growing evidence linking metabolic dysfunction with neurodegeneration and underscores the potential of insulin resistance markers in Alzheimer’s research.
Source: Data presented at: Alzheimer’s Association International Conference; July 2025; Amsterdam, the Netherlands. Abstract OPR-066.
