A Simple Metabolic Marker Could Transform Alzheimer’s Care by Identifying High-Risk Patients Early

In a groundbreaking development for Alzheimer’s disease management, researchers have discovered that a routine blood test, already widely available in hospitals, could predict which patients with early-stage Alzheimer’s are at risk of rapid cognitive decline. This finding, presented at the European Academy of Neurology (EAN) Congress 2025 in Helsinki, Finland, on June 23, 2025, offers a new avenue for personalized treatment and early intervention, potentially altering the trajectory of this devastating neurodegenerative disease. The test, known as the triglyceride-glucose (TyG) index, measures insulin resistance—a metabolic condition linked to type 2 diabetes—and may now serve as a critical tool in the fight against Alzheimer’s progression.

The Study: Uncovering a Metabolic Link to Alzheimer’s Progression

Led by Dr. Bianca Gumina, a neurology resident at the University of Brescia’s Brain Health Center in Italy, the research team analyzed medical records from 315 non-diabetic patients experiencing cognitive deficits. Of these, 200 had biologically confirmed Alzheimer’s disease, verified through cerebrospinal fluid analysis or other diagnostic methods. The study, which spanned three years, focused on patients in the prodromal stage of Alzheimer’s—often referred to as mild cognitive impairment (MCI)—where memory and cognitive challenges begin to emerge but are not yet severe.

The TyG index, calculated using levels of triglycerides and fasting blood glucose from routine blood tests, emerged as a powerful predictor of cognitive decline. Patients with the highest TyG index scores—indicating greater insulin resistance—were four times more likely to experience rapid cognitive decline, defined as losing more than 2.5 points per year on the Mini-Mental State Examination (MMSE), a widely used tool to assess cognitive function. This correlation was specific to Alzheimer’s patients and did not appear in those with other neurodegenerative disorders, suggesting a unique metabolic vulnerability in Alzheimer’s disease.

Dr. Gumina emphasized the practical implications: “Families always want to know how quickly Alzheimer’s will progress once mild cognitive impairment is diagnosed. Our findings show that a simple, cost-effective test can identify those at higher risk, enabling clinicians to prioritize them for targeted therapies or lifestyle interventions.” This discovery could shift the paradigm of Alzheimer’s care, moving from reactive treatment to proactive management.

Why Insulin Resistance Matters in Alzheimer’s

Insulin resistance, a condition where cells fail to respond effectively to insulin, leading to elevated blood sugar levels, is a hallmark of metabolic disorders like prediabetes and type 2 diabetes. While its role in diabetes is well-established, its connection to Alzheimer’s has gained increasing attention. The brain relies heavily on glucose for energy, and insulin plays a critical role in regulating glucose uptake in neurons. When insulin signaling falters, it can disrupt brain function, promote the accumulation of toxic beta-amyloid proteins, impair the blood-brain barrier, and fuel inflammation—all key drivers of Alzheimer’s pathology.

The Brescia study found that high TyG levels were associated with blood-brain barrier disruption and increased cardiovascular risk, further underscoring the metabolic underpinnings of Alzheimer’s progression. Notably, insulin resistance did not interact with the APOE ε4 genotype, a well-known genetic risk factor for Alzheimer’s, suggesting that metabolic and genetic risks operate independently. This distinction opens the door to interventions that target metabolism separately from genetic predispositions, broadening the scope of potential treatments.

A Global Health Crisis: The Urgency of Early Detection

Alzheimer’s disease affects an estimated 69 million people worldwide in its prodromal stage, with numbers projected to rise as populations age. In 2021, global dementia cases reached 57 million, and the World Health Organization estimates that this figure could double by 2050 due to increasing life expectancy and lifestyle-related risk factors. The economic burden is staggering, with Alzheimer’s care costing the United States alone over $360 billion annually in 2024, according to the Alzheimer’s Association. Early detection and intervention are critical to reducing this burden and improving quality of life for patients and their families.

Current diagnostic tools, such aselderly patients, and the TyG index offers a non-invasive, scalable alternative. Dr. Howard Fillit, co-founder and chief scientific officer of the Alzheimer’s Drug Discovery Foundation, noted, “While these findings are preliminary and based on a relatively small sample, they contribute to a growing body of evidence linking insulin resistance to Alzheimer’s. If validated in larger studies, the TyG index could become a standard tool for stratifying patients in clinical settings.”

Implications for Treatment and Future Research

The TyG index’s potential extends beyond diagnosis to guiding personalized treatment strategies. Patients identified as high-risk through elevated TyG scores could benefit from closer monitoring, enrollment in clinical trials for anti-amyloid or anti-tau therapies, or lifestyle interventions aimed at improving insulin sensitivity. Research has shown that lifestyle changes—such as regular physical exercise, weight loss, and a Mediterranean diet rich in flavonoids, curcumin, and omega-3 fatty acids—can reduce peripheral insulin resistance and may slow cognitive decline in the early stages of Alzheimer’s. For example, a 2023 study in The Lancet Neurology found that a Mediterranean diet supplemented with omega-3 fatty acids improved cognitive outcomes in patients with mild cognitive impairment.

Pharmacological interventions also hold promise. GLP-1 analogs, such as exenatide and liraglutide, approved by the FDA for type 2 diabetes, have shown potential in preclinical studies to restore brain insulin responsiveness and reduce Alzheimer’s pathology. A 2020 clinical trial published in JAMA Neurology demonstrated that intranasal insulin improved cognition in some patients with mild cognitive impairment, though larger trials are needed to confirm these findings. Dr. Gumina’s team is now investigating whether TyG levels correlate with neuroimaging biomarkers, such as PET scans, which could further enhance early detection and treatment planning.

Challenges and Next Steps

While the TyG index is a promising tool, the Brescia study’s findings are preliminary and await validation in larger, peer-reviewed studies. The study’s sample size of 315 patients, while robust for a single-center study, is relatively small, and its retrospective design limits causal inferences. Dr. Fillit cautioned, “These results need replication in larger, more diverse populations to ensure generalizability. The predominance of male participants (nearly 80% in the Alzheimer’s subgroup) also warrants further investigation into potential sex-based differences.”

Additionally, the TyG index, while cost-effective and widely available, is less precise than the gold-standard insulin clamp method for measuring insulin resistance. However, its simplicity and accessibility make it a practical choice for widespread clinical use, particularly in resource-limited settings.

A New Era of Hope for Alzheimer’s Patients

The discovery of the TyG index as a predictor of rapid cognitive decline marks a significant step toward precision medicine in Alzheimer’s care. By identifying high-risk patients early, clinicians can tailor interventions to slow disease progression, potentially delaying the onset of severe dementia. For families grappling with the uncertainty of an Alzheimer’s diagnosis, this test offers a tangible tool to anticipate and prepare for the future.

As research progresses, the integration of metabolic markers like the TyG index with emerging therapies—such as anti-amyloid drugs like lecanemab and donanemab, approved by the FDA in 2023 and 2024, respectively—could redefine Alzheimer’s management. The global Alzheimer’s community, including advocacy groups like the Alzheimer’s Society, has welcomed these findings, emphasizing the importance of lifestyle factors like diet and exercise in reducing dementia risk.

In the words of Dr. Gumina, “If we can target metabolism to delay progression, we have a readily modifiable target that complements cutting-edge therapies. This is a game-changer for patients and their families.” As the world faces a growing Alzheimer’s epidemic, this simple blood test could be the key to unlocking earlier, more effective interventions, offering hope to millions.