Could heparin offer new hope in the fight against dementia?

New research shows that patients who received heparin therapy were diagnosed with Alzheimer’s disease up to two years later, suggesting a possible protective effect of this common anticoagulant.

Study: Heparin treatment is associated with delayed diagnosis of Alzheimer’s disease in electronic health records from two major healthcare systems in the United States. Image credits: TopMicrobialStock / Shutterstock

This is evident from a recent study published in the journal Molecular psychiatryresearchers examined the potential of heparin therapy in delaying the diagnosis of dementia caused by Alzheimer’s disease in people over 65 years of age. Their findings indicate that heparin therapy was associated with a one-year delay in dementia diagnoses in one healthcare system and a two-year delay. in another, suggesting the protective potential of this known anticoagulant.

Background

Alzheimer’s disease and associated dementia have serious consequences for the quality of life of people who have the disease. The national cost of caring for affected individuals in the United States was $345 billion annually by 2023. Estimates suggest that Alzheimer’s disease was the fifth leading cause of death among people over 65 in 2021, with more than 10 million new cases of the disease. dementia diagnosed every year around the world.

Recent research suggests that the risk of developing Alzheimer’s disease may be influenced by a specific protein called Apolipoprotein E (ApoE), which interacts with molecules on cell surfaces known as heparan sulfate proteoglycans (HSPGs). ApoE binds to HSPGs with varying affinity depending on the ApoE variant. ApoE4 is associated with the highest risk, while a rare form called ApoE binds Christchurch very weakly and appears to lower the risk of disease in people genetically predisposed to causing early-onset Alzheimer’s disease. This interaction between ApoE and HSPGs may be crucial in the development and progression of Alzheimer’s disease.

HSPGs also contribute to the build-up of tau, a protein involved in the brain damage seen in people with Alzheimer’s disease. Proteins that attach to HSPGs can accumulate in the brain for years before symptoms appear, and a specific gene involved in heparan sulfate production has been identified as a risk factor for Alzheimer’s disease.

Since the 1930s, heparin, a special form of heparan sulfate, has been administered to people to prevent blood clots during surgery or to treat pulmonary embolisms or deep vein thrombosis. Although heparin does not enter the brain, researchers hypothesize that its use could theoretically delay the onset of Alzheimer’s disease by disrupting ApoE-HSPG interactions.

About the study

Researchers examined medical records from two major health care systems, Mount Sinai Health System (MSHS) and Columbia University Medical Center (CUMC), and compared people who had received heparin treatment with those who had not, looking for evidence of developmental delays of Alzheimer’s disease. disease. The study used a longitudinal, retrospective design by looking back at past patient data.

Participants were 65 years or older and had been under observation for at least five years. Researchers identified people with Alzheimer’s disease based on whether they had at least two entries of the condition in their records or a prescription for medications used to treat the disease.

The analysis involved comparing the age at which patients were diagnosed between the two groups, those who received heparin and those without, after taking into account factors such as related medical conditions, number of hospital visits, gender and age.

Findings

There were 15,183 eligible patients in the first health care system (MSHS) and 6,207 in the second (CUMC). In the MSHS cohort, 24.7% had been treated with heparin and 75.3% had not, while in the CUMC cohort 51.5% had received heparin. On average, those who received heparin in the first health database (MSHS) were diagnosed with Alzheimer’s disease one year later than those who did not receive the treatment. In the second set of medical records (CUMC), those who received heparin were diagnosed with Alzheimer’s disease two years later than those who did not.

The results indicated that heparin treatment was linked to a later diagnosis of Alzheimer’s disease in both groups, with the effect observed in men and women. This supports the idea that heparin may act as a competitive inhibitor of ApoE binding to HSPGs, delaying diagnosis of the disease.

Conclusions

The researchers found that patients who used heparin were diagnosed with Alzheimer’s later, on average, than those who did not use the medication. The strength of the analysis is that it is based on extensive hospital data, with consistent findings across the two hospital groups, which increases the credibility of the findings. Heparin is believed to inhibit the specific damaging effects of the ApoE protein, which has been linked to the progression of Alzheimer’s disease.

However, the use of heparin may not directly prevent Alzheimer’s disease, but may be associated with better overall health care, which may delay diagnosis. Patients taking heparin tended to have more health problems, which could complicate the ability to determine whether the drug or other factors caused the delay in diagnosis. The study also did not take into account genetic risks, such as ApoE4 carrier status, that could influence the findings.

Although the study is an important step toward finding potential therapies for Alzheimer’s disease, it has several limitations, including the possibility that improved health care in the heparin-treated group may explain the observed delays in diagnosis. Further research, especially on the interaction of heparin with ApoE and HSPGs, is needed to confirm these findings and develop methods for prevention and treatment.