New research reveals that patients receiving 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 a delayed diagnosis of Alzheimer’s dementia in electronic health records from two large United States health systems. Image Credit: TopMicrobialStock / Shutterstock
In a recent study published in the journal Molecular Psychiatry, researchers explored the potential of heparin therapy in delaying the diagnosis of dementia caused by Alzheimer’s disease among people over 65. Their findings indicate that heparin therapy was associated with a one-year delay in dementia diagnoses in one health system and a two-year delay in another, suggesting the protective potential of this well-known anticoagulant.
Background
Alzheimer’s disease and associated dementia severely affect the quality of life for people who have it. The national cost of caring for affected individuals in the United States reached $345 billion annually in 2023. Estimates suggest that Alzheimer’s disease was the fifth-leading cause of death among people over the age of 65 in 2021, with more than 10 million new cases of dementia diagnosed around the world each year.
Recent research suggests that the risk of developing Alzheimer’s 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 Christchurch binds very weakly and has been found to lower the risk of disease in people who are genetically predisposed to cause early-onset Alzheimer’s. This interaction between ApoE and HSPGs may be crucial in the development and progression of Alzheimer's.
HSPGs also contribute to the buildup of tau, a protein implicated in the brain damage seen in people with Alzheimer’s. Proteins that attach to HSPGs can build up in the brain for many years before symptoms appear, and a specific gene involved in the production of heparan sulfate has been identified as an Alzheimer’s risk factor.
Since the 1930s, heparin, a particular form of heparan sulfate, has been administered to people to prevent blood clots during surgeries or to treat pulmonary embolisms or deep vein thrombosis. While heparin does not enter the brain, researchers hypothesize that its use could theoretically delay the onset of Alzheimer’s by interfering with ApoE-HSPG interactions.
About the study
Researchers examined medical records from two large health 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 delays in the development of Alzheimer’s disease. The study used a longitudinal, retrospective design by looking back at past patient data.
Participants were 65 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 mentions of the condition in their records or a prescription for medication used to treat it.
The analysis involved comparing the age at which patients were diagnosed between the two groups, those receiving heparin and those without, after accounting for factors such as related medical conditions, the number of hospital visits, sex, and age.
Findings
There were 15,183 eligible patients in the first health 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 one year later than those who had not received the treatment. In the second set of health records (CUMC), those who received heparin were diagnosed with Alzheimer’s two years later than those who had not.
The results indicated that heparin treatment was linked to a later diagnosis of Alzheimer’s in both groups, with the effect seen across men and women. This supports the idea that heparin may act as a competitive inhibitor of ApoE binding to HSPGs, delaying disease diagnosis.
Conclusions
The researchers found that patients taking heparin were, on average, diagnosed with Alzheimer’s later than those who did not take the medication. The analysis's strength is its reliance on extensive hospital data, with consistent findings across the two hospital groups, lending credibility to the findings. Heparin is thought to inhibit specific harmful effects of the ApoE protein, which has been linked to Alzheimer’s disease progression.
However, using heparin may not directly prevent Alzheimer’s but could be related to better overall healthcare, which may delay diagnosis. Patients who took heparin tended to have more health conditions, which might complicate the ability to determine whether the drug or other factors caused the delay in diagnosis. The research also did not account for genetic risk, such as ApoE4 carrier status, which could influence the findings.
While the study is an important step toward finding potential therapies for Alzheimer's, it has several limitations, including the possibility that improved healthcare in the heparin-treated group may explain the observed delays in diagnosis. Further research, particularly on heparin’s interaction with ApoE and HSPGs, is needed to confirm these findings and develop methods for prevention and treatment.
Journal reference:
- Heparin treatment is associated with a delayed diagnosis of Alzheimer’s dementia in electronic health records from two large United States health systems. Readhead, B., Klang, E., Gisladottir, U., Vandromme, M., Li, L., Quiroz, Y.T., Arboleda-Velasquez, J.F., Dudley, J.T., Tatonetti, N.P., Glicksberg, B.S., Reiman, E.M. Molecular Psychiatry (2024). DOI: 10.1038/s41380-024-02757-5, https://www.nature.com/articles/s41380-024-02757-5