Summary

Recent research indicates that HIV medications known as NRTIs may greatly lower the chances of developing Alzheimer’s disease. By examining two extensive health databases, scientists discovered that patients using NRTIs experienced a yearly reduction in Alzheimer’s risk ranging from 6% to 13%.

Unlike other HIV treatments, NRTIs inhibit inflammasomes, which are immune system elements linked to the progression of Alzheimer’s. Researchers are urging for clinical trials to explore the effectiveness of NRTIs—and a newer, safer drug called K9—in preventing Alzheimer’s, especially as the incidence of the disease rises worldwide.

Key Facts

• Reduced Risk: Patients on NRTIs showed a 6% to 13% annual decrease in Alzheimer’s risk.
• Unique Effect: This protective impact was only observed with NRTIs, not with other HIV medications.
• Next Steps: Calls have been made for clinical trials to assess the potential of NRTIs and K9 in Alzheimer’s prevention.

UVA Health scientists are advocating for clinical trials to examine whether NRTIs can help prevent Alzheimer’s disease following evidence that these drugs may reduce the likelihood of developing the condition significantly.

The team, led by Dr. Jayakrishna Ambati from UVA, previously uncovered a possible mechanism through which these drugs might hinder Alzheimer’s development.

This finding prompted an analysis of some of the largest health insurance databases in the U.S. to evaluate Alzheimer’s risk for patients taking these medications.

In their studies, they found that for every year patients used NRTIs, the risk of developing Alzheimer’s decreased by 6% in one database and 13% in another.

“It’s estimated that over 10 million people worldwide develop Alzheimer’s disease every year,” commented Ambati, who is also a professor at UVA’s School of Medicine. “Our findings suggest that these drugs could potentially prevent about 1 million new Alzheimer’s cases each year.”

Preventing Alzheimer’s

NRTIs, or nucleoside reverse transcriptase inhibitors, primarily function to prevent the HIV virus from multiplying within the body. However, Ambati and his team previously determined that these drugs might also stop the activation of inflammasomes, crucial immune system proteins that are thought to play a role in Alzheimer’s disease.

The researchers sought to determine if patients taking these inflammasome-blocking drugs had a lower likelihood of developing Alzheimer’s. To do this, they reviewed 24 years of data from the U.S. Veterans Health Administration and 14 years from the MarketScan database, which reflects a more diverse population.

They focused on patients aged 50 and older who were treated for HIV or hepatitis B with NRTIs, excluding anyone with a prior Alzheimer’s diagnosis.

More than 270,000 eligible patients were identified for analysis regarding their development of Alzheimer’s.

Even after accounting for existing health conditions, the researchers found a “significant and substantial” decrease in Alzheimer’s risk among those taking NRTIs, as detailed in a recent scientific publication.

Interestingly, those taking other HIV medications did not exhibit the same drop in Alzheimer’s risk, indicating that NRTIs require further clinical evaluation for their potential protective benefits.

This step is crucial as nearly 7 million Americans currently live with Alzheimer’s, a number projected to rise to 13 million by 2050. The annual cost of care for Alzheimer’s and related dementias could soar from $360 billion to nearly $1 trillion, as highlighted by the Alzheimer’s Association.

“We’ve also developed a new drug, K9, that blocks inflammasomes more effectively and safely than current NRTIs,” noted Ambati. “This drug is already undergoing trials for other conditions, and we plan to include K9 in Alzheimer’s disease trials as well.”

Findings Published

The research findings have been published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.

The research team includes Joseph Magagnoli, Meenakshi Ambati, Tammy Cummings, Joseph Nguyen, Claire C. Thomas, Vidya L. Ambati, S. Scott Sutton, Bradley D. Gelfand, and Jayakrishna Ambati. Ambati is a co-founder of iVeena Holdings and has numerous disclosures included in the publication.

Funding for this research came from various sources, including the UVA Strategic Investment Fund and multiple grants from the National Institutes of Health.