American scientists conducted a cohort study and found that taking certain antiviral drugs used to treat HIV infection and viral hepatitis B is associated with a significant reduction in the risk of developing Alzheimer's disease. The report was published in Alzheimer's & Dementia.
The main areas of research in the field of pharmacological therapy and prevention of Alzheimer's disease are focused on suppressing the accumulation of beta-amyloid in the brain and increasing the level of the neurotransmitter acetylcholine by inhibiting acetylcholinesterase (AChE). At the same time, there is considerable evidence that neuroinflammation plays an important role in the pathogenesis of the disease, and its mechanisms can serve as potential targets for therapy. Earlier, a scientific group led by Jayakrishna Ambati from the University of Kentucky showed that antiviral drugs from the group of nucleoside reverse transcriptase inhibitors (NRTIs) inhibit the activation of NLRP3 inflammasomes, reducing inflammatory reactions, among other things, significant in Alzheimer's disease.
Now Ambati, who has moved to the University of Virginia, and colleagues have analyzed the association between NRTI use and Alzheimer’s risk in two insurance databases: the Veterans Health Administration over 24 years (about 11 million people) and MarketScan employer insurance over 14 years (about 158 million people). Inclusion criteria for the main cohorts were age 50 or older, use of NRTIs for HIV or hepatitis B, and no diagnosis of Alzheimer’s. More than 72,000 people in the former database and more than 199,000 in the latter met these criteria.
Statistical analysis was performed using multivariable Cox regression with adjustments for demographic and socioeconomic factors, lifestyle, addiction, mental disorders, Parkinson's disease, biochemical parameters and comorbidities. Given that NRTI therapy was not randomized, the researchers performed an additional pseudo-randomization analysis (selection of a control cohort based on a predisposition indicator). Also, since in the case of chronic diseases, death from any cause can precede diagnosis, the authors analyzed the data taking into account this competing risk.
In both databases, there was an association between NRTI therapy and the risk of developing Alzheimer's disease that varied with the duration of treatment. In the VA cohort, each additional year of NRTI use was associated with a 4 percent reduction in the odds of developing the disease, and in MarketScan, it was 10.3 percent. In the quasi-randomized analysis, the association was even stronger, with a 6 percent reduction in risk per year of NRTI use in the VA cohort and a 13 percent reduction in risk in MarketScan. An analysis adjusting for the competing risk of death found a 32 percent overall reduction in the risk of developing Alzheimer's disease with NRTI use and a 37 percent reduction in risk in the quasi-randomized analysis.
These results suggest that NRTIs may reduce the risk of developing Alzheimer's disease, presumably by inhibiting inflammasome activation. They provide a rationale for testing the efficacy of inflammasome inhibition in Alzheimer's disease through randomized clinical trials of NRTIs or their less toxic derivatives, as well as mechanistic studies in animal models.
Previously, Italian researchers discovered substances in common hops that suppress the pathogenic mechanisms of Alzheimer's disease development at the molecular level, in cell culture and in transgenic model roundworms.
