American scientists conducted a cohort study and found that taking certain antiviral drugs used to treat HIV and 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 treatment and prevention of Alzheimer's disease are focused on suppressing beta-amyloid accumulation in the brain and increasing levels of the neurotransmitter acetylcholine by inhibiting acetylcholinesterase (AChE). At the same time, considerable evidence has been collected that neuroinflammation plays a key role in the pathogenesis of the disease, and its mechanisms may serve as potential targets for therapy. Previously, a research team led by Jayakrishna Ambati from the University of Kentucky demonstrated that antiviral drugs from the nucleoside reverse transcriptase inhibitor (NRTI) class inhibit the activation of NLRP3 inflammasomes, reducing inflammatory responses, including those significant in Alzheimer's disease.
Now, Ambati, who has moved to the University of Virginia, and his colleagues have analyzed the association between NRTI use and the risk of developing Alzheimer's disease in two insurance databases: the U.S. Veterans Health Administration (VHA) database over 24 years (approximately 11 million people) and the MarketScan employer insurance database over 14 years (approximately 158 million people). Inclusion criteria for the main cohorts were age 50 years or older, use of NRTIs for HIV or hepatitis B, and the absence of a diagnosis of Alzheimer's disease. More than 72,000 people in the first database and more than 199,000 in the second met these criteria.
Statistical analysis was performed using multivariable Cox regression, adjusting for demographic and socioeconomic factors, lifestyle, addictions, mental disorders, Parkinson's disease, biochemical parameters, and comorbidities. Given that NRTI therapy was not randomized, the researchers conducted an additional propensity-matched matched control cohort analysis. Also, since death from any cause can precede diagnosis in chronic diseases, the authors analyzed the data taking this competing risk into account.
In both databases, an association between NRTI therapy and the risk of developing Alzheimer's disease was observed, dependent on 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, while in MarketScan it was 10.3 percent. In a quasi-randomized analysis, this association was even stronger: in the VA cohort, a 6 percent reduction in risk per year of NRTI use was observed, while in MarketScan it was 13 percent. An analysis adjusting for the competing risk of death revealed a 32 percent overall reduction in the risk of developing Alzheimer's disease with NRTI use and a 37 percent reduction in the quasi-randomized analysis.
The results indicate that NRTI use may reduce the risk of developing Alzheimer's disease, presumably by inhibiting inflammasome activation. They provide grounds 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 roundworm models.
