Can Viagra Prevent Alzheimer’s Disease? | Today’s MedPage

New research suggests that sildenafil (Viagra, Levatio) may be a potential candidate for the prevention or treatment of Alzheimer’s disease.

Throughout 6 years of follow-up, sildenafil users were 69% less likely to develop Alzheimer’s disease than non-sildenafil users (HR 0.31, 95% CI 0.25-0.39, NS<1 × 10^-8), A large case-control analysis of insurance claims showed.

Sildenafil has also emerged as a potential disease risk modifier in the analysis of drugs that may be reused for Alzheimer’s disease, reports Dr. Feixiong Cheng of the Cleveland Clinic Institute for Genomic Medicine and co-authors.

In addition, phosphodiesterase 5 inhibitors approved for the treatment of erectile dysfunction and pulmonary arterial hypertension increase neurite growth and decrease phosphotau expression in a neuronal model derived from induced pluripotent stem cells. .. Nature aging..

Understanding Endophenotype Researchers said they could uncover a common underlying mechanism and lead to drugs that could be reused for diseases like Alzheimer’s disease.

“Recent studies show that the interaction between amyloid and tau contributes more to Alzheimer’s disease than it does,” Chen said in a statement. “Therefore, we hypothesized that drugs targeting the intersection of amyloid and tau endophenotype molecular networks should have the greatest potential for success.”

Researchers will combine genetic and other data to determine which of the more than 1,600 FDA-approved drugs are effective in treating Alzheimer’s disease, focusing on drugs that target both amyloid and tau. I matched. The researchers narrowed the list of candidates to look for drugs with ideal brain penetration, positive in vivo findings in a mouse model of Alzheimer’s disease, and sufficient patient data.

“Sildenafil, which has been shown to significantly improve cognition and memory in preclinical models, has been presented as the best drug candidate,” Chen said.

The team then looked up the diagnostic codes and pharmacy claims of 7.23 million people in the MarketScan Medicare Claims database from 2012 to 2017 and identified the relationship between sildenafil and Alzheimer’s disease in a case-controlled analysis.

To reduce the potential for indication confusion, the researchers also evaluated four comparative drugs: the antihypertensive drug losartan (Cozaar) and the biguanide metformin (Glucophage) used to treat type 2 diabetes. , Antihypertensive drug and calcium channel diltiazem (Cartia) blocker, and sulfonylurea drug glymepyrid (amalyl) used in the treatment of type 2 diabetes. Of the four comparators Losartan When Metformin Currently, clinical trials for Alzheimer’s disease are underway.

After adjusting for age, gender, race, and comorbidity, glimepiride has a 55% risk of Alzheimer’s disease compared to losartan, 63% compared to metformin, 65% compared to diltiazem, and glimepiride. It showed a decrease of 64% compared to.

People with coronary artery disease, hypertension, and type 2 diabetes reduced the likelihood of Alzheimer’s disease across all comparative drug groups. Even excluding people with these comorbidities, the results were consistent.

Researchers also tested sildenafil in a model based on human microglia and neurons derived from pluripotent stem cells derived from Alzheimer’s disease patients, where the drug increased neurite growth and expressed p-tau 181. Was found to reduce.

“There is Some data So far, sildenafil treatment has been suggested to be associated with increased neurogenesis and decreased inflammation, but further research is needed, “said the Alzheimer’s Association in Chicago, who was not involved in the study. Dr. Claire Sexton said.

“More than ever, researchers with Alzheimer’s disease understand that different approaches are needed for effective treatment of the disease-probably used in combination-“, says Sexton. Told Today’s Med Page.

“Scientists are more extensively testing the potential benefits of drugs approved for other illnesses for the treatment of dementia,” she pointed out. “By diverting existing drugs to new uses, we can speed up the research process. Scientists are based on previous research, so much is already known about the potential side effects of drugs. Drug testing and clinical trials can take less time. May be cheaper. “

Subgroup analysis showed that sildenafil was associated with a reduced risk of Alzheimer’s disease in all male comparatives, but only when compared to female diltiazem. This may be because sildenafil is prescribed primarily to men and there were not enough females to empower studies of statistical significance, Chen and co-authors said.

The team acknowledged that the study had other limitations. Potential literature bias and data incompleteness may have affected network analysis. In addition, Alzheimer’s disease was defined using the ICD code, which can be inaccurate.

“The association between sildenafil use and reduced incidence of Alzheimer’s disease does not establish a causal relationship and requires randomized controlled trials,” the researchers added.