PDE5 inhibitors do not reduce risk of Alzheimer's disease and other dementias: DREAM study

Researchers have found in a new research that treatment with PDE5 inhibitors was not associated with reduced risk for Alzheimer's disease and dementia. Therefore phosphodiesterase-5 inhibitors can't be repurposed for Alzheimer's disease and related dementia.

The study was published in the journal Brain Communications. 

Alzheimer's disease is the most common progressive disease of the brain causing memory loss and the ability to carry out activities of daily living. Based on the hypothesis that phosphodiesterase-5 inhibitors like sildenafil and tadalafil, may be associated with decreased incidence of Alzheimer's disease and related dementia, researchers carried out a study to find the incidence of Alzheimer's disease and related dementia among patients with pulmonary hypertension after phosphodiesterase-5 inhibitor initiation versus endothelin receptor antagonist initiation. 

A patient-level cohort study using the data collected from Medicare claims and cell culture-based phenotypic assays was done among patients with pulmonary hypertension after controlling for 76 confounding variables through propensity-score matching. Four different analytic approaches were designed to address specific types of biases including informative censoring, reverse causality, and outcome misclassification. 

Findings: 

• Reduced risk of Alzheimer's disease and related dementia was not found after phosphodiesterase-5 inhibitors with a hazard ratio of 0.99, 1.00, 0.67, and 1.15.
• Sildenafil was not found to ameliorate the molecular abnormalities relevant to Alzheimer's disease in most cell culture-based phenotypic assays.
• No difference in the risk of Alzheimer's disease-related dementia was found between PDE5 inhibitors and endothelin receptor antagonists. 

Thus, the study did not find any evidence to support the hypothesis that phosphodiesterase-5 inhibitors are promising repurposing candidates for Alzheimer's disease and related dementia. 

For further reading, click here: https://doi.org/10.1093/braincomms/fcac247 

Rishi J Desai, Mufaddal Mahesri, Su Been Lee, Vijay R Varma, Tina Loeffler, Irene Schilcher, Tobias Gerhard, Jodi B Segal, Mary E Ritchey, Daniel B Horton, Seoyoung C Kim, Sebastian Schneeweiss, Madhav Thambisetty, No association between initiation of phosphodiesterase-5 inhibitors and risk of incident Alzheimer's disease and related dementia: results from the Drug Repurposing for Effective Alzheimer's Medicines (DREAM) study, Brain Communications, 2022; fcac247.