Sacubitril/valsartan is a new medication for the treatment of heart failure with reduced ejection fraction; it has been hypothesized that the long-term use of sacubitril, a neprilysin inhibitor, might be associated with increased risk for Alzheimer’s disease.

Pre-clinical and clinical studies have shown promising safety results, but have been criticized due to the short period of follow-up and inclusion of healthy, young volunteers.

The Prospective Evaluation of Cognitive Function in Heart Failure: Efficacy and Safety of Entresto compared to Valsartan on Cognitive Function in Patients with Chronic Heart Failure and Preserved Ejection Fraction (PERSPECTIVE) trial is assessing the long-term neurocognitive safety of sacubitril/valsartan, and results are expected in 2022.