Currently, apart from the recently approved anti-β-amyloid (anti-Aβ) therapy, there are no effective treatments for Alzheimer's disease (AD) that can delay the progression of the disease. While anti-Aβ therapy had accelerated approval, the Centres for Medicare and Medicaid Services (CMS) announced that Medicare (the Federal health insurance program in the US) would cover the drug on condition that the drug manufacturer collected more data on its effectiveness and safety. Medicare will cover the drug only for participants enrolled in a clinical trial approved by CMS or supported by the National Institutes of Health (NIH). Alternative therapies are being sought that target many different mechanisms and may hold therapeutic promise in targeting early stages of the disease. Tadalafil is a drug (also known as Cialis) licensed for erectile dysfunction and Pulmonary Arterial Hypertension (high blood pressure in the lung) that can enter the brain and has been shown to improve damage to the blood vessels in the brain, as well as many signs and symptoms of AD, and improve intellectual performance, in animal models of AD. Evidence from human AD studies has shown increased blood flow in the brain, improved brain oxygen consumption, and promoted nerve cell health after tadalafil administration.  

In this multicentre study, we aim to establish the safety and tolerability of tadalafil in early AD patients (mild AD or memory problems). Secondly, the study aims to examine the influence of tadalafil on several signs of AD and to look at markers in the blood, along with mental performance and activities of daily living. We aim to have 244 individuals randomly assigned to receive either treatment with the active drug or with a dummy (inactive) drug in equal numbers. This study should inform us whether tadalafil is a safe and effective treatment to use in patients with early AD.