Science disconnected: the translational gap between basic science, clinical trials, and patient care in Alzheimer's disease

Both research and clinical practice have traditionally centred on the dementia syndrome of Alzheimer's disease rather than its preclinical and prodromal stages. However, there is a strong scientific and ethical impetus to shift focus to earlier disease stages to improve brain health outcomes and help to keep affected individuals symptom-free (dementia-free) for as long as possible. We provide an overview of recent advancements in early detection, drug development, and trial methodology that should be utilised in the development of new therapies for use in brain health clinics. We propose a triad approach to Alzheimer's disease clinical trials, encompassing (1) experimental medicine studies to gather greater knowledge of disease mechanisms, (2) a more comprehensive platform of phase 2 learning trials to inform phase 3 confirmatory trials, and (3) precision medicine involving smaller subgroups of patients with shared characteristics. This triad would ensure that treatment targets are identified accurately, trial methodology focuses on at-risk populations, and sensitive outcome measures capture potential treatment effects. Clinical services around the world must embrace the brain health clinic model so that neurodegenerative diseases can be detected in their earliest phase to quicken drug development pipelines and potentially improve prognosis.