Alzheimer's disease outlook: controversies and future directions
Giovanni B. Frisoni, Emil Aho, Carol Brayne, Olga Ciccarelli, Bruno Dubois, Nick C. Fox, Kristian Steen Frederiksen, Cem Gabay, Valentina Garibotto, Thomas Hofmarcher, Clifford R. Jack, Miia Kivipelto, Ronald Petersen, Federica Ribaldi, Christopher C. Rowe, Sebastian Walsh, Henrik Zetterberg, Oskar Hansson
Abstract
For the first time, reductions in cerebral β-amyloid pathology load and rate of cognitive and functional decline have been achieved in Alzheimer's disease, through pharmacological intervention in randomised controlled trials. However, the results from phase 3 randomised controlled trials of anti-β amyloid monoclonal antibodies are interpreted in different ways, with some experts supporting a clinically meaningful disease-modifying effect, and others judging insufficient benefit-to-risk ratio and opposing market authorisation. In the final paper of this Series, we discuss these contrasting views, all of which wish to contribute to improvements in the quality of life of people with, or at risk of, Alzheimer's disease. We contrast the efficacy, societal costs, and generalisability of monoclonal antibodies for Alzheimer's disease to biologics for other conditions (eg, cancer, multiple sclerosis, and rheumatoid arthritis) and set this debate in the larger context of modern personalised medicine. We discuss current practice implications, future developments directed to β-amyloid and non-amyloid targets that might have more clinical efficacy and less adverse effects for those with the disease, and large-scale prevention interventions for those at risk.