Dementia research in 2023: the year of anti-amyloid immunotherapy

In 2023, important milestones were reached in the field of Alzheimer's disease and other dementias. After 20 years of unsuccessful or controversial clinical trials, amyloid has been validated as a therapeutic target in Alzheimer's disease by two positive clinical trials. Lecanemab, a humanised monoclonal antibody preferentially targeting amyloid β soluble protofibrils, slowed cognitive decline by 27% at 18 months after treatment in people with early Alzheimer's disease and amyloid biomarkers (CLARITY trial, n=1795). 1 van Dyck CH Swanson CJ Aisen P et al. Lecanemab in early Alzheimer's disease. N Engl J Med. 2023; 388: 9-21 Crossref PubMed Scopus (679) Google Scholar Donanemab, another anti-amyloid antibody targeting brain amyloid plaques, also showed a clinical effect on cognition in people with early Alzheimer's disease (TRAILBLAZER-ALZ 2 trial, n=1736). 2 Sims JR Zimmer JA Evans CD et al. Donanemab in early symptomatic Alzheimer disease: the TRAILBLAZER-ALZ 2 randomized clinical trial. JAMA. 2023; 330: 512-527 Crossref PubMed Scopus (93) Google Scholar The benefit on cognition seemed to be greatest in participants with low or medium tau pathology, assessed by PET, with a slowing in cognitive decline by about 35% at 18 months after initiation of treatment. Both therapies reduced cerebral amyloid burden, with amyloid clearance occurring in 68% of participants in the lecanemab phase 3 trial, and in 80% in the donanemab phase 3 trial.