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Alzheimer's disease outlook : controversies and future directions

Frisoni, Giovanni B. ; Aho, Emil ; Brayne, Carol ; Ciccarelli, Olga ; Dubois, Bruno ; Fox, Nick C. ; Frederiksen, Kristian S. ; Gabay, Cem ; Garibotto, Valentina and Hofmarcher, Thomas LU , et al. (2025) In The Lancet 406(10510). p.1424-1442
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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
The Lancet
volume
406
issue
10510
pages
19 pages
publisher
Elsevier
external identifiers
  • pmid:40997840
  • scopus:105016875372
ISSN
0140-6736
DOI
10.1016/S0140-6736(25)01389-3
language
English
LU publication?
yes
id
659a9a9e-62bf-43cf-b0fa-e854a1db861b
date added to LUP
2025-11-26 14:00:59
date last changed
2025-12-10 23:14:00
@article{659a9a9e-62bf-43cf-b0fa-e854a1db861b,
  abstract     = {{<p>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.</p>}},
  author       = {{Frisoni, Giovanni B. and Aho, Emil and Brayne, Carol and Ciccarelli, Olga and Dubois, Bruno and Fox, Nick C. and Frederiksen, Kristian S. and Gabay, Cem and Garibotto, Valentina and Hofmarcher, Thomas and Jack, Clifford R. and Kivipelto, Miia and Petersen, Ronald C. and Ribaldi, Federica and Rowe, Christopher C. and Walsh, Sebastian and Zetterberg, Henrik and Hansson, Oskar}},
  issn         = {{0140-6736}},
  language     = {{eng}},
  number       = {{10510}},
  pages        = {{1424--1442}},
  publisher    = {{Elsevier}},
  series       = {{The Lancet}},
  title        = {{Alzheimer's disease outlook : controversies and future directions}},
  url          = {{http://dx.doi.org/10.1016/S0140-6736(25)01389-3}},
  doi          = {{10.1016/S0140-6736(25)01389-3}},
  volume       = {{406}},
  year         = {{2025}},
}