Dementia prevention needs funding
Authors: Larry W Chambers, Charles Alessi, Muir Gray
Journal: The Lancet Healthy Longevity (2021)

The US Food and Drug Administration approval of aducanumab1Alexander GC Knopman DS Emerson SS et al.Revisiting FDA approval of aducanumab.N Engl J Med. 2021; 385: 769-771Crossref PubMed Scopus (54) Google Scholar highlights the disconnect between evidence and our response to population ageing and the associated increase of people who are at high risk of dementia.The approval of aducanumab heightens discussion about what constitutes necessary and sufficient evidence around the licensing of novel therapeutic interventions, particularly with regard to the selection of surrogate endpoints.Studies of aducanumab show reductions in amyloid, which can be a sufficient condition for approving the drug. However, it is not a necessary condition because there are other outcomes that should be measured in trials of aducanumab for dementia treatment. For example, if aducanumab does not reduce amyloid, it could still have an effect on behavioural outcomes such as ability to manage financial affairs, maintain self-care and personal hygiene, clean living space, and drive.2Committee on the Public Health Dimensions of Cognitive AgingBoard on Health Sciences PolicyInstitute of MedicineCognitive aging: progress in understanding and opportunities for action. National Academies Press, Washington, DC2015Google ScholarDementia risk reduction in the general population is largely ignored and programmes are not deployed globally despite there being robust and unequivocal evidence for delaying or preventing dementia.The certainty of the evidence regarding the effects of dementia prevention3Livingston G Huntley J Sommerlad A et al.Dementia prevention, intervention, and care: 2020 report of the Lancet Commission.Lancet. 2020; 396: 413-446Summary Full Text Full Text PDF PubMed Scopus (1799) Google Scholar, 4Anstey KJ Ee N Eramudugolla R A systematic review of meta-analyses that evaluate risk factors for dementia to evaluate the quantity, quality, and global representativeness of evidence.J Alzheimers Dis. 2019; 70: S165-S186Crossref PubMed Scopus (53) Google Scholar is much greater than the effect of dementia treatment.5Fink HA Linskens EJ MacDonald R et al.Benefits and harms of prescription drugs and supplements for treatment of clinical Alzheimer-type dementia.Ann Intern Med. 2020; 172: 656-668Crossref PubMed Scopus (28) Google Scholar Systematic reviews on the treatment of dementia with anti-amyloid drugs have shown borderline (4% absolute risk reduction)5Fink HA Linskens EJ MacDonald R et al.Benefits and harms of prescription drugs and supplements for treatment of clinical Alzheimer-type dementia.Ann Intern Med. 2020; 172: 656-668Crossref PubMed Scopus (28) Google Scholar or no absolute effects and the use of amount of amyloid in the brain as the main outcome used in these trials is questionable.By contrast, systematic reviews about dementia prevention are more precise, showing absolute positive effects (40% absolute risk reduction)3Livingston G Huntley J Sommerlad A et al.Dementia prevention, intervention, and care: 2020 report of the Lancet Commission.Lancet. 2020; 396: 413-446Summary Full Text Full Text PDF PubMed Scopus (1799) Google Scholar on three outcomes. First, protecting the brain from harmful effects due to situations such as poor sleep, stress, and prescribed and self-prescribed drugs. Second, keeping oxygen supply flowing to the brain. Finally, keeping engaged and positive, continuing to socialise, find new challenges, and resist negative thoughts of inevitable decline.Governmental and non-governmental organisations should focus on the evidence and highlight simple but effective lifestyle changes that anyone can make. Everyone can take positive action to increase their so-called brainability. The Lancet Commission on dementia prevention, intervention, and care3Livingston G Huntley J Sommerlad A et al.Dementia prevention, intervention, and care: 2020 report of the Lancet Commission.Lancet. 2020; 396: 413-446Summary Full Text Full Text PDF PubMed Scopus (1799) Google Scholar is important and can be used to inform action policies. The US Food and Drug Administration approval of aducanumab1Alexander GC Knopman DS Emerson SS et al.Revisiting FDA approval of aducanumab.N Engl J Med. 2021; 385: 769-771Crossref PubMed Scopus (54) Google Scholar highlights the disconnect between evidence and our response to population ageing and the associated increase of people who are at high risk of dementia. The approval of aducanumab heightens discussion about what constitutes necessary and sufficient evidence around the licensing of novel therapeutic interventions, particularly with regard to the selection of surrogate endpoints. Studies of aducanumab show reductions in amyloid, which can be a sufficient condition for approving the drug. However, it is not a necessary condition because there are other outcomes that should be measured in trials of aducanumab for dementia treatment. For example, if aducanumab does not reduce amyloid, it could still have an effect on behavioural outcomes such as ability to manage financial affairs, maintain self-care and personal hygiene, clean living space, and drive.2Committee on the Public Health Dimensions of Cognitive AgingBoard on Health Sciences PolicyInstitute of MedicineCognitive aging: progress in understanding and opportunities for action. National Academies Press, Washington, DC2015Google Scholar Dementia risk reduction in the general population is largely ignored and programmes are not deployed globally despite there being robust and unequivocal evidence for delaying or preventing dementia. The certainty of the evidence regarding the effects of dementia prevention3Livingston G Huntley J Sommerlad A et al.Dementia prevention, intervention, and care: 2020 report of the Lancet Commission.Lancet. 2020; 396: 413-446Summary Full Text Full Text PDF PubMed Scopus (1799) Google Scholar, 4Anstey KJ Ee N Eramudugolla R A systematic review of meta-analyses that evaluate risk factors for dementia to evaluate the quantity, quality, and global representativeness of evidence.J Alzheimers Dis. 2019; 70: S165-S186Crossref PubMed Scopus (53) Google Scholar is much greater than the effect of dementia treatment.5Fink HA Linskens EJ MacDonald R et al.Benefits and harms of prescription drugs and supplements for treatment of clinical Alzheimer-type dementia.Ann Intern Med. 2020; 172: 656-668Crossref PubMed Scopus (28) Google Scholar Systematic reviews on the treatment of dementia with anti-amyloid drugs have shown borderline (4% absolute risk reduction)5Fink HA Linskens EJ MacDonald R et al.Benefits and harms of prescription drugs and supplements for treatment of clinical Alzheimer-type dementia.Ann Intern Med. 2020; 172: 656-668Crossref PubMed Scopus (28) Google Scholar or no absolute effects and the use of amount of amyloid in the brain as the main outcome used in these trials is questionable. By contrast, systematic reviews about dementia prevention are more precise, showing absolute positive effects (40% absolute risk reduction)3Livingston G Huntley J Sommerlad A et al.Dementia prevention, intervention, and care: 2020 report of the Lancet Commission.Lancet. 2020; 396: 413-446Summary Full Text Full Text PDF PubMed Scopus (1799) Google Scholar on three outcomes. First, protecting the brain from harmful effects due to situations such as poor sleep, stress, and prescribed and self-prescribed drugs. Second, keeping oxygen supply flowing to the brain. Finally, keeping engaged and positive, continuing to socialise, find new challenges, and resist negative thoughts of inevitable decline. Governmental and non-governmental organisations should focus on the evidence and highlight simple but effective lifestyle changes that anyone can make. Everyone can take positive action to increase their so-called brainability. The Lancet Commission on dementia prevention, intervention, and care3Livingston G Huntley J Sommerlad A et al.Dementia prevention, intervention, and care: 2020 report of the Lancet Commission.Lancet. 2020; 396: 413-446Summary Full Text Full Text PDF PubMed Scopus (1799) Google Scholar is important and can be used to inform action policies. We declare no competing interests.