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The epidemiology is promising, but the trial evidence is weak. Why pharmacological dementia risk reduction trials haven't lived up to expectations, and where do we go from here?

Peters, R; Dodge, H; James, S; Jicha, GA; Meyer, P-F; Richards, M; Smith, AD; Yassine, HN; Abner, E; Hainsworth, AH; et al. Peters, R; Dodge, H; James, S; Jicha, GA; Meyer, P-F; Richards, M; Smith, AD; Yassine, HN; Abner, E; Hainsworth, AH; Kehoe, PG; Beckett, N; Anderson, C; Anstey, KJ (2021) The epidemiology is promising, but the trial evidence is weak. Why pharmacological dementia risk reduction trials haven't lived up to expectations, and where do we go from here? Alzheimers & Dementia. ISSN 1552-5260 https://doi.org/10.1002/alz.12393
SGUL Authors: Hainsworth, Atticus Henry

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Abstract

There is an urgent need for interventions that can prevent or delay cognitive decline and dementia. Decades of epidemiological research have identified potential pharmacological strategies for risk factor modification to prevent these serious conditions, but clinical trials have failed to confirm the potential efficacy for such interventions. Our multidisciplinary international group reviewed seven high-potential intervention strategies in an attempt to identify potential reasons for the mismatch between the observational and trial results. In considering our findings, we offer constructive recommendations for the next steps. Overall, we observed some differences in the observational evidence base for the seven strategies, but several common methodological themes that emerged. These themes included the appropriateness of trial populations and intervention strategies, including the timing of interventions and other aspects of trials methodology. To inform the design of future clinical trials, we provide recommendations for the next steps in finding strategies for effective dementia risk reduction.

Item Type: Article
Additional Information: This is the peer reviewed version of the following article: Peters, R, Dodge, HH, James, S, et al. The epidemiology is promising, but the trial evidence is weak. Why pharmacological dementia risk reduction trials haven't lived up to expectations, and where do we go from here? Alzheimer's Dement. 2021; 1- 6, which has been published in final form at https://doi.org/10.1002/alz.12393. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.
Keywords: Geriatrics, 1109 Neurosciences, 1103 Clinical Sciences
SGUL Research Institute / Research Centre: Academic Structure > Molecular and Clinical Sciences Research Institute (MCS)
Journal or Publication Title: Alzheimers & Dementia
ISSN: 1552-5260
Dates:
DateEvent
2 November 2021Published Online
6 May 2021Accepted
Publisher License: Publisher's own licence
Projects:
Project IDFunderFunder ID
R01AG051628National Institutes of Healthhttp://dx.doi.org/10.13039/100000002
R01 AG056102National Institutes of Healthhttp://dx.doi.org/10.13039/100000002
U2CAG054397National Institutes of Healthhttp://dx.doi.org/10.13039/100000002
P30AG066518National Institutes of Healthhttp://dx.doi.org/10.13039/100000002
P30 AG008017National Institutes of Healthhttp://dx.doi.org/10.13039/100000002
P30AG024978National Institutes of Healthhttp://dx.doi.org/10.13039/100000002
R01AG056712National Institutes of Healthhttp://dx.doi.org/10.13039/100000002
R01AG0380651National Institutes of Healthhttp://dx.doi.org/10.13039/100000002
R21AG062679National Institutes of Healthhttp://dx.doi.org/10.13039/100000002
U2CAG057441National Institutes of Healthhttp://dx.doi.org/10.13039/100000002
R01AG069782National Institutes of Healthhttp://dx.doi.org/10.13039/100000002
R01 AG061111National Institutes of Healthhttp://dx.doi.org/10.13039/100000002
UH3 NS100606National Institutes of Healthhttp://dx.doi.org/10.13039/100000002
R01 AG054130National Institutes of Healthhttp://dx.doi.org/10.13039/100000002
R01 AG061848National Institutes of Healthhttp://dx.doi.org/10.13039/100000002
R01 AG054029National Institutes of Healthhttp://dx.doi.org/10.13039/100000002
R01 AG063689National Institutes of Healthhttp://dx.doi.org/10.13039/100000002
U19 AG010483National Institutes of Healthhttp://dx.doi.org/10.13039/100000002
R56 AG060608National Institutes of Healthhttp://dx.doi.org/10.13039/100000002
U24 AG057437National Institutes of Healthhttp://dx.doi.org/10.13039/100000002
R01 AG053798National Institutes of Healthhttp://dx.doi.org/10.13039/100000002
P30 AG028383National Institutes of Healthhttp://dx.doi.org/10.13039/100000002
R01 HD064993National Institutes of Healthhttp://dx.doi.org/10.13039/100000002
U19 AG024904National Institutes of Healthhttp://dx.doi.org/10.13039/100000002
R01 AG057187National Institutes of Healthhttp://dx.doi.org/10.13039/100000002
R01 NS116058National Institutes of Healthhttp://dx.doi.org/10.13039/100000002
R01 NS116990National Institutes of Healthhttp://dx.doi.org/10.13039/100000002
R21AG056518,National Institute on Aginghttp://dx.doi.org/10.13039/100000049
R01AG055770,National Institute on Aginghttp://dx.doi.org/10.13039/100000049
R01AG054434National Institute on Aginghttp://dx.doi.org/10.13039/100000049
R01AG067063National Institute on Aginghttp://dx.doi.org/10.13039/100000049
20140901Alzheimer's Drug Discovery FoundationUNSPECIFIED
1100579National Health and Medical Research Councilhttp://dx.doi.org/10.13039/501100000925
1102694National Health and Medical Research Councilhttp://dx.doi.org/10.13039/501100000925
CE170100005Australian Research Councilhttp://dx.doi.org/10.13039/501100000923
URI: https://openaccess.sgul.ac.uk/id/eprint/113273
Publisher's version: https://doi.org/10.1002/alz.12393

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