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?

Ruth Peters^{1

2}, Hiroko H Dodge³, Sarah James⁴, Gregory A Jicha⁵, Pierre-Francois Meyer⁶, Marcus Richards⁴, A David Smith⁷, Hussein N Yassine⁸, Erin Abner⁵, Atticus H Hainsworth^{9

10}, Patrick G Kehoe¹¹, Nigel Beckett¹², Craig S Anderson¹³, Kaarin J Anstey^{1

2}

Affiliations

¹ Neuroscience Research, Randwick, New South Wales, Australia.
² Department of Psychology, University of New South Wales, Sydney, New South Wales, Australia.
³ Department of Neurology, Oregon Health & Science University, Portland, Oregon, USA.
⁴ MRC Unit for Lifelong Health and Ageing at UCL, University College London, London, UK.
⁵ University of Kentucky, Lexington, Kentucky, USA.
⁶ Center for Studies on the Prevention of Alzheimer's Disease (PREVENT-AD), Verdun, Québec, Canada.
⁷ OPTIMA, Department of Pharmacology, University of Oxford, Oxford, UK.
⁸ Departments of Medicine and Neurology, University of Southern California, Los Angeles, California, USA.
⁹ Molecular and Clinical Sciences Research Institute, St Georges, University of London, London, UK.
¹⁰ Department of Neurology, St George's Hospital, London, UK.
¹¹ Bristol Medical School University of Bristol, Bristol, UK.
¹² Guys and St Thomas' NHS Foundation Trust, London, UK.
¹³ The George Institute for Global Health, Faculty of Medicine, University of New South Wales, Sydney, Australia.

PMID: 34726352
DOI: 10.1002/alz.12393

Observational Study

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?

Ruth Peters et al. Alzheimers Dement. 2022 Mar.

. 2022 Mar;18(3):507-512.

doi: 10.1002/alz.12393. Epub 2021 Nov 2.

Authors

Affiliations

¹ Neuroscience Research, Randwick, New South Wales, Australia.
² Department of Psychology, University of New South Wales, Sydney, New South Wales, Australia.
³ Department of Neurology, Oregon Health & Science University, Portland, Oregon, USA.
⁴ MRC Unit for Lifelong Health and Ageing at UCL, University College London, London, UK.
⁵ University of Kentucky, Lexington, Kentucky, USA.
⁶ Center for Studies on the Prevention of Alzheimer's Disease (PREVENT-AD), Verdun, Québec, Canada.
⁷ OPTIMA, Department of Pharmacology, University of Oxford, Oxford, UK.
⁸ Departments of Medicine and Neurology, University of Southern California, Los Angeles, California, USA.
⁹ Molecular and Clinical Sciences Research Institute, St Georges, University of London, London, UK.
¹⁰ Department of Neurology, St George's Hospital, London, UK.
¹¹ Bristol Medical School University of Bristol, Bristol, UK.
¹² Guys and St Thomas' NHS Foundation Trust, London, UK.
¹³ The George Institute for Global Health, Faculty of Medicine, University of New South Wales, Sydney, Australia.

PMID: 34726352
DOI: 10.1002/alz.12393

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.

Keywords: Alzheimer's disease; clinical trials; dementia; epidemiology.

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References

REFERENCES

1. Prince M, WA, Guerchet M, Ali G-C, Wu Y-T, Prina M, World Alzheimer Report 2015 The Global impact of dementia, in World Alzheimer Report. 2015. Alzheimer's Disease International. https://www.alzint.org/resource/world-alzheimer-report-2015/
1. Renewing priority for dementia: where do we stand?. in Policy Brief. 2018. https://www.oecd.org/health/dementia.htm.
1. Ramsay MAE. John Snow, MD: anaesthetist to the Queen of England and pioneer epidemiologist. Proc (Bayl Univ Med Cent). 2006;19(1):24-28.
1. Anstey KJ, Ee N, Eramudugolla R, Jagger C, Peters 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(s1):S165-S186.
1. Livingston G, Sommerlad A, Orgeta V, et al. Dementia prevention, intervention, and care. Lancet North Am Ed. 2017;390(10113):2673-2734.

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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?

Affiliations

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?

Authors

Affiliations

Abstract

References

REFERENCES

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical