Dementia risk reduction: why haven't the pharmacological risk reduction trials worked? An in-depth exploration of seven established risk factors

Ruth Peters; John Breitner; Sarah James; Gregory A. Jicha; Pierre Francois Meyer; Marcus Richards; A. David Smith; Hussein N. Yassine; Erin Abner; Atticus H. Hainsworth; Patrick G. Kehoe; Nigel Beckett; Christopher Weber; Craig Anderson; Kaarin J. Anstey; Hiroko H. Dodge

doi:10.1002/trc2.12202

Dementia risk reduction: why haven't the pharmacological risk reduction trials worked? An in-depth exploration of seven established risk factors

Ruth Peters
, John Breitner
, Sarah James
, Gregory A. Jicha
, Pierre Francois Meyer
, Marcus Richards
, A. David Smith
, Hussein N. Yassine
, Erin Abner
, Atticus H. Hainsworth
, Patrick G. Kehoe
, Nigel Beckett
, Christopher Weber
, Craig Anderson
, Kaarin J. Anstey
, Hiroko H. Dodge

Research output: Contribution to journal › Review article › peer-review

17 Scopus citations

Abstract

Identifying the leading health and lifestyle factors for the risk of incident dementia and Alzheimer's disease has yet to translate to risk reduction. To understand why, we examined the discrepancies between observational and clinical trial evidence for seven modifiable risk factors: type 2 diabetes, dyslipidemia, hypertension, estrogens, inflammation, omega-3 fatty acids, and hyperhomocysteinemia. Sample heterogeneity and paucity of intervention details (dose, timing, formulation) were common themes. Epidemiological evidence is more mature for some interventions (eg, non-steroidal anti-inflammatory drugs [NSAIDs]) than others. Trial data are promising for anti-hypertensives and B vitamin supplementation. Taken together, these risk factors highlight a future need for more targeted sample selection in clinical trials, a better understanding of interventions, and deeper analysis of existing data.

Original language	English
Article number	e12202
Journal	Alzheimer's and Dementia: Translational Research and Clinical Interventions
Volume	7
Issue number	1
DOIs	https://doi.org/10.1002/trc2.12202
State	Published - 2021

Bibliographical note

Publisher Copyright:
© 2021 The Authors. Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association.

Funding

Kaarin J. Anstey has received grants paid to her institution from the NHMRC, Australian Research Council, Australian Medical Research Futures Fund, Mindgardens Alliance, the NHMRC Dementia Centre for Research Collaboration, and the Australian Government in the last 36 months. She has received honoraria from the AARP, the University of British Columbia Member, Governance Committee of the Global Council on Brain Health. Leadership roles in the last 36 months include Advisor, Staying Sharp platform for AARP, and membership of the board of directors of the Dementia Australia Research Foundation. Patrick G. Kehoe has received grants paid to his institution from the Sigmund Gestetner Foundation Fellowship, the Alzheimer's Society, Alzheimer's Research UK, BRACE, the Bright Focus Foundation, the British Heart Foundation, the UK Medical Research Council, and the UK National Institute of Health Research (NIHR\u2010EME) in the last 36 months. Leadership roles in the last 36 months include membership of the Alzheimer's Society UK Research Advisory Council. and as a Trustee to the Research into Care of the Elderly (RICE) Centre, Bath, UK (unpaid) Atticus H. Hainsworth has received grants paid to his institution from the Alzheimer's Society (UK) and Alzheimer's Drug Discovery Foundation (Project Ref 20140901) in the last 36 months. Dr. Hainsworth has also received honoraria from Eli Lilly and NIA. Leadership roles in the last 36 months include ISTAART Clinical Trials and Vascular Cognitive Disorders Professional Interest Area Chair (unpaid) and membership of the Vascular Experimental Medicine group within DPUK (unpaid). Ruth Peters is supported by the Australian National Health and Medical Research Centre (NHMRC), Dementia Centre for Research Collaboration, and she has received grants paid to her institution from the NHMRC and the University of New South Wales in the past 36 months. Leadership roles in the last 36 months include Chair of the Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART) Clinical Trials and Methodology Professional Interest Area (unpaid). Marcus Richards has received grants from the UK Medical Research Council MC_UU_12019/1 and /3 and the UK Alzheimer's Society paid to his institution in the last 36 months. He is a member of several advisory groups and part of the steering committee for the Dementias Platform UK (DPUK) (unpaid).

Funders	Funder number
Australian Research Council
Bright Focus Foundation
Alzheimer’s Research United Kingdom
Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment
Mindgardens Alliance
National Institute for Health Research Health Protection Research Unit
BRACE
British Heart Foundation
Australian National Health and Medical Research Council
Sigmund Gestetner Foundation
NIHR‐EME
Australian National Health and Medical Research Centre
Australian Medical Research Futures Fund
University of New South Wales
UK Industrial Decarbonization Research and Innovation Centre
Medical Research Council-São Paulo Research Foundation	MR/L023784/2, MC_UU_12019/1
Alzheimer's Drug Discovery Foundation	20140901

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

ASJC Scopus subject areas

Clinical Neurology
Psychiatry and Mental health

Access to Document

10.1002/trc2.12202

Cite this

Peters, R., Breitner, J., James, S., Jicha, G. A., Meyer, P. F., Richards, M., Smith, A. D., Yassine, H. N., Abner, E., Hainsworth, A. H., Kehoe, P. G., Beckett, N., Weber, C., Anderson, C., Anstey, K. J., & Dodge, H. H. (2021). Dementia risk reduction: why haven't the pharmacological risk reduction trials worked? An in-depth exploration of seven established risk factors. Alzheimer's and Dementia: Translational Research and Clinical Interventions, 7(1), Article e12202. https://doi.org/10.1002/trc2.12202

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title = "Dementia risk reduction: why haven't the pharmacological risk reduction trials worked? An in-depth exploration of seven established risk factors",

abstract = "Identifying the leading health and lifestyle factors for the risk of incident dementia and Alzheimer's disease has yet to translate to risk reduction. To understand why, we examined the discrepancies between observational and clinical trial evidence for seven modifiable risk factors: type 2 diabetes, dyslipidemia, hypertension, estrogens, inflammation, omega-3 fatty acids, and hyperhomocysteinemia. Sample heterogeneity and paucity of intervention details (dose, timing, formulation) were common themes. Epidemiological evidence is more mature for some interventions (eg, non-steroidal anti-inflammatory drugs [NSAIDs]) than others. Trial data are promising for anti-hypertensives and B vitamin supplementation. Taken together, these risk factors highlight a future need for more targeted sample selection in clinical trials, a better understanding of interventions, and deeper analysis of existing data.",

author = "Ruth Peters and John Breitner and Sarah James and Jicha, \{Gregory A.\} and Meyer, \{Pierre Francois\} and Marcus Richards and Smith, \{A. David\} and Yassine, \{Hussein N.\} and Erin Abner and Hainsworth, \{Atticus H.\} and Kehoe, \{Patrick G.\} and Nigel Beckett and Christopher Weber and Craig Anderson and Anstey, \{Kaarin J.\} and Dodge, \{Hiroko H.\}",

note = "Publisher Copyright: {\textcopyright} 2021 The Authors. Alzheimer's \& Dementia: Translational Research \& Clinical Interventions published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association.",

year = "2021",

doi = "10.1002/trc2.12202",

language = "English",

volume = "7",

number = "1",

}

Peters, R, Breitner, J, James, S, Jicha, GA, Meyer, PF, Richards, M, Smith, AD, Yassine, HN, Abner, E, Hainsworth, AH, Kehoe, PG, Beckett, N, Weber, C, Anderson, C, Anstey, KJ & Dodge, HH 2021, 'Dementia risk reduction: why haven't the pharmacological risk reduction trials worked? An in-depth exploration of seven established risk factors', Alzheimer's and Dementia: Translational Research and Clinical Interventions, vol. 7, no. 1, e12202. https://doi.org/10.1002/trc2.12202

Dementia risk reduction: why haven't the pharmacological risk reduction trials worked? An in-depth exploration of seven established risk factors. / Peters, Ruth; Breitner, John; James, Sarah et al.
In: Alzheimer's and Dementia: Translational Research and Clinical Interventions, Vol. 7, No. 1, e12202, 2021.

Research output: Contribution to journal › Review article › peer-review

TY - JOUR

T1 - Dementia risk reduction

T2 - why haven't the pharmacological risk reduction trials worked? An in-depth exploration of seven established risk factors

AU - Peters, Ruth

AU - Breitner, John

AU - James, Sarah

AU - Jicha, Gregory A.

AU - Meyer, Pierre Francois

AU - Richards, Marcus

AU - Smith, A. David

AU - Yassine, Hussein N.

AU - Abner, Erin

AU - Hainsworth, Atticus H.

AU - Kehoe, Patrick G.

AU - Beckett, Nigel

AU - Weber, Christopher

AU - Anderson, Craig

AU - Anstey, Kaarin J.

AU - Dodge, Hiroko H.

PY - 2021

Y1 - 2021

N2 - Identifying the leading health and lifestyle factors for the risk of incident dementia and Alzheimer's disease has yet to translate to risk reduction. To understand why, we examined the discrepancies between observational and clinical trial evidence for seven modifiable risk factors: type 2 diabetes, dyslipidemia, hypertension, estrogens, inflammation, omega-3 fatty acids, and hyperhomocysteinemia. Sample heterogeneity and paucity of intervention details (dose, timing, formulation) were common themes. Epidemiological evidence is more mature for some interventions (eg, non-steroidal anti-inflammatory drugs [NSAIDs]) than others. Trial data are promising for anti-hypertensives and B vitamin supplementation. Taken together, these risk factors highlight a future need for more targeted sample selection in clinical trials, a better understanding of interventions, and deeper analysis of existing data.

AB - Identifying the leading health and lifestyle factors for the risk of incident dementia and Alzheimer's disease has yet to translate to risk reduction. To understand why, we examined the discrepancies between observational and clinical trial evidence for seven modifiable risk factors: type 2 diabetes, dyslipidemia, hypertension, estrogens, inflammation, omega-3 fatty acids, and hyperhomocysteinemia. Sample heterogeneity and paucity of intervention details (dose, timing, formulation) were common themes. Epidemiological evidence is more mature for some interventions (eg, non-steroidal anti-inflammatory drugs [NSAIDs]) than others. Trial data are promising for anti-hypertensives and B vitamin supplementation. Taken together, these risk factors highlight a future need for more targeted sample selection in clinical trials, a better understanding of interventions, and deeper analysis of existing data.

UR - https://www.scopus.com/pages/publications/85123883344

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U2 - 10.1002/trc2.12202

DO - 10.1002/trc2.12202

M3 - Review article

AN - SCOPUS:85123883344

VL - 7

JO - Alzheimer's and Dementia: Translational Research and Clinical Interventions

JF - Alzheimer's and Dementia: Translational Research and Clinical Interventions

IS - 1

M1 - e12202

ER -

Dementia risk reduction: why haven't the pharmacological risk reduction trials worked? An in-depth exploration of seven established risk factors

Abstract

Bibliographical note

Funding

UN SDGs

ASJC Scopus subject areas

Access to Document

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Cite this