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 journalReview articlepeer-review

6 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 languageEnglish
Article numbere12202
JournalAlzheimer's and Dementia: Translational Research and Clinical Interventions
Volume7
Issue number1
DOIs
StatePublished - 2021

Bibliographical note

Funding Information:
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).

Funding Information:
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).

Funding Information:
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.

Funding Information:
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).

Funding Information:
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‐EME) 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)

Funding Information:
Craig Anderson has received grants from the NHMRC paid to his institution and honoraria from Takeda China in the last 36 months.

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

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health

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