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.

Document Type

Review

Publication Date

12-8-2021

Notes/Citation Information

Published in Alzheimer's & Dementia, v. 7, issue 1, e12202.

© 2021 The Authors

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Digital Object Identifier (DOI)

https://doi.org/10.1002/trc2.12202

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).

John Breitner has received grants paid to his institution from the Canadian Institute for Health Research in the last 36 months. He has also participated on a data safety monitoring board or advisory board for which he has received honoraria in the last 36 months.

Gregory A. Jicha has received grants paid to his institution from NIH R01 AG061111, UH3 NS100606, R01AG054130, R01AG061848, R01AG054029, R01AG063689, U19AG010483, R01NS116990, R56AG060608, U24AG057437, R01AG053798, P30AG028383, U19AG068054, R01AG057187, R01NS116058, and U19AG024904, and research contracts with AbbVie, Alector, Biohaven, Esai, Lillyalso paid to his institution in the last 36 months.He has also participated on a data safety monitoring board or advisory board for which he has received honoraria in the last 36 months and received honoraria for speaking in the last 36 months. Leadership roles in the last 36 months include International Society to Advance Alzheimer's Research and Treatment (ISTAART) Clinical Trials and Methodology Professional Interest Area Chair (unpaid), and the National Institutes of Health (NIH)/National Institute on Aging (NIA) Clinical task Force and Clinical Core Steering Committee.

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).

David Smith is a member of the scientific advisory board for Elysium Health and a Consultant for Aprofol for which he has received payment. In the last 36 months he has been listed as an inventor on US Patent 10,966,947 B2.

Hussein N. Yassine has received grants paid to his institution R21AG056518, R01AG055770, R01AG054434, and R01AG067063 from the National Institute on Aging in the last 36 months. He is a member of the steering committee of the National Institute on Aging Research and Education Core. Leadership roles in the last 36 months include ISTAART NMD Professional Interest Area Co-Chair (unpaid).

Erin Abner reports no conflict of interest. Leadership roles in the last 36 months include ISTAART Clinical Trials and Methodology Professional Interest Area Professional Interest Area Co-Chair (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).

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)

Nigel Beckett reports no conflict of interest. Leadership roles in the last 36 months include Committee member with responsibility for research of British Geriatric Society - Cardiovascular Specialist Interest Group (unpaid).

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

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.

Hiroko H. Dodge has received grants paid to her institution from NIH grants R01AG051628, R01AG056102, R01AG069782, P30AG066518, R01AG072449, P30AG008017, P30AG024978, U2CAG054397, R01AG056712, R01AG0380651, R21AG062679, P30AG053760, U01NS100611, U2CAG057441, U01NS106670, and R01AG054484 over the last 36 months. She has received honoraria from the Alzheimer's Clinical Trials Consortium (ACTC) and has also participated on data safety monitoring boards/advisory boards in the last 36 months. Leadership roles in the last 36 months include membership of the ISTAART Advisory Board.

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