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Evidence-based prevention of Alzheimer's disease: systematic review and meta-analysis of 243 observational prospective studies and 153 randomised controlled trials
  1. Jin-Tai Yu1,
  2. Wei Xu2,
  3. Chen-Chen Tan2,
  4. Sandrine Andrieu3,
  5. John Suckling4,
  6. Evangelos Evangelou5,
  7. An Pan6,
  8. Can Zhang7,
  9. Jianping Jia8,
  10. Lei Feng9,
  11. Ee-Heok Kua9,
  12. Yan-Jiang Wang10,
  13. Hui-Fu Wang2,
  14. Meng-Shan Tan2,
  15. Jie-Qiong Li2,
  16. Xiao-He Hou2,
  17. Yu Wan2,
  18. Lin Tan2,
  19. Vincent Mok11,
  20. Lan Tan2,
  21. Qiang Dong1,
  22. Jacques Touchon12,
  23. Serge Gauthier13,
  24. Paul S Aisen14,
  25. Bruno Vellas15
  1. 1 Department of Neurology and Institute of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
  2. 2 Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China
  3. 3 Department of Epidemiology and Public Health, University of Toulouse III, Toulouse, France
  4. 4 Department of Psychiatry, Medical Research Council and Wellcome Trust Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK
  5. 5 Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece
  6. 6 Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
  7. 7 Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA
  8. 8 Department of Neurology, Xuan Wu Hospital, Capital Medical University, Beijing, China
  9. 9 Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
  10. 10 Department of Neurology, Daping Hospital, Third Military Medical University, Chongqing, China
  11. 11 Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong
  12. 12 Department of Neurology, University Hospital of Montpellier, Montpellier, France
  13. 13 McGill Center for Studies in Aging, McGill University, Montreal, Quebec, Canada
  14. 14 Alzheimer's Therapeutic Research Institute, University of Southern California, San Diego, California, USA
  15. 15 Department of Geriatrics, Purpan University Hospital, Toulouse, France
  1. Correspondence to Professor Jin-Tai Yu, Department of Neurology and Institute of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China; jintai_yu{at}


Background Evidence on preventing Alzheimer’s disease (AD) is challenging to interpret due to varying study designs with heterogeneous endpoints and credibility. We completed a systematic review and meta-analysis of current evidence with prospective designs to propose evidence-based suggestions on AD prevention.

Methods Electronic databases and relevant websites were searched from inception to 1 March 2019. Both observational prospective studies (OPSs) and randomised controlled trials (RCTs) were included. The multivariable-adjusted effect estimates were pooled by random-effects models, with credibility assessment according to its risk of bias, inconsistency and imprecision. Levels of evidence and classes of suggestions were summarised.

Results A total of 44 676 reports were identified, and 243 OPSs and 153 RCTs were eligible for analysis after exclusion based on pre-decided criteria, from which 104 modifiable factors and 11 interventions were included in the meta-analyses. Twenty-one suggestions are proposed based on the consolidated evidence, with Class I suggestions targeting 19 factors: 10 with Level A strong evidence (education, cognitive activity, high body mass index in latelife, hyperhomocysteinaemia, depression, stress, diabetes, head trauma, hypertension in midlife and orthostatic hypotension) and 9 with Level B weaker evidence (obesity in midlife, weight loss in late life, physical exercise, smoking, sleep, cerebrovascular disease, frailty, atrial fibrillation and vitamin C). In contrast, two interventions are not recommended: oestrogen replacement therapy (Level A2) and acetylcholinesterase inhibitors (Level B).

Interpretation Evidence-based suggestions are proposed, offering clinicians and stakeholders current guidance for the prevention of AD.

  • alzheimer's disease
  • epidemiology
  • meta-analysis
  • systematic reviews

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See:

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  • J-TY, WX and C-CT contributed equally.

  • Contributors JTY and BV conceived and designed the study. JTY, WX, CCT, HFW, MST and JQL selected the articles and extracted the data. JTY, WX, C-CT, HFW, M-ST, J-QL, XHH, YW, LT and LT proofread the data. JTY, WX, C-CT and AP analysed the data. WX and CCT generated the figures. JTY, WX, CCT wrote the first draft of the manuscript. JTY, WX, C-CT, SA, JS, EE, CZ, JJ, AP, LF, EHK, YJW, VM, JT, GS, PSA, QD, and BV interpreted the data and contributed to the writing of the final version of the manuscript. All authors agreed with the results and conclusions and approved the final draft.

  • Funding This study was supported by grants from the National Key R&D Program of China (2018YFC1314702), Shanghai Municipal Science and Technology Major Project (No. 2018SHZDZX03) and ZHANGJIANG LAB.

  • Competing interests JTY serves as an associate editor-in-chief for Annals of Translational Medicineand is senior editor for Journal of Alzheimer’s Disease. SA has received grants from Europe, Ipsen, and France Alzheimer, served as a consultant for Ipsen, Pierre Fabre, Lilly, Nestlé, Sanofi and Servier, and received non-financial support from Biogen, Nutrition Santé, Pfzer and Icon, and other support from the AMPA Association. GS has received clinical trial support from Lilly and Roche in DIAN-TU, TauRx Therapeutics (TauRx) and Lundbeck; has been a data safety monitoring board (DSMB) member of ADCS, ATRI, API and Eisai; and has been a scientific adviser to Affiris, Boehringer Ingelheim, Lilly, Roche, Servier, Sanofi, Schwabe, Takeda and TauRx. PSA has received grants from the US Alzheimer’s Association, Janssen, Lilly, the US National Institute on Aging and Toyama; and consulting fees from Abbott, Abbvie, Amgen, Anavex, AstraZeneca, Biogen Idec, Biotie, Bristol-Myers Squibb, Cardeus, Cohbar, Eisai, Elan, Eli Lilly, Genentech, Ichor, iPerian, Janssen, Lundbeck, Medivation, Merck, NeuroPhage, Novartis, Pfizer, Probiodrug, Roche, Somaxon and Toyama, outside the submitted work. BV reports grants from Pierre Fabre, Avid, Exonhit, AbbVie, Lilly, Lundbeck, MSD, Otsuka, Regenron, Sanofi, Roche, AstraZeneca, LPG Systems, Nestlé and Alzheon, and personal fees from Lilly, Lundbeck, MSD, Otsuka, Roche, Sanofi, Biogen, Nestlé, Transition Therapeutics and Takeda.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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