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
- systematic reviews
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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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