Evidence-based prevention of Alzheimer's disease: systematic review and meta-analysis of 243 observational prospective studies and 153 randomised controlled trials
http://orcid.org/0000-0002-7686-0547Jin-Tai Yu1, http://orcid.org/0000-0002-3310-5875
Wei Xu2, Chen-Chen Tan2, Sandrine Andrieu3, John Suckling4, Evangelos Evangelou5, An Pan6, Can Zhang7, Jianping Jia8, Lei Feng9, Ee-Heok Kua9, Yan-Jiang Wang10, Hui-Fu Wang2, Meng-Shan Tan2, Jie-Qiong Li2, Xiao-He Hou2, Yu Wan2, Lin Tan2, Vincent Mok11, Lan Tan2, Qiang Dong1, Jacques Touchon12, Serge Gauthier13, Paul S Aisen14, Bruno Vellas15
Correspondence to Professor Jin-Tai Yu, Department of Neurology and Institute of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China; firstname.lastname@example.org
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.