Evidence-based prevention of Alzheimer's disease: systematic review and meta-analysis of 243 observational prospective studies and 153 randomised controlled trials

J Neurol Neurosurg Psychiatry. 2020 Nov;91(11):1201-1209. doi: 10.1136/jnnp-2019-321913. Epub 2020 Jul 20.

Abstract

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.

Keywords: alzheimer's disease; epidemiology; meta-analysis; systematic reviews.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Alzheimer Disease / prevention & control*
  • Antihypertensive Agents / therapeutic use
  • Cognition
  • Craniocerebral Trauma / prevention & control
  • Depression / therapy
  • Diabetes Mellitus / therapy
  • Education
  • Evidence-Based Medicine*
  • Exercise
  • Humans
  • Hyperhomocysteinemia / drug therapy
  • Hypertension / drug therapy
  • Hypotension, Orthostatic / therapy
  • Life Style
  • Obesity / therapy
  • Observational Studies as Topic
  • Randomized Controlled Trials as Topic
  • Risk Reduction Behavior
  • Stress, Psychological / therapy

Substances

  • Antihypertensive Agents