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Yu JT, Xu W, Tan CC, et al. 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 Jul 20. pii: jnnp-2019-321913. doi: 10.1136/jnnp-2019-321913. (Evidence-based guideline)

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.

Discipline Area Score
Internal Medicine 6 / 7
Geriatrics 6 / 7
Family Medicine (FM)/General Practice (GP) 6 / 7
General Internal Medicine-Primary Care(US) 6 / 7
Public Health 6 / 7
Neurology 4 / 7
Comments from MORE raters

Internal Medicine rater

This is an important and large comprehensive review that provides guidance to providers caring for elderly population at risk of dementia and those with dementia.

Internal Medicine rater

This is well reviewed with good clinical suggestions.

Public Health rater

The paper represents and interesting meta-analysis reporting a number of significant results. The article is well-written and presented, properly sub-divided in paragraphs and presenting a linear flow, even for those who are not in the field. On top of the take-home messages, it presents the fact that the authors provided dedicated paragraphs on the manuscript flaws and future perspectives. Therefore, I believe this paper might represent an innovation in the field, easily understandable by any reader.

Public Health rater

This is a heroic effort - 44,676 reports reviewed and 243 observational studies and 153 RCTs included. While many results are to be expected, some are not widely known (e.g., obesity is a risk factor for AD up to age 65 but is protective after age 65).
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