Department of Neurology, Radboud University Medical Center, Donders Institute for Brain, Cognition, and Behavior, Nijmegen, The Netherlands.
Department of Public and Occupational Health, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Alzheimers Dement. 2023 Aug;19(8):3722-3730. doi: 10.1002/alz.13029. Epub 2023 Mar 24.
Observational studies have shown consistently that modifiable risk factors during life are associated with increased dementia risk in old age but randomized controlled trials (RCTs) on dementia prevention evaluating the treatment of these risk factors did not find consistent effects on cognitive outcomes. The discrepancy in findings is potentially attributable to inherent differences between the two study designs. Although RCTs are the gold standard for establishing causality, designing and conducting an RCT for dementia prevention is complex. Quasi-experimental studies (QESs) may contribute to investigating causality without randomization. QESs use variation in exposure to a risk factor or intervention in an observational setting to deduct causal effects. Design-specific approaches are used to control for confounding, the main caveat of QESs. In this article we address the challenges, opportunities, and limitations of QESs for research into dementia prevention. HIGHLIGHTS: Despite consistent associations between modifiable risk factors and dementia, the mostly neutral effects of randomized controlled trials (RCTs) challenge the causality of these associations. RCTs in the field of dementia prevention are often problematic due to ethical, practical, or financial constraints, and their results may have limited generalizability. Four quasi-experimental study (QES) designs may be suitable to study causality between risk factors and dementia; we critically appraise these study designs for dementia-prevention studies. We describe how specific QES designs can be used to study the effects of risk-factor modification for 12 known risk factors for dementia.
观察性研究一直表明，可改变的生活风险因素与老年痴呆症风险增加有关，但评估这些风险因素治疗效果的预防痴呆症的随机对照试验（RCT）并未发现对认知结果有一致的影响。研究结果的差异可能归因于这两种研究设计之间的固有差异。虽然 RCT 是确定因果关系的金标准，但设计和进行预防痴呆症的 RCT 非常复杂。准实验研究（QES）可能有助于在没有随机分组的情况下进行因果关系的研究。QES 使用观察性设置中对风险因素或干预的暴露差异来推断因果效应。设计特定的方法用于控制混杂，这是 QES 的主要注意事项。本文探讨了 QES 在预防痴呆症研究中的挑战、机遇和局限性。重点：尽管可改变的风险因素与痴呆症之间存在一致的关联，但随机对照试验（RCT）的中性结果对这些关联的因果关系提出了挑战。由于伦理、实际或财务限制，痴呆症预防领域的 RCT 往往存在问题，其结果可能具有有限的普遍性。有四种准实验研究（QES）设计可适用于研究风险因素与痴呆症之间的因果关系；我们批判性地评价了这些研究设计用于痴呆症预防研究。我们描述了如何使用特定的 QES 设计来研究 12 种已知痴呆症风险因素的风险因素改变的效果。
