Belessiotis-Richards Clara, Hayes Joseph, Feng Yap Ying, Talwar Shivangi, Eskinazi Michelle, Li Wenqianglong, Ward Harry, Letrondo Pilar A, Morelli-Batters Madeleine, Bruun Andrea, Lin Rongyu, Wright Talen, Mukadam Naaheed
Division of Psychiatry, University College London, London, United Kingdom.
North London NHS Foundation Trust, London, United Kingdom.
Mol Psychiatry. 2025 Jul 24. doi: 10.1038/s41380-025-03129-3.
Previous meta-analyses have found that systemic medications may modulate dementia risk. We aimed to provide an overview of this evidence to guide clinical practice and future research.
We conducted an umbrella review of meta-analyses (PROSPERO CRD42021226307), searching databases from inception to 15th April 2024. Only peer-reviewed meta-analyses examining dementia risk and systemic medications in humans were included. Two authors independently screened studies for inclusion, extracted study data and assessed quality of meta-analyses using the AMSTAR-2 tool. Three authors independently rated the certainty of evidence for each drug using the GRADE framework.
68 meta-analyses were included, across 11 drug categories. Across meta-analyses, available data were primarily observational. Confounding by indication and potential reverse causality were important limitations. Randomised-controlled data were rare but supported an association between treatment of hypertension and reduced dementia incidence. Overall, we found moderate certainty evidence of reduced risk of dementia associated with anti-hypertensives, statins, sodium-glucose transport protein 2 (SGLT2) inhibitors, and glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and moderate certainty of increased risk with anticholinergics.
Currently, there is insufficient evidence to advise repurposing any systemic drugs with the primary aim of reducing dementia risk. On the basis of our findings, we recommend proactive treatment of hypertension to reduce risk of all-cause dementia. Our findings did not find a difference between antihypertensive drug classes, but dementia risk was associated with blood pressure reading. In addition, we advise avoidance of anticholinergic drugs in cognitive impairment, with assessment of anticholinergic burden and consideration of alternatives during routine clinical contacts.
既往的荟萃分析发现，全身性药物可能会调节痴呆风险。我们旨在概述这一证据，以指导临床实践和未来研究。
我们对荟萃分析进行了一项伞状综述（PROSPERO CRD42021226307），检索了从数据库建立至2024年4月15日的文献。仅纳入了对人类痴呆风险和全身性药物进行研究的同行评审荟萃分析。两位作者独立筛选纳入研究，提取研究数据，并使用AMSTAR-2工具评估荟萃分析的质量。三位作者独立使用GRADE框架对每种药物的证据确定性进行评级。
纳入了68项荟萃分析，涉及11类药物。在所有荟萃分析中，现有数据主要为观察性数据。适应证混杂和潜在的反向因果关系是重要的局限性。随机对照数据很少，但支持高血压治疗与痴呆发病率降低之间的关联。总体而言，我们发现有中等确定性证据表明，抗高血压药、他汀类药物、钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂和胰高血糖素样肽-1受体激动剂（GLP-1 RAs）与痴呆风险降低相关，而抗胆碱能药物会增加风险的确定性为中等。
目前，没有足够的证据建议将任何全身性药物重新用于降低痴呆风险这一主要目的。根据我们的研究结果，我们建议积极治疗高血压以降低全因性痴呆风险。我们的研究结果未发现抗高血压药物类别之间存在差异，但痴呆风险与血压读数相关。此外，我们建议在认知障碍患者中避免使用抗胆碱能药物，并在常规临床接触中评估抗胆碱能负担并考虑替代药物。
