Department of Rehabilitation Medicine, The Third Affiliated Hospital, Sun Yat-sen University, No. 600, Tianhe Road, 510630, Guangzhou, Guangdong, China.
Clinical Medical College of Acupuncture, Guangzhou University of Chinese Medicine, 510006, Guangzhou, China.
BMC Psychiatry. 2024 Mar 4;24(1):178. doi: 10.1186/s12888-024-05624-3.
Observational studies have suggested a link between panic disorder (PD) and Alzheimer disease (AD). This study aimed to identify the underlying association of PD with the risk of AD using Mendelian randomization.
Genetic instrumental variables (IVs) were retrieved in the genome-wide association study between PD and AD. Then, five different models, namely inverse variance weighting (IVW), weighted median, weighted mode, MR-Egger and MR-robust adjusted profile scores (MR-RAPS), were used for MR Analysis. Finally, the heterogeneity and pleiotropy of identified IVs were verified by multiple sensitivity tests.
The Cochran's Q test based on MR Egger and IVW showed that no evidence of heterogeneity was found in the effects of instrumental variables, so a fixed-effect model was used. IVW analysis (OR 1.000479, 95% CI [1.000147056, 1.000811539], p = 0.005) indicated that PD was associated with an increased risk of AD, and a causal association existed between them. Meanwhile, weighted median (OR 1.000513373, 95% CI [1.000052145, 1.000974814], p = 0.029) and MR-RAPS (OR 1.000510118, 95% CI [1.000148046, 1.00087232], p = 0.006) also showed the similar findings. In addition, extensive sensitivity analyses confirmed the robustness and accuracy of these results.
This investigation provides evidence of a potential causal relationship between PD and the increased risk of AD. Based on our MR results, when diagnosing and treating patients with PD, clinicians should pay more attention to their AD-related symptoms to choose therapeutic measures or minimize comorbidities. Furthermore, the development of drugs that improve both PD and AD may better treat patients with these comorbidities.
观察性研究表明，惊恐障碍（PD）与阿尔茨海默病（AD）之间存在关联。本研究旨在使用孟德尔随机化来确定 PD 与 AD 风险之间的潜在关联。
从 PD 与 AD 的全基因组关联研究中检索遗传工具变量（IVs）。然后，使用五种不同的模型，即逆方差加权（IVW）、加权中位数、加权模式、MR-Egger 和 MR-稳健调整轮廓评分（MR-RAPS）进行 MR 分析。最后，通过多种敏感性测试验证鉴定的 IVs 的异质性和多效性。
基于 MR Egger 和 IVW 的 Cochran's Q 检验表明，工具变量的影响没有发现异质性证据，因此使用固定效应模型。IVW 分析（OR 1.000479，95%CI [1.000147056，1.000811539]，p=0.005）表明 PD 与 AD 风险增加相关，两者之间存在因果关系。同时，加权中位数（OR 1.000513373，95%CI [1.000052145，1.000974814]，p=0.029）和 MR-RAPS（OR 1.000510118，95%CI [1.000148046，1.00087232]，p=0.006）也显示了类似的发现。此外，广泛的敏感性分析证实了这些结果的稳健性和准确性。
本研究提供了 PD 与 AD 风险增加之间存在潜在因果关系的证据。基于我们的 MR 结果，在诊断和治疗 PD 患者时，临床医生应更加注意他们的 AD 相关症状，以选择治疗措施或尽量减少共病。此外，开发既能改善 PD 又能改善 AD 的药物可能会更好地治疗这些共病患者。
