Division of Hematology and Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan.
Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
JAMA Netw Open. 2020 Aug 3;3(8):e2015189. doi: 10.1001/jamanetworkopen.2020.15189.
It remains unclear whether androgen deprivation therapy (ADT) is associated with subsequent dementia risk in patients with prostate cancer. There are limited data regarding dementia risk across ADT types.
To examine the association between all-cause dementia, including Alzheimer disease (AD), and different ADT types in patients with prostate cancer.
DESIGN, SETTING, AND PARTICIPANTS: This cohort study used linked data from the Taiwan National Cancer Registry, the National Health Insurance Research Database, and the Taiwan National Death Registry. A cohort of 23 651 patients with newly diagnosed prostate cancer between January 1, 2008, and December 31, 2015, was identified and followed up from 1 year after diagnosis until December 31, 2017. Data analysis was performed between January 2019 and May 2020.
Patients who received and did not receive ADT, including gonadotropin-releasing hormone (GnRH) agonists, orchiectomy, or antiandrogen monotherapy.
The primary outcomes were all-cause dementia or AD. Stabilized inverse probability of treatment weighting was used to balance baseline covariates. The association between dementia and various ADT types was examined using the Cox proportional hazards model. Furthermore, a multivariate Cox proportional model with age as the time scale was conducted for complementary comparison.
In the cohort of 23 651 male patients (median [interquartile range] age, 73 [66-79] years), 6904 (29.2%) did not receive ADT, 11 817 (50.0%) received GnRH agonists, 876 (3.7%) received orchiectomy, and 4054 (17.1%) received antiandrogen monotherapy. Overall, 1525 patients were diagnosed with incident dementia (1.72 per 100 person-years) during a median (interquartile range) follow-up of 3.46 (1.92-5.51) years. Compared with those who did not receive ADT, those using antiandrogen monotherapy showed an increased risk of dementia (weighted hazard ratio [HR], 1.34; 95% CI, 1.16-1.55) and AD (weighted HR, 1.52; 95% CI, 1.13-2.04). The risk of dementia was similar between GnRH agonist use or orchiectomy and no ADT use (GnRH agonist: weighted HR, 1.13; 95% CI, 1.00-1.28; orchiectomy: 1.00; 95% CI, 0.74-1.37). Several sensitivity analyses revealed consistent findings for both outcomes.
In this study, the use of antiandrogen monotherapy was associated with increased risk of dementia or AD, while GnRH agonist use and orchiectomy had no significant difference compared with patients who did not receive ADT. Further prospective studies are warranted to confirm these findings.
重要性：雄激素剥夺疗法（ADT）是否与前列腺癌患者的后续痴呆风险相关仍不清楚。关于 ADT 类型与痴呆风险的相关数据有限。
目的：研究前列腺癌患者中全因痴呆（包括阿尔茨海默病（AD））与不同 ADT 类型之间的关联。
设计、地点和参与者：这项队列研究使用了来自台湾国家癌症登记处、国家健康保险研究数据库和台湾国家死亡登记处的关联数据。确定了 2008 年 1 月 1 日至 2015 年 12 月 31 日期间新诊断为前列腺癌的 23651 例患者队列，并在诊断后 1 年开始进行随访，直至 2017 年 12 月 31 日。数据分析于 2019 年 1 月至 2020 年 5 月之间进行。
暴露：接受 ADT 与未接受 ADT 的患者，包括促性腺激素释放激素（GnRH）激动剂、睾丸切除术或抗雄激素单药治疗。
主要结局和测量：主要结局是全因痴呆或 AD。采用稳定的逆概率治疗加权法来平衡基线协变量。使用 Cox 比例风险模型来检查痴呆与各种 ADT 类型之间的关联。此外，还使用以年龄为时间尺度的多变量 Cox 比例模型进行补充比较。
结果：在 23651 名男性患者的队列中（中位数[四分位数间距]年龄，73[66-79]岁），6904 名（29.2%）未接受 ADT，11817 名（50.0%）接受 GnRH 激动剂，876 名（3.7%）接受睾丸切除术，4054 名（17.1%）接受抗雄激素单药治疗。在中位（四分位数间距）随访 3.46（1.92-5.51）年期间，共有 1525 名患者被诊断为新发痴呆（1.72/100人年）。与未接受 ADT 的患者相比，接受抗雄激素单药治疗的患者痴呆（加权风险比[HR]，1.34；95%CI，1.16-1.55）和 AD（加权 HR，1.52；95%CI，1.13-2.04）的风险增加。GnRH 激动剂使用或睾丸切除术与未接受 ADT 相比，痴呆风险相似（GnRH 激动剂：加权 HR，1.13；95%CI，1.00-1.28；睾丸切除术：1.00；95%CI，0.74-1.37）。几项敏感性分析对两种结局均得出一致的结果。
结论和相关性：在这项研究中，抗雄激素单药治疗与痴呆或 AD 风险增加相关，而 GnRH 激动剂使用和睾丸切除术与未接受 ADT 的患者相比无显著差异。需要进一步的前瞻性研究来证实这些发现。
