Department of Applied Health Sciences, University of Birmingham, Birmingham, United Kingdom.
Action Against Age-Related Macular Degeneration, London, United Kingdom.
JAMA Netw Open. 2024 Oct 1;7(10):e2441166. doi: 10.1001/jamanetworkopen.2024.41166.
Age-related macular degeneration (AMD) is the leading cause of blindness among people aged 50 years or older worldwide. There is a need for new strategies for the prevention and treatment of AMD. There is some limited evidence to suggest the possibility of a protective association of dementia medications with the development of some types of AMD, but the evidence is weak.
To investigate whether the dementia medications memantine and donepezil are associated with the risk of developing AMD.
DESIGN, SETTING, AND PARTICIPANTS: Three population-based cohort studies were performed using data from the Clinical Practice Research Datalink GOLD and Aurum databases from May 15, 2002, to June 21, 2022. Participants included individuals with dementia (vascular dementia, nonvascular dementia, or Alzheimer disease) aged 40 years or older. Statistical analysis was carried out between February and November 2023.
Exposures were dementia medications. Cohort 1 compared patients prescribed donepezil with those prescribed rivastigmine or galantamine using the new-user design. Cohort 2 compared memantine with donepezil, rivastigmine, or galantamine using the prevalent new-user design. In a sensitivity analysis, cohort 3 compared memantine with rivastigmine or galantamine only.
New diagnosis of AMD.
There were 132 846 individuals (mean [SD] age, 80.4 [7.6] years; 61.8% women; mean [SD] body mass index [BMI], 25.5 [4.6]) with a diagnosis of dementia included in cohort 1, 159 419 individuals (mean [SD] age, 81.2 [7.6] years; 59.7% women; mean [SD] body mass index [BMI], 25.6 [4.7]) with a diagnosis of dementia included in cohort 2, and 92 328 individuals with a diagnosis of dementia included in cohort 3 (mean [SD] age, 80.9 [7.7] years; 58.5% women; mean [SD] body mass index [BMI], 25.5 [4.7]). The adjusted hazard ratio (HR) for donepezil compared with rivastigmine or galantamine (cohort 1) was 0.95 (95% CI, 0.67-1.35). The adjusted HR for memantine compared with donepezil, rivastigmine, or galantamine (cohort 2) was 1.03 (95% CI, 0.83-1.27). The adjusted HR for memantine vs rivastigmine or galantamine only (cohort 3) was 1.24 (95% CI, 0.83-1.86).
This cohort study of patients with dementia found no significant associations between memantine or donepezil compared with other dementia medications and the risk of development of AMD. Further research is recommended to examine any possible pathophysiological protective action of memantine and other dementia medications against the development of AMD.
年龄相关性黄斑变性（AMD）是全球 50 岁及以上人群致盲的主要原因。因此，我们需要新的策略来预防和治疗 AMD。有一些有限的证据表明痴呆症药物与某些类型的 AMD 的发展之间存在可能的保护关联，但证据很薄弱。
研究痴呆症药物美金刚和多奈哌齐是否与 AMD 的发病风险相关。
设计、地点和参与者：这项基于人群的队列研究共纳入了来自 2002 年 5 月 15 日至 2022 年 6 月 21 日期间 Clinical Practice Research Datalink GOLD 和 Aurum 数据库中的三个队列研究的数据。参与者包括年龄在 40 岁及以上的痴呆症（血管性痴呆、非血管性痴呆或阿尔茨海默病）患者。统计分析于 2023 年 2 月至 11 月进行。
暴露因素为痴呆症药物。队列 1 将接受多奈哌齐治疗的患者与接受利凡斯的明或加兰他敏治疗的患者进行了比较，采用新用户设计。队列 2 将美金刚与多奈哌齐、利凡斯的明或加兰他敏进行了比较，采用现患新用户设计。在敏感性分析中，队列 3 仅将美金刚与利凡斯的明或加兰他敏进行了比较。
AMD 的新诊断。
队列 1 纳入了 132846 名（平均[标准差]年龄，80.4[7.6]岁；61.8%为女性；平均[标准差]体重指数[BMI]，25.5[4.6]）被诊断为痴呆症的患者，队列 2 纳入了 159419 名（平均[标准差]年龄，81.2[7.6]岁；59.7%为女性；平均[标准差]体重指数[BMI]，25.6[4.7]）被诊断为痴呆症的患者，队列 3 纳入了 92328 名被诊断为痴呆症的患者（平均[标准差]年龄，80.9[7.7]岁；58.5%为女性；平均[标准差]体重指数[BMI]，25.5[4.7]）。与利凡斯的明或加兰他敏相比，多奈哌齐的调整后的危险比（HR）为 0.95（95%置信区间，0.67-1.35）。与多奈哌齐、利凡斯的明或加兰他敏相比，美金刚的调整后 HR 为 1.03（95%CI，0.83-1.27）。与仅利凡斯的明或加兰他敏相比，美金刚的调整后 HR 为 1.24（95%CI，0.83-1.86）。
这项针对痴呆症患者的队列研究未发现美金刚或多奈哌齐与其他痴呆症药物相比与 AMD 发病风险之间存在显著关联。建议进一步研究以检查美金刚和其他痴呆症药物对 AMD 发展可能存在的潜在保护作用。
