背景:阿尔茨海默病(AD)是一种常见的疾病,复杂和多因素的疾病,可能需要在多种转诊途径中进行筛查,以便早期发现并随后在未来实施量身定制的干预措施。基于血液和眼睛的生物标志物显示出低成本的希望,可扩展和患者友好的早期AD检测工具,因为它们能够提供有关AD病理生理变化和视网膜表现的信息,分别。眼科诊所提供了一个有趣的现实世界的概念验证设置,以评估这些潜在的AD筛查工具的性能,考虑到眼睛和大脑之间的复杂连接,在患有眼部疾病的老年人群中,AD病理学的推测富集,以及对认识不足的患者群体加速诊断途径的潜力。
方法:BeyeOMARKER研究是一项前瞻性研究,观察,纵向队列研究旨在包括访问眼科诊所的个人。纳入标准要求年龄≥50岁,且先前没有痴呆诊断。排除的眼部疾病包括创伤性侮辱,浅表炎症,和不参与视觉的眼睛周围结构的条件。BeyeOMARKER队列(n=700)将在眼科诊所进行血液收集以评估血浆p-tau217水平和简短的认知筛查。随后将邀请所有参与者进行年度纵向随访,包括远程管理的认知筛查和问卷调查。BeyeOMARKER+队列(n=150),由100名血浆p-tau217阳性参与者和50名匹配的阴性对照组成,选自BeyeOMARKER队列,还将接受Aβ-PET和tau-PET,MRI,视网膜成像包括高光谱成像(主要),宽场成像,光学相干断层扫描(OCT)和OCT-血管造影(二级),以及认知和皮层视觉评估。
结果:我们的目标是在2024年4月至2027年3月之间实施当前的协议。主要结果包括血浆p-tau217和高光谱视网膜成像以检测AD病理(使用Aβ-和tau-PET视觉读取作为参考标准)和检测认知下降。最初的随访时间约为2年,但可能会延长额外的资金。
结论:我们设想BeyeOMARKER研究将证明在替代筛查环境中基于血液和眼睛生物标志物的早期AD检测的可行性。并将提高我们对眼脑连接的理解。
背景:BeyeOMARKER研究(EudamedCIVID:CIV-NL-23-09-044086;注册日期:2024年3月19日)已获得阿姆斯特丹UMC伦理审查委员会的批准。
BACKGROUND: Alzheimer\'s disease (AD) is a common, complex and multifactorial disease that may require screening across multiple routes of referral to enable early detection and subsequent future implementation of tailored interventions. Blood- and eye-based biomarkers show promise as low-cost, scalable and patient-friendly tools for early AD detection given their ability to provide information on AD pathophysiological changes and manifestations in the retina, respectively. Eye clinics provide an intriguing real-world proof-of-concept setting to evaluate the performance of these potential AD screening tools given the intricate connections between the eye and brain, presumed enrichment for AD pathology in the aging population with eye disorders, and the potential for an accelerated diagnostic pathway for under-recognized patient groups.
METHODS: The BeyeOMARKER study is a prospective, observational, longitudinal cohort study aiming to include individuals visiting an eye-clinic. Inclusion criteria entail being ≥ 50 years old and having no prior dementia diagnosis. Excluded eye-conditions include traumatic insults, superficial inflammation, and conditions in surrounding structures of the eye that are not engaged in vision. The BeyeOMARKER cohort (n = 700) will undergo blood collection to assess plasma p-tau217 levels and a brief cognitive screening at the eye clinic. All participants will subsequently be invited for annual longitudinal follow-up including remotely administered cognitive screening and questionnaires. The BeyeOMARKER + cohort (n = 150), consisting of 100 plasma p-tau217 positive participants and 50 matched negative controls selected from the BeyeOMARKER cohort, will additionally undergo Aβ-PET and tau-PET, MRI, retinal imaging including hyperspectral imaging (primary), widefield imaging, optical coherence tomography (OCT) and OCT-Angiography (secondary), and cognitive and cortical vision assessments.
RESULTS: We aim to implement the current protocol between April 2024 until March 2027. Primary outcomes include the performance of plasma p-tau217 and hyperspectral retinal imaging to detect AD pathology (using Aβ- and tau-PET visual read as reference standard) and to detect cognitive decline. Initial follow-up is ~ 2 years but may be extended with additional funding.
CONCLUSIONS: We envision that the BeyeOMARKER study will demonstrate the feasibility of early AD detection based on blood- and eye-based biomarkers in alternative screening settings, and will improve our understanding of the eye-brain connection.
BACKGROUND: The BeyeOMARKER study (Eudamed CIV ID: CIV-NL-23-09-044086; registration date: 19th of March 2024) is approved by the ethical review board of the Amsterdam UMC.