Prospective validation and implementation of high-performing blood biomarkers and digital cognitive tests for detection of Alzheimer's disease in specialist memory clinic and primary care settings

前瞻性验证和实施高性能血液生物标志物和数字认知测试，用于在专业记忆诊所和初级保健机构中检测阿尔茨海默病

• 批准号: 10738367
• 负责人: Oskar Hansson
• 金额: $ 50万
• 依托单位: LUND UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2028-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10738367
• 关键词: Adopted; Alzheimer disease detection; Alzheimer' s Disease; Alzheimer' s disease blood test; Alzheimer' s disease diagnosis; Alzheimer' s disease diagnostic; Alzheimer' s disease pathology; Alzheimer' s disease patient; Alzheimer' s disease therapy; Alzheimer’s disease biomarker; Authorization documentation; Biological Assay; Biological Markers; Blood; Blood Tests; Brain; Caregivers; Caring; Cellular Phone; Cerebrospinal Fluid; Clinic; Clinical; Cognitive; Consensus; Country; Dementia; Development; Diagnosis; Diagnostic; Diagnostic Procedure; Disease; Disease Marker; Evaluation; Future; Goals; Healthcare; Hematological Disease; Immunoassay; Impaired cognition; Individual; Infrastructure; International; Intervention; Interview; Life; Magnetic Resonance Imaging; Mass Spectrum Analysis; Measures; Memory; Memory impairment; Methods; Neurobehavioral Manifestations; Neuropsychological Tests; Outcome; Paper; Patient Care; Patients; Persons; Physicians; Plasma; Population; Positron-Emission Tomography; Primary Care; Prospective Studies; Protocols documentation; Publishing; Recommendation; Reference Standards; Research; Research Personnel; Sampling; Specialist; Sweden; Tablets; Test Result; Testing; Time; Validation; Visit; authority; blood-based biomarker; care systems; clinical diagnostics; clinical implementation; clinical practice; cognitive testing; comorbidity; cost effective; diagnostic accuracy; diagnostic algorithm; digital; experience; improved; informant; mild cognitive impairment; novel; novel diagnostics; novel marker; patient prognosis; primary care setting; prognostic; prognostic algorithm; prognostic tool; prospective; recruit; speech recognition; tool; treatment as usual

SUMMARY The recent major breakthroughs in the development of accurate blood-based Alzheimer’s disease (AD) biomarkers, including phospho-tau217 (pTau217), have the potential to truly revolutionize AD diagnostics. However, these novel biomarkers must now be thoroughly validated in a prospective fashion in clinical practice before they can be implemented in the diagnostic and prognostic work-up of AD in specialist clinics and primary care globally. This validation is urgently needed because of the relatively low accuracy of the clinical diagnostic work-up without support of accurate AD biomarkers, resulting in misdiagnoses of 25-30% of AD patients in specialist memory clinics and >50% in primary care. Furthermore, it is important to determine in which patients and real-world clinical settings these novel blood AD biomarkers clearly improve diagnosis, treatment, and care, which is essential for reimbursement in many countries. Finally, we also need accurate prognostic tools to identify those individuals with early AD who are most likely to show imminent clinical decline, because this group may benefit most from targeted interventions. This is highly timely considering the recent advent of disease-modifying AD therapies that may soon become widely available. Given the excellent infrastructure of the primary care system in Sweden and research biomarker protocols already approved and fully integrated in clinical practice, we have a unique opportunity to test these novel blood AD markers in broad, diverse, and unselected populations that are generalizable to other real-world settings. To achieve this ambitious goal, we will conduct two novel and unique prospective studies in specialist memory clinic (n=800) and general primary care (n=800) settings. First, we aim to prospectively validate plasma AD biomarkers for the diagnosis of patients with cognitive symptoms evaluated in either specialist memory clinics or in primary care. Following recent expert consensus recommendations, we will use i) predefined biomarker cut-offs, ii) bi- weekly analysis of the plasma samples and iii) appropriate reference standards (i.e., PET/CSF). We anticipate that we will identify - within 48 months - AD blood biomarkers with high potential for implementation in memory clinic and/or primary care settings. Second, we will determine whether blood-based AD biomarkers improve patient management in specialist memory clinic settings and general primary care settings. Demonstrating improvements of the AD diagnostic work-up and treatment when compared to “care-as-usual” is essential for regulatory authorities to approve future reimbursement of blood-based biomarkers. Third, we aim to optimize the prognosis of patients with early AD by combining (prospectively analyzed) plasma AD biomarkers with brief digital cognitive tests. The expected outcome is a combination of easily accessible and time- and cost-effective blood biomarkers and digital cognitive tests that can predict short-term cognitive decline and progression to AD dementia in primary care. At the end of this project, our expected goal is that blood-based biomarkers and prognostic algorithms will be ready for clinical implementation in both specialist clinics and primary care.

概括 在基于血液基的阿尔茨海默氏病（AD）生物标志物发展方面的主要突破， 包括磷酸-TAU217（PTAU217），有可能真正彻底改变AD诊断。但是，这些 现在必须在临床实践中以潜在的方式对新颖的生物标志物进行彻底验证，然后才能成为 在全球专业诊所和初级保健中的广告诊断和预后进行的实施。这 由于没有临床诊断检查的相对较低的精度，因此迫切需要验证 支持准确的AD生物标志物，导致专业记忆中25-30％的AD患者诊断 诊所，初级保健> 50％。此外，确定哪些患者和现实世界的临床很重要 设置这些新颖的血AD生物标志物显然可以改善诊断，治疗和护理，这对于 许多国家的报销。最后，我们还需要准确的预后工具来识别那些与 早期的广告最有可能显示临床下降，因为该组可能会受益于目标 干预措施。考虑到疾病改良的广告疗法的近期进展可能很快，这是非常及时的 广泛可用。 鉴于瑞典初级保健系统的出色基础设施和研究生物标志物方案 我们已经批准并完全融入了临床实践，我们有一个独特的机会来测试这些新型血液 广泛，潜水员和未选择的人群中的广告标记可推广到其他现实世界中。到 实现这个雄心勃勃的目标，我们将在专业记忆诊所进行两项新颖而独特的前瞻性研究 （n = 800）和一般初级保健（n = 800）设置。首先，我们的目标是前瞻性验证等离子体AD生物标志物 为了诊断在专业记忆诊所或初级记忆中评估的认知症状患者 关心。按照最近的专家共识建议，我们将使用i）预定义的生物标志物截断，ii）bi- 血浆样品的每周分析和III）适当的参考标准（即PET/CSF）。我们预料到这一点 我们将在48个月内 - 在记忆诊所实施高潜力的AD血液生物标志物 和/或初级保健设置。其次，我们将确定基于血液的AD生物标志物是否改善患者 专业记忆诊所设置和一般初级保健环境中的管理。展示改进 与“照顾态度”相比，广告诊断的检查和治疗对于监管机构至关重要 批准未来的基于血液的生物标志物的报销。第三，我们旨在优化患者的预后 通过将（前瞻性分析）等离子体AD生物标志物与简短的数字认知测试相结合（前瞻性分析）的AD。这 预期的结果是易于访问和时间和成本效益的血液生物标志物以及数字的结合 可以预测初级保健中短期认知下降并发展为AD痴呆的认知测试。 在该项目的最后，我们的预期目标是基于血液的生物标志物和预后算法是 准备在专业诊所和初级保健中进行临床实施。