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.

总结 最近在开发精确的基于血液的阿尔茨海默病（AD）生物标志物方面取得了重大突破， 包括磷酸化-tau 217（pTau 217），具有真正革新AD诊断的潜力。但这些 新的生物标志物现在必须在临床实践中以前瞻性的方式彻底验证， 在全球的专科诊所和初级保健中用于AD的诊断和预后检查。这 由于临床诊断检查的准确性相对较低， 支持准确的AD生物标志物，导致25-30%的AD患者在专家记忆中误诊 诊所和>50%的初级保健。此外，重要的是要确定哪些患者和真实世界的临床 这些新的血液AD生物标志物明显改善了诊断，治疗和护理，这对于 在许多国家的报销。最后，我们还需要准确的预后工具来识别那些患有 早期AD患者最有可能表现出即将到来的临床衰退，因为这一群体可能从靶向治疗中获益最多。 干预措施。考虑到最近出现的疾病修饰AD疗法， 变得广泛可用。 鉴于瑞典初级保健系统的良好基础设施和研究生物标志物协议， 已经获得批准并完全融入临床实践，我们有一个独特的机会来测试这些新的血液 AD标记物在广泛的，多样化的，可推广到其他现实世界的设置，并在人群中。到 为了实现这一宏伟目标，我们将在专门的记忆诊所进行两项新颖独特的前瞻性研究。 （n=800）和一般初级保健（n=800）设置。首先，我们的目标是前瞻性地验证血浆AD生物标志物 对于在记忆专科诊所或初级记忆专科诊所评估的具有认知症状的患者的诊断， 在乎根据最近的专家共识建议，我们将使用i）预定义的生物标志物临界值，ii）双 每周分析血浆样本和iii）适当的参考标准品（即，PET/CSF）。我们预计 我们将在48个月内确定在记忆诊所中具有高潜力的AD血液生物标志物， 和/或初级保健设置。第二，我们将确定基于血液的AD生物标志物是否能改善患者的病情。 管理在专家记忆诊所设置和一般初级保健设置。展示改进 与“常规治疗”相比， 批准未来对血液生物标志物的报销。第三，我们的目标是优化患者的预后 通过将（前瞻性分析的）血浆AD生物标志物与简短的数字认知测试相结合，的 预期的结果是易于获得和时间和成本效益的血液生物标志物和数字 认知测试可以预测短期认知能力下降和初级保健中AD痴呆的进展。 在这个项目的最后，我们的预期目标是，基于血液的生物标志物和预后算法将是 准备在专科诊所和初级保健的临床实施。