阿尔茨海默病血浆生物标志物在高龄老人中的预后价值：一项基于初级保健的前瞻性研究。
Prognostic value of Alzheimer's disease plasma biomarkers in the oldest-old: a prospective primary care-based study.
作者信息
Martino-Adami Pamela V, Chatterjee Madhurima, Kleineidam Luca, Weyerer Siegfried, Bickel Horst, Wiese Birgitt, Riedel-Heller Steffi G, Scherer Martin, Blennow Kaj, Zetterberg Henrik, Wagner Michael, Schneider Anja, Ramirez Alfredo
机构信息
Division of Neurogenetics and Molecular Psychiatry, Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany.
German Center for Neurodegenerative Diseases (DZNE), Venusberg-Campus 1, 53127, Bonn, Germany.
出版信息
Lancet Reg Health Eur. 2024 Aug 16;45:101030. doi: 10.1016/j.lanepe.2024.101030. eCollection 2024 Oct.
BACKGROUND
Blood-based biomarkers offer a promising, less invasive, and more cost-effective alternative for Alzheimer's disease screening compared to cerebrospinal fluid or imaging biomarkers. However, they have been extensively studied only in memory clinic-based cohorts. We aimed to validate them in a more heterogeneous, older patient population from primary care.
METHODS
We measured plasma Aβ42/Aβ40, P-tau181, NfL, and GFAP in 1007 individuals without dementia, aged 79-94 years, from the longitudinal, primary care-based German AgeCoDe study. We assessed the association with cognitive decline, disease progression, and the capacity to predict future dementia of the Alzheimer's type (DAT). We also evaluated biomarker dynamics in 305 individuals with a follow-up sample (∼8 years later).
FINDINGS
Higher levels of P-tau181 (HR = 1.32 [95% CI: 1.17-1.51]), NfL (HR = 1.19 [95% CI: 1.03-1.36]), and GFAP (HR = 1.36 [95% CI: 1.22-1.52]), and a lower Aβ42/Aβ40 ratio (HR = 0.80 [95% CI: 0.68-0.95]) were associated with an increased risk of progressing to clinically-diagnosed DAT. Additionally, higher levels of P-tau181 (β = -0.49 [95% CI: -0.71 to 0.26]), NfL (β = -0.29 [95% CI: -0.52 to 0.06]), and GFAP (β = -0.60 [95% CI: -0.83 to 0.38]) were linked to faster cognitive decline. A two-step DAT prediction strategy combining initial MMSE with biomarkers improved the identification of individuals in the prodromal stage for potential treatment eligibility. Biomarker levels changed over time, with increases in P-tau181 (β = 0.19 [95% CI: 0.14-0.25]), NfL (β = 2.88 [95% CI: 2.18-3.59]), and GFAP (β = 8.23 [95% CI: 6.71-9.75]). NfL (β = 2.47 [95% CI: 1.04-3.89]) and GFAP (β = 4.45 [95% CI: 1.38-7.51]) exhibited a faster increase in individuals progressing to DAT.
INTERPRETATION
Evaluating plasma biomarkers, alongside brief cognitive assessments, might enhance the precision of risk assessment for DAT progression in primary care.
FUNDING
Alzheimer Forschung Initiative, Bundesministerium für Bildung und Forschung.
背景
与脑脊液或影像学生物标志物相比，基于血液的生物标志物为阿尔茨海默病筛查提供了一种有前景、侵入性较小且成本效益更高的替代方法。然而，它们仅在基于记忆门诊的队列中得到广泛研究。我们旨在在来自初级保健的更具异质性的老年患者群体中对其进行验证。
方法
我们在基于初级保健的德国AgeCoDe纵向研究中，对1007名年龄在79 - 94岁、无痴呆的个体测量了血浆Aβ42/Aβ40、P-tau181、NfL和GFAP。我们评估了其与认知衰退、疾病进展以及预测未来阿尔茨海默病型痴呆（DAT）的能力之间的关联。我们还在305名有随访样本（约8年后）的个体中评估了生物标志物动态变化。
研究结果
较高水平的P-tau181（风险比[HR]=1.32[95%置信区间（CI）：1.17 - 1.51]）、NfL（HR = 1.19[95% CI：1.03 - 1.36]）和GFAP（HR = 1.36[95% CI：1.22 - 1.52]），以及较低的Aβ42/Aβ40比值（HR = 0.80[95% CI：0.68 - 0.95]）与进展为临床诊断的DAT的风险增加相关。此外，较高水平的P-tau181（β=-0.49[95% CI：-0.71至-0.26]）、NfL（β=-0.29[95% CI：-0.52至0.06]）和GFAP（β=-0.60[95% CI：-0.83至-0.38]）与更快的认知衰退相关。将初始简易精神状态检查表（MMSE）与生物标志物相结合的两步DAT预测策略改善了前驱期个体的识别，以确定其潜在的治疗资格。生物标志物水平随时间变化，P-tau181（β = 0.19[95% CI：0.14 - 0.25]）、NfL（β = 2.88[95% CI：2.18 - 3.59]）和GFAP（β = 8.23[95% CI：6.71 - 9.75]）升高。在进展为DAT的个体中，NfL（β = 2.47[95% CI：1.04 - 3.89]）和GFAP（β = 4.45[95% CI：1.38 - 7.51]）升高更快。
解读
在初级保健中，评估血浆生物标志物并结合简短的认知评估，可能会提高DAT进展风险评估的准确性。
资金来源
阿尔茨海默病研究倡议，联邦教育与研究部。
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