Therapeutic time window of disease-modifying therapy for early Alzheimer's disease

IF 4.9 Q1 CLINICAL NEUROLOGY

Alzheimer''s and Dementia: Translational Research and Clinical Interventions Pub Date : 2025-05-29 DOI:10.1002/trc2.70102

Saki Nakashima, Kenichiro Sato, Yoshiki Niimi, Ryoko Ihara, Kazushi Suzuki, Atsushi Iwata, Tatsushi Toda, Takeshi Iwatsubo, for Alzheimer's Disease Neuroimaging Initiative

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引用次数: 0

Abstract

Introduction

Recently approved disease-modifying therapies (DMT) for early Alzheimer's disease (AD), including lecanemab and donanemab, require patients to meet specific eligibility criteria for treatment. These criteria define a limited “therapeutic time window,” after which patients become ineligible as the disease advances. Understanding factors influencing this window may help clinicians optimize patient management and reduce lost treatment opportunities.

Methods

We analyzed longitudinal data from two observational cohorts, the National Alzheimer's Coordinating Center (NACC) and the Alzheimer's Disease Neuroimaging Initiative (ADNI). At each visit, individuals were deemed eligible if they were amyloid-positive and had a Mini-Mental State Examination (MMSE) score of 22–30 (lecanemab) or 20–30 (donanemab), plus a Clinical Dementia Rating-Global Score (CDR-GS) of 0.5 or 1. We then applied survival analyses and Cox proportional hazards models to estimate time-to-ineligibility based on baseline cognitive status.

Results

Across both datasets, higher baseline CDR-GS and MMSE were associated with a lower risk of becoming ineligible (pooled hazard ratio of 1.601 for CDR-GS of 1 vs. 0.5, and pooled hazard ratio of 0.660 per 1-point increase in MMSE score above the lower limit of eligibility). The estimated 75% survival time for patients with baseline CDR-GS 0.5 was over 12 months, suggesting only 25% would become ineligible within 12 months. For those with CDR-GS 1, the estimated 50% survival time was approximately 12 months, depending on the data, indicating that half might become ineligible within 1 year.

Discussion

We quantitatively outlined the duration of the therapeutic time window for early AD patients who qualify for lecanemab or donanemab, which is significantly influenced by baseline CDR-GS and MMSE scores. These findings will support more proactive patient management, ensuring timely evaluations and prioritization of patients at higher risk of ineligibility, particularly where DMT access is limited.

Highlights

We examined the “therapeutic time window” eligibility for disease-modifying therapy.
Longitudinal data from National Alzheimer's Coordinating Center (NACC) and Alzheimer's Disease Neuroimaging Initiative (ADNI) were used to quantify eligibility duration.
Higher Clinical Dementia Rating-Global Score (CDR-GS) or lower Mini-Mental State Examination (MMSE) at baseline were associated with shorter window length.
Our results will help optimize the management of the wait time for disease-modifying therapies (DMT) treatment.

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早期阿尔茨海默病疾病改善治疗的治疗时间窗

最近批准的用于早期阿尔茨海默病（AD）的疾病修饰疗法（DMT），包括lecanemab和donanemab，要求患者满足特定的治疗资格标准。这些标准定义了一个有限的“治疗时间窗”，在此之后，随着疾病的进展，患者就不符合条件了。了解影响这一窗口期的因素可能有助于临床医生优化患者管理并减少治疗机会的损失。方法我们分析了来自两个观察性队列的纵向数据，即国家阿尔茨海默病协调中心（NACC）和阿尔茨海默病神经影像学倡议（ADNI）。在每次访问中，如果患者淀粉样蛋白呈阳性，并且迷你精神状态检查（MMSE）得分为22-30 （lecanemab）或20-30 (donanemab)，加上临床痴呆评分-全局评分（CDR-GS）为0.5或1，则认为他们符合条件。然后，我们应用生存分析和Cox比例风险模型来估计基于基线认知状态的不合格时间。结果在两个数据集中，基线CDR-GS和MMSE越高，不合格风险越低（CDR-GS为1比0.5的合并风险比为1.601，MMSE评分高于合格下限每增加1分合并风险比为0.660）。基线CDR-GS为0.5的患者估计75%的生存时间超过12个月，这表明只有25%的患者在12个月内不符合生存条件。对于CDR-GS - 1患者，根据数据，估计50%的生存时间约为12个月，这表明一半患者可能在1年内不符合条件。我们定量地概述了早期AD患者有资格使用莱卡耐单抗或多纳耐单抗的治疗时间窗口的持续时间，这受到基线CDR-GS和MMSE评分的显着影响。这些发现将支持更积极主动的患者管理，确保及时评估和优先考虑风险较高的患者，特别是在DMT获取有限的情况下。我们检查了“治疗时间窗”对疾病改善治疗的资格。来自国家阿尔茨海默病协调中心（NACC）和阿尔茨海默病神经影像学倡议（ADNI）的纵向数据用于量化合格持续时间。基线时较高的临床痴呆评分-全局评分（CDR-GS）或较低的迷你精神状态检查（MMSE）与较短的窗口长度相关。我们的结果将有助于优化疾病改善疗法（DMT）治疗的等待时间管理。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Alzheimer''s and Dementia: Translational Research and Clinical Interventions Medicine-Psychiatry and Mental Health

CiteScore

10.10

自引率

2.10%

发文量

134

审稿时长

10 weeks

期刊介绍： Alzheimer''s & Dementia: Translational Research & Clinical Interventions (TRCI) is a peer-reviewed, open access,journal from the Alzheimer''s Association®. The journal seeks to bridge the full scope of explorations between basic research on drug discovery and clinical studies, validating putative therapies for aging-related chronic brain conditions that affect cognition, motor functions, and other behavioral or clinical symptoms associated with all forms dementia and Alzheimer''s disease. The journal will publish findings from diverse domains of research and disciplines to accelerate the conversion of abstract facts into practical knowledge: specifically, to translate what is learned at the bench into bedside applications. The journal seeks to publish articles that go beyond a singular emphasis on either basic drug discovery research or clinical research. Rather, an important theme of articles will be the linkages between and among the various discrete steps in the complex continuum of therapy development. For rapid communication among a multidisciplinary research audience involving the range of therapeutic interventions, TRCI will consider only original contributions that include feature length research articles, systematic reviews, meta-analyses, brief reports, narrative reviews, commentaries, letters, perspectives, and research news that would advance wide range of interventions to ameliorate symptoms or alter the progression of chronic neurocognitive disorders such as dementia and Alzheimer''s disease. The journal will publish on topics related to medicine, geriatrics, neuroscience, neurophysiology, neurology, psychiatry, clinical psychology, bioinformatics, pharmaco-genetics, regulatory issues, health economics, pharmacoeconomics, and public health policy as these apply to preclinical and clinical research on therapeutics.