Assessing the clinical meaningfulness of slowing CDR-SB progression with disease-modifying therapies for Alzheimer's disease

IF 6.8 Q1 CLINICAL NEUROLOGY Alzheimer''s and Dementia: Translational Research and Clinical Interventions Pub Date : 2025-02-13 DOI:10.1002/trc2.70033

Sarah M. Hartz, Suzanne E. Schindler, Marissa L. Streitz, Krista L. Moulder, Jessica Mozersky, Guoqiao Wang, Chengjie Xiong, John C. Morris

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Abstract

INTRODUCTION

For many patients and caregivers, a major goal of disease-modifying treatments (DMTs) for Alzheimer's disease (AD) dementia is to extend independence in instrumental and basic activities of daily living (IADLs and BADLs). The goal of this study was to estimate the effect of treatments on the time remaining independent in IADLs and BADLs.

METHODS

Participants at the Knight Alzheimer Disease Research Center (Knight ADRC) who met eligibility criteria for recent DMT trials were studied: age ≥60 years at baseline, clinical diagnosis of very mild or mild AD dementia (global Clinical Dementia Rating [CDR] score 0.5 or 1), biomarker confirmation of amyloid pathology, and at least one follow-up CDR assessment within 5 years. For IADLs, a subset of the Functional Assessment Questionnaire (FAQ) was examined that rated the degree of independence in the following: paying bills, driving, remembering medications and appointments, and preparing meals. For BADLs, the Personal Care domain of the CDR was used. Mixed-effects logistic and ordinal regression models were used to examine the relationship between CDR Sum of Boxes (CDR-SB) and the individual functional outcomes and their components. The change in CDR-SB over time was estimated with linear mixed-effects models.

RESULTS

A total of 282 participants were followed for an average of 2.9 years (standard deviation [SD] 1.3 years). For 50% of individuals, loss of independence in IADLs occurred at CDR-SB >4.5 and in BADLs at CDR-SB >11.5. For individuals with a baseline CDR-SB = 2, treatment with lecanemab would extend independence in IADLs for 10 months (95% confidence interval [CI] 4–18 months) and treatment with donanemab in the low/medium tau group would extend independence in IADLs by 13 months (95% CI 6–24 months).

DISCUSSION

Independence in ADLs can be related to CDR-SB and used to demonstrate the effect of AD treatments in extending the time of independent function, a meaningful outcome for patients and their families.

Highlights

We estimated time to loss of independence for people with AD dementia
Estimating time to loss of independence can help with clinical decision-making
Disease-modifying treatments for AD dementia can extend independence

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评估阿尔茨海默病疾病改善疗法减缓CDR-SB进展的临床意义

对于许多患者和护理人员来说，阿尔茨海默病（AD）痴呆的疾病修饰治疗（dmt）的主要目标是延长日常生活工具和基本活动（IADLs和BADLs）的独立性。本研究的目的是评估治疗对iadl和badl独立维持时间的影响。方法：奈特阿尔茨海默病研究中心（Knight ADRC）符合近期DMT试验资格标准的参与者被研究：基线年龄≥60岁，临床诊断为极轻度或轻度AD痴呆（全球临床痴呆评分[CDR]评分0.5或1），淀粉样蛋白病理生物标志物确认，5年内至少进行一次随访CDR评估。对于iadl，检查了功能评估问卷（FAQ）的一个子集，评估了以下方面的独立程度：支付账单，驾驶，记住药物和预约，以及准备饭菜。对于badl，使用了CDR的Personal Care域。采用混合效应logistic和有序回归模型检验CDR盒子和（CDR- sb）与个体功能结局及其组成部分之间的关系。用线性混合效应模型估计CDR-SB随时间的变化。结果282名参与者平均随访2.9年（标准差[SD] 1.3年）。对于50%的个体，在CDR-SB >；4.5和CDR-SB >；11.5时，发生了iadl的独立性丧失。对于基线CDR-SB = 2的个体，莱卡耐单抗治疗可延长iadl独立性10个月（95%可信区间[CI] 4-18个月），低/中tau组多纳耐单抗治疗可延长iadl独立性13个月（95% CI 6-24个月）。adl的独立性可能与CDR-SB有关，并用于证明AD治疗在延长独立功能时间方面的作用，这对患者及其家属来说是一个有意义的结果。我们估计了阿尔茨海默病患者失去独立性的时间，估计失去独立性的时间可以帮助临床决策，阿尔茨海默病患者的疾病调节治疗可以延长独立性

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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.