Clinically meaningful changes in cognitive and functional outcomes in a population-based study of cognitive aging

IF 6.8 Q1 CLINICAL NEUROLOGY

Alzheimer''s and Dementia: Translational Research and Clinical Interventions Pub Date : 2025-09-24 DOI:10.1002/trc2.70160

Jeremiah A. Aakre, Anna M. Castillo, Jonathan Graff-Radford, Prashanthi Vemuri, Mary M. Machulda, Clifford R. Jack Jr, David S. Knopman, Ronald C. Petersen, Maria Vassilaki

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引用次数: 0

Abstract

INTRODUCTION

Research is limited regarding meaningful change thresholds for individual patients on clinical outcome assessments (COAs) frequently used in clinical trials for Alzheimer's disease and related dementias (ADRD), particularly in population-based studies early in the disease course.

METHODS

There were 646 study participants in the population-based Mayo Clinic Study of Aging (MCSA), 54–99 years old (47% females), who developed the clinical syndromes of mild cognitive impairment (MCI) with complete data to establish clinically meaningful within-patient change thresholds in cognitive and functional COAs.

RESULTS

Using the diagnosis of incident MCI as the anchor, mean (95% confidence interval [CI]) annualized estimates of change were: Clinical Dementia Rating (CDR) scale Sum of Boxes (SB) 0.49 (0.43, 0.55), Mini-Mental State Examination (MMSE) −1.01 (−1.12, −0.91), and Functional Activities Questionnaire (FAQ) score 1.04 (0.82, 1.26).

DISCUSSION

This study provides within-patient estimates of clinically meaningful change early in disease progression in a community-based sample.

Highlights

We studied incident mild cognitive impairment (MCI) participants from a population-based study.
Within-patient change thresholds were estimated for clinical outcome assessments (COAs) used in clinical trials for Alzheimer's disease and related dementia (ADRD).
These estimates may be used to plan and evaluate clinical trials involving disease-modifying therapies (DMTs).

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一项基于人群的认知衰老研究中认知和功能结果的临床意义变化

在阿尔茨海默病和相关痴呆（ADRD）临床试验中经常使用的临床结果评估（COAs）的个体患者有意义的变化阈值方面的研究有限，特别是在疾病病程早期的基于人群的研究中。方法在基于人群的梅奥临床衰老研究（MCSA）中，有646名研究参与者，年龄54-99岁（47%为女性），出现轻度认知障碍（MCI）的临床综合征，数据完整，以建立具有临床意义的患者内认知和功能coa变化阈值。结果：以MCI诊断为锚点，平均（95%置信区间[CI]）年化估计变化为：临床痴呆评分（CDR）量表盒和（SB） 0.49(0.43, 0.55)，简易精神状态检查(MMSE) - 1.01(- 1.12, - 0.91)，功能活动问卷（FAQ）评分1.04（0.82,1.26）。本研究在社区样本中提供了疾病进展早期临床有意义变化的患者内估计。我们研究了一项基于人群的研究中的轻度认知障碍（MCI）参与者。用于阿尔茨海默病和相关痴呆（ADRD）临床试验的临床结果评估（COAs）的患者内变化阈值进行了估计。这些估计可用于计划和评估涉及疾病改善疗法（dmt）的临床试验。

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.