Dissociable spatial topography of cortical atrophy in early-onset and late-onset Alzheimer's disease: A head-to-head comparison of the LEADS and ADNI cohorts

IF 11.1 1区医学 Q1 CLINICAL NEUROLOGY Alzheimer's & Dementia Pub Date : 2025-02-19 DOI:10.1002/alz.14489

Yuta Katsumi, Alexandra Touroutoglou, Michael Brickhouse, Ani Eloyan, Ryan Eckbo, Alexander Zaitsev, Renaud La Joie, Julien Lagarde, Daniel Schonhaut, Maryanne Thangarajah, Alexander Taurone, Prashanthi Vemuri, Clifford R. Jack Jr., Jeffrey L. Dage, Kelly N. H. Nudelman, Tatiana Foroud, Dustin B. Hammers, Bernardino Ghetti, Melissa E. Murray, Kathy L. Newell, Angelina J. Polsinelli, Paul Aisen, Rema Reman, Laurel Beckett, Joel H. Kramer, Alireza Atri, Gregory S. Day, Ranjan Duara, Neill R. Graff-Radford, Ian M. Grant, Lawrence S. Honig, Erik C. B. Johnson, David T. Jones, Joseph C. Masdeu, Mario F. Mendez, Erik Musiek, Chiadi U. Onyike, Meghan Riddle, Emily Rogalski, Stephen Salloway, Sharon Sha, R. Scott Turner, Thomas S. Wingo, David A. Wolk, Kyle Womack, Maria C. Carrillo, Gil D. Rabinovici, Liana G. Apostolova, Bradford C. Dickerson, the LEADS Consortium for the Alzheimer's Disease Neuroimaging Initiative

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Abstract

INTRODUCTION

Early-onset and late-onset Alzheimer's disease (EOAD and LOAD, respectively) have distinct clinical manifestations, with prior work based on small samples suggesting unique patterns of neurodegeneration. The current study performed a head-to-head comparison of cortical atrophy in EOAD and LOAD, using two large and well-characterized cohorts (LEADS and ADNI).

METHODS

We analyzed brain structural magnetic resonance imaging (MRI) data acquired from 377 sporadic EOAD patients and 317 sporadicLOAD patients who were amyloid positive and had mild cognitive impairment (MCI) or mild dementia (i.e., early-stage AD), along with cognitively unimpaired participants.

RESULTS

After controlling for the level of cognitive impairment, we found a double dissociation between AD clinical phenotype and localization/magnitude of atrophy, characterized by predominant neocortical involvement in EOAD and more focal anterior medial temporal involvement in LOAD.

DISCUSSION

Our findings point to the clinical utility of MRI-based biomarkers of atrophy in differentiating between EOAD and LOAD, which may be useful for diagnosis, prognostication, and treatment.

Highlights

Early-onset Alzheimer's disease (EOAD) and late-onset AD (LOAD) patients showed distinct and overlapping cortical atrophy patterns.
EOAD patients showed prominent atrophy in widespread neocortical regions.
LOAD patients showed prominent atrophy in the anterior medial temporal lobe.
Regional atrophy was correlated with the severity of global cognitive impairment.
Results were comparable when the sample was stratified for mild cognitive impairment (MCI) and dementia.

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早发性和晚发性阿尔茨海默病皮质萎缩的可分离空间地形：LEADS和ADNI队列的正面比较

早发性和晚发性阿尔茨海默病（分别为EOAD和LOAD）具有不同的临床表现，先前基于小样本的工作提示独特的神经变性模式。目前的研究使用两个大型且特征明确的队列（LEADS和ADNI），对EOAD和LOAD患者的皮质萎缩进行了正面比较。方法：我们分析了377例散发性EOAD患者和317例散发性load患者的脑结构磁共振成像（MRI）数据，这些患者均为淀粉样蛋白阳性，患有轻度认知障碍（MCI）或轻度痴呆（即早期AD），以及认知未受损的参与者。结果：在控制认知障碍水平后，我们发现阿尔茨海默病的临床表型与萎缩的定位/大小之间存在双重分离，其特征是EOAD主要累及新皮质，而LOAD则更多地灶性地累及颞前部内侧。讨论：我们的研究结果指出了基于mri的萎缩生物标志物在区分EOAD和LOAD方面的临床应用，这可能对诊断、预后和治疗有用。重点：早发性阿尔茨海默病（EOAD）和晚发性阿尔茨海默病（LOAD）患者表现出明显重叠的皮层萎缩模式。EOAD患者在广泛的新皮质区域表现出明显的萎缩。LOAD患者表现为颞叶前部内侧明显萎缩。局部萎缩与整体认知障碍的严重程度相关。当样本按轻度认知障碍（MCI）和痴呆分层时，结果具有可比性。

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 & Dementia 医学-临床神经学

CiteScore

14.50

自引率

5.00%

发文量

299

审稿时长

3 months

期刊介绍： Alzheimer's & Dementia is a peer-reviewed journal that aims to bridge knowledge gaps in dementia research by covering the entire spectrum, from basic science to clinical trials to social and behavioral investigations. It provides a platform for rapid communication of new findings and ideas, optimal translation of research into practical applications, increasing knowledge across diverse disciplines for early detection, diagnosis, and intervention, and identifying promising new research directions. In July 2008, Alzheimer's & Dementia was accepted for indexing by MEDLINE, recognizing its scientific merit and contribution to Alzheimer's research.