Alzheimer's disease heterogeneity revealed by neuroanatomical normative modeling.

IF 4 Q1 CLINICAL NEUROLOGY

Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring Pub Date : 2024-03-13 eCollection Date: 2024-01-01 DOI:10.1002/dad2.12559

Flavia Loreto, Serena Verdi, Seyed Mostafa Kia, Aleksandar Duvnjak, Haneen Hakeem, Anna Fitzgerald, Neva Patel, Johan Lilja, Zarni Win, Richard Perry, Andre F Marquand, James H Cole, Paresh Malhotra

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Abstract

Introduction: Overlooking the heterogeneity in Alzheimer's disease (AD) may lead to diagnostic delays and failures. Neuroanatomical normative modeling captures individual brain variation and may inform our understanding of individual differences in AD-related atrophy.

Methods: We applied neuroanatomical normative modeling to magnetic resonance imaging from a real-world clinical cohort with confirmed AD (n = 86). Regional cortical thickness was compared to a healthy reference cohort (n = 33,072) and the number of outlying regions was summed (total outlier count) and mapped at individual- and group-levels.

Results: The superior temporal sulcus contained the highest proportion of outliers (60%). Elsewhere, overlap between patient atrophy patterns was low. Mean total outlier count was higher in patients who were non-amnestic, at more advanced disease stages, and without depressive symptoms. Amyloid burden was negatively associated with outlier count.

Discussion: Brain atrophy in AD is highly heterogeneous and neuroanatomical normative modeling can be used to explore anatomo-clinical correlations in individual patients.

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神经解剖规范模型揭示阿尔茨海默病的异质性。

导言：忽视阿尔茨海默病（AD）的异质性可能导致诊断延误和失败。神经解剖学规范建模能捕捉大脑个体差异，可帮助我们了解阿尔茨海默病相关萎缩的个体差异：我们将神经解剖常模应用于确诊为 AD 的真实世界临床队列（n = 86）的磁共振成像。我们将区域皮层厚度与健康参考队列（n = 33,072）进行了比较，并对离群区域的数量进行了加总（总离群计数），然后绘制了个体和群体层面的图谱：结果：颞上沟的异常值比例最高（60%）。其他患者的萎缩模式重叠率较低。非躁狂症患者、疾病晚期患者和无抑郁症状患者的离群值平均总数较高。淀粉样蛋白负荷与离群点数量呈负相关：讨论：注意力缺失症患者的脑萎缩具有高度异质性，神经解剖常模可用于探索个体患者的解剖与临床相关性。

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 and Dementia: Diagnosis, Assessment and Disease Monitoring Medicine-Psychiatry and Mental Health

CiteScore

7.80

自引率

7.50%

发文量

101

审稿时长

8 weeks

期刊介绍： Alzheimer''s & Dementia: Diagnosis, Assessment & Disease Monitoring (DADM) is an open access, peer-reviewed, journal from the Alzheimer''s Association® that will publish new research that reports the discovery, development and validation of instruments, technologies, algorithms, and innovative processes. Papers will cover a range of topics interested in the early and accurate detection of individuals with memory complaints and/or among asymptomatic individuals at elevated risk for various forms of memory disorders. The expectation for published papers will be to translate fundamental knowledge about the neurobiology of the disease into practical reports that describe both the conceptual and methodological aspects of the submitted scientific inquiry. Published topics will explore the development of biomarkers, surrogate markers, and conceptual/methodological challenges. Publication priority will be given to papers that 1) describe putative surrogate markers that accurately track disease progression, 2) biomarkers that fulfill international regulatory requirements, 3) reports from large, well-characterized population-based cohorts that comprise the heterogeneity and diversity of asymptomatic individuals and 4) algorithmic development that considers multi-marker arrays (e.g., integrated-omics, genetics, biofluids, imaging, etc.) and advanced computational analytics and technologies.