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言语运动区域与年龄相关的皮质变薄先于海马体衰退:对阿尔茨海默病的启示。

Age-Associated Cortical Thinning in Speech Motor Regions Precedes Hippocampal Decline: Implications for Alzheimer's Disease.

作者信息

Hanford Lindsay C, Jacoby John, Salat David H, Arnold Steven E, Eshghi Marziye

机构信息

Department of Psychology, Harvard University, Cambridge, Massachusetts, USA.

Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Harvard Medical School, Massachusetts General Hospital, Charlestown, Massachusetts, USA.

出版信息

Hum Brain Mapp. 2025 Aug 1;46(11):e70288. doi: 10.1002/hbm.70288.


DOI:10.1002/hbm.70288
PMID:40698900
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12284906/
Abstract

Speech-motor and cognitive impairments are commonly observed in age-related neurodegenerative diseases, including mild cognitive impairment (MCI) and Alzheimer's Disease (AD). Although there is a strong interaction between motor and cognitive functions, intact speech motor control is a crucial yet often-overlooked component of cognitive functioning. Additionally, motor decline can occur independently and may precede the onset of cognitive impairment in neurodegenerative conditions. These impairments can confound measures of higher-order cognition, typically assessed through behavioral performance. Notably, the associations between cognitive performance and biological indices of speech motor production have been largely unexplored. This study is the first to examine cognitive associations of cortical thickness in brain regions implicated in speech motor performance across the adult lifespan, and to investigate whether age-related structural changes in speech motor regions precede those seen in the hippocampus. Our sample included 699 cognitively healthy adults (56% female) spanning 35-90 years from the Human Connectome Project (HCP)-Aging dataset. Cognition was estimated using standard neuropsychological assessments including: the Trail Making Task A/B (TMT), the Rey Auditory Verbal Learning Test (RAVLT), and a cognitive composite score (summating cognitive performance across multiple tasks). Whole-brain T1- and T2-weighted MRI images were acquired using 3-Tesla scanners across multiple study sites. Structural images were preprocessed using the HCP minimal preprocessed pipelines to reconstruct cortical surfaces. Volume-based estimates including hippocampal volume and total gray matter volume were adjusted for head size using an adjusted measure of estimated Total Intracranial Volume (eTIV). Speech motor regions were investigated relative to well-characterized relationships with hippocampal volume (a hallmark region for memory and cognition and AD-related atrophy). Estimates of cortical thickness were extracted from 14 bilateral speech motor control regions spanning premotor, motor, somatosensory, insular, and prefrontal cortices. Performance across all cognitive tasks and estimates of brain structure were all highly correlated with age. After controlling for the effects of age, greater hippocampal volume remained correlated with better cognitive performance across all cognitive tasks. However, only cognitive associations with greater total gray matter volume survived correction for multiple comparisons. As expected, age associations with hippocampal volume differed between early (-0.191%/year) and late adulthood (-0.714%/year) (T = 6.179, p = 0.0002). Age associations with speech motor control regions significantly differed from the associations seen in GMV, mCT, and/or hippocampal volume across the lifespan (Pcor < 0.0001) and during late adulthood when compared separately. Half the speech motor control regions explored showed decelerated estimated percent difference per year from early and late adulthood. Our results suggest that neurocognitive relationships are highly impacted and often confounded by age. The thickness of several speech motor regions was not associated with cognitive performance and can therefore provide a more intrinsic measure of aging. Additionally, speech motor control regions decline earlier in adulthood than hippocampal volume and may therefore serve as a target and early indicator of AD-related neurodegeneration. This nuanced understanding is critical for refining early diagnostic criteria for neurodegenerative diseases, including AD, and sheds light on the complex interplay between age-related changes, disease pathology, and cognitive decline.

摘要

言语运动和认知障碍在与年龄相关的神经退行性疾病中很常见,包括轻度认知障碍(MCI)和阿尔茨海默病(AD)。尽管运动和认知功能之间存在强烈的相互作用,但完整的言语运动控制是认知功能的一个关键但经常被忽视的组成部分。此外,运动功能衰退可能独立发生,并且可能在神经退行性疾病中认知障碍发作之前出现。这些障碍可能会混淆通常通过行为表现评估的高阶认知测量。值得注意的是,认知表现与言语运动产生的生物学指标之间的关联在很大程度上尚未得到探索。本研究首次考察了成年期言语运动表现所涉及脑区皮质厚度的认知关联,并调查了言语运动区域与年龄相关的结构变化是否先于海马体中的变化。我们的样本包括来自人类连接组计划(HCP)-衰老数据集的699名认知健康的成年人(56%为女性),年龄跨度为35至90岁。使用包括:连线测验A/B(TMT)、雷伊听觉词语学习测验(RAVLT)以及认知综合评分(汇总多个任务的认知表现)等标准神经心理学评估来估计认知。在多个研究地点使用3特斯拉扫描仪获取全脑T1加权和T2加权MRI图像。使用HCP最小预处理管道对结构图像进行预处理以重建皮质表面。使用估计的总颅内体积(eTIV)的调整测量对包括海马体体积和总灰质体积在内的基于体积的估计进行头部大小调整。相对于与海马体体积(记忆、认知和AD相关萎缩的标志性区域)的明确关系来研究言语运动区域。从跨越运动前区、运动区、体感区、岛叶和前额叶皮质的14个双侧言语运动控制区域提取皮质厚度估计值。所有认知任务的表现和脑结构估计值均与年龄高度相关。在控制年龄影响后,更大的海马体体积在所有认知任务中仍与更好的认知表现相关。然而,只有与更大总灰质体积的认知关联在多重比较校正后仍然显著。正如预期的那样,海马体体积与年龄的关联在成年早期(-0.191%/年)和成年晚期(-0.714%/年)之间有所不同(T = 6.179,p = 0.0002)。言语运动控制区域与年龄的关联在整个生命周期中以及成年晚期分别比较时,与灰质体积(GMV)、平均皮质厚度(mCT)和/或海马体体积的关联显著不同(Pcor < 0.0001)。所研究的言语运动控制区域中有一半显示成年早期和晚期每年估计的百分比差异减速。我们的结果表明,神经认知关系受到年龄的高度影响且常常被混淆。几个言语运动区域的厚度与认知表现无关,因此可以提供更内在的衰老测量指标。此外,言语运动控制区域在成年期比海马体体积更早衰退,因此可能作为AD相关神经退行性变的一个靶点和早期指标。这种细致入微的理解对于完善包括AD在内的神经退行性疾病的早期诊断标准至关重要,并有助于揭示与年龄相关变化、疾病病理和认知衰退之间的复杂相互作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1451/12284906/1f1c2aaa8c47/HBM-46-e70288-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1451/12284906/180685eef9ab/HBM-46-e70288-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1451/12284906/41db3fe50ab5/HBM-46-e70288-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1451/12284906/1f1c2aaa8c47/HBM-46-e70288-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1451/12284906/180685eef9ab/HBM-46-e70288-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1451/12284906/41db3fe50ab5/HBM-46-e70288-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1451/12284906/1f1c2aaa8c47/HBM-46-e70288-g003.jpg

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