Relationship between MRI brain-age heterogeneity, cognition, genetics and Alzheimer's disease neuropathology.

IF 9.7 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
EBioMedicine Pub Date : 2024-11-01 Epub Date: 2024-10-21 DOI:10.1016/j.ebiom.2024.105399
Mathilde Antoniades, Dhivya Srinivasan, Junhao Wen, Guray Erus, Ahmed Abdulkadir, Elizabeth Mamourian, Randa Melhem, Gyujoon Hwang, Yuhan Cui, Sindhuja Tirumalai Govindarajan, Andrew A Chen, Zhen Zhou, Zhijian Yang, Jiong Chen, Raymond Pomponio, Susan Sotardi, Yang An, Murat Bilgel, Pamela LaMontagne, Ashish Singh, Tammie Benzinger, Lori Beason-Held, Daniel S Marcus, Kristine Yaffe, Lenore Launer, John C Morris, Duygu Tosun, Luigi Ferrucci, R Nick Bryan, Susan M Resnick, Mohamad Habes, David Wolk, Yong Fan, Ilya M Nasrallah, Haochang Shou, Christos Davatzikos
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引用次数: 0

Abstract

Background: Brain ageing is highly heterogeneous, as it is driven by a variety of normal and neuropathological processes. These processes may differentially affect structural and functional brain ageing across individuals, with more pronounced ageing (older brain age) during midlife being indicative of later development of dementia. Here, we examined whether brain-ageing heterogeneity in unimpaired older adults related to neurodegeneration, different cognitive trajectories, genetic and amyloid-beta (Aβ) profiles, and to predicted progression to Alzheimer's disease (AD).

Methods: Functional and structural brain age measures were obtained for resting-state functional MRI and structural MRI, respectively, in 3460 cognitively normal individuals across an age range spanning 42-85 years. Participants were categorised into four groups based on the difference between their chronological and predicted age in each modality: advanced age in both (n = 291), resilient in both (n = 260) or advanced in one/resilient in the other (n = 163/153). With the resilient group as the reference, brain-age groups were compared across neuroimaging features of neuropathology (white matter hyperintensity volume, neuronal loss measured with Neurite Orientation Dispersion and Density Imaging, AD-specific atrophy patterns measured with the Spatial Patterns of Abnormality for Recognition of Early Alzheimer's Disease index, amyloid burden using amyloid positron emission tomography (PET), progression to mild cognitive impairment and baseline and longitudinal cognitive measures (trail making task, mini mental state examination, digit symbol substitution task).

Findings: Individuals with advanced structural and functional brain-ages had more features indicative of neurodegeneration and they had poor cognition. Individuals with a resilient brain-age in both modalities had a genetic variant that has been shown to be associated with age of onset of AD. Mixed brain-age was associated with selective cognitive deficits.

Interpretation: The advanced group displayed evidence of increased atrophy across all neuroimaging features that was not found in either of the mixed groups. This is in line with biomarkers of preclinical AD and cerebrovascular disease. These findings suggest that the variation in structural and functional brain ageing across individuals reflects the degree of underlying neuropathological processes and may indicate the propensity to develop dementia in later life.

Funding: The National Institute on Aging, the National Institutes of Health, the Swiss National Science Foundation, the Kaiser Foundation Research Institute and the National Heart, Lung, and Blood Institute.

核磁共振成像脑年龄异质性、认知、遗传和阿尔茨海默氏症神经病理学之间的关系。
背景:大脑老化是由多种正常和神经病理过程驱动的,因此具有高度异质性。这些过程可能会对不同个体的大脑结构和功能老化产生不同的影响,中年时期更明显的老化(脑龄变大)可能预示着日后痴呆症的发展。在此,我们研究了未受损老年人的脑老化异质性是否与神经变性、不同的认知轨迹、遗传和淀粉样蛋白-β(Aβ)特征以及阿尔茨海默病(AD)的预测进展有关:方法:对 3460 名年龄跨度为 42-85 岁、认知正常的人进行静息态功能磁共振成像和结构磁共振成像,分别测量其脑功能和结构年龄。根据每种模式下参与者的实际年龄与预测年龄之间的差异将其分为四组:两种模式下均为高龄组(n = 291)、两种模式下均为恢复力强组(n = 260)或一种模式下为高龄组/另一种模式下为恢复力强组(n = 163/153)。以恢复力强的组为参照,比较脑年龄组的神经病理学特征(白质高密度体积、神经元定向弥散和密度成像测量的神经元缺失、用识别早期阿尔茨海默病的异常空间模式指数测量的AD特异性萎缩模式)、淀粉样蛋白正电子发射断层扫描(PET)测量的淀粉样蛋白负荷、轻度认知障碍的进展以及基线和纵向认知测量(追踪任务、小型精神状态检查、数字符号替换任务)。研究结果脑结构和功能晚期患者的神经退行性变特征较多,认知能力较差。在两种模式下都具有抗逆性脑年龄的人有一种基因变异,这种变异已被证明与注意力缺失症的发病年龄有关。混合脑龄与选择性认知缺陷有关:高龄组在所有神经影像学特征方面都显示出萎缩加剧的迹象,而混合组则没有这种迹象。这与临床前期注意力缺失症和脑血管疾病的生物标志物相符。这些发现表明,不同个体大脑结构和功能老化的差异反映了潜在神经病理学过程的程度,并可能预示着晚年患痴呆症的倾向:美国国家老龄化研究所、美国国家卫生研究院、瑞士国家科学基金会、凯撒基金会研究所和美国国家心肺血液研究所。
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来源期刊
EBioMedicine
EBioMedicine Biochemistry, Genetics and Molecular Biology-General Biochemistry,Genetics and Molecular Biology
CiteScore
17.70
自引率
0.90%
发文量
579
审稿时长
5 weeks
期刊介绍: eBioMedicine is a comprehensive biomedical research journal that covers a wide range of studies that are relevant to human health. Our focus is on original research that explores the fundamental factors influencing human health and disease, including the discovery of new therapeutic targets and treatments, the identification of biomarkers and diagnostic tools, and the investigation and modification of disease pathways and mechanisms. We welcome studies from any biomedical discipline that contribute to our understanding of disease and aim to improve human health.
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