Early Cortical Microstructural Changes in Aging Are Linked to Vulnerability to Alzheimer’s Disease Pathology

IF 8.3 2区材料科学 Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY

ACS Applied Materials & Interfaces Pub Date : 2024-10-01 DOI:10.1016/j.bpsc.2024.05.012

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引用次数: 0

Abstract

Background

Early identification of Alzheimer’s disease (AD) risk is critical for improving treatment success. Cortical thickness is a macrostructural measure used to assess neurodegeneration in AD. However, cortical microstructural changes appear to precede macrostructural atrophy and may improve early risk identification. Currently, whether cortical microstructural changes in aging are linked to vulnerability to AD pathophysiology remains unclear in nonclinical populations, who are precisely the target for early risk identification.

Methods

In 194 adults, we calculated magnetic resonance imaging–derived maps of changes in cortical mean diffusivity (microstructure) and cortical thickness (macrostructure) over 5 to 6 years (mean age: time 1 = 61.82 years; time 2 = 67.48 years). Episodic memory was assessed using 3 well-established tests. We obtained positron emission tomography–derived maps of AD pathology deposition (amyloid-β, tau) and neurotransmitter receptors (cholinergic, glutamatergic) implicated in AD pathophysiology. Spatial correlational analyses were used to compare pattern similarity among maps.

Results

Spatial patterns of cortical macrostructural changes resembled patterns of cortical organization sensitive to age-related processes (r = −0.31, p < .05), whereas microstructural changes resembled the patterns of tau deposition in AD (r = 0.39, p = .038). Individuals with patterns of microstructural changes that more closely resembled stereotypical tau deposition exhibited greater memory decline (β = 0.22, p = .029). Microstructural changes and AD pathology deposition were enriched in areas with greater densities of cholinergic and glutamatergic receptors (ps < .05).

Conclusions

Patterns of cortical microstructural changes were more AD-like than patterns of macrostructural changes, which appeared to reflect more general aging processes. Microstructural changes may better inform early risk prediction efforts as a sensitive measure of vulnerability to pathological processes prior to overt atrophy and cognitive decline.

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衰老过程中皮层微结构的早期变化与阿尔茨海默病的病理变化有关。

背景：早期识别阿尔茨海默病（AD）风险对于提高治疗成功率至关重要。皮质厚度是用于评估阿尔茨海默病神经变性的宏观结构指标。然而，皮质微观结构的变化似乎先于宏观结构的萎缩，这可能会改善早期风险识别。目前，在非临床人群中，衰老过程中皮质微观结构的变化是否与AD病理生理学的易感性有关仍不清楚，而非临床人群恰恰是早期风险识别的目标人群：在194名成年人中，我们计算了5-6年间（平均年龄：时间1=61.82；时间2=67.48）皮质平均弥散度（微观结构）和皮质厚度（宏观结构）的MRI衍生变化图。外显记忆采用三种成熟的测试方法进行评估。我们获得了AD病理沉积（β-淀粉样蛋白、tau）和与AD病理生理学有关的神经递质受体（胆碱能、谷氨酸能）的PET衍生图。利用空间相关性分析比较各地图之间的模式相似性：结果：皮质宏观结构变化的空间模式与对年龄相关过程敏感的皮质组织模式相似（r=-0.31，p结论：皮质微观结构变化的空间模式与年龄相关过程敏感的皮质组织模式相似：皮质微观结构变化的模式比宏观结构变化的模式更像AD，后者似乎反映了更普遍的衰老过程。微观结构的变化作为在明显萎缩和认知能力下降之前易受病理过程影响的敏感指标，可以更好地为早期风险预测工作提供信息。

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

ACS Applied Materials & Interfaces 工程技术-材料科学：综合

CiteScore

16.00

自引率

6.30%

发文量

4978

审稿时长

1.8 months

期刊介绍： ACS Applied Materials & Interfaces is a leading interdisciplinary journal that brings together chemists, engineers, physicists, and biologists to explore the development and utilization of newly-discovered materials and interfacial processes for specific applications. Our journal has experienced remarkable growth since its establishment in 2009, both in terms of the number of articles published and the impact of the research showcased. We are proud to foster a truly global community, with the majority of published articles originating from outside the United States, reflecting the rapid growth of applied research worldwide.