Heterogeneity of cerebral atrophic rate in mild cognitive impairment and its interactive association with proteins related to microglia activity on longitudinal cognitive changes

IF 3.5 3区医学 Q2 GERIATRICS & GERONTOLOGY Archives of gerontology and geriatrics Pub Date : 2024-07-19 DOI:10.1016/j.archger.2024.105582

Jingyi Tang , Zhiyu Cao , Ming Lei , Qun Yu , Yingren Mai , Jiaxin Xu , Wang Liao , Yuting Ruan , Lin Shi , Lianhong Yang , Jun Liu , Alzheimer's Disease Neuroimaging Initiative

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引用次数: 0

Abstract

Background

Heterogeneity of cerebral atrophic rate commonly exists in mild cognitive impairment (MCI), which may be associated with microglia-involved neuropathology and have an influence on cognitive outcomes.

Objective

We aim to explore the heterogeneity of cerebral atrophic rate among MCI and its association with plasma proteins related to microglia activity, with further investigation of their interaction effects on long-term cognition.

Subjects

A total of 630 MCI subjects in the ADNI database were included, of which 260 subjects were available with baseline data on plasma proteins.

Methods

Group-based multi-trajectory modeling (GBMT) was used to identify the latent classes with heterogeneous cerebral atrophic rates. Associations between latent classes and plasma proteins related to microglia activity were investigated with generalized linear models. Linear mixed effect models (LME) were implemented to explore the interaction effects between proteins related to microglia activity and identified latent classes on longitudinal cognitive changes.

Results

Two latent classes were identified and labeled as the slow-atrophy class and the fast-atrophy class. Associations were found between such heterogeneity of atrophic rates and plasma proteins related to microglia activity, especially AXL receptor tyrosine kinase (AXL), CD40 antigen (CD40), and tumor necrosis factor receptor-like 2 (TNF-R2). Interaction effects on longitudinal cognitive changes showed that higher CD40 was associated with faster cognitive decline in the slow-atrophy class and higher AXL or TNF-R2 was associated with slower cognitive decline in the fast-atrophy class.

Conclusions

Heterogeneity of atrophic rates at the MCI stage is associated with several plasma proteins related to microglia activity, which show either protective or adverse effects on long-term cognition depending on the variability of atrophic rates.

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轻度认知障碍患者脑萎缩率的异质性及其与小胶质细胞活性相关蛋白的交互关联对认知纵向变化的影响

背景轻度认知障碍（MCI）患者的脑萎缩率通常存在异质性，这可能与小胶质细胞参与的神经病理学有关，并对认知结果产生影响。目的我们旨在探讨MCI患者脑萎缩率的异质性及其与小胶质细胞活性相关的血浆蛋白的关联，并进一步研究它们对长期认知的交互影响。方法采用基于组的多轨迹建模（GBMT）来识别具有异质性脑萎缩率的潜在类别。用广义线性模型研究了潜在类别和与小胶质细胞活性相关的血浆蛋白之间的关联。采用线性混合效应模型（LME）探讨了与小胶质细胞活性相关的蛋白质和已识别的潜在类别对纵向认知变化的交互作用。研究发现，萎缩率的异质性与小胶质细胞活性相关的血浆蛋白，尤其是AXL受体酪氨酸激酶（AXL）、CD40抗原（CD40）和肿瘤坏死因子受体样2（TNF-R2）之间存在关联。对纵向认知变化的交互影响显示，CD40越高，慢萎缩组的认知能力下降越快，而AXL或TNF-R2越高，快萎缩组的认知能力下降越慢。

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

Archives of gerontology and geriatrics 医学-老年医学

CiteScore

7.30

自引率

5.00%

发文量

198

审稿时长

16 days

期刊介绍： Archives of Gerontology and Geriatrics provides a medium for the publication of papers from the fields of experimental gerontology and clinical and social geriatrics. The principal aim of the journal is to facilitate the exchange of information between specialists in these three fields of gerontological research. Experimental papers dealing with the basic mechanisms of aging at molecular, cellular, tissue or organ levels will be published. Clinical papers will be accepted if they provide sufficiently new information or are of fundamental importance for the knowledge of human aging. Purely descriptive clinical papers will be accepted only if the results permit further interpretation. Papers dealing with anti-aging pharmacological preparations in humans are welcome. Papers on the social aspects of geriatrics will be accepted if they are of general interest regarding the epidemiology of aging and the efficiency and working methods of the social organizations for the health care of the elderly.