Neuroimaging and biomarker evidence of neurodegeneration in asthma,Journal of Allergy and Clinical Immunology

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Neuroimaging and biomarker evidence of neurodegeneration in asthma
Journal of Allergy and Clinical Immunology ( IF 11.4 ) Pub Date : 2021-09-15 , DOI: 10.1016/j.jaci.2021.09.010
Melissa A Rosenkranz ₁ , Douglas C Dean ₂ , Barbara B Bendlin ₃ , Nizar N Jarjour ₄ , Stephane Esnault ₄ , Henrik Zetterberg ₅ , Amanda Heslegrave ₆ , Michael D Evans ₇ , Richard J Davidson ₈ , William W Busse ₄

Affiliation

Department of Psychiatry, University of Wisconsin-Madison, Madison, Wisc; Center for Healthy Minds, University of Wisconsin-Madison, Madison, Wisc.
Department of Pediatrics, University of Wisconsin-Madison, Madison, Wisc; Department of Medical Physics, University of Wisconsin-Madison, Madison, Wisc; Waisman Center, University of Wisconsin-Madison, Madison, Wisc.
Department of Medicine, University of Wisconsin-Madison, Madison, Wisc; Wisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, Madison, Wisc.
Department of Medicine, University of Wisconsin-Madison, Madison, Wisc.
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease, UCL Institute of Neurology, London, United Kingdom; UK Dementia Research Institute at UCL, London, United Kingdom.
UK Dementia Research Institute at UCL, London, United Kingdom.
Biostatistical Design and Analysis Center, Clinical and Translational Science Institute, University of Minnesota, Minneapolis, Minn.
Department of Psychiatry, University of Wisconsin-Madison, Madison, Wisc; Center for Healthy Minds, University of Wisconsin-Madison, Madison, Wisc; Department of Psychology, University of Wisconsin-Madison, Madison, Wisc.

Background

Epidemiologic studies have shown that Alzheimer's disease (AD) and related dementias (ADRD) are seen more frequently with asthma, especially with greater asthma severity or exacerbation frequency.

Objective

To examine the changes in brain structure that may underlie this phenomenon, we examined diffusion-weighted magnetic resonance imaging (dMRI) and blood-based biomarkers of AD (phosphorylated tau 181, p-Tau181), neurodegeneration (neurofilament light chain, NfL), and glial activation (glial fibrillary acidic protein, GFAP).

Methods

dMRI data were obtained in 111 individuals with asthma, ranging in disease severity from mild to severe, and 135 healthy controls. Regression analyses were used to test the relationships between asthma severity and neuroimaging measures, as well as AD pathology, neurodegeneration, and glial activation, indexed by plasma p-Tau181, NfL, and GFAP, respectively. Additional relationships were tested with cognitive function.

Results

Asthma participants had widespread and large-magnitude differences in several dMRI metrics, which were indicative of neuroinflammation and neurodegeneration, and which were robustly associated with GFAP and, to a lesser extent, NfL. The AD biomarker p-Tau181 was only minimally associated with neuroimaging outcomes. Further, asthma severity was associated with deleterious changes in neuroimaging outcomes, which in turn were associated with slower processing speed, a test of cognitive performance.

Conclusions

Asthma, particularly when severe, is associated with characteristics of neuroinflammation and neurodegeneration, and may be a potential risk factor for neural injury and cognitive dysfunction. There is a need to determine how asthma may affect brain health and whether treatment directed toward characteristics of asthma associated with these risks can mitigate these effects.

中文翻译：

哮喘神经变性的神经影像学和生物标志物证据

背景

流行病学研究表明，阿尔茨海默病 (AD) 和相关痴呆 (ADRD) 更常见于哮喘，尤其是哮喘严重程度或发作频率较高的患者。

客观的

为了检查可能导致这种现象的大脑结构的变化，我们检查了弥散加权磁共振成像 (dMRI) 和 AD 的血液生物标志物（磷酸化 tau 181、p-Tau181）、神经退行性变（神经丝轻链，NfL）、和神经胶质激活（神经胶质纤维酸性蛋白，GFAP）。

方法

dMRI 数据来自 111 名哮喘患者（疾病严重程度从轻度到重度）和 135 名健康对照者。回归分析用于测试哮喘严重程度与神经影像学测量以及 AD 病理学、神经变性和神经胶质激活之间的关系，分别以血浆 p-Tau181、NfL 和 GFAP 为索引。通过认知功能测试了其他关系。

结果

哮喘参与者在几个 dMRI 指标上存在广泛且大幅度的差异，这些指标表明神经炎症和神经退行性变，并且与 GFAP 密切相关，并且在较小程度上与 NfL 相关。AD 生物标志物 p-Tau181 与神经影像学结果的相关性极小。此外，哮喘的严重程度与神经影像学结果的有害变化有关，而神经影像学结果又与较慢的处理速度（认知能力测试）有关。