成年唐氏综合征患者阿尔茨海默病诊断进展与脑血管疾病和神经炎症相关

IF 11.1 1区 医学 Q1 CLINICAL NEUROLOGY
Natalie C. Edwards, Patrick J. Lao, Mohamad J. Alshikho, Olivia M. Ericsson, Batool Rizvi, Melissa E. Petersen, Sid O'Bryant, Lisi Flores-Aguilar, Sabrina Simoes, Mark Mapstone, Dana L. Tudorascu, Shorena Janelidze, Oskar Hansson, Benjamin L. Handen, Bradley T. Christian, Joseph H. Lee, Florence Lai, H Diana Rosas, Shahid Zaman, Ira T. Lott, Michael A. Yassa, Alzheimer's Biomarkers Consortium–Down Syndrome (ABC-DS) Investigators, José Gutierrez, Donna M. Wilcock, Elizabeth Head, Adam M. Brickman
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引用次数: 0

摘要

尽管没有血管危险因素,唐氏综合征(DS)患者有脑血管疾病(CVD)和神经炎症的MRI证据,并随着阿尔茨海默病(AD)的严重程度而恶化。我们研究了心血管疾病和炎症标志物是否与退行性椎体滑移患者ad相关的诊断进展相关。方法:我们纳入了来自阿尔茨海默病生物标志物联盟-唐氏综合征的149名参与者(平均年龄[SD] = 44.6[9]),他们进行了两次(n = 24)或三次随访(n = 125)。我们获得了基线时白质高强度(WMH)体积和血浆生物标志物(胶质纤维酸性蛋白[GFAP]、β淀粉样蛋白[Aβ]42/Aβ40、高磷酸化tau-217 [p-tau217]和神经丝光[NfL])浓度,并研究了它们与临床诊断进展的关系。结果:较高的基线WMH体积和较高的GFAP与更大的诊断进展可能性相关。与单独使用AD生物标志物相比,将WMH和GFAP与p-tau217联合使用可提高临床转换分类的准确性。在有淀粉样变证据的个体中,WMH和GFAP都与临床进展有关。在退行性痴呆中,CVD和炎症标志物与临床AD进展独立且协同相关。较高的基线白质高强度(WMH)体积和血浆胶质纤维酸性蛋白(GFAP)浓度与唐氏综合征患者从认知稳定发展为轻度认知障碍或临床阿尔茨海默病的可能性较高相关。WMH体积和GFAP浓度可区分进展者和未进展者。包括WMH和GFAP的独立和相互作用在内的模型更准确地区分了诊断进展的参与者和没有进展的参与者。有淀粉样蛋白病理证据的个体,如果WMH或GFAP也升高,则更有可能进展。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Alzheimer's disease diagnostic progression is associated with cerebrovascular disease and neuroinflammation in adults with Down syndrome

Alzheimer's disease diagnostic progression is associated with cerebrovascular disease and neuroinflammation in adults with Down syndrome

INTRODUCTION

Despite having few vascular risk factors, people with Down syndrome (DS) have MRI evidence of cerebrovascular disease (CVD) and neuroinflammation that worsens with Alzheimer's disease (AD) severity. We investigated whether markers of CVD and inflammation are associated with AD-related diagnostic progression in people with DS.

METHODS

We included 149 participants (mean age [SD] = 44.6 [9]) from the Alzheimer's Biomarkers Consortium–Down Syndrome who had two (n = 24) or three follow-up visits (n = 125). We derived white matter hyperintensity (WMH) volume and plasma biomarker (glial fibrillary acidic protein [GFAP], amyloid beta [Aβ]42/Aβ40, hyperphosphorylated tau-217 [p-tau217], and neurofilament light [NfL]) concentrations at baseline and examined their association with progression in clinical diagnosis.

RESULTS

Higher baseline WMH volume and higher GFAP were associated with a greater likelihood of diagnostic progression. Combining WMH and GFAP with p-tau217 improved clinical conversion classification accuracy over AD biomarkers alone. Among individuals with evidence of amyloidosis, both WMH and GFAP were associated with clinical progression.

DISCUSSION

In DS, markers of CVD and inflammation are independently and synergistically associated with clinical AD progression.

Highlights

  • Higher baseline white matter hyperintensity (WMH) volume and plasma glial fibrillary acidic protein (GFAP) concentration were associated with a higher likelihood of progressing from cognitively stable to either mild cognitive impairment or clinical Alzheimer's disease in Down syndrome.
  • WMH volume and GFAP concentration discriminated between those who progressed and those who did not.
  • Models including the independent and interactive effects of WMH and GFAP more accurately discriminated between participants who progressed diagnostically from those who did not.
  • Individuals with evidence of amyloid pathology were more likely to progress if they also had elevated WMH or GFAP.
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来源期刊
Alzheimer's & Dementia
Alzheimer's & Dementia 医学-临床神经学
CiteScore
14.50
自引率
5.00%
发文量
299
审稿时长
3 months
期刊介绍: Alzheimer's & Dementia is a peer-reviewed journal that aims to bridge knowledge gaps in dementia research by covering the entire spectrum, from basic science to clinical trials to social and behavioral investigations. It provides a platform for rapid communication of new findings and ideas, optimal translation of research into practical applications, increasing knowledge across diverse disciplines for early detection, diagnosis, and intervention, and identifying promising new research directions. In July 2008, Alzheimer's & Dementia was accepted for indexing by MEDLINE, recognizing its scientific merit and contribution to Alzheimer's research.
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