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脑白质病变与神经退行性痴呆患者脑脊液生物标志物及认知功能下降的相关性。

Association of Superficial White Matter Alterations with Cerebrospinal Fluid Biomarkers and Cognitive Decline in Neurodegenerative Dementia.

机构信息

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Neuroradiology Unit, Milan, Italy.

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Neurodegenerative Disease Unit, Milan, Italy.

出版信息

J Alzheimers Dis. 2022;85(1):431-442. doi: 10.3233/JAD-215003.

Abstract

BACKGROUND

Superficial white matter (SWM) alterations correlated with cognitive decline have been described in Alzheimer's disease (AD).

OBJECTIVE

The study aims to extend the investigation of the SWM alterations to AD and non-AD neurodegenerative dementia (ND) and explore the relationship with cerebrospinal fluid (CSF) biomarkers and clinical data.

METHODS

From a database of 323 suspected dementia cases, we retrospectively recruited 55 ND with abnormal amyloid-β42 (AD) and 38 ND with normal amyloid-β42 (non-AD) and collected clinical data, CSF biomarkers, and magnetic resonance images. Ten healthy controls (HC) were recruited for imaging and Mini-Mental State Examination (MMSE). Diffusion tensor imaging (DTI) measurements were performed in the lobar SWM regions and Kruskal Wallis tests were used for among-group comparison. Spearman's correlation tests were performed between DTI measures, CSF biomarkers, and clinical data.

RESULTS

AD and non-AD showed significant differences in the DTI measures across the SWM compared to HC. Significant differences between AD and non-AD were detected in the left parietal lobe. DTI measures correlated with amyloid-β42 and MMSE diffusely in the SWM, less extensively with total-tau and phosphorylated tau, and with disease duration in the parietal lobe bilaterally.

CONCLUSION

Widespread SWM alterations occur in both AD and non-AD ND and AD shows appreciably more severe alterations in the parietal SWM. Notably, the alterations in the SWM are strongly linked not only to the cognitive decline but also to the diagnostic CSF biomarkers. Further studies are encouraged to evaluate the DTI measures in the SWM as in vivo non-invasive biomarkers in the preclinical phase.

摘要

背景

在阿尔茨海默病(AD)中,已描述与认知能力下降相关的浅层脑白质(SWM)改变。

目的

本研究旨在将 SWM 改变的研究扩展到 AD 和非 AD 神经退行性痴呆(ND),并探讨其与脑脊液(CSF)生物标志物和临床数据的关系。

方法

从 323 例疑似痴呆症的数据库中,我们回顾性招募了 55 例 AD 患者(异常淀粉样蛋白-β42)、38 例非 AD 患者(正常淀粉样蛋白-β42)和收集临床数据、CSF 生物标志物和磁共振成像。招募了 10 名健康对照者(HC)进行成像和简易精神状态检查(MMSE)。在脑叶 SWM 区域进行扩散张量成像(DTI)测量,并使用 Kruskal-Wallis 检验进行组间比较。对 DTI 测量值、CSF 生物标志物和临床数据进行 Spearman 相关性检验。

结果

AD 和非 AD 患者的 SWM 中的 DTI 测量值与 HC 相比存在显著差异。在左顶叶发现 AD 和非 AD 之间存在显著差异。SWM 中的 DTI 测量值与淀粉样蛋白-β42 和 MMSE 广泛相关,与总 tau 和磷酸化 tau 相关程度较低,与双侧顶叶的疾病持续时间相关。

结论

AD 和非 AD ND 均存在广泛的 SWM 改变,而 AD 在顶叶 SWM 中表现出明显更严重的改变。值得注意的是,SWM 的改变不仅与认知能力下降密切相关,还与诊断性 CSF 生物标志物密切相关。鼓励进一步研究将 SWM 中的 DTI 测量值作为临床前阶段的非侵入性生物标志物。

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