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右中颞叶葡萄糖代谢可能是主观认知下降的潜在生物标志物:一项汉族人群研究。

Glucose metabolism in the right middle temporal gyrus could be a potential biomarker for subjective cognitive decline: a study of a Han population.

机构信息

Key laboratory of Specialty Fiber Optics and Optical Access Networks, Joint International Research Laboratory of Specialty Fiber Optics and Advanced Communication, School of Information and Communication Engineering, Shanghai University, Shanghai, China.

Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China.

出版信息

Alzheimers Res Ther. 2021 Apr 7;13(1):74. doi: 10.1186/s13195-021-00811-w.

Abstract

INTRODUCTION

Subjective cognitive decline (SCD) represents a cognitively normal state but at an increased risk for developing Alzheimer's disease (AD). Recognizing the glucose metabolic biomarkers of SCD could facilitate the location of areas with metabolic changes at an ultra-early stage. The objective of this study was to explore glucose metabolic biomarkers of SCD at the region of interest (ROI) level.

METHODS

This study was based on cohorts from two tertiary medical centers, and it was part of the SILCODE project (NCT03370744). Twenty-six normal control (NC) cases and 32 SCD cases were in cohort 1; 36 NCs, 23 cases of SCD, 32 cases of amnestic mild cognitive impairment (aMCIs), 32 cases of AD dementia (ADDs), and 22 cases of dementia with Lewy bodies (DLBs) were in cohort 2. Each subject underwent [18F]fluoro-2-deoxyglucose positron emission tomography (PET) imaging and magnetic resonance imaging (MRI), and subjects from cohort 1 additionally underwent amyloid-PET scanning. The ROI analysis was based on the Anatomical Automatic Labeling (AAL) template; multiple permutation tests and repeated cross-validations were conducted to determine the metabolic differences between NC and SCD cases. In addition, receiver operating characteristic curves were used to evaluate the capabilities of potential glucose metabolic biomarkers in distinguishing different groups. Pearson correlation analysis was also performed to explore the correlation between glucose metabolic biomarkers and neuropsychological scales or amyloid deposition.

RESULTS

Only the right middle temporal gyrus (RMTG) passed the methodological verification, and its metabolic levels were correlated with the degrees of complaints (R = - 0.239, p = 0.009), depression (R = - 0.200, p = 0.030), and abilities of delayed memory (R = 0.207, p = 0.025), and were weakly correlated with cortical amyloid deposition (R = - 0.246, p = 0.066). Furthermore, RMTG metabolism gradually decreased across the cognitive continuum, and its diagnostic efficiency was comparable (NC vs. ADD, aMCI, or DLB) or even superior (NC vs. SCD) to that of the metabolism of the posterior cingulate cortex or precuneus.

CONCLUSIONS

These findings suggest that the hypometabolism of RMTG could be a typical feature of SCD, and the large-scale hypometabolism in patients with symptomatic stages of AD may start from the RMTG, which gradually progresses starting in the preclinical stage. The specificity of identifying SCD from the perspective of self-perceived symptoms is likely to be increased by the detection of RMTG metabolism.

摘要

简介

主观认知下降(SCD)代表认知正常,但发生阿尔茨海默病(AD)的风险增加。识别 SCD 的葡萄糖代谢生物标志物可以促进在超早期发现代谢变化区域。本研究的目的是在感兴趣区域(ROI)水平探索 SCD 的葡萄糖代谢生物标志物。

方法

本研究基于两个三级医疗中心的队列,是 SILCODE 项目(NCT03370744)的一部分。26 例正常对照(NC)病例和 32 例 SCD 病例为队列 1;36 例 NC、23 例 SCD、32 例遗忘型轻度认知障碍(aMCI)、32 例 AD 痴呆(ADD)和 22 例路易体痴呆(DLB)为队列 2。每位受试者均进行 [18F]氟-2-脱氧葡萄糖正电子发射断层扫描(PET)成像和磁共振成像(MRI),且队列 1 的受试者还进行淀粉样蛋白-PET 扫描。ROI 分析基于解剖自动标记(AAL)模板;进行多次置换检验和重复交叉验证,以确定 NC 和 SCD 病例之间的代谢差异。此外,还使用受试者工作特征曲线评估潜在葡萄糖代谢生物标志物在区分不同组别的能力。还进行了 Pearson 相关分析,以探讨葡萄糖代谢生物标志物与神经心理学量表或淀粉样蛋白沉积之间的相关性。

结果

只有右侧颞中回(RMTG)通过了方法学验证,其代谢水平与抱怨程度(R=-0.239,p=0.009)、抑郁(R=-0.200,p=0.030)和延迟记忆能力(R=0.207,p=0.025)相关,与皮质淀粉样蛋白沉积呈弱相关(R=-0.246,p=0.066)。此外,RMTG 代谢在认知连续体中逐渐降低,其诊断效率与(NC 与 ADD、aMCI 或 DLB)相当(或甚至优于)后扣带回或楔前叶的代谢。

结论

这些发现表明,RMTG 的代谢低下可能是 SCD 的一个典型特征,AD 症状阶段患者的大区域代谢低下可能从 RMTG 开始,并且在临床前阶段开始逐渐进展。从自我感知症状的角度识别 SCD 的特异性可能会通过检测 RMTG 代谢而提高。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c81/8028241/5d367e8c77ee/13195_2021_811_Fig1_HTML.jpg

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