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轻度认知障碍中β-淀粉样蛋白与皮质厚度之间的纵向关联

Longitudinal associations between β-amyloid and cortical thickness in mild cognitive impairment.

作者信息

Mak Elijah, Zhang Liwen, Tan Chin Hong, Reilhac Anthonin, Shim Hee Youn, Wen Marcus Ong Qin, Wong Zi Xuen, Chong Eddie Jun Yi, Xu Xin, Stephenson Mary, Venketasubramanian Narayanaswamy, Zhou Juan Helen, O'Brien John T, Chen Christopher Li-Hsian

机构信息

Department of Psychiatry, University of Cambridge, Cambridge, CB2 2QQ, United Kingdom.

Memory Aging and Cognition Centre, Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 119228, Singapore.

出版信息

Brain Commun. 2023 Jul 4;5(4):fcad192. doi: 10.1093/braincomms/fcad192. eCollection 2023.

Abstract

How beta-amyloid accumulation influences brain atrophy in Alzheimer's disease remains contentious with conflicting findings. We aimed to elucidate the correlations of regional longitudinal atrophy with cross-sectional regional and global amyloid in individuals with mild cognitive impairment and no cognitive impairment. We hypothesized that greater cortical thinning over time correlated with greater amyloid deposition, particularly within Alzheimer's disease characteristic regions in mild cognitive impairment, and weaker or no correlations in those with no cognitive impairment. 45 patients with mild cognitive impairment and 12 controls underwent a cross-sectional [C]-Pittsburgh Compound B PET and two retrospective longitudinal structural imaging (follow-up: 23.65 ± 2.04 months) to assess global/regional amyloid and regional cortical thickness, respectively. Separate linear mixed models were constructed to evaluate relationships of either global or regional amyloid with regional cortical thinning longitudinally. In patients with mild cognitive impairment, regional amyloid in the right banks of the superior temporal sulcus was associated with longitudinal cortical thinning in the right medial orbitofrontal cortex ( = 0.04 after False Discovery Rate correction). In the mild cognitive impairment group, greater right banks amyloid burden and less cortical thickness in the right medial orbitofrontal cortex showed greater visual and verbal memory decline over time, which was not observed in controls. Global amyloid was not associated with longitudinal cortical thinning in any locations in either group. Our findings indicate an increasing influence of amyloid on neurodegeneration and memory along the preclinical to prodromal spectrum. Future multimodal studies that include additional biomarkers will be well-suited to delineate the interplay between various pathological processes and amyloid and memory decline, as well as clarify their additive or independent effects along the disease deterioration.

摘要

β-淀粉样蛋白的积累如何影响阿尔茨海默病中的脑萎缩,这一问题仍存在争议,研究结果相互矛盾。我们旨在阐明轻度认知障碍和无认知障碍个体中区域纵向萎缩与横断面区域及全脑淀粉样蛋白之间的相关性。我们假设,随着时间推移,更大程度的皮质变薄与更多的淀粉样蛋白沉积相关,特别是在轻度认知障碍患者的阿尔茨海默病特征区域内,而在无认知障碍的个体中相关性较弱或无相关性。45例轻度认知障碍患者和12例对照者接受了横断面[C]-匹兹堡复合物B正电子发射断层扫描(PET)以及两次回顾性纵向结构成像(随访时间:23.65±2.04个月),分别用于评估全脑/区域淀粉样蛋白和区域皮质厚度。构建单独的线性混合模型,纵向评估全脑或区域淀粉样蛋白与区域皮质变薄之间的关系。在轻度认知障碍患者中,颞上沟右岸的区域淀粉样蛋白与右侧内侧眶额皮质的纵向皮质变薄相关(错误发现率校正后P = 0.04)。在轻度认知障碍组中,右侧颞上沟右岸更大的淀粉样蛋白负荷以及右侧内侧眶额皮质更薄的皮质厚度显示,随着时间推移视觉和言语记忆下降更明显,而在对照组中未观察到这种情况。两组中任何位置的全脑淀粉样蛋白均与纵向皮质变薄无关。我们的研究结果表明,在临床前到前驱期范围内,淀粉样蛋白对神经退行性变和记忆的影响越来越大。未来纳入更多生物标志物的多模态研究将非常适合描绘各种病理过程与淀粉样蛋白及记忆衰退之间的相互作用,以及阐明它们在疾病恶化过程中的累加或独立作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b92e/10358322/69c71b6e4e4c/fcad192_ga1.jpg

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