脑结构和功能作为淀粉样蛋白对记忆影响的介导因素。

Brain structure and function as mediators of the effects of amyloid on memory.

作者信息

Mattsson Niklas, Insel Philip S, Aisen Paul S, Jagust William, Mackin Scott, Weiner Michael

机构信息

From the Department of Veterans Affairs Medical Center (N.M., P.S.I., S.M., M.W.), Center for Imaging of Neurodegenerative Diseases, San Francisco, CA; Clinical Neurochemistry Laboratory (N.M.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Department of Radiology and Biomedical Imaging (N.M., P.S.I., M.W.), University of California, San Francisco; Alzheimer's Disease Cooperative Study (P.S.A.), Department of Neurosciences, University of California, San Diego, La Jolla; Helen Wills Neuroscience Institute and School of Public Health (W.J.), University of California, Berkeley; and Department of Psychiatry (S.M.), University of California, San Francisco.

出版信息

Neurology. 2015 Mar 17;84(11):1136-44. doi: 10.1212/WNL.0000000000001375. Epub 2015 Feb 13.

DOI:10.1212/WNL.0000000000001375

PMID:25681451

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4371407/

Abstract

OBJECTIVE

The objective of this study was to test whether effects of β-amyloid (Aβ) pathology on episodic memory were mediated by metabolism and gray matter volume in the early stages of Alzheimer disease.

METHODS

This was a prospective cohort study. We measured baseline Aβ (using florbetapir-PET), brain function (using fluorodeoxyglucose-PET), and brain structure (using MRI). A mediation analysis was performed to test whether statistical effects of Aβ positivity on cross-sectional and longitudinal episodic memory were mediated by hypometabolism or regional gray matter volume in cognitively healthy controls (CN, n = 280) and mild cognitive impairment (MCI, n = 463).

RESULTS

Lower memory scores were associated with Aβ positivity (CN, mildly; MCI, strongly), smaller gray matter volumes (CN, few regions, including hippocampus; MCI, widespread), and hypometabolism. Smaller volumes and hypometabolism mediated effects of Aβ in MCI but not in CN. The strongest individual regions mediated up to approximately 25%. A combination of brain structure and function mediated up to approximately 40%. In several regions, gray matter atrophy and hypometabolism predicted episodic memory without being associated (at p < 0.05) with Aβ positivity.

CONCLUSIONS

Changes in brain structure and function appear to be, in part, downstream events from Aβ pathology, ultimately resulting in episodic memory deficits. However, Aβ pathology is also strongly related to memory deficits through mechanisms that are not quantified by these imaging measurements, and episodic memory decline is partly caused by Alzheimer disease-like brain changes independently of Aβ pathology.

摘要

目的

本研究旨在测试β-淀粉样蛋白（Aβ）病理改变对情景记忆的影响是否由阿尔茨海默病早期的代谢和灰质体积介导。

方法

这是一项前瞻性队列研究。我们测量了基线Aβ（使用氟代贝他吡PET）、脑功能（使用氟脱氧葡萄糖PET）和脑结构（使用MRI）。进行中介分析以测试Aβ阳性对认知健康对照者（CN，n = 280）和轻度认知障碍者（MCI，n = 463）的横断面和纵向情景记忆的统计学效应是否由代谢减退或区域灰质体积介导。

结果

较低的记忆分数与Aβ阳性相关（CN为轻度；MCI为重度）、灰质体积较小（CN为少数区域，包括海马体；MCI为广泛区域）以及代谢减退。体积较小和代谢减退介导了Aβ在MCI中的效应，但在CN中未介导。最强的单个区域介导的效应高达约25%。脑结构和功能的组合介导的效应高达约40%。在几个区域，灰质萎缩和代谢减退可预测情景记忆，且与Aβ阳性无关联（p < 0.05）。