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使用 BOLD fMRI 观察到阿尔茨海默病患者的脑 CO2 血管反应性受损。

Impaired cerebral vasoreactivity to CO2 in Alzheimer's disease using BOLD fMRI.

机构信息

Inserm, U836, Grenoble, France.

出版信息

Neuroimage. 2011 Sep 15;58(2):579-87. doi: 10.1016/j.neuroimage.2011.06.070. Epub 2011 Jul 1.

DOI:10.1016/j.neuroimage.2011.06.070
PMID:21745581
Abstract

OBJECTIVE

To evaluate the cerebral vasoreactivity using blood oxygenation level dependent functional MRI during carbogen inhalation with 7% CO(2) in Alzheimer's disease and amnestic mild cognitive impairment.

PARTICIPANTS AND METHODS

Thirty nine subjects were included to be investigated using blood oxygenation level dependent (BOLD) functional MRI at 1.5T during a block-design carbogen inhalation paradigm, with a high concentration face-mask under physiological monitoring. Basal cerebral perfusion was measured using pulsed arterial spin labeling. Image analyses were conducted using Matlab® and SPM5 with physiological regressors and corrected for partial volume effect.

RESULTS

Among selected participants, 12 subjects were excluded because of incomplete protocol, leaving for analysis 27 subjects without significant microangiopathy diagnosed for Alzheimer's disease (n=9), amnestic mild cognitive impairment (n=7), and matched controls (n=11). No adverse reaction related to the CO(2) challenge was reported. Carbogen inhalation induced a whole-brain signal increase, predominant in the gray matter. In patients, signal changes corrected for gray matter partial volume were decreased (0.36±0.13% BOLD/mmHg in Alzheimer's disease, 0.36±0.12 in patients with mild cognitive impairment, 0.62±0.20 in controls). Cerebral vasoreactivity impairments were diffuse but seemed predominant in posterior areas. The basal hypoperfusion in Alzheimer's disease was not significantly different from patients with mild cognitive impairment and controls. Among clinical and biological parameters, no effect of apoE4 genotype was detected. Cerebral vasoreactivity values were correlated with cognitive performances and hippocampal volumes. Among age and hippocampal atrophy, mean CVR was the best predictor of the mini-mental status examination.

CONCLUSION

This BOLD functional MRI study on CO(2) challenge shows impaired cerebral vasoreactivity in patients with Alzheimer's disease and amnestic mild cognitive impairment at the individual level. These preliminary findings using a new MRI approach may help to better characterize patients with cognitive disorders in clinical practice and further investigate vaso-protective therapeutics.

摘要

目的

在阿尔茨海默病和遗忘型轻度认知障碍患者中,利用血氧水平依赖功能磁共振成像(BOLD fMRI)评估在吸入 7%二氧化碳(CO2)的碳化氧合作用下的脑血管反应性。

参与者和方法

共纳入 39 名受试者,在生理监测下,使用高浓度面罩进行 BOLD fMRI 块设计碳化氧合吸入实验,采用脉冲动脉自旋标记法测量基础脑灌注。使用 Matlab®和 SPM5 进行图像分析,使用生理回归器进行分析,并校正部分容积效应。

结果

在选择的参与者中,有 12 名因方案不完整而被排除,27 名无明显微血管病变的参与者(阿尔茨海默病 9 名,遗忘型轻度认知障碍 7 名,匹配对照组 11 名)被纳入分析。未报告与 CO2 挑战相关的不良反应。碳化氧合吸入诱导了全脑信号增加,主要集中在灰质。在患者中,校正灰质部分容积的信号变化减少(阿尔茨海默病患者为 0.36±0.13%BOLD/mmHg,轻度认知障碍患者为 0.36±0.12,对照组为 0.62±0.20)。脑血管反应性损伤弥漫,但似乎主要在后区。阿尔茨海默病患者的基础低灌注与轻度认知障碍患者和对照组无显著差异。在临床和生物学参数中,未检测到载脂蛋白 E4 基因型的影响。脑血管反应性值与认知表现和海马体积相关。在年龄和海马萎缩中,平均 CVR 是 mini-mental 状态检查的最佳预测因子。

结论

这项关于 CO2 挑战的 BOLD fMRI 研究显示,在阿尔茨海默病和遗忘型轻度认知障碍患者中存在个体水平的脑血管反应性受损。这些使用新 MRI 方法的初步发现可能有助于更好地在临床实践中描述认知障碍患者,并进一步研究血管保护治疗。

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