连续四周口服 Phe 对早期苯丙酮尿症成人神经激活和脑血流的影响

IF 3.4 2区 医学 Q2 NEUROIMAGING
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引用次数: 0

摘要

背景苯丙酮尿症(PKU)是一种罕见的先天性代谢异常,其特点是将氨基酸苯丙氨酸(Phe)分解成酪氨酸的过程出现障碍。横断面研究表明,早期接受过 PKU 治疗的成年人在认知能力和神经激活方面会有轻微改变。然而,关于高 Phe 水平对成年后大脑功能的影响的研究仍然不足。因此,我们旨在探索为期四周的口服 Phe(模拟在受控情况下停止 Phe 限制并将 Phe 提高到非饮食水平)对工作记忆相关神经激活和脑血流(CBF)的影响。方法我们进行了一项随机、安慰剂对照、双盲、交叉、非劣效试验,以评估高 Phe 负荷对经典型 PKU 早期治疗的成人工作记忆相关神经激活和 CBF 的影响。该试验共纳入了27名接受早期治疗的典型PKU患者,在使用Phe和安慰剂进行为期四周的干预之前和之后,他们接受了工作记忆网络功能磁共振成像(fMRI)和动脉自旋标记(ASL)磁共振成像以评估CBF。在四次研究考察中的每次考察中,都会获得 fMRI 工作记忆任务的表现(反应时间和准确性)以及血浆 Phe、酪氨酸和色氨酸水平。结果 Phe 干预后,血浆 Phe 和大脑 Phe 显著增加。然而,与安慰剂相比,Phe 对神经激活和 CBF 没有明显影响。关于 fMRI 任务表现,观察到 Phe 干预对 1 回反应时间有明显影响,Phe 干预后反应时间变慢,而 Phe 干预后 3 回反应时间和准确性与安慰剂干预相比没有差异。这些结果进一步促进了有关成年期安全 Phe 水平的讨论,并表明停止 Phe 限制饮食四周不会对大脑功能产生重大变化。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Effect of a four-week oral Phe administration on neural activation and cerebral blood flow in adults with early-treated phenylketonuria

Background

Phenylketonuria (PKU) is a rare inborn error of metabolism characterized by impaired catabolism of the amino acid phenylalanine (Phe) into tyrosine. Cross-sectional studies suggest slight alterations in cognitive performance and neural activation in adults with early-treated PKU. The influence of high Phe levels on brain function in adulthood, however, remains insufficiently studied. Therefore, we aimed to explore the effect of a four-week period of oral Phe administration − simulating a controlled discontinuation of Phe restriction and raising Phe to an off-diet scenario − on working memory-related neural activation and cerebral blood flow (CBF).

Methods

We conducted a randomized, placebo-controlled, double-blind, crossover, non-inferiority trial to assess the effect of a high Phe load on working memory-related neural activation and CBF in early-treated adults with classical PKU. Twenty-seven patients with early-treated classical PKU were included and underwent functional magnetic resonance imaging (fMRI) of the working memory network and arterial spin labeling (ASL) MRI to assess CBF before and after a four-week intervention with Phe and placebo. At each of the four study visits, fMRI working memory task performance (reaction time and accuracy) and plasma Phe, tyrosine, and tryptophan levels were obtained. Additionally, cerebral Phe was determined by 1H-MR spectroscopy.

Results

Plasma Phe and cerebral Phe were significantly increased after the Phe intervention. However, no significant effect of Phe compared to placebo was found on neural activation and CBF. Regarding fMRI task performance, a significant impact of the Phe intervention on 1-back reaction time was observed with slower reaction times following the Phe intervention, whereas 3-back reaction time and accuracy did not differ following the Phe intervention compared to the placebo intervention.

Conclusion

Results from this present trial simulating a four-week discontinuation of the Phe-restricted diet showed that a high Phe load did not uniformly affect neural markers and cognition in a statistically significant manner. These results further contribute to the discussion on safe Phe levels during adulthood and suggest that a four-week discontinuation of Phe-restricted diet does not demonstrate significant changes in brain function.

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来源期刊
Neuroimage-Clinical
Neuroimage-Clinical NEUROIMAGING-
CiteScore
7.50
自引率
4.80%
发文量
368
审稿时长
52 days
期刊介绍: NeuroImage: Clinical, a journal of diseases, disorders and syndromes involving the Nervous System, provides a vehicle for communicating important advances in the study of abnormal structure-function relationships of the human nervous system based on imaging. The focus of NeuroImage: Clinical is on defining changes to the brain associated with primary neurologic and psychiatric diseases and disorders of the nervous system as well as behavioral syndromes and developmental conditions. The main criterion for judging papers is the extent of scientific advancement in the understanding of the pathophysiologic mechanisms of diseases and disorders, in identification of functional models that link clinical signs and symptoms with brain function and in the creation of image based tools applicable to a broad range of clinical needs including diagnosis, monitoring and tracking of illness, predicting therapeutic response and development of new treatments. Papers dealing with structure and function in animal models will also be considered if they reveal mechanisms that can be readily translated to human conditions.
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