Department of Diabetes, Endocrinology, Nutritional Medicine and Metabolism, Inselspital, Bern University Hospital and University of Bern, Switzerland; Graduate School for Health Sciences, University of Bern, Switzerland; Translational Imaging Center (TIC), Swiss Institute for Translational and Entrepreneurial Medicine, Bern, Switzerland.
Department of Diabetes, Endocrinology, Nutritional Medicine and Metabolism, Inselspital, Bern University Hospital and University of Bern, Switzerland; Graduate School for Health Sciences, University of Bern, Switzerland; Support Center for Advanced Neuroimaging (SCAN), Institute of Diagnostic and Interventional Neuroradiology, Inselspital, Bern University Hospital and University of Bern, Switzerland; Translational Imaging Center (TIC), Swiss Institute for Translational and Entrepreneurial Medicine, Bern, Switzerland.
Neuroimage Clin. 2022;34:102974. doi: 10.1016/j.nicl.2022.102974. Epub 2022 Feb 26.
Phenylketonuria (PKU) is an inborn error of metabolism affecting the conversion of phenylalanine (Phe) into tyrosine. Previous research has found cognitive and functional brain alterations in individuals with PKU even if treated early. However, little is known about working memory processing and its association with task performance and metabolic parameters. The aim of the present study was to examine neural correlates of working memory and its association with metabolic parameters in early-treated adults with PKU.
This cross-sectional study included 20 early-treated adults with PKU (mean age: 31.4 years ± 9.0) and 40 healthy controls with comparable age, sex, and education (mean age: 29.8 years ± 8.2). All participants underwent functional magnetic resonance imaging (fMRI) of working memory to evaluate the fronto-parietal working memory network. Fasting blood samples were collected from the individuals with PKU to acquire a concurrent plasma amino acid profile, and retrospective Phe concentrations were obtained to estimate an index of dietary control.
On a cognitive level, early-treated adults with PKU displayed significantly lower accuracy but comparable reaction time in the working memory task compared to the control group. Whole-brain analyses did not reveal differences in working memory-related neural activation between the groups. Exploratory region-of-interest (ROI) analyses indicated reduced neural activation in the left and right middle frontal gyri and the right superior frontal gyrus in the PKU group compared to the control group. However, none of the ROI analyses survived correction for multiple comparisons. Neural activation was related to concurrent Phe, tyrosine, and tryptophan concentrations but not to retrospective Phe concentrations.
In early-treated adults with PKU, cognitive performance and neural activation are slightly altered, a result that is partly related to metabolic parameters. This study offers a rare insight into the complex interplay between metabolic parameters, neural activation, and cognitive performance in a sample of individuals with PKU.
苯丙酮尿症（PKU）是一种代谢性遗传疾病，会影响苯丙氨酸（Phe）转化为酪氨酸。既往研究发现，即使早期治疗，PKU 患者也存在认知和功能脑改变。然而，对于工作记忆处理及其与任务表现和代谢参数的关系，人们知之甚少。本研究旨在探讨早期治疗的 PKU 成人的工作记忆的神经相关性及其与代谢参数的关系。
本横断面研究纳入了 20 名早期治疗的 PKU 成人（平均年龄：31.4±9.0 岁）和 40 名年龄、性别和教育程度相匹配的健康对照者（平均年龄：29.8±8.2 岁）。所有参与者均接受了工作记忆功能磁共振成像（fMRI）检查，以评估额顶叶工作记忆网络。从 PKU 个体中采集空腹血样以获得同时的血浆氨基酸谱，并回顾性获取 Phe 浓度以估计饮食控制指数。
在认知水平上，与对照组相比，早期治疗的 PKU 成人的工作记忆任务准确性显著降低，但反应时间相当。全脑分析未发现两组之间与工作记忆相关的神经激活存在差异。探索性的感兴趣区（ROI）分析表明，与对照组相比，PKU 组的左、右额中回和右额上回的神经激活减少。然而，这些 ROI 分析均未通过多重比较校正。神经激活与同时的 Phe、酪氨酸和色氨酸浓度相关，但与回顾性的 Phe 浓度无关。
在早期治疗的 PKU 成人中，认知表现和神经激活略有改变，这在一定程度上与代谢参数有关。本研究为代谢参数、神经激活和认知表现之间的复杂相互作用提供了一个难得的视角，在 PKU 患者样本中进行了研究。
