Neural correlates of working memory and its association with metabolic parameters in early-treated adults with phenylketonuria

Abgottspon, Stephanie; Muri, Raphaela; Christ, Shawn E.; Hochuli, Michel; Radojewski, Piotr; Trepp, Roman; Everts, Regula

doi:10.1016/j.nicl.2022.102974

Cited by 13 publications

(15 citation statements)

References 48 publications

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“…A recent study by our group found a relationship between neural activation during a working memory task and concurrent but not historical Phe levels within a subsample of the present cohort. 13 Christ et al 34 found a similar relationship between recent Phe levels and decreased functional connectivity. Since plasma Phe levels correlate with brain Phe levels, 51 it seems reasonable to assume that plasma Phe levels on the day of testing or shortly before can directly influence functional neural correlates.…”

Section: Discussionmentioning

confidence: 83%

“…Similarly, our group has previously shown lower accuracy in visuospatial working memory. 13 Accordingly, these results point toward subtle cognitive alterations in adult patients with PKU.…”

Section: Discussionmentioning

confidence: 93%

“…Plasma Phe, Tyrosine (Tyr), and Tryptophan (Trp) levels were measured by high‐performance ion‐exchange liquid chromatography with postcolumn photometric detection of ninhydrin‐derivatized amino acids. Further details about laboratory analysis methods can be found elsewhere 13 . Additionally, concurrent Phe and Tyr levels were used to calculate the Phe:Tyr ratio (see Table 2 for concurrent metabolic parameters in patients).…”

Section: Methodsmentioning

confidence: 99%

“…Further details about laboratory analysis methods can be found elsewhere. 13 Additionally, concurrent Phe and Tyr levels were used to calculate the Phe:Tyr ratio (see Table 2 for concurrent metabolic parameters in patients). In 26.7% (8 out of 30) of patients, concurrent Phe levels were within the target range recommended by the current European guidelines.…”

Section: Methodsmentioning

confidence: 99%

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Cortical thickness and its relationship to cognitive performance and metabolic control in adults with phenylketonuria

Muri

Maissen‐Abgottspon

Rummel

et al. 2022

J of Inher Metab Disea

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Despite good control of phenylalanine (Phe) levels during childhood and adolescence, adults with phenylketonuria (PKU) often show abnormalities in the white matter of the brain, which have been associated with poorer cognitive performance. However, whether such a relationship exists with cortical gray matter is still unknown. Therefore, we investigated cortical thickness and surface area in adults with early-treated PKU and their relationship to cognitive functions and metabolic control. We included 30 adult patients with early-treated and metabolically well-controlled PKU (median age: 35.5 years) and 54 healthy controls (median age: 29.3 years). Surface-based morphometry was derived from T1-weighted magnetic resonance images using FreeSurfer, and general intelligence, executive functions, and attention were assessed. Concurrent plasma Phe, tyrosine, and tryptophan levels were measured in patients. In addition, Phe levels were collected retrospectively to calculate the index of dietary control.Patients showed a thinner cortex than controls in regions of the bilateral Roman Trepp and Regula Everts shared co-last authorship.

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Section: Discussionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 93%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Cortical thickness and its relationship to cognitive performance and metabolic control in adults with phenylketonuria

Muri

Maissen‐Abgottspon

Rummel

et al. 2022

J of Inher Metab Disea

Self Cite

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“…Abgottspon et al examined the neural activity and working memory performance in individuals with PKU compared to controls using fMRI [ 40 ]. Their cohort was early-treated adults with PKU and aged matched normal adult controls.…”

Section: Rare Diseasesmentioning

confidence: 99%

Review of Applications of Near-Infrared Spectroscopy in Two Rare Disorders with Executive and Neurological Dysfunction: UCD and PKU

Khaksari

Chen

Gropman

2022

Genes

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Studying rare diseases, particularly those with neurological dysfunction, is a challenge to researchers and healthcare professionals due to their complexity and small population with geographical dispersion. Universal and standardized biomarkers generated by tools such as functional neuroimaging have been forged to collect baseline data as well as treatment effects. However, the cost and heavily infrastructural requirement of those technologies have substantially limited their availability. Thus, developing non-invasive, portable, and inexpensive modalities has become a major focus for both researchers and clinicians. When considering neurological disorders and diseases with executive dysfunction, EEG is the most convenient tool to obtain biomarkers which can correlate the objective severity and clinical observation of these conditions. However, studies have also shown that EEG biomarkers and clinical observations alone are not sensitive enough since not all the patients present classical phenotypical features or EEG evidence of dysfunction. This article reviews disorders, including two rare disorders with neurological dysfunction and the usefulness of functional near-infrared spectroscopy (fNIRS) as a non-invasive optical modality to obtain hemodynamic biomarkers of diseases and for screening and monitoring the disease.

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Reversible white matter changes following a 4‐week high phenylalanine exposure in adults with phenylketonuria

Muri,

Reed,

Maissen‐Abgottspon

et al. 2024

J of Inher Metab Disea

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Alterations in brain structure are frequently observed in adults with early‐treated phenylketonuria (PKU) compared to healthy controls, with cerebral white matter (WM) being particularly affected. The extent to which temporary elevation of phenylalanine (Phe) levels impacts WM remains unclear. We conducted a double‐blind, randomised, placebo‐controlled crossover trial to investigate the effects of a 4‐week high Phe exposure on cerebral WM and its relationship to cognitive performance and metabolic parameters in adults with PKU. In this study, 27 adults with early‐treated classical PKU (aged 19–48 years) underwent diffusion tensor imaging (DTI) before and after the 4‐week Phe and placebo interventions. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were analysed using tract‐based spatial statistics. Neuropsychological examinations at each timepoint evaluated executive functions and attention. Additionally, brain Phe levels were measured using MR spectroscopy, and blood levels of Phe, tyrosine, and tryptophan were assessed after an overnight fast. Following the Phe period, significant decreases in AD, MD, and RD were observed compared to the placebo period, particularly in the posterior corona radiata and optic radiation. Notably, these WM changes were reversible in patients who first received Phe (n = 13). Cognitive performance and metabolic parameters were not significantly related to DTI scalars after the Phe period. In conlcusion, a 4‐week Phe elevation induced reversible microstructural alterations in cerebral WM. Further investigation is necessary to determine the clinical implication of these changes.

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Neural correlates of working memory and its association with metabolic parameters in early-treated adults with phenylketonuria

Cited by 13 publications

References 48 publications

Cortical thickness and its relationship to cognitive performance and metabolic control in adults with phenylketonuria

Cortical thickness and its relationship to cognitive performance and metabolic control in adults with phenylketonuria

Review of Applications of Near-Infrared Spectroscopy in Two Rare Disorders with Executive and Neurological Dysfunction: UCD and PKU

Reversible white matter changes following a 4‐week high phenylalanine exposure in adults with phenylketonuria

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