AI Article Synopsis

  • The study investigates the impact of phenylketonuria (PKU) on white matter microstructure in adults, focusing on how it correlates with metabolic control and cognitive performance.
  • Using diffusion tensor imaging and H spectroscopy, researchers analyzed 30 PKU patients and 54 healthy controls, revealing significant reductions in white matter metrics like mean diffusivity and fractional anisotropy in patients.
  • The findings indicate that these microstructural changes are linked to cognitive functions such as inhibition and cognitive flexibility, suggesting that PKU may have broader effects on brain structure and function than previously understood.

Article Abstract

Despite increasing knowledge about the effects of phenylketonuria on brain structure and function, it is uncertain whether white matter microstructure is affected and if it is linked to patients' metabolic control or cognitive performance. Thus, we quantitatively assessed white matter characteristics in adults with phenylketonuria and assessed their relationship to concurrent brain and blood phenylalanine levels, historical metabolic control and cognitive performance. Diffusion tensor imaging and H spectroscopy were performed in 30 adults with early-treated classical phenylketonuria (median age 35.5 years) and 54 healthy controls (median age 29.3 years). Fractional anisotropy and mean, axial and radial diffusivity were investigated using tract-based spatial statistics, and white matter lesion load was evaluated. Brain phenylalanine levels were measured with H spectroscopy whereas concurrent plasma phenylalanine levels were assessed after an overnight fast. Retrospective phenylalanine levels were collected to estimate historical metabolic control, and a neuropsychological evaluation assessed the performance in executive functions, attention and processing speed. Widespread reductions in mean diffusivity, axial diffusivity and fractional anisotropy occurred in patients compared to controls. Mean diffusivity and axial diffusivity were decreased in several white matter tracts and were most restricted in the optic radiation (effect size = 0.66 to 0.78, < 0.001) and posterior corona radiata ( = 0.83 to 0.90, < 0.001). Lower fractional anisotropy was found in the optic radiation and posterior corona radiata ( = 0.43 to 0.49, < 0.001). White matter microstructure in patients was significantly associated with cognition. Specifically, inhibition was related to axial diffusivity in the external capsule ( = -0.69, < 0.001) and the superior ( = -0.58, < 0.001) and inferior longitudinal fasciculi ( = -0.60, < 0.001). Cognitive flexibility was associated with mean diffusivity of the posterior limb of the internal capsule ( = -0.62, < 0.001), and divided attention correlated with fractional anisotropy of the external capsule ( = -0.61, < 0.001). Neither concurrent nor historical metabolic control was significantly associated with white matter microstructure. White matter lesions were present in 29 out of 30 patients (96.7%), most often in the parietal and occipital lobes. However, total white matter lesion load scores were unrelated to patients' cognitive performance and metabolic control. In conclusion, our findings demonstrate that white matter alterations in early-treated phenylketonuria persist into adulthood, are most prominent in the posterior white matter and are likely to be driven by axonal damage. Furthermore, diffusion tensor imaging metrics in adults with phenylketonuria were related to performance in attention and executive functions.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10231812PMC
http://dx.doi.org/10.1093/braincomms/fcad155DOI Listing

Publication Analysis

Top Keywords

white matter
44
metabolic control
20
cognitive performance
16
phenylalanine levels
16
fractional anisotropy
16
adults phenylketonuria
12
matter microstructure
12
historical metabolic
12
axial diffusivity
12
matter
11

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!