Emotional health in early-treated adults with phenylketonuria (PKU): Relationship with cognitive abilities and blood phenylalanine.

Introduction: Mental health, physical health, and cognitive skills have been scarcely investigated in the same sample of adults with PKU (AwPKU). This is striking since emotional difficulties may potentially contribute to cognitive impairments and vice-versa. Here we aim to fill this gap.Method: Thirty-six early-treated AwPKU and 40 controls were given an extensive battery of cognitive tasks assessing complex executive functions, inhibitory control, short-term memory, sustained attention, visuospatial attention, language production (reading and naming), visuomotor coordination, spoken language and orthographic processing. In addition, participants were given tasks tapping emotion recognition and completed questionnaires to assess depression (BDI-II), empathy (IRI) and mental/physical health-related quality of life (SF-36).Results: As a group, AwPKU performed significantly worse than controls especially in tasks tapping complex executive functions and across tasks when speed was measured but did not differ for emotional-health and physical health. In the PKU group, cognitive measures and measures of physical health-related quality of life were inter-correlated (differently than in the control group), and both measures were associated with metabolic control: better metabolic control, better cognition, and better physical health. Instead, cognitive measures and measures of emotional-health/mental-health-related quality of life did not correlate with one another and better metabolic control was not associated with better emotional health. Instead, some negative correlations were found. Better metabolic control was associated with worse perspective taking and more distress in socially stressful situations. Furthermore, difficulties in keeping the diet were associated with less emotional well-being.Conclusions: Taken together, these results indicate the advantages, but also possible emotional difficulties related to maintain a PKU diet, suggesting the importance of developing alternative therapy options.

Cognitive outcomes in early-treated adults with phenylketonuria (PKU): A comprehensive picture across domains.

OBJECTIVE: Phenylketonuria (PKU) is an inherited metabolic disease which affects cognitive functions due to an inability to metabolize phenylalanine which leads to the accumulation of toxic by-products (Phe) in the brain. PKU can be effectively treated with a low phenylalanine diet, but some cognitive deficits remain. Studies have reported impairments, especially for processing speed and executive functions, but there is a lack of comprehensive assessment across cognitive domains. Moreover, it is important to establish outcomes in early treated adults with PKU (AwPKU) who have better metabolic control than groups previously reported in the literature. METHOD: We tested 37 AwPKU with an unprecedented number of tasks (N = 28) and measures (N = 44) and compared results with 30 controls matched for age and education. RESULTS: We found (a) group impairments, particularly in tasks tapping speed of processing and complex executive functions; (b) high variability across participants, with a sizable number of AwPKU with completely normal performance (about 38%); (c) but also a sizable number of participants who were clearly impaired (about 24%); and (d) good performance in tasks tapping verbal learning, verbal memory and orthographic processing, indicating no generalized learning impairment. CONCLUSION: Our results indicate good outcomes, but also that deficits are still present with current treatment policies. (PsycINFO Database Record

The impact of phenylalanine levels on cognitive outcomes in adults with phenylketonuria: Effects across tasks and developmental stages.

OBJECTIVE: Phenylketonuria (PKU) is due to an inability to metabolize the amino acid phenylalanine (Phe), leading to its accumulation in the brain. Phe levels can be controlled following a protein-free diet, but cognitive impairments are still present. A number of questions remain to be answered related to which type of metabolic control is important, the age when it is important, the cognitive functions which are most affected and, the best tests to use to monitor cognitive health. METHOD: We investigated the impact of metabolic control at different ages on cognitive performance in 37 early treated adults with PKU. RESULTS: (a) Phe variation was as associated to performance as average Phe showing that stable dietary control is as important as strict control; (b) For some tasks, current and adult Phe were stronger predictors of performance than childhood or adolescent Phe, showing the importance of a strict diet even in adulthood; and (c) The relationship between performance and Phe levels varied depending on time and cognitive domain. For some functions (sustained attention, visuomotor coordination), Phe at the time of testing was the best predictor. While for other functions (visual attention, executive functions) there was a diminishing or stable relationship across time. CONCLUSION: Results show the importance of selecting the right tasks to monitor outcomes across ages, but also that the impact of bio-chemical disruptions is different for different functions, at different ages. We show how inherited metabolic diseases offer us a unique vantage point to inform our understanding of brain development and functioning. (PsycINFO Database Record

The interrelation between cognitive and motor development in typically developing children aged 4-11 years is underpinned by visual processing and fine manual control.

We charted the interrelation between cognitive and motor skills in typically developing children aged 4-11 years across broad ability measures from standardized tests and investigated the nature of this relationship by examining effects of age and sex. Results indicated a significant, moderate correlation between gross cognitive and motor scores across all participants. Correlations between indices of the standardized measures and a principal component analysis revealed that visual processing (VP) and fine manual control (FMC) largely accounted for the interrelation between the overall domains. Age and sex affected the strength of gross correlation: 7-year-olds showed a weaker correlation than all other ages and females exhibited a significantly stronger correlation than males. However, the correlation between VP and FMC was constant across all age and sex groups, except 4-year-old males. These findings advance evidence that from an early age, cognitive and motor development is linked by elucidating the underlying nature of this relationship. These results have important implications for clinical, educational, and experimental practice.