Work

Cognition and wellbeing in middle-aged early treated people with phenylketonuria: Preliminary results and methodological lessons

Year: 2024

Type: article

Abstract: The first cohort of early-treated adults with phenylketonuria (PKU) is reaching middle-age and moving towards old age. We do not know if and how the effects of an aging brain may interact with the effect of PKU. This study compared wellbeing and cognition in 19 middle-aged adults with PKU (age 40+ mean = 45.8) and in a younger adult PKU group (age 18–36 mean = 26.7). The middle-aged PKU group demonstrated more anxiety and depression, and more negative effects of the COVID-19 pandemic, compared to age-matched controls. They also demonstrated a steep deterioration of quality of life compared to younger adults with PKU. These last results confounded age with the effects of the pandemic, since only the older participants were tested during the COVID-19 pandemic, but taken together, results consistently point to AwPKU being less resilient to age and other life stressors affecting wellbeing. Regarding cognition, the older PKU group demonstrated significantly worse performance than the younger group, and within the middle-age groups, the effect of age was stronger in the PKU group than in the control, even though this was not statistically significant. In contrast, size of impairment relative to an age-matched control group was numerically smaller in older, middle-age PKU group. We discuss possible methodological confounders related to this last result. Our study points to the challenges of using cross-sectional results to track performance across the lifespan and to the need to acquire more corroborating evidence before concluding there is no accelerating brain aging in PKU. • In early treated middle-aged adults with PKU, wellbeing was worse than in age-matched controls; • Cognitive performance was worse than in younger adults with PKU; • The pattern of cognitive deterioration was similar to healthy controls; • The effect of age was numerically stronger in the middle-aged PKU group than in controls; • Performance relative to controls did not worsen with age, but this may be due younger and older controls not being well matched; • Studies with better matching of clinical and control groups, with more representative PKU groups and with older cohorts are needed.

Source: Molecular Genetics and Metabolism Reports

DOI: 10.1016/j.ymgmr.2024.101160

Authors: Lucie Thomas, Lynne Aitkenhead, Karolina M. Stepien, Alison Woodall, Anita Macdonald, Cristina Romani

Institutions: Aston University, University College London, Northern Care Alliance NHS Foundation Trust, Birmingham Women’s and Children’s NHS Foundation Trust

Language: English

Topic: Metabolism and Genetic Disorders

Subfield: Clinical Biochemistry

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,410