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

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+ m...

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Main Authors: Lucie Thomas, Lynne Aitkenhead, Karolina M. Stepien, Alison Woodall, Anita Macdonald, Cristina Romani
Format: Article
Language:English
Published: Elsevier 2024-12-01
Series:Molecular Genetics and Metabolism Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2214426924001137
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author Lucie Thomas
Lynne Aitkenhead
Karolina M. Stepien
Alison Woodall
Anita Macdonald
Cristina Romani
author_facet Lucie Thomas
Lynne Aitkenhead
Karolina M. Stepien
Alison Woodall
Anita Macdonald
Cristina Romani
author_sort Lucie Thomas
collection DOAJ
description 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.
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spelling doaj-art-bc96889e66eb45c29db255dd92a756ca2024-12-17T04:59:48ZengElsevierMolecular Genetics and Metabolism Reports2214-42692024-12-0141101160Cognition and wellbeing in middle-aged early treated people with phenylketonuria: Preliminary results and methodological lessonsLucie Thomas0Lynne Aitkenhead1Karolina M. Stepien2Alison Woodall3Anita Macdonald4Cristina Romani5Aston University, UKUniversity College London Hospitals, UKSalford Royal Organization, Northern Care Alliance NHS Foundation Trust, UKSalford Royal Organization, Northern Care Alliance NHS Foundation Trust, UKBirmingham Women's and Children's NHS Foundation Trust, UKAston University, UK; Corresponding author at: School of Life and Health Sciences, Aston University, Aston Triangle, Birmingham B4 7ET, UK.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.http://www.sciencedirect.com/science/article/pii/S2214426924001137PKUAgingCognitionWellbeingQuality of life
spellingShingle Lucie Thomas
Lynne Aitkenhead
Karolina M. Stepien
Alison Woodall
Anita Macdonald
Cristina Romani
Cognition and wellbeing in middle-aged early treated people with phenylketonuria: Preliminary results and methodological lessons
Molecular Genetics and Metabolism Reports
PKU
Aging
Cognition
Wellbeing
Quality of life
title Cognition and wellbeing in middle-aged early treated people with phenylketonuria: Preliminary results and methodological lessons
title_full Cognition and wellbeing in middle-aged early treated people with phenylketonuria: Preliminary results and methodological lessons
title_fullStr Cognition and wellbeing in middle-aged early treated people with phenylketonuria: Preliminary results and methodological lessons
title_full_unstemmed Cognition and wellbeing in middle-aged early treated people with phenylketonuria: Preliminary results and methodological lessons
title_short Cognition and wellbeing in middle-aged early treated people with phenylketonuria: Preliminary results and methodological lessons
title_sort cognition and wellbeing in middle aged early treated people with phenylketonuria preliminary results and methodological lessons
topic PKU
Aging
Cognition
Wellbeing
Quality of life
url http://www.sciencedirect.com/science/article/pii/S2214426924001137
work_keys_str_mv AT luciethomas cognitionandwellbeinginmiddleagedearlytreatedpeoplewithphenylketonuriapreliminaryresultsandmethodologicallessons
AT lynneaitkenhead cognitionandwellbeinginmiddleagedearlytreatedpeoplewithphenylketonuriapreliminaryresultsandmethodologicallessons
AT karolinamstepien cognitionandwellbeinginmiddleagedearlytreatedpeoplewithphenylketonuriapreliminaryresultsandmethodologicallessons
AT alisonwoodall cognitionandwellbeinginmiddleagedearlytreatedpeoplewithphenylketonuriapreliminaryresultsandmethodologicallessons
AT anitamacdonald cognitionandwellbeinginmiddleagedearlytreatedpeoplewithphenylketonuriapreliminaryresultsandmethodologicallessons
AT cristinaromani cognitionandwellbeinginmiddleagedearlytreatedpeoplewithphenylketonuriapreliminaryresultsandmethodologicallessons