Thomas Lucie, Aitkenhead Lynne, Stepien Karolina M, Woodall Alison, Macdonald Anita, Romani Cristina
Aston University, UK.
University College London Hospitals, UK.
Mol Genet Metab Rep. 2024 Nov 21;41:101160. doi: 10.1016/j.ymgmr.2024.101160. eCollection 2024 Dec.
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.
首批接受早期治疗的成年苯丙酮尿症（PKU）患者已步入中年并逐渐走向老年。我们尚不清楚衰老大脑的影响是否以及如何与PKU的影响相互作用。本研究比较了19名中年PKU成人（年龄40岁及以上，平均年龄 = 45.8岁）和年轻PKU成人组（年龄18 - 36岁，平均年龄 = 26.7岁）的幸福感和认知能力。与年龄匹配的对照组相比，中年PKU组表现出更多的焦虑和抑郁，以及更多COVID - 19大流行带来的负面影响。与年轻的PKU患者相比，他们的生活质量也出现了急剧下降。由于只有年龄较大的参与者在COVID - 19大流行期间接受了测试，所以最后的这些结果将年龄与大流行的影响混淆了，但综合来看，结果一致表明成年期苯丙酮尿症（AwPKU）对年龄和其他影响幸福感的生活压力源的恢复力较低。在认知方面，年龄较大的PKU组表现明显比年轻组差，并且在中年组中，PKU组的年龄影响比对照组更强，尽管这在统计学上并不显著。相比之下，年龄较大的中年PKU组相对于年龄匹配对照组的损伤程度在数值上较小。我们讨论了与这最后一个结果相关的可能的方法学混杂因素。我们的研究指出了使用横断面结果来追踪整个生命周期表现的挑战，以及在得出PKU不存在加速脑衰老的结论之前需要获得更多确证证据的必要性。
