Neuropsychological Assessment in Inherited Metabolic Diseases: Tracking Outcomes in Phenyketonuria (PKU)

Abstract

Whilst treating PKU early dramatically reduces impairments caused by excess Phe, individuals with early-treated PKU demonstrate mild impairments in cognition, well-being, neuropathology, and neurophysiology. Information in the current literature about how metabolic control can impact these impairments in adulthood, however, remains limited. Furthermore, there remains a lack of understanding about how these impairments may interact with age-related neuropathological and neurophysiological alterations as early-treated adults with PKU begin to reach older age. This thesis includes two empirical investigations and one systematic review. The first empirical investigation compared impairments exhibited by young adults with PKU and healthy older adults to extrapolate how impairments may interact as adults with PKU reach older age. This investigation identified key overlaps in the profiles of cognitive impairment demonstrated by each population, in particular in the domains of speed of processing and executive function. The second empirical investigation explored whether middle-aged adults with PKU demonstrate accelerated effects of ageing on neuropsychological function by comparing outcomes in this population with both age-matched controls and younger adults with PKU. Overlaps in impaired cognitive domains between young and middle-aged AwPKU were identified, as well as poorer well-being in the middle-aged cohort compared to age-matched controls. The severity of impairments compared to healthy controls of the same age, however, was less significant in middle-aged cohorts. In addition, no significant impact of adult metabolic control on outcomes was identified in the middle-aged AwPKU included in this study. Finally, a systematic review considered within-participant studies investigating the effects of manipulating metabolic control on cognitive, well-being, and neurological outcomes in children and adults with PKU. The review indicated that metabolic control has a significant impact on all outcomes in both children and adults with PKU, as well as demonstrating that impairments in these domains may be reversible through decreasing current Phe levels at any age.