Speed of processing and executive functions in adults with phenylketonuria: Quick in finding the word, but not the ladybird

Abstract

A reduction in processing speed is widely reported in phenylketonuria (PKU), possibly due to white matter pathology. We investigated possible deficits and their relationships with executive functions in a sample of 37 early-treated adults with PKU (AwPKUs). AwPKUs were not characterized by a generalized speed deficit, but instead their performance could be explained by two more specific impairments: (a) a deficit in the allocation of visuo-spatial attention that reduced speed in visual search tasks, in some reading conditions and visuo-motor coordination tasks; and (b) a more conservative decision mechanism that slowed down returning an answer across domains. These results suggest that the impairments in executive functions seen in AwPKUs are not the consequence of a generalized speed deficit. They also suggest that processing speed is linked to the efficiency of a particular cognitive component and cannot be considered a general function spanning domains. Similarities with patterns in ageing are discussed.

A systematic review of cognitive functioning in early treated adults with phenylketonuria

“…simple reaction time), apart from in off-diet ET AwPKU [35, 38]. As suggested by Romani et al [17], these findings could indicate that ET AwPKU may not suffer from a processing speed deficit per se. Reductions in speed of performance across multiple cognitive domains are more likely to be the result of speed-accuracy trade-offs due to slower or more cautious executive decision-making processes.…”

“…However, the observed correlations were not in the expected direction, suggesting that attentional capacity was better with higher concurrent levels of Phe. Several papers reported significant correlations with metabolic control during childhood [33, 36, 46], adulthood [17, 45] as well as throughout life [46], with the majority ( n  = 10/11, see Additional file 2: Table S2) suggesting lower Phe levels were associated with better task performance. However, no correlations between adolescent Phe levels and attentional capacity were reported.…”

“…It is not uncommon for ET AwPKU to be slower, but not less accurate on various measures spanning different cognitive domains. Romani et al [17] investigated processing speed in ET AwPKU. Their results suggest that ET AwPKU do not suffer from an overarching deficit in speed of processing, but rather that reduced speed of performance on tasks across multiple cognitive domains could be the result of slower or more cautious executive decision-making processes [17].…”

“…Again, these discrepancies in reporting make it difficult to compare study outcomes and obtain a clear picture of how metabolic control throughout life influences cognition in ET AwPKU. Only a few of the studies included in this review explored the relationship between cognitive performance and Phe variation throughout life [17, 46, 47] and these found correlations across cognitive domains. Moreover, only one of the studies included measures of Phe:Tyr ratio but did not explore the relationship between this outcome and cognitive performance [48].…”

“…Furthermore, it has been suggested that high brain Phe concentrations cause neurotoxicity, which is thought to interfere with cerebral protein synthesis, increase myelin turnover, and inhibit neurotransmitter synthesis [16]. In addition to uncertainties about the exact mechanism underlying suboptimal cognitive functioning, it is unclear whether observed deficits in EFs are the consequence of reduced speed of processing or whether impairments in speed of processing are the consequence of deficits of EF [17]. …”