JMIR Publications

ABSTRACT

Background:

Phenylketonuria (PKU) is a rare, hereditary disease that causes disruption in phenylalanine (Phe) metabolism. Despite early intervention, individuals with PKU may have difficulty in several different cognitive domains, including verbal fluency, processing speed, and executive functioning.

Objective:

The overarching goal of the Evaluating Fluctuations in Cognitive and Speech Characteristics in Phenylketonuria study (CSP Study) is to characterize the relationships among cognition, speech, mood, and blood-based biomarkers (Phe, Tyr) in individuals with early treated PKU. We describe our initial optimization pilot results that are guiding the ongoing CSP Study, while establishing feasibility and reliability of using ecological momentary assessment (EMA) in this clinical population.

Methods:

Twenty adults with PKU were enrolled in this study between December 2022 and March 2023 through the National PKU Alliance. All participants completed an extended baseline assessment followed by six ecological momentary assessments (EMAs) over the span of one month. The EMAs included digital cognitive tests measuring processing speed, sustained attention, executive functioning, and semantic fluency, as well as speech and mood measures. Participants had 60 minutes to complete the assessment; completion rates were around 70% (on average 4.78 measurements out of six).

Results:

Based on scores recorded and completion rates above 70%, results suggest stable performance across EMAs, as well as baseline measures, and reflect the ability of participants to complete this type of repeated assessment. Between person reliability (BP reliability) of the EMA measures, representing the variance that is due to differences between individuals versus within individuals, is satisfactory with values close to (semantic fluency BP reliability: 0.7, sustained attention BP reliability: 0.72) or exceeding (processing speed: 0.93, executive functioning: 0.88) those data collected from a large normative database (N= 5039-10703), as well as slightly below or matching a prior study using a clinical group (N=18).

Conclusions:

: Individuals with PKU face a substantial healthcare burden, often enduring numerous hospital visits and requiring continuous self-monitoring. Preliminary results of this study have demonstrated strong reliability of cognitive EMA, indicating that EMA is a promising tool for evaluating fluctuations in cognitive status this population. Future work should refine and expand the utility of these digital tools, determine how variable EMA frequencies might better characterize changes in functioning as they relate to blood-based biomarkers, and validate a singular battery that could be rapidly administered at scale and in clinical trials to determine progression of disease.