Leveraging Cognitive and Speech Ecological Momentary Assessment in Individuals With Phenylketonuria: Development and Usability Study of Cognitive Fluctuations in a Rare Disease Population
BackgroundPhenylketonuria (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...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
JMIR Publications
2025-06-01
|
| Series: | JMIR Formative Research |
| Online Access: | https://formative.jmir.org/2025/1/e63644 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849697042407882752 |
|---|---|
| author | Shifali Singh Lisa Kluen Katelin Curtis Raquel Norel Carla Agurto Elizabeth Grinspoon Zoe Hawks Shawn Christ Susan Waisbren Guillermo Cecchi Laura Germine |
| author_facet | Shifali Singh Lisa Kluen Katelin Curtis Raquel Norel Carla Agurto Elizabeth Grinspoon Zoe Hawks Shawn Christ Susan Waisbren Guillermo Cecchi Laura Germine |
| author_sort | Shifali Singh |
| collection | DOAJ |
| description |
BackgroundPhenylketonuria (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.
ObjectiveThe overarching goal of this study is to characterize the relationships among cognition, speech, mood, and blood-based biomarkers (Phe, tyrosine) in individuals with early treated PKU. We describe our initial optimization pilot results that are guiding this study while establishing the feasibility and reliability of using ecological momentary assessment (EMA) in this clinical population.
MethodsIn total, 20 adults with PKU were enrolled in this study between December 2022 and March 2023 through the National PKU Alliance. Of the total, 18 participants completed an extended baseline assessment followed by 6 EMAs over 1 month. The EMAs included digital cognitive tests measuring processing speed, sustained attention, and executive functioning, as well as speech (semantic fluency) and mood measures. Participants had 60 minutes to complete the assessment.
ResultsCompletion rates of EMAs were above 70% (on average 4.78 out of 6 EMAs), with stable performances across baseline measures and EMAs. Between-person reliability (BPR) of the EMAs, representing the variance due to differences between individuals versus within individuals, is satisfactory with values close to (semantic fluency BPR: 0.7, sustained attention BPR: 0.72) or exceeding (processing speed: 0.93, executive functioning: 0.88) data collected from a large normative database (n=5039-10,703), as well as slightly below or matching a previous study using a clinical group (n=18). As applicable, within-person reliability was also computed; we demonstrated strong reliability for processing speed (0.87). A control analysis ensured that time of day (ie, morning, afternoon, and evening) did not impact performance; performance on tasks did not decrease if tested earlier versus later in the day (all P values >.09). Similarly, to assess variability in task performance over the course of all EMAs, the coefficient of variability was computed; 28% for the task measuring sustained attention, 37% for semantic fluency, 15.8% for the task measuring executive functioning, and 17.6% for processing speed. Performance appears more stable in tasks measuring processing speed and executive functioning than on tasks of sustained attention and semantic fluency.
ConclusionsPreliminary results of this study demonstrate strong reliability of cognitive EMA, indicating that EMA is a promising tool for evaluating fluctuations in cognitive status in 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 the progression of disease. |
| format | Article |
| id | doaj-art-edbc7ca4b93c4847b928c35d9e616c38 |
| institution | DOAJ |
| issn | 2561-326X |
| language | English |
| publishDate | 2025-06-01 |
| publisher | JMIR Publications |
| record_format | Article |
| series | JMIR Formative Research |
| spelling | doaj-art-edbc7ca4b93c4847b928c35d9e616c382025-08-20T03:19:17ZengJMIR PublicationsJMIR Formative Research2561-326X2025-06-019e6364410.2196/63644Leveraging Cognitive and Speech Ecological Momentary Assessment in Individuals With Phenylketonuria: Development and Usability Study of Cognitive Fluctuations in a Rare Disease PopulationShifali Singhhttps://orcid.org/0000-0003-1312-665XLisa Kluenhttps://orcid.org/0009-0007-3370-7060Katelin Curtishttps://orcid.org/0009-0002-6872-8738Raquel Norelhttps://orcid.org/0000-0001-7737-4172Carla Agurtohttps://orcid.org/0000-0002-0617-4488Elizabeth Grinspoonhttps://orcid.org/0000-0002-5608-8254Zoe Hawkshttps://orcid.org/0000-0002-3796-0289Shawn Christhttps://orcid.org/0000-0002-7206-528XSusan Waisbrenhttps://orcid.org/0000-0003-0013-700XGuillermo Cecchihttps://orcid.org/0000-0003-1013-8348Laura Germinehttps://orcid.org/0000-0001-8690-8412 BackgroundPhenylketonuria (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. ObjectiveThe overarching goal of this study is to characterize the relationships among cognition, speech, mood, and blood-based biomarkers (Phe, tyrosine) in individuals with early treated PKU. We describe our initial optimization pilot results that are guiding this study while establishing the feasibility and reliability of using ecological momentary assessment (EMA) in this clinical population. MethodsIn total, 20 adults with PKU were enrolled in this study between December 2022 and March 2023 through the National PKU Alliance. Of the total, 18 participants completed an extended baseline assessment followed by 6 EMAs over 1 month. The EMAs included digital cognitive tests measuring processing speed, sustained attention, and executive functioning, as well as speech (semantic fluency) and mood measures. Participants had 60 minutes to complete the assessment. ResultsCompletion rates of EMAs were above 70% (on average 4.78 out of 6 EMAs), with stable performances across baseline measures and EMAs. Between-person reliability (BPR) of the EMAs, representing the variance due to differences between individuals versus within individuals, is satisfactory with values close to (semantic fluency BPR: 0.7, sustained attention BPR: 0.72) or exceeding (processing speed: 0.93, executive functioning: 0.88) data collected from a large normative database (n=5039-10,703), as well as slightly below or matching a previous study using a clinical group (n=18). As applicable, within-person reliability was also computed; we demonstrated strong reliability for processing speed (0.87). A control analysis ensured that time of day (ie, morning, afternoon, and evening) did not impact performance; performance on tasks did not decrease if tested earlier versus later in the day (all P values >.09). Similarly, to assess variability in task performance over the course of all EMAs, the coefficient of variability was computed; 28% for the task measuring sustained attention, 37% for semantic fluency, 15.8% for the task measuring executive functioning, and 17.6% for processing speed. Performance appears more stable in tasks measuring processing speed and executive functioning than on tasks of sustained attention and semantic fluency. ConclusionsPreliminary results of this study demonstrate strong reliability of cognitive EMA, indicating that EMA is a promising tool for evaluating fluctuations in cognitive status in 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 the progression of disease.https://formative.jmir.org/2025/1/e63644 |
| spellingShingle | Shifali Singh Lisa Kluen Katelin Curtis Raquel Norel Carla Agurto Elizabeth Grinspoon Zoe Hawks Shawn Christ Susan Waisbren Guillermo Cecchi Laura Germine Leveraging Cognitive and Speech Ecological Momentary Assessment in Individuals With Phenylketonuria: Development and Usability Study of Cognitive Fluctuations in a Rare Disease Population JMIR Formative Research |
| title | Leveraging Cognitive and Speech Ecological Momentary Assessment in Individuals With Phenylketonuria: Development and Usability Study of Cognitive Fluctuations in a Rare Disease Population |
| title_full | Leveraging Cognitive and Speech Ecological Momentary Assessment in Individuals With Phenylketonuria: Development and Usability Study of Cognitive Fluctuations in a Rare Disease Population |
| title_fullStr | Leveraging Cognitive and Speech Ecological Momentary Assessment in Individuals With Phenylketonuria: Development and Usability Study of Cognitive Fluctuations in a Rare Disease Population |
| title_full_unstemmed | Leveraging Cognitive and Speech Ecological Momentary Assessment in Individuals With Phenylketonuria: Development and Usability Study of Cognitive Fluctuations in a Rare Disease Population |
| title_short | Leveraging Cognitive and Speech Ecological Momentary Assessment in Individuals With Phenylketonuria: Development and Usability Study of Cognitive Fluctuations in a Rare Disease Population |
| title_sort | leveraging cognitive and speech ecological momentary assessment in individuals with phenylketonuria development and usability study of cognitive fluctuations in a rare disease population |
| url | https://formative.jmir.org/2025/1/e63644 |
| work_keys_str_mv | AT shifalisingh leveragingcognitiveandspeechecologicalmomentaryassessmentinindividualswithphenylketonuriadevelopmentandusabilitystudyofcognitivefluctuationsinararediseasepopulation AT lisakluen leveragingcognitiveandspeechecologicalmomentaryassessmentinindividualswithphenylketonuriadevelopmentandusabilitystudyofcognitivefluctuationsinararediseasepopulation AT katelincurtis leveragingcognitiveandspeechecologicalmomentaryassessmentinindividualswithphenylketonuriadevelopmentandusabilitystudyofcognitivefluctuationsinararediseasepopulation AT raquelnorel leveragingcognitiveandspeechecologicalmomentaryassessmentinindividualswithphenylketonuriadevelopmentandusabilitystudyofcognitivefluctuationsinararediseasepopulation AT carlaagurto leveragingcognitiveandspeechecologicalmomentaryassessmentinindividualswithphenylketonuriadevelopmentandusabilitystudyofcognitivefluctuationsinararediseasepopulation AT elizabethgrinspoon leveragingcognitiveandspeechecologicalmomentaryassessmentinindividualswithphenylketonuriadevelopmentandusabilitystudyofcognitivefluctuationsinararediseasepopulation AT zoehawks leveragingcognitiveandspeechecologicalmomentaryassessmentinindividualswithphenylketonuriadevelopmentandusabilitystudyofcognitivefluctuationsinararediseasepopulation AT shawnchrist leveragingcognitiveandspeechecologicalmomentaryassessmentinindividualswithphenylketonuriadevelopmentandusabilitystudyofcognitivefluctuationsinararediseasepopulation AT susanwaisbren leveragingcognitiveandspeechecologicalmomentaryassessmentinindividualswithphenylketonuriadevelopmentandusabilitystudyofcognitivefluctuationsinararediseasepopulation AT guillermocecchi leveragingcognitiveandspeechecologicalmomentaryassessmentinindividualswithphenylketonuriadevelopmentandusabilitystudyofcognitivefluctuationsinararediseasepopulation AT lauragermine leveragingcognitiveandspeechecologicalmomentaryassessmentinindividualswithphenylketonuriadevelopmentandusabilitystudyofcognitivefluctuationsinararediseasepopulation |