Total choline intake and working memory performance in adults with phenylketonuria

Meriah S Schoen; Kelly M Boland; Shawn E Christ; Xiangqin Cui; Usha Ramakrishnan; Thomas R Ziegler; Jessica A Alvarez; Rani H Singh

doi:10.1186/s13023-023-02842-y

Total choline intake and working memory performance in adults with phenylketonuria

Orphanet J Rare Dis. 2023 Jul 29;18(1):222. doi: 10.1186/s13023-023-02842-y.

Authors

Meriah S Schoen¹, Kelly M Boland², Shawn E Christ², Xiangqin Cui³, Usha Ramakrishnan⁴, Thomas R Ziegler⁵, Jessica A Alvarez⁵, Rani H Singh⁶

Affiliations

¹ Department of Human Genetics, Emory University School of Medicine, 101 Woodruff Circle, Suite 7130, Atlanta, GA, 30322, USA. msschoe@emory.edu.
² Department of Psychological Sciences, University of Missouri, Columbia, MO, USA.
³ Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
⁴ Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
⁵ Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
⁶ Department of Human Genetics, Emory University School of Medicine, 101 Woodruff Circle, Suite 7130, Atlanta, GA, 30322, USA.

Abstract

Background: Despite early diagnosis and compliance with phenylalanine (Phe)-restricted diets, many individuals with phenylketonuria (PKU) still exhibit neurological changes and experience deficits in working memory and other executive functions. Suboptimal choline intake may contribute to these impairments, but this relationship has not been previously investigated in PKU. The objective of this study was to determine if choline intake is correlated with working memory performance, and if this relationship is modified by diagnosis and metabolic control.

Methods: This was a cross-sectional study that included 40 adults with PKU and 40 demographically matched healthy adults. Web-based neurocognitive tests were used to assess working memory performance and 3-day dietary records were collected to evaluate nutrient intake. Recent and historical blood Phe concentrations were collected as measures of metabolic control.

Results: Working memory performance was 0.32 z-scores (95% CI 0.06, 0.58) lower, on average, in participants with PKU compared to participants without PKU, and this difference was not modified by total choline intake (F[1,75] = 0.85, p = 0.36). However, in a subgroup with complete historical blood Phe data, increased total choline intake was related to improved working memory outcomes among participants with well controlled PKU (Phe = 360 µmol/L) after adjusting for intellectual ability and mid-childhood Phe concentrations (average change in working memory per 100 mg change in choline = 0.11; 95% CI 0.02, 0.20; p = 0.02). There also was a trend, albeit nonsignificant (p = 0.10), for this association to be attenuated with increased Phe concentrations.

Conclusions: Clinical monitoring of choline intake is essential for all individuals with PKU but may have important implications for working memory functioning among patients with good metabolic control. Results from this study should be confirmed in a larger controlled trial in people living with PKU.

Keywords: Choline; Diet; Executive function; PKU; Phenylketonuria; Working memory.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Child
Choline
Cognition
Cross-Sectional Studies
Humans
Memory, Short-Term*
Phenylketonurias*

Substances

Choline