The impact of docosahexaenoic acid status and phenylalanine control on cognitive performance in females of reproductive age with phenylketonuria Öffentlichkeit
Yi, Sarah (2010)
Published
Abstract
Subtle cognitive deficits are reported in people treated early for phenylketonuria (PKU). This dissertation examines the impact of phenylalanine (Phe) and docosahexaenoic acid (DHA), one known factor and one hypothesized factor, on cognitive status in females of reproductive age with PKU.
First, we assessed the impact of a 1-week camp intervention on cognitive processing speed in females with PKU. Second, we examined the association between biomarkers of DHA status and performance on tasks of verbal ability, processing speed, and executive function in a cross-sectional study. Third, we tested the effect of supplemental DHA on processing speed and executive function in a 4.5-month parallel, randomized, placebo-controlled, double-blinded study.
In the first study, a positive effect of the camp intervention was seen on measures of cognitive processing speed and plasma Phe control at the end of the camp. Improved performance exceeded a practice effect in both measures when compared with the test-retest sample; however, a larger sample size is needed to reach statistical significance. Changes in the processing speed task requiring sustained attention corresponded with changes in plasma Phe after controlling for verbal ability. In the second study, we confirmed low levels of DHA in plasma and red blood cell (RBC) total lipid percent DHA and in the diet of participants. We found a significant relationship between RBC total lipid percent DHA and verbal ability before and after controlling for concurrent plasma Phe. Associations between DHA and measures of processing speed and executive function were not seen. In the third study, supplementation with DHA appeared to be safe and effective in increasing biomarkers of DHA; however, we failed to find an effect of DHA on measures of processing speed and executive function.
Improved DHA status in addition to adequate Phe control may benefit aspects of cognitive performance in this population. Further research is needed to clarify which domains are affected by changes in DHA status, and the length and amount of DHA that is required to see these changes. Future investigations assessing the cognitive effect of DHA should measure domains more likely to be affected including verbal ability, memory, and learning.
Table of Contents
Chapter 1. Introduction
Theoretical Underpinnings
Specific Aims & Hypotheses
Main outcome measures
Chapter 2. Background
Chapter 3. Preliminary Studies
Plasma Phe control consistently improves at the end of Metabolic Camp
Consumers of medical foods without fat do not compensate for the missing fat
Biomarkers of DHA status may not differ by type of medical food used
Biomarkers of EPA and DHA status are reduced in females with PKU
Chapter 4. Methods
Cognitive Testing
Blood collection and analysis
Diet assessment
Neurological status
Questionnaires
Study 3 Methods
Participant assessment
Monthly data collection
Study log books
Unused supplement
Protection of Human Subjects
Inclusion of Women and Minorities
Participation of persons under the age of 21
Biostatistical Design and Analysis
Sample size calculations for Study 3
Chapter 5. Short term changes in plasma phenylalanine and cognitive processing speed in females of reproductive age with phenylketonuria attending a metabolic camp
Abstract
Introduction
Methods
Results
Discussion
Conclusion
Chapter 6. Verbal performance is associated with red blood cell docosahexaenoic acid accounting for plasma phenylalanine in females of reproductive age with phenylketonuria
Summary
Introduction
Participants and Methods
Results
Discussion and Conclusions
Chapter 7. A randomized, placebo-controlled, double-blind trial of supplemental docosahexaenoic acid on cognitive processing speed and executive function in females of reproductive age with phenylketonuria: a pilot study
Abstract
1. Introduction
2. Materials and Methods
3. Results
4. Discussion
5. Conclusions
Chapter 8. Conclusions
Clinical implications
Suggestions for future research
Chapter 9. Appendix: Background
Chapter 10. Appendix: Methods
Outpatient Procedure
Inpatient Procedure
Blood processing instructions
Off Site Procedure
Group Testing (W-J III): Room Map
Group Testing (W-J III): Research Assistant Data Collection Sheet
Scoring Datasheet for W-J III Tests
Website for Study 3
Logbook for Study 3
Questionnaires
Randomization plan
Chapter 11. Appendix: Results
Study 1
Study 2
Study 3
Chapter 12. Literature Cited
About this Dissertation
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