Gray Matter Thickness of Inferior Frontal Cortex Mediates the Relationship between Phosphatidylcholine and Executive Functions in Healthy, Older Adults
Authors: Zamroziewicz Marta Karolina , Das Tapas , Pereira Suzette L. , Barbey Aron K. 
Published: November 2023

Although diet has a substantial influence on the aging brain, the relationship between biomarkers of diet and aspects of brain health remains unclear. This study examines the neural mechanisms that mediate the relationship between phosphatidylcholine (PC) and executive functions (EF) in cognitively intact older adults. PC belongs to a class of phospholipids that are essential for cell membrane integrity, neurotransmitter synthesis, and cell signaling. These phospholipids are thought to be protective against age‐related declines in EF and prefrontal cortex (PFC) structure. EF, a range of cognitive abilities including set shifting, inhibition, and goal monitoring, are sensitive to subtle age‐related changes in the structural integrity of the PFC. Given that this class of phospholipids has been linked to EF and PFC structure, and that PFC structure impacts EF, we hypothesized that higher serum levels of PC are associated with better performance on EF tasks, and that this relationship is mediated by gray matter structure of regions within the PFC.We examined 70 cognitively intact adults between the ages of 65 and 75 to investigate the relationship between blood biomarkers of PC, tests of EF, and gray matter structure of regions within the PFC. EF were assessed in terms of cognitive flexibility using the Delis‐Kaplan Executive Function System Trail Making Test, which controlled for underlying letter and number sequencing processes. Gray matter thickness of regions within the PFC was measured using the Freesurfer imaging analysis suite. A three‐step mediation analysis was implemented using multivariate linear regressions to control for age, sex, education, income, depression status, and body mass index.The mediation analysis revealed that gray matter thickness of one region within the PFC, the left inferior frontal cortex (Brodmann's Area 45), mediates the relationship between PC blood biomarkers and cognitive flexibility. First, higher levels of PC were related to better cognitive flexibility (p=0.052). Second, higher levels of PC were linked to greater thickness of the left inferior frontal cortex when controlling for thickness of the left frontal cortex (p=0.023). Finally, greater thickness in the left inferior frontal cortex significantly mediated the relationship between PC levels and cognitive flexibility (p=0.0315).These results suggest that the inferior frontal cortex acts as a mediator of the relationship between PC and cognitive flexibility in cognitively intact older adults. The individual relationships reported within the mediation, including those between phospholipid levels and cognitive flexibility, between phospholipid levels and PFC structure, and between the inferior frontal cortex and cognitive flexibility, are substantiated by prior findings; however, this is the first report of a specific structural mediation between serum PC levels and cognitive flexibility. Future work should examine the potential mechanisms underlying this mediation, including PC‐dependent cell membrane integrity of the inferior frontal cortex and PC‐dependent acetylcholine projections to the inferior frontal cortex.Support or Funding InformationSupported by Abbott Nutrition.