Oral Choline Reduced Working Memory-Related Brain Activation in Postmenopausal Women: A Pilot Study

<b>Background/Objectives</b>: Choline plays an important role in maintaining normal cellular function and overall physiology. Endogenous choline availability depends on the synthesis of phosphatidylcholine via the phosphatidylethanolamine <i>N</i>-methyltransferase (PEMT) pathway. Expression of PEMT is influenced by estrogen, as its promoter contains multiple estrogen-responsive elements that enhance enzyme activity. How a low estrogenic condition like menopause influences choline's effect on the brain is not yet fully understood. <b>Methods</b>: In this pilot study, 20 women participated in two study days, with 1650 mg of oral choline bitartrate or a matching placebo administered three hours before a functional and structural magnetic resonance imaging (MRI) scan. Blood oxygen level dependent (BOLD) functional MRI scans were collected on each study day while subjects performed an <i>N</i>-back working memory task. <b>Results</b>: In this pilot study, no differences in working memory performance were observed, but decreased activation was found for the choline compared to the placebo during the 2-back compared to 0-back conditions in regions of the right temporal lobe (<i>p</i> < 0.001 voxel-level threshold, and <i>p</i>-FDR < 0.05 cluster-size threshold). When we seeded the right planum temporale to examine its functional connectivity with the rest of the brain, we found that choline modulated a large portion of the working memory network during the difficult memory load condition. <b>Conclusions</b>: These results in this pilot study illustrate the effect of choline on working memory-related brain activation and functional connectivity in postmenopausal women. We propose that choline may increase brain functional efficiency in low estrogenic conditions like menopause, but further studies are needed.