Abstract

Objective: Plasmalogens (Pls) are a special class of glycerophospholipids containing a vinyl ether bond at the sn-1 position. Recently, it has become clear that Pls are closely related to Alzheimer’s disease (AD). Pls levels have been found to be decreased in the brain and blood of patients with AD. We previously reported that Pls could improve cognitive function in AD animal models and in a randomized controlled trial of patients with mild cognitive impairment and mild AD. This study aimed to investigate the effect of Pls on patients with moderate-to-severe AD in an open-label study.
Methods: Eligible patients were Japanese patients aged 60-85 years who had <20 points of the Mini-Mental State Examination (MMSE) score. They received 1.0 mg or 0.5 mg of scallop-derived Pls per day for 12 weeks. The primary outcome was the MMSE score, and the secondary one was blood concentration of phosphatidylethanolamine Pls (PlsPE).
Results: A total of 157 patients were enrolled, and 142 participants completed the study. The patients showed a statistically significant improvement in the MMSE score after the treatment, and the increase did not differ by treatment dose. Erythrocyte and plasma PlsPE, which were prominently lower than those of normal subjects at baseline, increased significantly after the treatment in the whole patients. While the increase in erythrocyte PlsPE did not significantly differ in the 1.0 mg and 0.5 mg groups, plasma PlsPE increased more markedly in the 0.5 mg group
than in the 1.0 mg group (P=0.001). The change in erythrocyte PlsPE, but not the change in plasma PlsPE, showed a modest degree of correlation with the change in MMSE score (Pearson’s r=0.20, P=0.01).
Conclusion: These findings suggest that orally administered scallop-derived Pls improve cognitive function and that the measurement of blood Pls is valuable to assess the severity and treatment progress in patients with moderate-to-severe AD.

Keywords: Plasmalogen; Scallop; Alzheimer’s disease; Moderate-tosevere AD; Cognitive function; Biomarker of severity; Mini-mental state examination