Efficacy and Blood Plasmalogen Changes by Oral Administration of Plasmalogen in Patients with Mild Alzheimer's Disease and Mild Cognitive Impairment: A Multicenter, Randomized, Double-blind, Placebo-controlled Trial

Autor: Tatsuo Yamada, Yoshio Tsuboi, Chikako Wakana, Takehiko Fujino, Suminori Kono, Takashi Asada, Shiro Mawatari
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Zdroj: EBioMedicine
EBioMedicine, Vol 17, Iss C, Pp 199-205 (2017)
ISSN: 2352-3964
Popis: Background Plasmalogens (Pls) reportedly decreased in postmortem brain and in the blood of patients with Alzheimer's disease (AD). Recently we showed that intraperitoneal administration of Pls improved cognitive function in experimental animals. In the present trial, we tested the efficacy of oral administration of scallop-derived purified Pls with respect to cognitive function and blood Pls changes in patients with mild AD and mild cognitive impairment (MCI). Methods The study was a multicenter, randomized, double-blind, placebo-controlled trial of 24 weeks. Participants were 328 patients aged 60 to 85 years who had 20 to 27 points in Mini Mental State Examination-Japanese (MMSE-J) score and five or less points in Geriatric Depression Scale-Short Version-Japanese (GDS-S-J). They were randomized to receive either 1 mg/day of Pls purified from scallop or placebo. The patients and study physicians were masked to the assignment. The primary outcome was MMSE-J. The secondary outcomes included Wechsler Memory Scale-Revised (WMS-R), GDS-S-J and concentration of phosphatidyl ethanolamine plasmalogens (PlsPE) in erythrocyte membrane and plasma. This trial is registered with the University Hospital Medical Information Network, number UMIN000014945. Findings Of 328 patients enrolled, 276 patients completed the trial (140 in the treatment group and 136 in the placebo group). In an intention-to-treat analysis including both mild AD (20 ≤ MMSE-J ≤ 23) and MCI (24 ≤ MMSE-J ≤ 27), no significant difference was shown between the treatment and placebo groups in the primary and secondary outcomes, with no severe adverse events in either group. In mild AD patients, WMS-R improved significantly in the treatment group, and the between group difference was nearly significant (P = 0.067). In a subgroup analysis of mild AD patients, WMS-R significantly improved among females and those aged below 77 years in the treatment group, and the between-group differences were statistically significant in females (P = 0.017) and in those aged below 77 years (P = 0.029). Patients with mild AD showed a significantly greater decrease in plasma PlsPE in the placebo group than in the treatment group. Interpretation Oral administration of scallop-derived purified Pls may improve cognitive functions of mild AD. Funding The Japanese Plasmalogen Society.
Highlights • Plasmalogens (Pls), a kind of phospholipid, are reduced in the brain and blood of patients with Alzheimer’s disease (AD). • Scallop-derived purified Pls were orally administered to patients with mild AD and mild cognitive impairment by RCT. • Oral administration of scallop-derived purified Pls may improve cognitive functions of mild AD. It is well known that Plasmalogens (Pls), a special class of glycerophospholipid, are decreased in the brain and blood of patients with Alzheimer’s disease (AD), and inhibit γ-secretase activity. Our recent studies showed that intraperitoneal administration of purified Pls improved cognitive function in the animal model of AD. We tested the efficacy of Pls for Alzheimer’s disease by a multicenter, randomized, double-blind, placebo-controlled trial and showed that oral administration of scallop-derived purified Pls may improve cognitive functions of patients with mild AD.
Databáze: OpenAIRE
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