Institute of Rheological Functions of Food, 2241-1 Kubara, Hisayama-machi, Kasuya-gun, Fukuoka 811-2501, Japan.
Gotanda Rehabilitation Hospital, 8-8-20 Nishigotanda, Shinagawa-ku, Tokyo 141-0031, Japan.
EBioMedicine. 2017 Mar;17:199-205. doi: 10.1016/j.ebiom.2017.02.012. Epub 2017 Feb 24.
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).
The study was a multicenter, randomized, double-blind, placebo-controlled trial of 24weeks. Participants were 328 patients aged 60 to 85years 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 1mg/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.
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 77years in the treatment group, and the between-group differences were statistically significant in females (P=0.017) and in those aged below 77years (P=0.029). Patients with mild AD showed a significantly greater decrease in plasma PlsPE in the placebo group than in the treatment group.
Oral administration of scallop-derived purified Pls may improve cognitive functions of mild AD.
The Japanese Plasmalogen Society.
据报道，血浆髓鞘磷脂（Pls）在死后大脑和阿尔茨海默病（AD）患者的血液中减少。最近我们发现，腹腔内给予 Pls 可改善实验动物的认知功能。在本试验中，我们测试了口服扇贝来源的纯化 Pls 对轻度 AD 和轻度认知障碍（MCI）患者认知功能和血液 Pls 变化的疗效。
这是一项多中心、随机、双盲、安慰剂对照的 24 周试验。参与者为 328 名年龄在 60 至 85 岁之间的患者，其 Mini Mental State Examination-Japanese（MMSE-J）评分在 20 至 27 分之间，老年抑郁量表-简短版-Japanese（GDS-S-J）评分在 5 分以下。他们被随机分为每天服用 1 毫克来自扇贝的 Pls 或安慰剂。患者和研究医生对分配情况不知情。主要结局是 MMSE-J。次要结局包括韦氏记忆量表修订版（WMS-R）、GDS-S-J 和红细胞膜及血浆中磷脂乙醇胺髓鞘磷脂（PlsPE）的浓度。这项试验已在大学医院医学信息网络注册，编号为 UMIN000014945。
在纳入的 328 名患者中，有 276 名患者完成了试验（治疗组 140 名，安慰剂组 136 名）。在包括轻度 AD（20≤MMSE-J≤23）和 MCI（24≤MMSE-J≤27）在内的意向治疗分析中，治疗组和安慰剂组在主要和次要结局上均无显著差异，两组均无严重不良事件。在轻度 AD 患者中，治疗组的 WMS-R 显著改善，组间差异接近显著（P=0.067）。在轻度 AD 患者的亚组分析中，治疗组女性和年龄在 77 岁以下的患者 WMS-R 显著改善，女性（P=0.017）和年龄在 77 岁以下的患者（P=0.029）的组间差异有统计学意义。轻度 AD 患者的血浆 PlsPE 在安慰剂组的下降幅度明显大于治疗组。
口服扇贝来源的纯化 Pls 可能改善轻度 AD 的认知功能。
日本髓鞘磷脂协会。
