Ding Qiong, Tanigawa Kitora, Kaneko Jun, Totsuka Mamoru, Katakura Yoshinori, Imabayashi Etsuko, Matsuda Hiroshi, Hisatsune Tatsuhiro
1Department of Integrated Biosciences, Graduate School of Frontier Sciences, and.
2Department of Applied Biochemistry, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Tokyo, Japan.
Aging Dis. 2018 Jun 1;9(3):334-345. doi: 10.14336/AD.2017.0809. eCollection 2018 Jun.
In a previously reported double-blind, randomized controlled trial (RCT), we demonstrated that daily supplementation with anserine (750 mg) and carnosine (250 mg) improves brain blood flow and memory function in elderly people. Here, we conducted a sub-analysis of MRI data and test scores from the same RCT to determine whether anserine/carnosine supplementation specifically benefits elderly people carrying the APOE e4 allele, which is a risk gene for accelerated brain aging and for the onset of Alzheimer's Disease. We collected data from 68 participants aged 65 years or older who received anserine/carnosine supplementation (ACS) or placebo for 12 months. Subjects were assessed at the start and end of the trial using several neuropsychological tests, including the Wechsler Memory Scale-Logical Memory (WMS-LM). We also collected two types of MRI data, arterial spin labeling (ASL) and diffusion tensor imaging (DTI) at the start and end of the trial. We found that ACS significantly preserved verbal memory (WMS-LM, F[1,65] = 4.2003, = 0.0445) and blood flow at frontal areas of the brain (FWE, < 0.001). Sub-analysis based on the APOE4 genotype showed a significant preservation of blood flow ( = 0.002, by ASL analysis) and white-matter microstructure ( = 0.003, by DTI analysis) at prefrontal areas in APOE4 subjects in the active group, while there was no significant difference between APOE4 subjects in the active and placebo groups. The effect of ACS in preserving brain structure and function in elderly people carrying APOE4 should be verified by further studies.
在之前报道的一项双盲随机对照试验（RCT）中，我们证明，每日补充鹅肌肽（750毫克）和肌肽（250毫克）可改善老年人的脑血流量和记忆功能。在此，我们对同一RCT的MRI数据和测试分数进行了亚分析，以确定补充鹅肌肽/肌肽是否对携带APOE e4等位基因的老年人有特别益处，该等位基因是脑加速老化和阿尔茨海默病发病的风险基因。我们收集了68名65岁及以上参与者的数据，这些参与者接受了12个月的鹅肌肽/肌肽补充剂（ACS）或安慰剂治疗。在试验开始和结束时，使用包括韦氏记忆量表 - 逻辑记忆（WMS - LM）在内的多种神经心理学测试对受试者进行评估。我们还在试验开始和结束时收集了两种MRI数据，即动脉自旋标记（ASL）和扩散张量成像（DTI）。我们发现，ACS显著保留了言语记忆（WMS - LM，F[1,65] = 4.2003，P = 0.0445）和大脑额叶区域的血流量（FWE，P < 0.001）。基于APOE4基因型的亚分析显示，在活跃组的APOE4受试者中，前额叶区域的血流量（通过ASL分析，P = 0.002）和白质微观结构（通过DTI分析，P = 0.003）得到了显著保留，而活跃组和安慰剂组的APOE4受试者之间没有显著差异。ACS对携带APOE4的老年人脑结构和功能的保护作用应通过进一步研究来验证。
