目的 探究酵母β-葡聚糖干预对轻度认知障碍（mild cognitive impairment，MCI）患者认知功能的影响并探讨潜在机制。方法 在湖北省十堰市招募50～80岁的MCI患者，按照随机、双盲原则分为干预组（酵母-葡聚糖，1 g/d）和安慰剂组（麦芽糊精，1 g/d），干预6个月；研究期间采用蒙特利尔认知评估量表（Montreal cognitive assessment，MoCA）和画钟测验、连线测验、数字广度测验、言语流畅测验、数字符号转换测验对受试者分别进行总体认知功能和单个领域认知功能评估，同时完成基本信息问卷调查、体格测量、3 d 24 h膳食回顾调查、载脂蛋白E（apolipoprotein E，APOE）基因分型鉴定（ε2/ε3/ε4）、血常规、血生化、T/B/NK细胞和C反应蛋白（C-reactive protein，CRP）检测；采用广义线性混合模型进行干预效果分析。结果 共有115例MCI患者完成干预，平均年龄63.7±8.7岁。与安慰剂组相比，酵母β-葡聚糖补充6个月后干预组的MoCA评分显著提高1.45分（95%CI 0.71~2.18，P6个月＜0.001），且存在显著时间×组别交互作用（P for interaction＝0.006）；干预组的画钟测验得分也显著增加（P6个月＝0.007），但其他单个领域评分未出现显著组间差异。相比于安慰剂组，酵母β-葡聚糖补充能够显著增加外周血中B细胞的绝对计数（P3个月＝0.002，P6个月＝0.005，P for interaction＝0.013）；在干预6个月时，CD4+ T细胞的绝对计数显著上升（P6个月＝0.030）；淋巴细胞的绝对计数在干预3个月时显著上升（P3个月＝0.004），但在6个月时逐渐恢复（P6个月＝0.079，P for interaction＝0.045）；CRP的含量在干预后未出现显著组间差异。结论 酵母-葡聚糖能够显著改善MCI患者的认知功能，可能与免疫调节有关。
Abstract
Objective To examine the effects of yeast β-glucan intervention on cognitive function in patients with mild cognitive impairment (MCI) and to explore the potential mechanisms. Methods Patients aged 50 to 80 years in Shiyan City were randomly assigned to the intervention group (yeast β-glucan, 1 g/d) or the placebo group (maltodextrin, 1 g/d) for 6 months. Global cognitive function was assessed using the Montreal cognitive assessment (MoCA) scale, and specific cognitive functions were evaluated using the clock drawing test (CDT), digit span test (DST), trail making test (TMT), verbal fluency test (VFT), and digit symbol substitution test (DSST). Besides, basic questionnaire, 3-day 24-hour dietary recall, BMI, SBP, DBP, APOE ε2/ε3/ε4, FPG, insulin, HbA1C, TC, TG, HDL-C, LDL-C, ALT, AST, neutrophils, monocytes, lymphocytes, T cells, CD4+ T cells, CD8+ T cells, B cells, NK cells and CRP were performed or detected. Generalized linear mixed model (GLMM) was used to analyze the intervention effects. Results A total of 115 patients with MCI, aged 63.7±8.7 years, completed the intervention. Compared to the placebo group, MoCA scores in the intervention group remarkably increased by 1.45 points (95% CI 0.71 to 2.18, P6 month<0.001) after 6 months of yeast β-glucan supplementation, with a significant time×group interaction effect (P for interaction=0.006). Additionally, CDT scores also improved significantly at 6 months (P6 month=0.007), whereas no significant between-group differences were observed in other single cognitive domains. Yeast β-glucan supplementation could significantly increase the absolute counts of B cells (P3 month=0.002, P6 month=0.005, P for interaction=0.013) and CD4+ T cells (P6 month=0.030). Moreover, the absolute count of lymphocytes significantly increased at 3 months (P3 month=0.004), but gradually declined at 6 months (P6 month=0.079, P for interaction=0.045). Nevertheless, CRP showed no significant between-group difference after the intervention. Conclusion Yeast β-glucan could significantly improve cognitive function in patients with MCI, which may be related to immune regulation.
关键词
轻度认知障碍 /
酵母β-葡聚糖 /
随机对照试验 /
免疫调节 /
认知评估
Key words
mild cognitive impairment /
yeast β-glucan /
randomized controlled trial /
immunomodulation /
cognitive assessment
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] Alzheimer's Disease International. World Alzheimer report2024: Global changes in attitudes to dementia[R/OL].(2024-09-20)[2025-01-10].https://www.alzint.org/resource/world-alzheimer-report-2024/.
[2] Petersen RC.Mild cognitive impairment[J]. New Engl J Med, 2011, 364: 2227–2234.
[3] 中国痴呆与认知障碍诊治指南写作组、中国医师协会神经内科医师分会认知障碍疾病专业委员会. 2018中国痴呆与认知障碍诊治指南(五):轻度认知障碍的诊断与治疗[J]. 中华医学杂志, 2018, 98: 1294–1301.
[4] Vega JN, Newhouse PA.Mild cognitive impairment: diagnosis, longitudinal course, and emerging treatments[J]. Curr Psychiatry Rep, 2014, 16: 490.
[5] 葛晨希, 张晨, 王丽娜,等. 知觉压力与轻度认知障碍[J]. 中华行为医学与脑科学杂志, 2021, 30: 180–186.
[6] Qin Y, Han H, Li Y, et al. Estimating bidirectional transitions and identifying predictors of mild cognitive impairment[J]. Neurology, 2023, 100: e297–e307.
[7] Wani SM, Gani A, Mir SA, et al. β-Glucan: a dual regulator of apoptosis and cell proliferation[J]. Int J Biol Macromol, 2021, 182: 1229–1237.
[8] Jayachandran M, Chen J, Chung SSM, et al. A critical review on the impacts of β-glucans on gut microbiota and human health[J]. J Nutr Biochem, 2018, 61: 101–110.
[9] De Marco Castro E, Calder PC, Roche HM. β-1, 3/1,6-Glucans and immunity: state of the art and future directions[J]. Mol Nutr Food Res, 2021, 65: e1901071.
[10] Wang H, Chen G, Li X, et al. Yeast β-glucan, a potential prebiotic, showed a similar probiotic activity to inulin[J]. Food Funct, 2020, 11: 10386–10396.
[11] Shi H, Yu Y, Lin D, et al. β-glucan attenuates cognitive impairment via the gut-brain axis in diet-induced obese mice[J]. Microbiome, 2020, 8: 143.
[12] Xu M, Mo X, Huang H, et al. Yeast β-glucan alleviates cognitive deficit by regulating gut microbiota and metabolites in Aβ1-42-induced AD-like mice[J]. Int J Biol Macromol, 2020, 161: 258–270.
[13] Fortier M, Castellano CA, St-Pierre V, et al. A ketogenic drink improves cognition in mild cognitive impairment: results of a 6-month RCT[J]. Alzheimers Dement, 2021, 17: 543–552.
[14] European Union. Commission Implementing Decision (EU) 2017/2078 of 10 November 2017: authorising an extension of use of yeast beta-glucans as a novel food ingredient under Regulation (EC) No 258/97 of the European Parliamentand of the Council[S/0L]. (2017-11-14)[2025-01-10]. https://eur-lex.europa.eu/legal-content/EN/TXT/?uri=CELEX%3A02017D2078-20190819.
[15] Wang X, Qu Y, Wang Y, et al. β-1,6-glucan from Pleurotus eryngii Modulates the immunity and gut microbiota[J]. Front Immunol, 2022, 13: 859923.
[16] Leng F, Edison P.Neuroinflammation and microglial activation in Alzheimer disease: where do we go from here?[J]. Nat Rev Neurol, 2021, 17: 157–172.
[17] Kubick N, Flournoy PCH, Enciu AM, et al. Drugs modulating CD4+ T cells blood-brain barrier interaction in Alzheimer's disease[J]. Pharmaceutics, 2020, 12: 880.
[18] Dansokho C, Ait Ahmed D, Aid S, et al. Regulatory T cells delay disease progression in Alzheimer-like pathology[J]. Brain, 2016, 139(Pt 4): 1237–1251.
[19] Xiong LL, Xue LL, Du RL, et al. Single-cell RNA sequencing reveals B cell-related molecular biomarkers for Alzheimer's disease[J]. Exp Mol Med, 2021, 53: 1888–1901.
[20] Bai Y, Ding J, He L, et al. β-Glucan induced plasma B cells differentiation to enhance antitumor immune responses by Dectin-1[J]. BMC Immunol, 2025, 26: 2.
[21] Sanges S, Tian W, Dubucquoi S, et al. B-cells in pulmonary arterial hypertension: friend, foe or bystander?[J]. Eur Respir J, 2024, 63:2301949.
[22] Calsolaro V, Edison P.Neuroinflammation in Alzheimer's disease: current evidence and future directions[J]. Alzheimers Dement, 2016, 12: 719–732.
[23] Lai KSP, Liu CS, Rau A, et al. Peripheral inflammatory markers in Alzheimer's disease: a systematic review and meta-analysis of 175 studies[J]. J Neurol Neurosurg Psychiatry, 2017, 88: 876–882.
[24] Griseta C, Battista P, Castellana F, et al. Serum levels of IL-6 are associated with cognitive impairment in the salus in apulia population-based study[J]. Heliyon, 2023, 9: e13972.
[25] Mo X, Sun Y, Liang X, et al. Insoluble yeast β-glucan attenuates high-fat diet-induced obesity by regulating gut microbiota and its metabolites[J]. Carbohydr Polym, 2022, 281: 119046.
[26] Zhang Q, Zhao W, Hou Y, et al. β-Glucan attenuates cognitive impairment of APP/PS1 mice via regulating intestinal flora and its metabolites[J]. CNS Neurosci Ther, 2023, 29: 1690–1704.
[27] Mo X, Cheng R, Shen L, et al. Yeast β-glucan alleviates high-fat diet-induced Alzheimer's disease-like pathologies in rats via the gut-brain axis[J]. Int J Biol Macromol, 2024, 278(Pt 4):134939
基金
国家重点研发计划（No.2022YFA0806100）; 安琪纽特营养基金（No.AF2022003）; 湖北省自然科学基金联合项目（No.2024AFD203）
PDF(1117 KB)
