Zhang Yasi, Li Jialin, Li Jincheng, Wang Yingzhe, Cui Mei, Li Wenyan, Chen Xingdong, Jiang Yanfeng
Human Phenome Institute, Research and Innovation Center, Shanghai Pudong Hospital, Zhangjiang Fudan International Innovation Center, Fudan University, Shanghai, 200433, China.
Fudan University Taizhou Institute of Health Sciences, Taizhou, 225,326, Jiangsu, China.
Geroscience. 2025 Jul 23. doi: 10.1007/s11357-025-01790-8.
Bile acids (BAs) may contribute to dementia by regulating neuroinflammation and influencing gut-brain axis signaling, especially in Alzheimer's disease (AD). However, their alterations in dementia development are rather complex and their impact on dementia risk remains inconclusive. To provide a comprehensive understanding of these associations, we systematically reviewed cross-sectional and longitudinal studies on circulating BAs and dementia. We conducted a systematic search of PubMed, EMBASE, and Cochrane Library from inception to August 15, 2024, for population-based observational studies investigating the changes in circulating BAs and the association between BAs and dementia risk. A total of twelve articles were eligible for inclusion, including eleven cross-sectional studies and three longitudinal studies (with two studies overlapping). Cross-sectional studies showed that, compared to cognitively normal individuals, the circulating level of primary BAs such as cholic acid (CA) is reduced, while glycochenodeoxycholic acid (GCDCA) and most secondary bile acids are increased in dementia. Longitudinal studies further support the findings and found that reduced CA, elevated GCDCA, elevated secondary BAs (glycoursodeoxycholic acid, lithocholic acid (LCA), glycolithocholic acid, and glycodeoxycholic acid (GDCA), and ratios of GDCA: CA, taurodeoxycholic acid: CA correlate with an increased risk of dementia. In addition, CA, chenodeoxycholic acid, allocholic acid, and LCA may be of significance in distinguishing AD patients from healthy people. Multiple evidence showed that reduced CA (primary BAs) level and elevated conjugated or secondary BAs levels are linked to a higher risk of dementia. Bile acids play a complex role in the pathogenesis of dementia.
胆汁酸（BAs）可能通过调节神经炎症和影响肠-脑轴信号传导而导致痴呆，尤其是在阿尔茨海默病（AD）中。然而，它们在痴呆症发展过程中的变化相当复杂，其对痴呆风险的影响仍无定论。为了全面了解这些关联，我们系统回顾了关于循环胆汁酸与痴呆的横断面和纵向研究。我们对PubMed、EMBASE和Cochrane图书馆进行了系统检索，检索时间从数据库建立至2024年8月15日，以查找基于人群的观察性研究，这些研究调查了循环胆汁酸的变化以及胆汁酸与痴呆风险之间的关联。共有12篇文章符合纳入标准，包括11篇横断面研究和3篇纵向研究（其中2篇研究有重叠）。横断面研究表明，与认知正常个体相比，痴呆患者中胆酸（CA）等初级胆汁酸的循环水平降低，而甘氨鹅脱氧胆酸（GCDCA）和大多数次级胆汁酸增加。纵向研究进一步支持了这些发现，并发现CA降低、GCDCA升高、次级胆汁酸（甘氨熊脱氧胆酸、石胆酸（LCA）甘氨石胆酸和甘氨脱氧胆酸（GDCA））升高以及GDCA:CA、牛磺脱氧胆酸:CA的比值与痴呆风险增加相关。此外，CA、鹅脱氧胆酸、别胆酸和LCA在区分AD患者与健康人方面可能具有重要意义。多项证据表明，初级胆汁酸CA水平降低以及结合或次级胆汁酸水平升高与痴呆风险较高有关。胆汁酸在痴呆症的发病机制中起着复杂的作用。
