Liver-targeted therapies for improving mild cognitive impairment: Mechanism of action and treatment strategies

Jinyu Li; Heng Jiang; Duiping Feng; Jisheng Nie

doi:10.12449/JCH260838

Volume 42 Issue 8

Aug. 2026

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Article Navigation > Journal of Clinical Hepatology > 2026 > 42(8): 1996-2000

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Liver-targeted therapies for improving mild cognitive impairment: Mechanism of action and treatment strategies

DOI: 10.12449/JCH260838

Jinyu Li^{1, 2},
Heng Jiang³,
Duiping Feng²,
Jisheng Nie^{3
,
,
,}

1.
School of Forensic Medicine，Shanxi Medical University，Taiyuan 030001，China
2.
Department of Oncology and Vascular Intervention，The First Hospital of Shanxi Medical University，Taiyuan 030001，China
3.
School of Public Health，MOE Key Laboratory of Coal Environmental Pathogenicity and Prevention，Shanxi Medical University，Taiyuan 030001，China

Research funding:

National Natural Science Foundation of China (82200650);

Natural Science Foundation of Shanxi Province (202203021212046)

More Information

Corresponding author: Nie Jisheng， niejisheng@sxmu.edu.cn （ORCID： 0000-0003-4351-2017）
Received Date: 2025-12-26
Accepted Date: 2026-03-05
Published Date: 2026-08-25

Abstract

Abstract

Mild cognitive impairment （MCI） is a critical precursor stage of Alzheimer’s disease， and the development of MCI is closely associated with liver function. As a core metabolic organ， the liver regulates cognitive function through the liver-brain axis. Epidemiological studies have shown the association between liver function parameters and MCI. The liver affects cognitive function by clearing peripheral β-amyloid （mainly via the PPARα-LRP-1 pathway）， secreting hepatic factors such as FGF21 and sEH to modulate neuronal energy metabolism， and mediating oxidative stress and systemic inflammatory responses. Anti-inflammatory/antioxidant measures， dietary pattern adjustments， and aerobic exercise are currently effective strategies for regulating liver function and mitigating mild cognitive impairment. This article systematically reviews the role and mechanism of the liver-brain axis in MCI， in order to provide new perspectives for developing liver-targeted therapies for cognitive impairment.
- Cognitive Dysfunction,
- Liver-Brain Axis,
- Therapeutics

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References(29)

References

[1]	Zhao Y, Zhang H X, Cheng J, et al. Association between dyslipidaemia and cognitive impairment: A meta-analysis of cohort and case-control studies[J]. J Integr Neurosci, 2024, 23( 2): 40. DOI: 10.31083/j.jin2302040.
[2]	Mikkelsen A C D, Kjærgaard K, Schapira A H V, et al. The liver-brain axis in metabolic dysfunction-associated steatotic liver disease[J]. Lancet Gastroenterol Hepatol, 2025, 10( 3): 248- 258. DOI: 10.1016/S2468-1253(24)00320-0.
[3]	Mian M, Tahiri J, Eldin R, et al. Overlooked cases of mild cognitive impairment: Implications to early Alzheimer’s disease[J]. Ageing Res Rev, 2024, 98: 102335. DOI: 10.1016/j.arr.2024.102335.
[4]	Cong L, Ren Y F, Wang Y X, et al. Mild cognitive impairment among rural-dwelling older adults in China: A community-based study[J]. Alzheimers Dement, 2023, 19( 1): 56- 66. DOI: 10.1002/alz.12629.
[5]	Qin Y, Han HJ, Li Y, et al. Estimating bidirectional transitions and identifying predictors of mild cognitive impairment[J]. Neurology, 2023, 100( 3): e297- e307. DOI: 10.1212/WNL.0000000000201386.
[6]	Chen Zeqi, Chen Guolin, Jin Yiqiang, et al. Studies on the pathophysiological basis of the liver Qi stagnation syndrome[J]. China J Mod Med, 2000, 10( 10): 21- 23, 26. DOI: 10.3969/j.issn.1005-8982.2000.10.008. 陈泽奇, 陈国林, 金益强, 等. 肝气郁结证病理生理学基础研究[J]. 中国现代医学杂志, 2000, 10( 10): 21- 23, 26. DOI: 10.3969/j.issn.1005-8982.2000.10.008.
[7]	Deng Mingjie, Cai Jiarong, Shi Peimei, et al. Pathogenesis and treatment of hepatic encephalopathy: Research progress[J]. Acad J Nav Med Univ, 2025, 46( 6): 784- 789. DOI: 10.16781/j.CN31-2187/R.20240719. 邓明杰, 蔡加荣, 时培美, 等. 肝性脑病发病机制及治疗研究进展[J]. 海军军医大学学报, 2025, 46( 6): 784- 789. DOI: 10.16781/j.CN31-2187/R.20240719.
[8]	Weinstein G, O’Donnell A, Davis-Plourde K, et al. Non-alcoholic fatty liver disease, liver fibrosis, and regional amyloid-β and tau pathology in middle-aged adults: The Framingham study[J]. J Alzheimers Dis, 2022, 86( 3): 1371- 1383. DOI: 10.3233/JAD-215409.
[9]	Sharma A, Shrivastava S, Shukla S. Oxidative damage in the liver and brain of the rats exposed to frequency-dependent radiofrequency electromagnetic exposure: Biochemical and histopathological evidence[J]. Free Radic Res, 2021, 55( 5): 535- 546. DOI: 10.1080/10715762.2021.1966001.
[10]	Nho K, Kueider-Paisley A, Ahmad S, et al. Association of altered liver enzymes with Alzheimer disease diagnosis, cognition, neuroimaging measures, and cerebrospinal fluid biomarkers[J]. JAMA Netw Open, 2019, 2( 7): e197978. DOI: 10.1001/jamanetworkopen.2019.7978.
[11]	Tang Z Y, Chen X Y, Zhang W R, et al. Association between gamma-glutamyl transferase and mild cognitive impairment in Chinese women[J]. Front Aging Neurosci, 2021, 13: 630409. DOI: 10.3389/fnagi.2021.630409.
[12]	Nabizadeh F, Valizadeh P, Fallahi M S. Bile acid profile associated with CSF and PET biomarkers in Alzheimer’s disease[J]. Aging Clin Exp Res, 2024, 36( 1): 62. DOI: 10.1007/s40520-024-02729-3.
[13]	Chen T L, Pan F F, Huang Q, et al. Metabolic phenotyping reveals an emerging role of ammonia abnormality in Alzheimer’s disease[J]. Nat Commun, 2024, 15( 1): 3796. DOI: 10.1038/s41467-024-47897-y.
[14]	Markan K R, Naber M C, Ameka M K, et al. Circulating FGF21 is liver derived and enhances glucose uptake during refeeding and overfeeding[J]. Diabetes, 2014, 63( 12): 4057- 4063. DOI: 10.2337/db14-0595.
[15]	Peng X, Zhang X, Xu Z, et al. Peripheral amyloid-β clearance mediates cognitive impairment in non-alcoholic fatty liver disease[J]. EBioMedicine, 2024, 102: 105079. DOI: 10.1016/j.ebiom.2024.105079.
[16]	Cheng Y, He C Y, Tian D Y, et al. Physiological β-amyloid clearance by the liver and its therapeutic potential for Alzheimer’s disease[J]. Acta Neuropathol, 2023, 145( 6): 717- 731. DOI: 10.1007/s00401-023-02559-z.
[17]	Huang Z H, Lin H W K, Zhang Q G, et al. Targeting Alzheimer’s disease: The critical crosstalk between the liver and brain[J]. Nutrients, 2022, 14( 20): 4298. DOI: 10.3390/nu14204298.
[18]	Wu Y, Dong J H, Dai Y F, et al. Hepatic soluble epoxide hydrolase activity regulates cerebral Aβ metabolism and the pathogenesis of Alzheimer’s disease in mice[J]. Neuron, 2023, 111( 18): 2847- 2862. DOI: 10.1016/j.neuron.2023.06.002.
[19]	Zheng X, Toyama T, Siu S, et al. Selenoprotein P expression in glioblastoma as a regulator of ferroptosis sensitivity: Preservation of GPX4 via the cycling-selenium storage[J]. Sci Rep, 2024, 14( 1): 682. DOI: 10.1038/s41598-024-51259-5.
[20]	Mclean Diaz P, Vannier A, Joshi A D, et al. Serum fibroblast growth factor-21 discriminates between decompensated alcohol-associated cirrhosis and severe alcohol-associated hepatitis[J]. Clin Transl Gastroenterol, 2023, 14( 6): e00585. DOI: 10.14309/ctg.0000000000000585.
[21]	Gallego J J, Ballester M P, Fiorillo A, et al. Ammonia and beyond-biomarkers of hepatic encephalopathy[J]. Metab Brain Dis, 2025, 40( 1): 100. DOI: 10.1007/s11011-024-01512-7.
[22]	Lu J Y, Zuo H T, Feng R, et al. Parishin A reduces hepatic encephalopathy via gut microbiota increasing the activity of intestinal EAAT3 to reduce blood ammonia[J]. Pharmacol Res, 2025, 222: 108030. DOI: 10.1016/j.phrs.2025.108030.
[23]	Lu B J, Wu C, Azami N L B, et al. Babao Dan improves neurocognitive function by inhibiting inflammation in clinical minimal hepatic encephalopathy[J]. Biomed Pharmacother, 2021, 135: 111084. DOI: 10.1016/j.biopha.2020.111084.
[24]	Song D, Li Y, Yang L L, et al. Bridging systemic metabolic dysfunction and Alzheimer’s disease: The liver interface[J]. Mol Neurodegener, 2025, 20( 1): 61. DOI: 10.1186/s13024-025-00849-6.
[25]	Wang J, Li L, Li L, et al. Lycopene alleviates age-related cognitive deficit via activating liver-brain fibroblast growth factor-21 signalling[J]. Redox Biol, 2024, 77: 103363. DOI: 10.1016/j.redox.2024.103363.
[26]	Ahuja H, Sharma B C, Sachdeva S, et al. A double blind randomized controlled trial to assess efficacy of nutritional therapy for prevention of recurrence of hepatic encephalopathy in patients with cirrhosis[J]. J Gastroenterol Hepatol, 2023, 38( 3): 433- 440. DOI: 10.1111/jgh.16096.
[27]	Kim M, Liotta E M, Maas M B, et al. Rest-activity rhythm disturbance in liver cirrhosis and association with cognitive impairment[J]. Sleep, 2021, 44( 6): zsaa288. DOI: 10.1093/sleep/zsaa288.
[28]	Xiong Xin, Long Fuli. A review of traditional Chinese medicine exercise prescriptions for the prevention and treatment of metabolism related(non-alcoholic) fatty liver disease[J]. Tradit Chin Med, 2025, 14( 1): 367- 374. DOI: 10.12677/tcm.2025.141057. 熊欣, 龙富立. 中医运动处方防治代谢相关(非酒精性)脂肪性肝病的综述[J]. 中医学, 2025, 14( 1): 367- 374. DOI: 10.12677/tcm.2025.141057.
[29]	Wang Guibao, Wang Yuangang, Xu Kangmin, et al. The effect of Wuqinxi exercise on reactive inhibition ability of elderly people with mild cognitive impairment[J]. J Mudanjiang Norm Univ Nat Sci Ed, 2025( 4): 51- 56. DOI: 10.3969/j.issn.1003-6180.2025.04.010. 王桂宝, 王元刚, 许康敏, 等. 五禽戏锻炼对轻度认知障碍老年人反应性抑制能力的影响[J]. 牡丹江师范学院学报(自然科学版), 2025( 4): 51- 56. DOI: 10.3969/j.issn.1003-6180.2025.04.010.

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Liver-targeted therapies for improving mild cognitive impairment: Mechanism of action and treatment strategies

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