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ORIGINAL RESEARCH article

Front. Aging Neurosci.
Sec. Alzheimer's Disease and Related Dementias
Volume 16 - 2024 | doi: 10.3389/fnagi.2024.1436171
This article is part of the Research Topic Advances of lipid metabolism in neurological diseases and mental disorders View all articles

Role of Metabolic Characteristics in the Co-occurrence of Insomnia, Alzheimer's Disease, and Parkinson's Disease: A Mendelian Randomization Study

Provisionally accepted
Liu Chengyong Liu Chengyong 1Chi Wang Chi Wang 2Jing Jiang Jing Jiang 1*Yuyang Bo Yuyang Bo 1*Lixiu Nan Lixiu Nan 1*Ying Zhang Ying Zhang 1Kongxi Zhu Kongxi Zhu 1*Xiaoqiu Wang Xiaoqiu Wang 1Xinxin Feng Xinxin Feng 3*Xiaoyang Lian Xiaoyang Lian 1*Shan Qin Shan Qin 1*
  • 1 Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China, Nanjing, Liaoning Province, China
  • 2 Shanghai University of Traditional Chinese Medicine, Shanghai, Shanghai Municipality, China
  • 3 Ningbo Traditional Chinese Medicine Hospital, Ningbo, Zhejiang Province, China

The final, formatted version of the article will be published soon.

    Objective: There reportedly exists a significant comorbidity between insomnia and neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD), indicative of a potential link to serum metabolic dysregulation.To elucidate shared pathophysiological mechanisms between insomnia and AD/PD, we performed comprehensive two-sample Mendelian randomization (MR) analyses, investigating 1,400 serum metabolic characteristics for their causal relationships with the risks of insomnia, AD, widely defined AD (WDAD), and PD. We employed publicly available genetic data; the primary estimate was determined using inverse-variance weighting, supplemented by weighted median, simple mode, weighted mode, and the MR-PRESSO and MR-Egger methods to evaluate heterogeneity and pleiotropy.The ratio of N-palmitoyl-sphingosine to N-palmitoyl-sphinganine is linked to higher risks of insomnia (OR 1.137, 95% CI 1.015-1.273, P = 0.026) and AD (OR 1.090, 95% CI 1.005-1.183, P = 0.037).The acetylcarnitine to propionylcarnitine ratio is a risk factor for insomnia (OR 1.190, 95% CI 1.003-1.370, P = 0.016) but has protective effects against AD (OR 0.868, 95% CI 0.784-0.961, P = 0.006) and WDAD (OR = 0.892, 95% CI = 0.817-0.973, P = 0.010). Glutamine conjugate of C7H12O2 levels are associated with reduced risk of insomnia (OR 0.863, 95% CI 0.749-0.995, P = 0.042) and PD (OR 0.856, 95% CI 0.746-0.981, P = 0.026).Our findings highlight the crucial role of serum metabolic characteristics in the comorbidity of insomnia with neurodegenerative diseases, providing valuable insights into prospective therapeutic targets and diagnostic markers.

    Keywords: insomnia, Neurodegenerative Diseases, Alzheimer's disease, Parkinson's disease, Mendelian randomization

    Received: 21 May 2024; Accepted: 25 Nov 2024.

    Copyright: © 2024 Chengyong, Wang, Jiang, Bo, Nan, Zhang, Zhu, Wang, Feng, Lian and Qin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Jing Jiang, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China, Nanjing, Liaoning Province, China
    Yuyang Bo, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China, Nanjing, Liaoning Province, China
    Lixiu Nan, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China, Nanjing, Liaoning Province, China
    Kongxi Zhu, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China, Nanjing, Liaoning Province, China
    Xinxin Feng, Ningbo Traditional Chinese Medicine Hospital, Ningbo, Zhejiang Province, China
    Xiaoyang Lian, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China, Nanjing, Liaoning Province, China
    Shan Qin, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China, Nanjing, Liaoning Province, China

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