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Open access
Frontiers Media S.A.
Frontiers in Aging Neuroscience
,  volume 16

Role of metabolic characteristics in the co-occurrence of insomnia, Alzheimer’s disease, and Parkinson’s disease: a Mendelian randomization study

Chengyong Liu 1
, 
Chi Wang 2
, 
Jing Jiang 1
, 
Yuyang Bo 1
, 
Lixiu Nan 1
, 
Ying Zhang 1
, 
Kongxi Zhu 1
, 
Xiaoqiu Wang 1
, 
Xinxin Feng 3
, 
Xiaoyang Lian 1
, 
Shan Qin 1
1
 
2
 
3
 
Ningbo Traditional Chinese Medicine Hospital, Ningbo, Zhejiang Province, China | 
Publication type: Journal Article
Publication date: 2025-01-06
Frontiers Media S.A.
scimago Q1
wos Q1
SJR: 1.479
CiteScore: 8.6
Impact factor: 4.5
ISSN: 16634365
Abstract
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.

Method

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.

Results

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).

Conclusion

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.

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Liu C. et al. Role of metabolic characteristics in the co-occurrence of insomnia, Alzheimer’s disease, and Parkinson’s disease: a Mendelian randomization study // Frontiers in Aging Neuroscience. 2025. Vol. 16.
GOST all authors (up to 50) Copy
Liu C., Wang C., Jiang J., Bo Y., Nan L., Zhang Y., Zhu K., Wang X., Feng X., Lian X., Qin S. Role of metabolic characteristics in the co-occurrence of insomnia, Alzheimer’s disease, and Parkinson’s disease: a Mendelian randomization study // Frontiers in Aging Neuroscience. 2025. Vol. 16.
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RIS Copy
TY - JOUR
DO - 10.3389/fnagi.2024.1436171
UR - https://www.frontiersin.org/articles/10.3389/fnagi.2024.1436171/full
TI - Role of metabolic characteristics in the co-occurrence of insomnia, Alzheimer’s disease, and Parkinson’s disease: a Mendelian randomization study
T2 - Frontiers in Aging Neuroscience
AU - Liu, Chengyong
AU - Wang, Chi
AU - Jiang, Jing
AU - Bo, Yuyang
AU - Nan, Lixiu
AU - Zhang, Ying
AU - Zhu, Kongxi
AU - Wang, Xiaoqiu
AU - Feng, Xinxin
AU - Lian, Xiaoyang
AU - Qin, Shan
PY - 2025
DA - 2025/01/06
PB - Frontiers Media S.A.
VL - 16
SN - 1663-4365
ER -
BibTex
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@article{2025_Liu,
author = {Chengyong Liu and Chi Wang and Jing Jiang and Yuyang Bo and Lixiu Nan and Ying Zhang and Kongxi Zhu and Xiaoqiu Wang and Xinxin Feng and Xiaoyang Lian and Shan Qin},
title = {Role of metabolic characteristics in the co-occurrence of insomnia, Alzheimer’s disease, and Parkinson’s disease: a Mendelian randomization study},
journal = {Frontiers in Aging Neuroscience},
year = {2025},
volume = {16},
publisher = {Frontiers Media S.A.},
month = {jan},
url = {https://www.frontiersin.org/articles/10.3389/fnagi.2024.1436171/full},
doi = {10.3389/fnagi.2024.1436171}
}