Serum and CSF Metabolites in Stroke-Free Patients Are Associated With Vascular Risk Factors and Cognitive Performance
Background and purpose: The aggregation of vascular risk factors (VRFs) can aggravate cognitive impairment in stroke-free patients. Metabolites in serum and cerebrospinal fluid (CSF) may irreversibly reflect early functional deterioration. This study evaluated small-molecule metabolites (<1,0...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-07-01
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| Series: | Frontiers in Aging Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fnagi.2020.00193/full |
| _version_ | 1811323761473880064 |
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| author | Sisi Peng Ying Shen Min Wang Junjian Zhang |
| author_facet | Sisi Peng Ying Shen Min Wang Junjian Zhang |
| author_sort | Sisi Peng |
| collection | DOAJ |
| description | Background and purpose: The aggregation of vascular risk factors (VRFs) can aggravate cognitive impairment in stroke-free patients. Metabolites in serum and cerebrospinal fluid (CSF) may irreversibly reflect early functional deterioration. This study evaluated small-molecule metabolites (<1,000 Da) in the serum and CSF of patients with different degrees of cerebrovascular burden and investigated the correlation between metabolism and cognitive performance associated with VRFs.Methods: The subjects were divided into a low-risk group (10-year stroke risk ≤ 5%), a middle-risk group (10-year stroke risk >5% and <15%), and a high-risk group (10 years stroke risk ≥ 15%) according to the Framingham stroke risk profile (FSRP) score, which was used to quantify VRFs. We assess the cognitive function of the participants. We semiquantitatively quantified the small molecules using liquid chromatography–tandem mass spectrometry (LC-MS/MS). The correlation between the small molecules and cognitive function, along with VRFs, was investigated to identify key small molecules and possible underlying metabolic pathways.Results: When the FSRP scores increased, the cognitive performances of the subjects decreased, specifically the performance regarding the tasks of immediate memory, delayed recall, and executive function. Seven metabolites (2-aminobutyric acid, Asp Asp Ser, Asp Thr Arg, Ile Cys Arg, 1-methyluric acid, 3-tert-butyladipic acid, and 5α-dihydrotestosterone glucuronide) in serum and three metabolites [Asp His, 13-HOTrE(r), and 2,5-di-tert-Butylhydroquinone] in CSF were significantly increased, and one metabolite (arachidonoyl PAF C-16) in serum was significantly decreased in high-risk group subjects. Among these metabolites, 1-methyluric acid, 3-tert-butyladipic, acid and Ile Cys Arg in serum and 13-HOTrE(r), 2,5-di-tert-butylhydroquinone, and Asp His in CSF were found to be negatively related with cognitive performance in the high-risk group. Arachidonoyl PAF C-16 in serum was found to be associated with better cognitive performance. Caffeine metabolism and the tricarboxylic acid cycle (TCA cycle) were identified as key pathways.Conclusions: 1-Methyluric acid, 3-tert-butyladipic acid, arachidonoyl PAF C-16, and Ile Cys Arg in serum and 13-HOTrE(r), 2,5-di-tert-butylhydroquinone, and Asp His in CSF were identified as potential biomarkers of vascular cognitive impairment (VCI) at the early stage. Caffeine metabolism and the TCA cycle may play important roles in the pathophysiology of VRF-associated cognitive impairment. |
| first_indexed | 2024-04-13T14:01:33Z |
| format | Article |
| id | doaj.art-994d55c3127e4cea8734086fed5fd19d |
| institution | Directory Open Access Journal |
| issn | 1663-4365 |
| language | English |
| last_indexed | 2024-04-13T14:01:33Z |
| publishDate | 2020-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging Neuroscience |
| spelling | doaj.art-994d55c3127e4cea8734086fed5fd19d2022-12-22T02:44:02ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652020-07-011210.3389/fnagi.2020.00193504959Serum and CSF Metabolites in Stroke-Free Patients Are Associated With Vascular Risk Factors and Cognitive PerformanceSisi Peng0Ying Shen1Min Wang2Junjian Zhang3Department of Neurology, Zhongnan Hospital of Wuhan University, Wuhan, ChinaDepartment of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaPublic Technological Service Center, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, ChinaDepartment of Neurology, Zhongnan Hospital of Wuhan University, Wuhan, ChinaBackground and purpose: The aggregation of vascular risk factors (VRFs) can aggravate cognitive impairment in stroke-free patients. Metabolites in serum and cerebrospinal fluid (CSF) may irreversibly reflect early functional deterioration. This study evaluated small-molecule metabolites (<1,000 Da) in the serum and CSF of patients with different degrees of cerebrovascular burden and investigated the correlation between metabolism and cognitive performance associated with VRFs.Methods: The subjects were divided into a low-risk group (10-year stroke risk ≤ 5%), a middle-risk group (10-year stroke risk >5% and <15%), and a high-risk group (10 years stroke risk ≥ 15%) according to the Framingham stroke risk profile (FSRP) score, which was used to quantify VRFs. We assess the cognitive function of the participants. We semiquantitatively quantified the small molecules using liquid chromatography–tandem mass spectrometry (LC-MS/MS). The correlation between the small molecules and cognitive function, along with VRFs, was investigated to identify key small molecules and possible underlying metabolic pathways.Results: When the FSRP scores increased, the cognitive performances of the subjects decreased, specifically the performance regarding the tasks of immediate memory, delayed recall, and executive function. Seven metabolites (2-aminobutyric acid, Asp Asp Ser, Asp Thr Arg, Ile Cys Arg, 1-methyluric acid, 3-tert-butyladipic acid, and 5α-dihydrotestosterone glucuronide) in serum and three metabolites [Asp His, 13-HOTrE(r), and 2,5-di-tert-Butylhydroquinone] in CSF were significantly increased, and one metabolite (arachidonoyl PAF C-16) in serum was significantly decreased in high-risk group subjects. Among these metabolites, 1-methyluric acid, 3-tert-butyladipic, acid and Ile Cys Arg in serum and 13-HOTrE(r), 2,5-di-tert-butylhydroquinone, and Asp His in CSF were found to be negatively related with cognitive performance in the high-risk group. Arachidonoyl PAF C-16 in serum was found to be associated with better cognitive performance. Caffeine metabolism and the tricarboxylic acid cycle (TCA cycle) were identified as key pathways.Conclusions: 1-Methyluric acid, 3-tert-butyladipic acid, arachidonoyl PAF C-16, and Ile Cys Arg in serum and 13-HOTrE(r), 2,5-di-tert-butylhydroquinone, and Asp His in CSF were identified as potential biomarkers of vascular cognitive impairment (VCI) at the early stage. Caffeine metabolism and the TCA cycle may play important roles in the pathophysiology of VRF-associated cognitive impairment.https://www.frontiersin.org/article/10.3389/fnagi.2020.00193/fullvascular cognitive impairmentcerebrovascular risk factorsFramingham stroke risk profilecerebrospinal fluidmetabolomics |
| spellingShingle | Sisi Peng Ying Shen Min Wang Junjian Zhang Serum and CSF Metabolites in Stroke-Free Patients Are Associated With Vascular Risk Factors and Cognitive Performance Frontiers in Aging Neuroscience vascular cognitive impairment cerebrovascular risk factors Framingham stroke risk profile cerebrospinal fluid metabolomics |
| title | Serum and CSF Metabolites in Stroke-Free Patients Are Associated With Vascular Risk Factors and Cognitive Performance |
| title_full | Serum and CSF Metabolites in Stroke-Free Patients Are Associated With Vascular Risk Factors and Cognitive Performance |
| title_fullStr | Serum and CSF Metabolites in Stroke-Free Patients Are Associated With Vascular Risk Factors and Cognitive Performance |
| title_full_unstemmed | Serum and CSF Metabolites in Stroke-Free Patients Are Associated With Vascular Risk Factors and Cognitive Performance |
| title_short | Serum and CSF Metabolites in Stroke-Free Patients Are Associated With Vascular Risk Factors and Cognitive Performance |
| title_sort | serum and csf metabolites in stroke free patients are associated with vascular risk factors and cognitive performance |
| topic | vascular cognitive impairment cerebrovascular risk factors Framingham stroke risk profile cerebrospinal fluid metabolomics |
| url | https://www.frontiersin.org/article/10.3389/fnagi.2020.00193/full |
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