Serum and CSF Metabolites in Stroke-Free Patients Are Associated With Vascular Risk Factors and Cognitive Performance

Area of Science:

• Neuroscience
• Metabolomics
• Vascular Biology

Background:

• Aggregation of vascular risk factors (VRFs) exacerbates cognitive impairment, even in stroke-free individuals.
• Serum and cerebrospinal fluid (CSF) metabolites may serve as early indicators of functional deterioration.
• Understanding the link between VRFs, metabolism, and cognitive function is crucial for early intervention.

Purpose of the Study:

• To evaluate small-molecule metabolites (<1,000 Da) in serum and CSF across varying degrees of cerebrovascular burden.
• To investigate the correlation between specific metabolites, cognitive performance, and VRFs.
• To identify key metabolites and metabolic pathways implicated in VRF-associated cognitive impairment.

Main Methods:

• Subjects categorized into low, middle, and high-risk groups based on the Framingham Stroke Risk Profile (FSRP) score.
• Cognitive function assessed using standardized tests focusing on memory and executive function.
• Small molecules quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Main Results:

• Increased FSRP scores correlated with decreased cognitive performance, particularly in immediate memory, delayed recall, and executive function.
• Seven serum metabolites (e.g., 1-methyluric acid, Ile Cys Arg) and three CSF metabolites (e.g., Asp His, 2,5-di-tert-Butylhydroquinone) were elevated in the high-risk group.
• Specific metabolites (e.g., 1-methyluric acid, Ile Cys Arg in serum; 13-HOTrE(r), Asp His in CSF) negatively correlated with cognitive performance, while arachidonoyl PAF C-16 showed a positive association.

Conclusions:

• Identified potential early-stage biomarkers for vascular cognitive impairment (VCI), including 1-methyluric acid and Ile Cys Arg in serum, and Asp His and 2,5-di-tert-Butylhydroquinone in CSF.
• Caffeine metabolism and the tricarboxylic acid (TCA) cycle are highlighted as potentially significant pathways in VRF-associated cognitive impairment.
• These findings suggest a metabolic basis for early VCI linked to vascular risk factors.