Cognitive Function Correlates With Serum Fatty Acid And Carbonyl Compound Profiles In Carotid Atherosclerosis

Objective Carotid atherosclerosis is an independent risk factor for cognitive impairment.Serum metabolomic analysis holds significant promise for uncovering the relationship between carotid atherosclerosis and cognitive impairment.In this study,we aimed to evaluate serum fatty acid and carbonyl compound profiles in carotid atherosclerosis patients,and to explore the relationship between these serum metabolites and cognitive function.Methods This is a cross-sectional study with a small sample size in Zhongnan Hospital of Wuhan University.All the participants were 50 years old⁷5 years old.Using carotid ultrasound assessment,the partivipants were divided into the carotid atherosclerosis group（n=50）and the control group（n=44）,and we evaluated their carotid intima-media thickness（C-IMT）.The following clinical characteristics were collected:age,sex,education level,body mass index（BMI）,hypertension,diabetes,smoking,alcohol drinking,serum total cholesterol（TC）,serum triglyceride（TG）,serum high-density lipoprotein cholesterol（HDL-C）,and serum low-density lipoprotein cholesterol（LDL-C）.All the participants were subjected to the following neuropsychological assessments:Mini-Mental State Examination（MMSE）and Montreal Cognitive Assessment（MoCA）for global cognition,Rey Auditory Verbal Learning Test（RAVLT）for memory,Digit Span Test（DST）for working memory and attention,Verbal Learning Test（VFT）for language fluency,Digit Symbol Substitution Test（DSST）for executive function,Trail Making Test A/B（TMT-A/B）for visual attention and executive function,Hamilton Anxiety Scale（HAMA）to exclude obvious anxiety,Hamilton Depression Scale（HAMD）to exclude obvious depression.The fasting serum samples were collected for isotope-labeling strategy combined with liquid chromatography-mass spectrometry（IL-LC-MS）analysis.Further,we explored the relationship between changed metabolites and cognitive performance.Results Compared with the control,the carotid atherosclerosis group showed larger C-IMT（P<0.01）.The other clinical characteristics didn’t show intergroup differences.As to neuropsychological assessment,the carotid atherosclerosis group showed lower scores than the control group in MoCA（P<0.01）,immediate memory in RAVLT（P<0.05）,VFT（P<0.05）,and DSST（P<0.05）.Meanwhile,the carotid atherosclerosis individuals spent more time on TMT-A（P<0.05）and TMT-B（P<0.05）.C-IMT was correlated negatively with the scores of MoCA（P<0.01）,immediate memory in RAVLT（P<0.01）,VFT（P<0.05）and DSST（P<0.01）;and was correlated positively with the time of TMT-A（P<0.01）and TMT-B（P<0.01）.Ater adjustment for age,sex and education level,the above associations remained the same.Ater adjustment for those recorded vascular risk factors,C-IMT was still correlated negatively with the scores of MoCA（P<0.01）,immediate memory in RAVLT（P<0.01）and DSST（P<0.01）;and was correlated positively with the time of TMT-A（P<0.05）and TMT-B（P<0.01）.For IL-LC-MS analysis,181 potential fatty acid candidates and 149 potential carbonyl compound candidates were discovered in the pooled serum.Partial least squares-discriminant analysis（PLS-DA）showed that fatty acid profiles（R²X（cum）=0.163,R²Y（cum）=0.839,Q₂（cum）=0.677）and carbonyl compound profiles（R²X（cum）=0.261,R²Y（cum）=0.810,Q₂（cum）=0.727）can be distinguished distinctly between two groups.In carotid atherosclerosis serum,3 fatty acid candidates and 41carbonyl compound candidates showed significantly increased levels（P<0.05）;55 fatty acid candidates and 14 carbonyl compound candidates showed significantly decreased levels（P<0.05）.Among these candidates,22 fatty acid candidates and 14 carbonyl compound candidates showed the single name in METLIN and HMDB databases.The subsequent pathway analysis showed that these compounds were associated with the metabolism of polyunsaturated fatty acids（PUFAs）.In addition,cognitive performance was correlated positively with 3 n-3 PUFAs（α-linolenic acid,eicosapentaenoic acid,docosahexenoic acid）,3 n-6 PUFAs（linoleic acid,eicosadienoic acid,arachidonic acid）,oleic acid,pentadecanoic acid,arachidic acid,palmitoleic acid,acetophenone and 1-（3-aminopropyl）-4-aminobutanal.Four carbonyl compounds involved in the oxidation of PUFAs and vitamin E（octanal,nonanal,heptanal andα-tocopherolquinone）were correlated negatively with cognitive performance.Conclusion In summary,the carotid atherosclerosis individuals have poor cognitive performance,especially in immediate memory,language fluency,visual attention and executive function.C-IMT is associated with cognitive function,and may reflect cognitive impairment induced by carotid atherosclerosis to some degree.Meanwhile,the carotid atherosclerosis individuals have aberrant serum fatty acid and carbonyl compound profiles.Fatty acids and carbonyl compounds involved in the metabolism of PUFAs and vitamin E could be correlated with cognitive impairment.