Omega‐3 fatty acid derivatives associated with reduced risk of cognitive impairment in older adults

Abstract

AbstractBackgroundCognitive decline etiology is not fully understood, and many pathways undoubtedly play a role. Oxidative stress, inflammation, and other factors likely modify one’s risk. To understand metabolic underpinnings of cognitive impairment, untargeted metabolomics were performed, and the data analyzed.MethodUntargeted metabolomics were conducted, using UPLC‐mass spectrometry, in 167 fasted plasma samples obtained from the Wake Forest Alzheimer’s Disease Research Center. Subjects without diagnosis of mild cognitive impairment or any form of dementia per the National Alzheimer’s Coordinating Center’s criteria were deemed cognitively normal (n = 102), and comparisons were made between these subjects and subjects diagnosed with cognitive impairment (n = 65). For each of the 1,627 biochemicals assessed, Mann‐Whitney U tests were performed to determine if differences existed between cognition groups. Further investigation was performed via multinomial regression stratified by APOE genotype and by BMI category (<18.5, 18.5‐24.9, 25‐29.9, 30+ kg/m2), adjusted for sex, age, race, and educational attainment.ResultMann‐Whitney U testing identified 101 metabolites significantly different among those with cognitive impairment versus those without. Adjusted, stratified regression abrogated most associations, though several metabolites continued to show notable differences between groups. Elevation of eicosenedioate was associated with increased odds of cognitive impairment for both normal weight (OR 1.62, 95% CI [0.93,2.82], p = 0.08) and overweight/obesity groups (OR 1.79, CI [0.88,10.51], p = 0.07), nearing statistical significance. In those with overweight or obesity, elevation of three omega‐3‐derived fatty acids were significantly associated with decreased odds of being cognitively impaired (OR 0.08‐0.13, CI[0.006,0.99), p = 0.009‐0.049). Five omega‐3 derived fatty acids were also significantly associated with decreased risk of cognitive impairment among those APOE genotype E3/E3 (OR 0.09‐0.21, CI [0.01,0.82], p = 0.01‐0.02). Several additional metabolites of interest, including alpha‐tocopherol (OR 0.06, CI [0.06,1.45]), ergothioneine (OR 0.27, CI [0.06,1.18]), and carotene diols (OR 0.08, CI [0.006,1.24]) approached significance in association with reduced cognitive impairment risk.ConclusionIn untargeted metabolomics, metabolites across a range of pathways were found to be associated with cognitive impairment. Upon adjustment for key, many omega‐3 fatty acid‐ derived metabolites continued to be associated with reduced risk of cognitive impairment.