Table 3.
Metabolites associated with cognition that were retained in LASSO penalized regression models (N = 736)
| HMBD | Biochemical | Super Pathway | Sub Pathway | βwhole a cohort | βwithoutb diabetesb | βmedDietc |
|---|---|---|---|---|---|---|
| POSITIVELY ASSOCIATED METABOLITES | ||||||
| – | 4-methoxyphenol sulfate | Amino Acid | Tyrosine Metabolism | 0.631 | 0.073 | 0.228 |
| – | N-stearoylserine* | Lipid | Endocan-binoid | 0.582 | – | 0.479 |
| HMDB01999 | eicosapentaenoate (EPA; 20 : 5n3) | Lipid | Polyunsaturated Fatty Acid (n3 and n6) | 0.494 | 0.051 | 0.104 |
| – | 3-hydroxyhexanoate | Lipid | Fatty Acid, Monohydroxy | 0.346 | – | – |
| HMDB02329 | oxalate (ethanedioate) | Cofactors and Vitamins | Ascorbate and Aldarate Metabolism | 0.328 | – | – |
| HMDB07218 | oleoyl-oleoyl-glycerol (18 : 1/18 : 1) [1]* | Lipid | Diacylglycerol | 0.288 | – | – |
| – | lignoceroyl sphingomyelin (d18 : 1/24 : 0) | Lipid | Sphingolipid Metabolism | 0.188 | – | – |
| HMDB00574 | Cysteine | Amino Acid | Methionine, Cysteine, SAM and Taurine Metabolism | 0.152 | – | – |
| HMDB04705 | 12,13-DiHOME | Lipid | Fatty Acid, Dihydroxy | 0.128 | 0.088 | – |
| HMDB02823 | docosatrienoate (22 : 3n3) | Lipid | Polyunsaturated Fatty Acid (n3 and n6) | 0.118 | – | – |
| HMDB33844 | beta-cryptoxanthin | Cofactors and Vitamins | Vitamin A Metabolism | 0.108 | 0.195 | – |
| HMDB08141 | 1-linoleoyl-2-linolenoyl-GPC (18:2/18:3)* | Lipid | Phosphatidylcholine (PC) | 0.089 | – | 0.002 |
| HMDB00345 | 3-hydroxyadipate* | Lipid | Fatty Acid, Dicarboxylate | 0.065 | – | – |
| – | 1-stearoyl-2-oleoyl-GPG (18 : 0/18 : 1) | Lipid | Phosphatidylglycerol (PG) | 0.065 | – | – |
| HMDB00017 | Pyridoxate | Cofactors and Vitamins | Vitamin B6 Metabolism | 0.048 | – | – |
| HMDB00661 | glutarate (C5-DC) | Lipid | Fatty Acid, Dicarboxylate | 0.045 | – | – |
| HMDB61115 | tryptophan betaine | Amino Acid | Tryptophan Metabolism | 0.025 | – | 0.240 |
| HMDB00202 | methylmalo-te (MMA) | Lipid | Fatty Acid Metabolism (also BCAA Metabolism) | 0.013 | – | 0.046 |
| HMDB00760 | Hyocholate | Lipid | Secondary Bile Acid Metabolism | – | – | 0.002 |
| NEGATIVELY ASSOCIATED METABOLITES | ||||||
| HMDB61684 | N-acetylisoleucine | Amino Acid | Leucine, Isoleucine and Valine Metabolism | −0.660 | −0.287 | −0.824 |
| – | sphingomyelin (d18:2/16: 0, d18 : 1/16 : 1)* | Lipid | Sphingolipid Metabolism | −0.546 | – | −0.339 |
| – | (N(1)+N(8))-acetylspermidine | Amino Acid | Polyamine Metabolism | −0.405 | – | −0.169 |
| – | arabote/xylote | Carbohydrate | Pentose Metabolism | −0.351 | – | – |
| HMDB00190 | lactate | Carbohydrate | Glycolysis, Gluconeogenesis, and Pyruvate Metabolism | −0.281 | – | – |
| – | glycosyl-N-(2-hydroxynervonoyl)-sphingosine (d18 : 1/24: 1(2OH))* | Lipid | Ceramides | −0.277 | −0.051 | −0.071 |
| HMDB06409 | tyramine O-sulfate | Amino Acid | Tyrosine Metabolism | −0.256 | −0.053 | −0.086 |
| HMDB00063 | Cortisol | Lipid | Corticosteroids | −0.237 | – | – |
| – | 3-methylcytidine | Nucleotide | Pyrimidine Metabolism, Cytidine containing | −0.237 | – | – |
| – | gamma-glutamylcitrulline* | Peptide | Gamma-glutamyl Amino Acid | −0.231 | – | – |
| HMDB07257 | linoleoyl-arachidonoyl-glycerol (18:2/20 : 4) [1]* | Lipid | Diacylglycerol | −0.228 | −0.168 | – |
| – | sphingomyelin (d18 : 2/18 : 1)* | Lipid | Sphingolipid Metabolism | −0.224 | – | – |
| HMDB03464 | 4-guanidinobutanoate | Amino Acid | Guanidino and Acetamido Metabolism | −0.201 | – | – |
| HMDB02802 | cortisone | Lipid | Corticosteroids | −0.174 | – | – |
| HMDB00258 | sucrose | Carbohydrate | Disaccharides and Oligosaccharides | −0.162 | −0.070 | −0.160 |
| HMDB07228 | oleoyl-arachidonoyl-glycerol (18:1/20:4) [2]* | Lipid | Diacylglycerol | −0.151 | – | – |
| HMDB00126 | glycerol 3-phosphate | Lipid | Glycerolipid Metabolism | −0.113 | – | −0.169 |
| HMDB09069 | 1-oleoyl-2-arachidonoyl-GPE (18:1/20:4)* | Lipid | Phosphatidylethanolamine (PE) | −0.106 | −0.092 | −0.108 |
| HMDB00012 | 2’-deoxyuridine | Nucleotide | Pyrimidine Metabolism, Uracil containing | −0.100 | – | – |
| HMDB11745 | N-acetylmethionine | Amino Acid | Methionine, Cysteine, SAM and Taurine Metabolism | −0.097 | – | – |
| – | acisoga | Amino Acid | Polyamine Metabolism | −0.095 | −0.372 | – |
| HMDB00522 | 3-methylglutaco-te | Amino Acid | Leucine, Isoleucine and Valine Metabolism | −0.089 | – | – |
| HMDB01547 | corticosterone | Lipid | Corticosteroids | −0.082 | – | −0.195 |
| – | cis-4-decenoylcarnitine (C10: 1) | Lipid | Fatty Acid Metabolism (Acyl Carnitine) | −0.082 | – | −0.085 |
| HMDB11756 | N-acetylleucine | Amino Acid | Leucine, Isoleucine and Valine Metabolism | −0.080 | −0.122 | – |
| HMDB00631 | glycodeoxycholate | Lipid | Secondary Bile Acid Metabolism | −0.066 | – | – |
| HMDB00122 | glucose | Carbohydrate | Glycolysis, Gluconeogenesis, and Pyruvate Metabolism | −0.063 | – | – |
| HMDB00754 | beta-hydroxyisovalerate | Amino Acid | Leucine, Isoleucine and Valine Metabolism | −0.062 | – | – |
| HMDB02820 | 1-methyl-4-imidazoleacetate | Amino Acid | Histidine Metabolism | −0.044 | – | – |
| HMDB09789 | 1-palmitoyl-2-arachidonoyl-GPI (16 : 0/20 : 4)* | Lipid | Phosphatidylinositol (PI) | −0.035 | – | – |
| HMDB00669 | 2-hydroxyphenylacetate | Amino Acid | Tyrosine Metabolism | −0.016 | – | −0.295 |
| HMDB04089 | N-formylanthranilic acid | Amino Acid | Tryptophan Metabolism | −0.012 | – | – |
| HMDB10395 | 1-arachidonoyl-GPC (20 : 4n6)* | Lipid | Lysophospholipid | −0.005 | – | – |
| HMDB01173 | 5-methylthioadenosine (MTA) | Amino Acid | Polyamine Metabolism | – | −0.034 | – |
| HMDB02331 | 1-ribosyl-imidazoleacetate* | Amino Acid | Histidine Metabolism | – | −0.133 | – |
| – | N-linoleoyltaurine* | Lipid | Endocanbinoid | – | −0.112 | – |
| – | sphingomyelin (d18 : 2/24 : 2)* | Lipid | Sphingolipid Metabolism | – | −0.197 | – |
| HMDB00232 | quinolite | Cofactors and Vitamins | Nicotite and Nicotimide Metabolism | – | – | −0.163 |
| HMDB00709 | cysteinylglycine disulfide* | Amino Acid | Glutathione Metabolism | – | – | −0.078 |
| HMDB00730 | isobutyrylglycine | Amino Acid | Leucine, Isoleucine and Valine Metabolism | – | – | −0.015 |
| HMDB00854 | formiminoglutamate | Amino Acid | Histidine Metabolism | – | – | −0.320 |
| – | glyco-beta-muricholate** | Lipid | Primary Bile Acid Metabolism | – | – | −0.219 |
| – | hexadecenedioate (C16 : 1-DC)* | Lipid | Fatty Acid, Dicarboxylate | – | – | −0.089 |
| – | N-palmitoyl-sphingadienine (d18 : 2/16 : 0)* | Lipid | Sphingolipid Metabolism | – | – | −0.186 |
a
beta coefficient from a LASSO regression that initially included all the metabolites among all partcipants (n = 736) with metabolomic measures.
b
beta coefficient from a LASSO regression that initially included all the metabolites among (n = 453) participants without diabetes.
c
beta coefficient from a LASSO regression that initially included all the metabolites among (n = 329) participants who had Mediterranean diet score of 5 or above.
d
metabolites also identified in linear regression analyses after FDR correction (Table 2). Results are only presented with FDR adjusted p-value <0.05.