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. 2017 Jul 18;7(7):e1173. doi: 10.1038/tp.2017.118

Table 5. Significant associations of metabolites with baseline cognitive function and 6-year cognitive change.

Test; baseline Metabolitea Pathway Platform Model 1 (N=1565)
        β s.e. Pb Mean (s.d.) Median Q1 Q3
DSST Mannose Fructose, mannose GC/MS −1.174 0.286 4.37 × 10−5 −0.052 (0.904) −0.211 −0.525 0.123
  N-acetyl-1-methylhistidine Histidine metabolism LC/MS pos −2.723 0.687 7.80 × 10−5 −0.060 (0.405) −0.083 −0.336 0.094
  X-12846 None LC/MS neg 6.591 1.681 9.24 × 10−5 −0.046 (0.166) −0.065 −0.229 0.035
  Andro steroid monosulfate 2 Sterol/steroid LC/MS neg −1.131 0.295 1.33 × 10−4 −0.067 (0.877) −0.328 −0.644 0.156
  Glucose Glycolysis GC/MS −1.045 0.283 2.26 × 10−4 −0.042 (0.917) −0.246 −0.452 −0.012
                     
        Model 2 (N=1355)
DSST Mannose Fructose, mannose GC/MS −0.437 0.347 0.208 −0.051 (0.917) −0.210 −0.522 0.116
  N-acetyl-1-methylhistidine Histidine metabolism LC/MS pos −2.414 0.734 1.04 × 10−3 −0.056 (0.417) −0.083 −0.335 0.096
  X-12846 None LC/MS neg −4.547 1.822 0.0127 −0.043 (0.168) −0.061 −0.194 0.036
  Andro steroid monosulfate 2 Sterol/steroid LC/MS neg −0.818 0.316 9.73 × 10−3 −0.051 (0.893) −0.314 −0.644 0.174
  Glucose Glycolysis GC/MS −0.306 0.355 0.390 −0.040 (0.929) −0.246 −0.452 −0.012
                     
6-Year change       Model 1 (N=1028)
DWRT N-acetyl-1-methylhistidine Histidine metabolism LC/MS pos −0.504 0.170 3.18 × 10−3 −0.086 (0.333) −0.096 −0.362 0.085
                     
        Model 2 (N=883)
DWRT N-acetyl-1-methylhistidine Histidine metabolism LC/MS pos −0.656 0.183 3.65 × 10−4 −0.086 (0.334) −0.098 −0.366 0.085
                     
        Model 1(N=1012)
DSST Docosapentaenoate (n-6 DPA) Essential fatty acid LC/MS neg 0.977 0.290 7.84 × 10−4 −0.045 (0.966) −0.113 −0.726 0.527
  X-12844 None LC/MS neg 1.127 0.356 1.59 × 10−3 −0.043 (0.787) −0.138 −0.578 0.325
                     
        Model 2 (N=870)
DSST Docosapentaenoate (n-6 DPA) Essential fatty acid LC/MS neg 1.254 0.320 9.47 × 10−5 −0.040 (0.952) −0.103 −0.714 0.527
  X-12844 None LC/MS neg 1.404 0.391 3.45 × 10−4 −0.041 (0.781) −0.140 −0.577 0.331

Abbreviations: β, beta coefficient; APOE, apolipoprotein E; BMI, body mass index; CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration; DPA, docosapentaenoate; DSST, Digit Symbol Substitution Test; DWRT, Delayed Word Recall Test; eGFR, estimated glomerular filtration rate; GC/MS, gas chromatography/mass spectrometry; LC/MS neg, liquid chromatography/mass spectrometry-negative ion mode; LC/MS pos, liquid chromatography/mass spectrometry-positive ion mode; Q1, quartile 1; Q3, quartile 3.

As many of the same metabolites have recently been measured in 1553 European American ARIC study participants, replication was sought for compounds that were identified using the fully adjusted models for both phenotypes (Supplelmentary Table S4). Among the available metabolites, 4-androsten-3-beta, 17-beta-diol disulfate 1 was also found to be significantly associated with incident hospitalized dementia in individuals of European ancestry after application of the same exclusion criteria used for African Americans (clinical and demographic characteristics are shown in Supplementary Tables S5 and S6).

Model 1, Adjusted for age, gender, education, eGFRCKD-EPI; Model 2, Model 1 + diabetes, hypertension, BMI, LDL cholesterol, current smoking, alcohol intake, APOE genotype (at least 1 ε4 allele/no ε4 allele).

a

All metabolites in Group 1, analyzed as continuous variables.

b

Threshold for statistical significance <3.9 × 10−4; bold P-values are statistically signifcant.