Table 4.

Ratios of bile acids reflective of gut microbiome and liver enzymatic activities and their correlation with disease status and cognitive function^a.

Ratios informative about metabolic processes	Ratios calculated	CN vs. AD (n=673) OR (95% CI); P-valueb	ADAS-Cog13 (n=1453) β(95% CI); P-value c
Bile acid synthesis: primary vs. alternative pathway	CA:CDCA	0.87(0.77,0.97);1.67E-02	−0.03(−0.07,0.01);1.27E-01
Conversion from primary to secondary BA by the gut microbiome	DCA:CA	1.25(1.16,1.35);1.53E-08	0.05(0.03,0.08);1.05E-05
	GDCA:CA	1.24(1.16,1.33);8.53E-10	0.06(0.04,0.08);1.20E-07
	TDCA:CA	1.16(1.10,1.24);9.83E-07	0.04(0.02,0.06);5.40E-05
	GLCA:CDCA	1.16(1.09,1.23);3.61E-06	0.04(0.02,0.06);9.15E-05
	TLCA:CDCA	1.09(1.03,1.16); 1.60E-03	0.03(0.01,0.05);1.50E-03
Glycine or Taurine conjugation of secondary bile acids by liver enzymes	GDCA:DCA	1.16(1.02,1.31);2.41E-02	0.05(0.02,0.10);5.49E-03
	TDCA:DCA	1.02(0.93,1.11);7.40E-01	0.01(−0.02,0.04);4.15E-01

^aSeveral ratios were calculated to inform about possible enzymatic activity changes in Alzheimer’s patients. These ratios reflect: (1) Shift in bile acid metabolism from primary to alternative pathway. (2) Changes in gut microbiome correlated with production of secondary bile acids. (3) Changes in glycine and taurine conjugation of secondary bile acids.

^bOutcome: Baseline diagnosis; Odds ratios and p-values were obtained from logistics regressions. Models were corrected for age, sex, body mass index, and APOE ε4 status; Bonferroni-adjusted critical value was set to 1.04E-03 based on 6 possible pairwise comparison of diagnosis groups (CN, EMCI, LMCI, and AD) for 8 ratios.

^cOutcome: Square root of ADASCog-13 (0 [best] to 85 [worst]); Models were corrected for age, sex, years of education, body mass index, and APOE ε4 status; Bonferroni-adjusted critical value was set to .11 × 10⁻⁴ (0.05 divided by all 23 metabolic traits times 7 phenotypes, which include cognitive function).