Table 4 Significant associations of metabolites with incident hospitalized dementia stratified by gender

Metabolite ^a	Pathway	Platform	Men (N=500)
			HR	95% CI	P^b,^c	Mean (s.d.)	Median	Q1	Q3
4-androsten-3 beta, 17 beta-diol disulfate 1	Sterol/steroid	LC/MS neg	1.29	1.12, 1.47	3.21 × 10 ⁻⁴	0.445 (1.58)	0.012	−0.232	0.464
X-11440	None	LC/MS neg	1.36	1.13, 1.64	1.35 × 10⁻³	0.493 (1.22)	0.189	−0.240	0.963
Pregnen-diol disulfate	Sterol/steroid	LC/MS neg	1.29	1.09, 1.53	3.38 × 10⁻³	0.587 (1.28)	0.237	−0.237	0.950
5 alpha-androstan-3 beta, 17 beta-diol disulfate	Sterol/steroid	LC/MS neg	1.25	1.10, 1.42	6.05 × 10⁻⁴	0.576 (1.42)	0.171	−0.160	0.776
X-12851	None	LC/MS neg	1.27	1.07, 1.49	4.76 × 10⁻³	−0.101 (0.884)	−0.366	−0.502	−0.130
			Women (N=848)
4-androsten-3 beta, 17 beta-diol disulfate 1	Sterol/steroid	LC/MS neg	1.19	0.75, 1.88	0.465	−0.208 (0.466)	−0.327	−0.458	−0.140
X-11440	None	LC/MS neg	0.29	0.97, 1.71	0.0791	−0.230 (0.806)	−0.389	−0.753	0.017
Pregnen-diol disulfate	Sterol/steroid	LC/MS neg	0.46	1.10, 1.93	7.92 × 10⁻³	−0.297 (0.691)	−0.440	−0.716	−0.137
5 alpha-androstan-3 beta, 17 beta-diol disulfate	Sterol/steroid	LC/MS neg	1.00	0.65, 1.55	0.980	−0.313 (0.405)	−0.421	−0.549	−0.242
X−12851	None	LC/MS neg	1.24	1.03, 1.50	0.0248	0.044 (1.02)	−0.296	−0.502	0.061

Abbreviations: APOE, apolipoprotein E; BMI, body mass index; CI, confidence interval; CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration; eGFR, estimated glomerular filtration rate; HR, hazard ratio; LC/MS neg, liquid chromatography/mass spectrometry-negative ion mode; LDL cholesterol, low-density lipoprotein cholesterol; Q1, quartile 1; Q3, quartile 3.
^aAll metabolites in Group 1, analyzed as continuous variables.
^bThreshold for statistical significance <3.9 × 10⁻⁴; bold P-values are statistically significant.
^cAdjusted for age, education, eGFR_CKD-EPI, diabetes, hypertension, BMI, LDL cholesterol, current smoking, alcohol intake, APOE genotype (at least 1 ɛ4 allele/no ɛ4 allele).

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