Table 2.

Associations between red blood cell docosahexaenoic acid and eicosapentaenoic acid (RBC DHA+EPA) content at baseline and the relative hazards (HRs) of incident probable dementia (PD), mild cognitive impairment (MCI), or the composite outcome (PD or MCI) during WHIMS and WHIMS-ECHO.

Time period	Exposure	Model	PD* (587 cases total; 213 in WHIMS; 374 in WHIMS-ECHO)				MCI (671 cases total; 325 in WHIMS; 346 in WHIMS-ECHO)				PD or MCI (1047 cases total; 455 in WHIMS; 592 in WHIMS-ECHO)
			HR	95°% CI		P value	HR	95°% CI		P value	HR	95°% CI		P value
WHIMS (1995–2007) and WHIMS-ECHO (2008–2016)	DHA+EPA† (per 1 SD)	1	0.92	0.84	1.00	0.0434	0.96	0.89	1.05	0.3751	0.95	0.89	1.02	0.1399
		2	0.92	0.84	1.00	0.0454	0.97	0.89	1.05	0.3880	0.95	0.90	1.02	0.1463
		3	0.92	0.84	1.00	0.0498	0.97	0.89	1.05	0.4466	0.96	0.90	1.02	0.1741
		S1	0.91	0.83	0.99	0.0293	0.95	0.88	1.03	0.2284	0.94	0.88	1.00	0.0647
		S2	0.92	0.83	1.01	0.0929	1.00	0.90	1.10	0.9501	0.96	0.89	1.04	0.3430
	DHA (per 1 SD)	3	0.92	0.85	1.01	0.0799	0.97	0.90	1.06	0.5226	0.96	0.90	1.02	0.2032
	EPA (per 1 SD)	3	0.93	0.85	1.02	0.1244	0.97	0.89	1.05	0.4376	0.97	0.91	1.03	0.3357
WHIMS	DHA+EPA (per 1 SD)	3	0.85	0.73	0.99	0.0429	0.95	0.86	1.07	0.4098	0.96	0.87	1.05	0.3575
WHIMS-ECHO	DHA+EPA (per 1 SD)	3	0.95	0.86	1.05	0.3162	0.98	0.87	1.09	0.6704	0.95	0.88	1.03	0.2344

Model 1 = RBC omega-3 FA content, HT trial arm (4 levels: estrogen-only trial: active treatment or placebo; estrogen and progestin trial: active treatment or placebo), age at baseline, education, race/ethnicity (black, white or other). Educational attainment was analyzed as an 11-level ordinal variable, ranging from 1 (no formal education) to 11 (doctoral degree). For simplicity, these 11 levels were collapsed to three broader categories in Table 1. Cubic spline transformations of age and education with knots at the 10^th, 50^th and 90^th percentiles were used to allow for non-linear relationships with the study outcomes.

Model 2 = Model 1 + cardiovascular disease, hypertension, diabetes.

Model 3 = Model 2 + BMI (cubic spline transformation), current smoking status, status as prior alcohol user, current average servings of alcohol per week (cubic spline transformation).

Model S1 (sensitivity analysis 1) = Model 3 + baseline 3MS score (cubic spline transformation).

Model S2 (sensitivity analysis 2) = Model 3 + APOE genotype (none vs. 1+ ε4 alleles). Note: the S2 sensitivity analysis included only participants for whom data on APOE genotype were available.

^*Probable dementia was the primary endpoint.

^†RBC DHA+EPA was the primary exposure.