Table 4.

Subgroup differences in the association of the joint associations of CMM5^a and depression on longitudinal cognitive function.

Interaction term	β (95% CI)	p-value	Stratified analyses when the interaction term is significant, β (95% CI)
Age interaction: age is classified as middle-life (≤65, N = 3158) and late-life (>65, N = 19,441)
CMM5 (−)/depression (+)∗Age∗Time	−0.005 (−0.020, 0.011)	0.496
CMM5 (+)/depression (−)∗Age∗Time	0.004 (−0.007, 0.014)	0.554
CMM5 (+)/depression (+)∗Age∗Time	0.003 (−0.012, 0.018)	0.671
Education interaction: education (years) is classified as low education (<8, N = 10,930) and high education ( ≥ 8, N = 11,616)
CMM5 (−)/depression (+)∗Education∗Time	0.001 (0.0001, 0.003)	0.029	−0.006 (−0.016, 0.003) for high −0.025 (−0.032, −0.018) for low
CMM5 (+)/depression (−)∗Education∗Time	0.001 (−0.001, 0.002)	0.077
CMM5 (+)/depression (+)∗Education∗Time	−0.001 (−0.002, 0.001)	0.277
Sex interaction: sex is classified as male (N = 8608) and female (N = 13,991)
CMM5 (−)/depression (+)∗Sex∗Time	0.009 (−0.006, 0.024)	0.246
CMM5 (+)/depression (−)∗Sex∗Time	0.014 (0.005, 0.024)	0.002	−0.030 (−0.036, −0.024) for female −0.017 (−0.024, −0.010) for male
CMM5 (+)/depression (+)∗Sex∗Time	0.029 (0.014, 0.040)	<0.001	−0.038 (−0.045, −0.031) for female −0.011 (−0.022, 0.001) for male
APOE genotype interaction: APOE genotype is classified as ε4 non-carriers (N = 12,579) and ε4 carriers (N = 3151)
CMM5 (−)/depression (+)∗APOE genotype∗Time	−0.003 (−0.024, 0.017)	0.747
CMM5 (+)/depression (−)∗APOE genotype∗Time	−0.013 (−0.026, −0.001)	0.040	−0.030 (−0.036, −0.024) for ε4 non−carriers −0.041 (−0.053, −0.030) for ε4 carriers
CMM5 (+)/depression (+)∗APOE genotype∗Time	−0.008 (−0.027, 0.010)	0.390
Study region interaction: study region is classified as HICsb (N = 12,969) and LMICsc (N = 9630)
CMM5 (−)/depression (+)∗Study region∗Time	−0.012 (−0.026, 0.002)	0.332
CMM5 (+)/depression (−)∗Study region∗Time	0.005 (−0.005, 0.015)	0.101
CMM5 (+)/depression (+)∗Study region∗Time	0.017 (0.003, 0.031)	0.015	−0.037 (−0.046, −0.270) for HICs −0.021 (−0.031, −0.011) for LMICs

Reference group was CMM5(−)/depression(−). Each model was adjusted for age, sex, education years, race, study region, and current smoking and drinking status (though not when the stratification variable, e.g. sex was not adjusted in the sex stratification).

^aCMM5: Cardiometabolic multimorbidity, defined as having two or more CMDs including hypertension, hyperlipidemia, diabetes, stroke, and heart disease.

^bHICs: high income countries.

^cLMICs:lower middle income countries. Effects were estimated using 11 COSMIC studies and 13,570 participants.