Table 4.
Mediation analysis. Total, direct, and indirect effects of TRAP (NOx) through type 2 diabetes on time to incident cognitive outcomes and proportion of total effect mediated through T2DM.
| All SALSA (n=1387)* |
Urban Only (n=1201) |
|||
|---|---|---|---|---|
| Associations | HR (95% CI) | Proportion Mediated | HR (95% CI) | Proportion Mediated |
| Total Effect: TRAP (NOx) (>2.68 ppb (T3) versus ≤ 2.68 ppb (ref)) → Dementia | 1.54 (0.96, 2.70) | 18% | 1.67 (1.01, 2.87) | 18% |
| Direct Effect: TRAP (NOx) → (M) → Dementia | 1.43 (0.88, 2.48) | 1.52 (0.92, 2.61) | ||
| Indirect Effect: TRAP (NOx) → T2DM → Dementia | 1.08 (1.03, 1.19) | 1.10 (1.03, 1.19) | ||
| Total Effect: TRAP (NOx) → CIND | 1.30 (0.71, 2.27) | 27% | 1.42 (0.79, 2.47) | 23% |
| Direct Effect: TRAP (NOx) → (M) → CIND | 1.21 (0.67, 2.08) | 1.31 (0.72, 2.25) | ||
| Indirect Effect: TRAP (NOx) → T2DM → CIND | 1.07 (1.01, 1.17) | 1.08 (1.02, 1.19) | ||
| Total Effect: TRAP (NOx) → Dementia/CIND | 1.40 (0.98, 2.07) | 20% | 1.59 (1.10, 2.26) | 18% |
| Direct Effect: TRAP (NOx) → (M) → Dementia/CIND | 1.32 (0.90, 1.92) | 1.46 (1.00, 2.09) | ||
| Indirect Effect: TRAP (NOx) → T2DM → Dementia/CIND | 1.06 (1.03, 1.14) | 1.09 (1.04, 1.17) | ||
Abbreviations: CIND=Cognitive Impairment, non-dementia; T3=tertile 3 (TRAP-NOx dichotomized at >T3); IQR=interquartile range (2.31 ppb) (M) = complete set of non-modeled mediators; i.e. all pathways not going through designated mediator Models control for baseline 3MSE score, baseline age, sex, years of education, primary language spoken, occupation for most of life (manual, non-manual, or other), NSES, IL-6 inflammation marker, cigarette smoking, a county indicator, and a rural/urban residential neighborhood indicator (excluded for urban only analysis)
Based on Cox proportional hazards models, time to event. Mediated proportion=IE/TE. 95% CI based on bootstrapping that accounts for clustering within census tracts (5,000 resamples; 2.5 and 97.5 percentiles).
This analysis differs from Table 2, in that we included IL-6 as a potential mediator-outcome confounder. As a result, 160 participants that did not have this information were excluded from the population used to calculate the estimates presented in this table. Thus, this slightly changes the sample size and model, and the total association therefore differs somewhat between Table 2 and Table 4.