Table 4.

Mean difference (95% CI) in rate of change in global score between vitamin D and placebo group: effect modification by risk factors for cognitive decline.

CI confidence interval; CTSC-Cog, subset that received in-person interviews at the Harvard Clinical and Translational Science Collaborative center for VITAL in Boston, MA; CVD cardiovascular disease; VITAL-Cog subset that received telephone cognitive interviews in VITAL.

For definitions of the global scores for the two populations, see footnote for Table 2.

^aMean difference in annual rate of decline of vitamin D—placebo groups from multivariable-adjusted linear mixed models: see footnotes for Table 3. The stratified analyses were done among those with non-missing data on the effect modifier.

^bInteraction terms across the two substudies were pooled using Dersimonian and Laird fixed-effects method for meta-analysis. There was significant heterogeneity (p < 0.05) for two pooled p-interactions, and for these, random effects were incorporated into the meta-analysis; the pooled p-for interaction was 0.48 for sex and 0.66 for Vitamin D supplement use (< 800 IU) outside of the trial. None of the interaction terms for the non-pre-specified modifiers were significant at the Bonferroni-adjusted p-value of 0.0038 (= 0.05/13 subgroup analyses): pooled p for interaction ≥ 0.18.

^cStratum-specific estimates were pooled using Dersimonian and Laird fixed-effects method for meta-analysis. There was significant heterogeneity (p-het < 0.05) for three strata, and for these, random effects were incorporated into the meta-analysis and presented in the Table. For reference, the fixed effects meta-analyzed pooled estimates were: 0.004 (95% CI − 0.01, 0.02) for females (p-het = 0.03), 0.003 (95% CI − 0.02, 0.02) for those with multiple CVD risk factors (p-het = 0.04) and 0.01 (95% CI − 0.01, 0.02) for those using Vitamin D supplements (< 800 IU) outside of the trial (p-het = 0.03).

^dSee footnote in Table 1 for definition of depression.

^eMedian for the global score was 0.05 in both the VITAL-Cog and the CTSC-Cog.

^fCompliance is defined as taking ≥ 2/3rd of pills on all of the follow-up questionnaires between the first and the second cognitive assessment and not initiating out-of-study fish oil supplementation.