Table 3.
Associations of lymphocyte subsets (per 1 SD) with cognitive outcomes. Analyses for cross-sectional 3MSE score and change in 3MSE score over seven years are based on multiple linear regression. Analysis of prevalent dementia is based on Poisson regression. Analysis of time to death from dementia is based on Cox proportional hazards regression. All analyses adjust for age, sex, Black race, systolic blood pressure, smoking, statin use, education, prevalent diabetes, APOE4 carrier status, BMI, CMV antibody titer, assay batch, and study site. Participants were censored at death without dementia or in 2015. All 1928 individuals are included in each analysis. Missing data were imputed, including covariates (see Table 1), immune cells (see Table 2), and outcomes. We imputed 20 cross-sectional cognitive scores, 996 changes in cognitive score, 402 statuses of prevalent dementia, and 19 times to death with dementia. Beta values that are negative indicate lower cognitive score and a greater decline in cognition over 7 years
| Cross-sectional 3 MSE score | Change over seven years | Cross-sectional dementia | Time to dementia death | |||||||||
| Cellular phenotype | Beta | 95% CI | p | Beta | 95% CI | p | Relative Risk | 95% CI | p | Hazard Ratio | 95% CI | p |
| Natural killer | 0.06 | –1.71, 1.84 | 0.94 | –0.09 | –3.90, 3.73 | 0.96 | 1.15 | 0.77, 1.70 | 0.50 | 1.16 | 0.80, 1.69 | 0.44 |
| Treg | –0.52 | –1.08, 0.03 | 0.065 | –1.30 | –2.36, –0.24 | 0.018 | 1.10 | 0.99, 1.22 | 0.086 | 1.13 | 0.78, 1.64 | 0.52 |
| CD4 + TEMRA | –0.12 | –0.80, 0.55 | 0.72 | 0.47 | –0.80, 1.73 | 0.47 | 0.98 | 0.83, 1.16 | 0.82 | 1.07 | 0.76, 1.52 | 0.68 |
| CD8 + TEMRA | 0.05 | –0.55, 0.65 | 0.86 | 0.24 | –0.91, 1.39 | 0.68 | 1.03 | 0.91, 1.18 | 0.63 | 1.05 | 0.74, 1.49 | 0.79 |
| γδ T cells | 0.41 | –1.81, 2.62 | 0.72 | –0.93 | –4.85, 2.99 | 0.64 | 1.00 | 0.66, 1.50 | 0.98 | 1.06 | 0.75, 1.50 | 0.76 |
| B cells | 0.26 | –0.22, 0.73 | 0.29 | 0.08 | –0.85, 1.01 | 0.86 | 0.97 | 0.87, 1.08 | 0.54 | 1.10 | 0.77, 1.57 | 0.60 |
| T helper cells | –0.15 | –0.33, 0.02 | 0.09 | –0.03 | –0.37, 0.31 | 0.86 | 1.01 | 0.97, 1.05 | 0.74 | 1.08 | 0.76, 1.53 | 0.67 |
| Cytotoxic T cells | 0.11 | –0.02, 0.25 | 0.09 | –0.07 | –0.31, 0.17 | 0.56 | 1.01 | 0.98, 1.04 | 0.70 | 1.08 | 0.76, 1.54 | 0.67 |
| Th1 | 0.14 | –0.17, 0.46 | 0.38 | –0.25 | –0.87, 0.37 | 0.44 | 0.99 | 0.92, 1.06 | 0.79 | 1.08 | 0.76, 1.53 | 0.67 |
| Th2 | –0.12 | –2.51, 2.28 | 0.92 | 1.59 | –4.50, 7.68 | 0.61 | 0.99 | 0.57, 1.71 | 0.97 | 1.08 | 0.75, 1.55 | 0.68 |
| Th17 | 0.34 | –2.88, 3.56 | 0.84 | 1.51 | –2.14, 5.16 | 0.42 | 0.99 | 0.53, 1.84 | 0.97 | 1.08 | 0.76, 1.53 | 0.68 |
| Naïve CD4 + cells | 0.12 | –0.42, 0.66 | 0.67 | 0.14 | –0.86, 1.15 | 0.78 | 0.90 | 0.79, 1.03 | 0.14 | 1.00 | 0.70, 1.43 | 0.99 |
| Memory CD4 + cells | –0.04 | –0.39, 0.30 | 0.81 | –0.13 | –0.83, 0.56 | 0.71 | 1.06 | 0.97, 1.15 | 0.19 | 1.01 | 0.71, 1.44 | 0.97 |
| Activated/mature CD4 + cells | 0.10 | –0.45, 0.64 | 0.73 | 0.24 | –0.73, 1.20 | 0.63 | 0.95 | 0.84, 1.08 | 0.45 | 1.09 | 0.77, 1.55 | 0.62 |
| Naïve CD8 + cells | 0.06 | –0.06, 0.17 | 0.33 | –0.13 | –0.36, 0.09 | 0.24 | 0.99 | 0.96, 1.02 | 0.47 | 1.08 | 0.76, 1.53 | 0.66 |
| Memory CD8 + cells | –0.25 | –0.59, 0.10 | 0.16 | 0.21 | –0.41, 0.82 | 0.51 | 1.04 | 0.96, 1.13 | 0.29 | 1.09 | 0.77, 1.54 | 0.64 |
| Activated/mature CD8 + cells | 0.10 | –0.45, 0.64 | 0.73 | 0.34 | –0.80, 1.48 | 0.56 | 0.97 | 0.85, 1.10 | 0.60 | 1.06 | 0.71, 1.57 | 0.79 |
| Memory B cells | –0.15 | –0.74, 0.45 | 0.63 | –1.00 | –2.29, 0.30 | 0.13 | 1.09 | 0.96, 1.23 | 0.21 | 1.16 | 0.81, 1.67 | 0.42 |
p-value threshold for the primary endpoints is 0.0125. Bolded cells are primary hypotheses. CI, Confidence Interval.