Table 3.
Age- and sex-adjusted effects of risk factors on ATN subgroups: multinomial logistic regression
| Predicting Alzheimer’s pathologic change | Predicting Alzheimer’s disease | Predicting AD/non-AD pathologic change | Predicting non-AD pathology | ||||||
|---|---|---|---|---|---|---|---|---|---|
| N | RRR (95% CI) | P | RRR (95% CI) | P | RRR (95% CI) | P | RRR (95% CI) | P | |
| Risk exposures | |||||||||
| 1. Age, years | 1010 | 1.02 (1.00, 1.05) | 0.08 | 1.14 (1.09, 1.19) | 1.3 × 10−09 | 0.97 (0.92, 1.02) | 0.25 | 1.07 (1.04, 1.10) | 2.9 × 10−06 |
| 2. Sex, female | 1010 | 0.80 (0.58, 1.10) | 0.17 | 0.93 (0.55, 1.56) | 0.78 | 0.71 (0.34, 1.47) | 0.36 | 1.05 (0.71, 1.56) | 0.79 |
| 3. Education, years | 1010 | 1.00 (0.96, 1.05) | 0.87 | 0.95 (0.89, 1.02) | 0.18 | 1.07 (0.97, 1.18) | 0.16 | 0.99 (0.94, 1.04) | 0.75 |
| 4. APOE4 | 955 | 1.93 (1.37, 2.72) | 1.6 × 10−04 | 6.48 (3.57, 11.8) | 8.5 × 10−10 | 1.09 (0.50, 2.36) | 0.82 | 1.27 (0.83, 1.93) | 0.27 |
| 5. Family history | 1010 | 1.00 (0.70, 1.44) | 0.99 | 4.12 (1.93, 8.77) | 2.5 × 10−04 | 0.63 (0.29, 1.37) | 0.25 | 0.75 (0.50, 1.14) | 0.18 |
| 6. Systolic BP | 1009 | 1.00 (1.00, 1.01) | 0.35 | 1.00 (0.98, 1.02) | 1.0 | 1.01 (0.99, 1.03) | 0.32 | 1.00 (0.99, 1.01) | 0.95 |
| 7. BMI | 1006 | 0.98 (0.94, 1.02) | 0.29 | 0.88 (0.82, 0.95) | 0.001 | 1.02 (0.94, 1.10) | 0.65 | 0.98 (0.93, 1.02) | 0.30 |
| 8. High cholesterol | 1010 | 0.75 (0.48, 1.18) | 0.21 | 0.49 (0.22, 1.08) | 0.08 | 0.52 (0.15, 1.77) | 0.30 | 0.84 (0.51, 1.40) | 0.51 |
| 9. Physical inactivity | 1005 | 0.86 (0.62, 1.19) | 0.36 | 1.01 (0.59, 1.71) | 0.98 | 0.83 (0.38, 1.79) | 0.64 | 1.13 (0.77, 1.67) | 0.53 |
| 10. Ever smoked | 1005 | 1.09 (0.79, 1.50) | 0.62 | 1.34 (0.79, 2.28) | 0.28 | 1.54 (0.72, 3.29) | 0.27 | 1.39 (0.94, 2.05) | 0.10 |
| 11. BP medication | 1010 | 0.61 (0.38, 0.97) | 0.04 | 0.48 (0.23, 1.04) | 0.06 | 0.87 (0.32, 2.40) | 0.79 | 0.69 (0.41, 1.18) | 0.18 |
| 12. Diabetes | 1010 | 0.32 (0.11, 0.94) | 0.04 | 0.81 (0.26, 2.51) | 0.72 | – | 1.44 (0.68, 3.05) | 0.34 | |
| 13. Prior CVD | 1010 | 0.68 (0.27, 1.73) | 0.42 | 0.71 (0.19, 2.57) | 0.60 | 2.00 (0.43, 9.23) | 0.38 | 1.10 (0.45, 2.70) | 0.84 |
| 14. Atrial fibrillation | 1010 | 0.87 (0.23, 3.27) | 0.84 | 0.81 (0.10, 6.73) | 0.84 | – | 2.22 (0.72, 6.86) | 0.17 | |
| 15. WML volume* | 988 | 1.008 (1.003, 1.014) | 0.002 | 1.014 (1.007, 1.020) | 4.0 × 10−05 | 1.012 (1.004, 1.021) | 0.005 | 1.002 (0.995, 1.010) | 0.52 |
| 16. MMSE | 1009 | 1.02 (0.90, 1.16) | 0.74 | 0.79 (0.68, 0.93) | 0.006 | 1.04 (0.77, 1.41) | 0.80 | 0.91 (0.79, 1.05) | 0.18 |
| 17. Episodic verbal memory | 1007 | 1.00 (0.96, 1.04) | 0.95 | 0.95 (0.89, 1.01) | 0.10 | 1.03 (0.94, 1.14) | 0.53 | 0.98 (0.93, 1.03) | 0.38 |
| 18. Executive function | 1007 | 0.98 (0.97, 1.00) | 0.05 | 0.97 (0.95, 1.00) | 0.02 | 0.99 (0.96, 1.03) | 0.70 | 0.98 (0.96, 1.00) | 0.08 |
| Composite scores | |||||||||
| 19. CAIDE | 1002 | 0.92 (0.77, 1.10) | 0.34 | 1.00 (0.75, 1.32) | 0.98 | 0.86 (0.56, 1.32) | 0.49 | 1.05 (0.85, 1.29) | 0.65 |
| 20. Framingham CVD | 1005 | 0.90 (0.70, 1.12) | 0.33 | 0.84 (0.57, 1.23) | 0.37 | 0.96 (0.56, 1.64) | 0.88 | 0.97 (0.74, 1.27) | 0.82 |
| 21. Framingham stroke | 1005 | 0.99 (0.78, 1.27) | 0.96 | 0.94 (0.65, 1.37) | 0.75 | 1.31 (0.77, 2.24) | 0.32 | 1.23 (0.93, 1.61) | 0.14 |
All models additionally adjust for study site (n = 21). Effects sizes are relative risk ratios (RRR) and their 95% confidence intervals. For the full sample (n = 1010) the groups sizes are as follows: normal AD biomarkers: n = 567; Alzheimer’s pathologic change: n = 211; AD: n = 67; AD and non-AD pathologic change: n = 31; non-AD pathologic change: n = 134. Composite scores are entered into models as z-scores. P values in bold survive Bonferroni correction (0.5/84 = 0.006)
*Proportion of total brain volume. No significant interaction terms were observed between individual vascular risk factors and age nor sex, respectively, except that sex and MMSE score in predicting Alzheimer’s pathologic change (p = 0.006), and age and APOE4 in predicting Alzheimer’s pathologic change (p < 0.001)