Table 4.
ROC curve results of predicting ATN biomarker groups according to individual and combined risk factors
| Basic model (model 1) | Model 1 + family history | Model 1 + BMI | Model 1 + WML volume | Model 1 + MMSE | Model 1 + all previous risk factors | Model 1 + CAIDE score | Model 1 + Framingham CVD score | Model 1 + Framingham stroke score | |
|---|---|---|---|---|---|---|---|---|---|
| Alzheimer’s pathologic change | |||||||||
| Age, years | 0.99 (0.96, 1.03) | 0.99 (0.96, 1.03) | 1.00 (0.96, 1.03) | 0.99 (0.96, 1.03) | 0.99 (0.96, 1.03) | 0.99 (0.96, 1.02) | 1.00 (0.97, 1.03) | 1.00 (0.96, 1.05) | 1.00 (0.96, 1.04) |
| Sex, female | 0.81 (0.57, 1.15) | 0.83 (0.58, 1.17) | 0.79 (0.55, 1.12) | 0.86 (0.61, 1.22) | 0.82 (0.65, 1.03) | 0.81 (0.64, 1.02) | 0.75 (0.52, 1.09) | 0.86 (0.59, 1.27) | 0.81 (0.57, 1.15) |
| APOE4* | 0.00 (0.00, 0.07) | 0.00 (0.00, 0.07) | 0.00 (0.00, 0.08) | 0.00 (0.00, 0.08) | 0.00 (0.00, 0.08) | 0.00 (0.00, 0.09) | 0.00 (0.00, 0.08) | 0.00 (0.00, 0.08) | 0.00 (0.00, 0.07) |
| Family history | 0.83 (0.56, 1.22) | 0.88 (0.59, 1.32) | |||||||
| BMI | 0.98 (0.94, 1.02) | 0.98 (0.94, 1.03) | |||||||
| WML volume† | 1.01 (1.01, 1.01) | 1.01 (1.00, 1.01) | |||||||
| MMSE score* | 0.00 (0.00, 0.12) | 0.00 (0.00, 0.21) | |||||||
| Composite risk score | 0.89 (0.72, 1.09) | 0.91 (0.71, 1.17) | 0.98 (0.76, 1.27) | ||||||
| AUC (95% CI) | 0.63 (0.58, 0.68) | 0.64 (0.59, 0.69) | 0.63 (0.58, 0.67) | 0.66 (0.61, 0.71) | 0.65 (0.60, 0.69) | 0.66 (0.61, 0.71) | 0.63 (0.58, 0.68) | 0.63 (0.58, 0.68) | 0.63 (0.58, 0.68) |
| P value | – | 0.33 | 0.70 | 0.02 | 0.25 | 0.09 | 0.84 | 0.95 | 0.68 |
| Alzheimer’s disease | |||||||||
| Age, years | 1.19 (1.13, 1.25) | 1.21 (1.15, 1.28) | 1.18 (1.13, 1.24) | 1.18 (1.12, 1.24) | 1.18 (1.12, 1.24) | 1.19 (1.13, 1.26) | 1.19 (1.13, 1.25) | 1.21 (1.33, 1.30) | 1.21 (1.14, 1.30) |
| Sex, female | 1.03 (0.57, 1.84) | 0.89 (0.49, 1.62) | 0.84 (0.46, 1.55) | 1.14 (0.62, 2.07) | 0.89 (0.49, 1.63) | 0.63 (0.32, 1.25) | 0.94 (0.50, 1.76) | 1.00 (0.56, 1.80) | 1.20 (0.63, 2.30) |
| APOE4 | 7.89 (4.18, 14.9) | 6.96 (3.68, 13.2) | 7.78 (4.11, 14.8) | 8.91 (4.59, 17.3) | 7.94 (4.19, 15.1) | 7.87 (3.96, 15.6) | 8.14 (4.28, 15.5) | 8.09 (4.27, 15.3) | 8.15 (4.30, 15.5) |
| Family history | 4.08 (1.70, 9.81) | 4.63 (1.79, 12.0) | |||||||
| BMI | 0.88 (0.81, 0.96) | 0.85 (0.76, 0.94) | |||||||
| †WML volume | 1.01 (1.00, 1.02) | 1.02 (1.01, 1.03) | |||||||
| MMSE score | 0.78 (0.66, 0.92) | 0.78 (0.65, 0.94) | |||||||
| Composite risk score | 0.89 (0.64, 1.22) | 0.82 (0.53, 1.26) | 0.78 (0.51, 1.21) | ||||||
| AUC (95% CI) | 0.82 (0.77, 0.88) | 0.84 (0.79, 0.89) | 0.84 (0.78, 0.89) | 0.84 (0.78, 0.90) | 0.84 (0.79, 0.89) | 0.89 (0.85, 0.93) | 0.82 (0.77, 0.88) | 0.82 (0.77, 0.88) | 0.83 (0.77, 0.88) |
| P value | – | 0.15 | 0.18 | 0.07 | 0.11 | 0.0002 | 0.80 | 0.80 | 0.45 |
| AD and non-AD pathologic change | |||||||||
| Age, years | 0.98 (0.92, 1.04) | 0.97 (0.91, 1.03) | 0.98 (0.92, 1.04) | 0.98 (0.91, 1.04) | 0.98 (0.92, 1.04) | 0.97 (0.91, 1.03) | 0.98 (0.92, 1.04) | 0.97 (0.90, 1.06) | 0.95 (0.87, 1.03) |
| Sex, female | 0.72 (0.34, 1.52) | 0.78 (0.36, 1.66) | 0.75 (0.35, 1.60) | 0.78 (0.37, 1.68) | 0.72 (0.34, 1.54) | 0.89 (0.41, 1.93) | 0.68 (0.31, 1.49) | 0.71 (0.31, 1.60) | 0.71 (0.34, 1.52) |
| APOE4 | 0.99 (0.44, 2.22) | 1.06 (0.47, 2.39) | 0.98 (0.44, 2.21) | 1.11 (0.49, 2.53) | 0.99 (0.44, 2.22) | 1.15 (0.50, 2.64) | 1.02 (0.45, 2.32) | 0.98 (0.43, 2.23) | 0.95 (0.42, 2.15) |
| Family history | 0.49 (0.22, 1.09) | 0.54 (0.24, 1.23) | |||||||
| BMI | 1.05 (0.96, 1.14) | 1.05 (0.96, 1.15) | |||||||
| WML volume† | 1.01 (1.00, 1.02) | 1.01 (1.00, 1.02) | |||||||
| MMSE score | 1.02 (0.75, 1.38) | 1.01 (0.74, 1.37) | |||||||
| Composite risk score | 0.90 (0.57, 1.42) | 1.03 (0.60, 1.75) | 1.35 (0.80, 2.27) | ||||||
| AUC (95% CI) | 0.56 (0.44, 0.68) | 0.62 (0.50, 0.72) | 0.57 (0.45, 0.68) | 0.63 (0.51, 0.75) | 0.56 (0.44, 0.68) | 0.68 (0.56, 0.80) | 0.56 (0.45, 0.68) | 0.56 (0.44, 0.68) | 0.58 (0.47, 0.69) |
| P value | – | 0.33 | 0.84 | 0.11 | 0.92 | 0.06 | 0.96 | 0.88 | 0.45 |
| Non-AD pathology | |||||||||
| Age, years | 1.07 (1.04, 1.11) | 1.07 (1.03, 1.10) | 1.07 (1.04, 1.11) | 1.07 (1.04, 1.11) | 1.07 (1.03, 1.10) | 1.06 (1.03, 1.10) | 1.07 (1.03, 1.11) | 1.05 (1.00, 1.09) | 1.07 (1.03, 1.12) |
| Sex, female | 1.11 (0.74, 1.68) | 1.14 (0.75, 1.72) | 1.10 (0.73, 1.66) | 1.13 (0.75, 1.71) | 1.08 (0.71, 1.63) | 1.09 (0.71, 1.66) | 1.19 (0.77, 1.84) | 1.14 (0.75, 1.72) | 1.11 (0.71, 1.74) |
| APOE4 | 1.38 (0.90, 2.13) | 1.43 (0.92, 2.21) | 1.39 (0.90, 2.14) | 1.39 (0.90, 2.15) | 1.38 (0.89, 2.12) | 1.44 (0.93, 2.23) | 1.35 (0.87, 2.09) | 1.35 (0.87, 2.08) | 1.38 (0.89, 2.13) |
| Family history | 0.68 (0.44, 1.04) | 0.68 (0.44, 1.04) | |||||||
| BMI | 0.99 (0.94, 1.04) | 0.98 (0.93, 1.03) | |||||||
| WML volume† | 1.00 (1.00, 1.01) | 1.00 (1.00, 1.01) | |||||||
| MMSE score | 0.89 (0.77, 1.03) | 0.88 (0.76, 1.02) | |||||||
| Composite risk score | 1.10 (0.88, 1.37) | 1.25 (0.95, 1.64) | 1.00 (0.76, 1.33) | ||||||
| AUC (95% CI) | 0.63 (0.58, 0.68) | 0.64 (0.59, 0.69) | 0.63 (0.58, 0.69) | 0.63 (0.58, 0.68) | 0.64 (0.59, 0.69) | 0.66 (0.60, 0.71) | 0.63 (0.58, 0.68) | 0.63 (0.58, 0.69) | 0.63 (0.58, 0.68) |
| P value | – | 0.32 | 0.31 | 0.52 | 0.37 | 0.08 | 0.92 | 0.55 | 0.78 |
All models estimate the discriminative accuracy of predicting ATN-defined biomarker group versus the normal AD biomarker group
*Models predicting AD pathologic change include age by APOE4 interaction term and sex by MMSE interaction. P values in bold survive Bonferroni correction (0.5/32 = 0.016)
†Proportion of total brain volume. Group sizes: n = 525 participants with normal AD biomarkers versus: Alzheimer’s pathologic change (n = 187); Alzheimer’s disease (n = 64); AD and non-AD pathologic change (n = 29); non-AD pathology (n = 122). P values in bold survive Bonferroni correction (0.5/32 = 0.016)