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Table 4 ROC curve results of predicting ATN biomarker groups according to individual and combined risk factors

From: Prediction of Alzheimer’s disease biomarker status defined by the ‘ATN framework’ among cognitively healthy individuals: results from the EPAD longitudinal cohort study

  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
  1. All models estimate the discriminative accuracy of predicting ATN-defined biomarker group versus the normal AD biomarker group
  2. *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)
  3. †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)
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Alzheimer's Research & Therapy

ISSN: 1758-9193