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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