Supplementary webappendix€¦ ·  · 2012-12-19when compared directly to a simple linear model....

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Supplementary webappendix This webappendix formed part of the original submission and has been peer reviewed. We post it as supplied by the authors. Supplement to: Fleisher AS, Chen K, Quiroz YT, et al. Florbetapir PET analysis of amyloid-β deposition in the presenilin 1 E280A autosomal dominant Alzheimer’s disease kindred: a cross-sectional study. Lancet Neurol 2012; published online Nov 6. http://dx.doi.org/10.1016/S1474-4422(12)70227-2

Transcript of Supplementary webappendix€¦ ·  · 2012-12-19when compared directly to a simple linear model....

Page 1: Supplementary webappendix€¦ ·  · 2012-12-19when compared directly to a simple linear model. AIC = Akaike's information criterion. Figure S1: Comparison of regression models

Supplementary webappendixThis webappendix formed part of the original submission and has been peer reviewed. We post it as supplied by the authors.

Supplement to: Fleisher AS, Chen K, Quiroz YT, et al. Florbetapir PET analysis of amyloid-β deposition in the presenilin 1 E280A autosomal dominant Alzheimer’s disease kindred: a cross-sectional study. Lancet Neurol 2012; published online Nov 6. http://dx.doi.org/10.1016/S1474-4422(12)70227-2

Page 2: Supplementary webappendix€¦ ·  · 2012-12-19when compared directly to a simple linear model. AIC = Akaike's information criterion. Figure S1: Comparison of regression models

Web Extra Materials:  Table S1  Table  S1  Regression Model Comparison 

Probability of correctness Probability of correctness

Sigmoidal vs 3 Segment piecewise

Difference in AIC Sigmoidal vs Simple Linear Difference in AIC

Mean Cortical

90.4%

9.6% -4.49 98.4% 1.6% -8.27

Precuneus 87.8%

12.2% -3.94 99.9% 0.06% -14.73

Basal Ganglia 77.6%

22.3% -2.49 99.9% 0.1% -13.36

Frontal 91.7%

8.3% -4.80 99.6% 0.4% -11.00

Anterior Cingulate

92.0%

8.0% -4.90 99.5% 0.5% -10.70

Parietal 57.9%

42.1% -0.63

96.3% 3.7% -6.54

Temporal 93.1%

6.9% -5.21 86.3% 13.6% -3.69

Posterior Cingulate

94.2%

5.8% -5.58 95.5% 4.4% -6.14

   Table S1: Goodness of fit comparison for three regression models: sigmoidal, three segment piecewise linear, and simple linear.  The  sigmoidal  regression model  had  higher  probabilities  of  correctly  fitting  the  relationship  between mean cortical and regional SUVRs  in relation to age than a 3 segment piecewise  linear modal, as well as better probabilities when compared directly to a simple linear model. AIC = Akaike's information criterion.    

Page 3: Supplementary webappendix€¦ ·  · 2012-12-19when compared directly to a simple linear model. AIC = Akaike's information criterion. Figure S1: Comparison of regression models

Figure S1: Comparison of regression models for age‐related accumulation of SUVRs compared to age  

 Figure S1: Three model comparison of mean cortical florbetapir F18 levels compared to age: A) simple linear model, B) 3 segment piecewise  linear model, C) sigmoidal model. The goodness‐of‐fit of each  individual model was assessed using R‐square  testing.  The  extra  sum of  squares  f‐test was used  to  compare  the  goodness‐of‐fit  between the  simple  linear  and piecewise  linear models.  Linear regression models were compared  to  the sigmoidal model using Akaike's information criterion (AIC) from information theory since the two models are not nested. The relationship between age and mean cortical SUVRs was best  represented by a  sigmoidal  shaped curve.   While  the  fit of a  simple linear  regression model  was  satisfactory  (R2=0.74  and  p=0.0002),  a  three  segment  piecewise  linear model  had  an improved  fit  compared  to  the  simple  linear model  (p=0.01). This piecewise  linear model demonstrated an  initial  flat slope, followed by an upward inflexion in mean cortical SUVR at age 29 and later plateauing at age 38. The probability of the  sigmoidal  model  properly  representing  the  data  was  98.4%  versus  a  1.6%  probability  that  the  simple  linear regression model was  correct. Similarly,  the  sigmoidal model  supported a  three  stage progression of  cortical  fibrillar amyloid associated with age and disease state, but showed a superior goodness‐of‐fit to the data compared to the three segment piecewise linear model (90.4% compared to 9.6%).