Baseline subject characteristics.

<p>Data shown as mean ± standard deviation. Education is presented in years. ADNI subset refers to the group of reverters and later converters which were used for validation of the model but were not included in the training of the model. AD = Alzheimer’s disease, MCI = Mild Cognitive Impairment, CTL = healthy control, MMSE = Mini Mental State Examination. CDR-SOB – Clinical Dementia Rating – Sum Of Boxes.</p

Distribution of the ORCHID (Ordinal Regression Characteristic Index of Dementia) score extracted from for the ADNI dataset representing the disease progressive continuum spanning CTL to MCI-s to MCI-c to AD.

<p>The lower portion of each plot represents the distributions for the CTL class (green) and the AD class (red). (a) represents the distribution of subjects with unstable labels across follow-ups, most of which appear to belong to either the CTL or MCI-s classes (N = 24). (b) represents the distribution of those who convert to AD by 12 month follow-up (N = 62) (i.e. MCI-c: the sample used for training and testing the ADNI-based ORGP model). (c) represents the distribution of those who convert to AD between the 12 and 24 month follow-up (N = 58). (d) represents the distribution of those who convert to AD between the 24 and 36 month follow-up (N = 29).</p

Multivariate discriminative weights computed using ordinal regression.

<p>For ordinal regression the weights can be interpreted as the projection of the data along the function space weight vector spanning CTL to MCI-s to MCI-s to AD. Note that the weights are symmetric across hemispheres. These weights are sensitive the spatial correlations in the data and therefore should not be interpreted in a univariate manner.</p

Visual assessment of the medial temporal lobe atrophy was performed on a single MR-slice posterior to the amygdala and the mamillary bodies.

<p>The was positioned so the hippocampus, the pons and the cerebral peduncles were all visible. The visual assessment included hippocampus proper, dentate gyrus, subiculum, parahippocampal gyrus, entorhinal cortex and surrounding CSF spaces such as temporal horn and choroid fissure. The right and left side were rated separately. Scores range from 0 (no atrophy) to 4 (end stage atrophy).</p

Performance curves and correlation plots for ordinal regression.

<p>(A): ROC curves for ordinal regression applied to the ADNI data set using 10-fold cross-validation (first panel) and using the AddNeuroMed data set as an independent test set. In both cases the ROC curves are shown from three contrasts. (B): Correlation plots of the MMSE score assessed at the 12 month follow-up against the Ordinal Regression Characteristic Index of Dementia (ORCHID) score for both the ADNI dataset and the AddNeuroMed dataset.</p

MCI prediction.

<p>AD = Alzheimer's disease, MCI = Mild Cognitive Impairment, CTL = healthy control, MCI-c = MCI converters and MCI-s = MCI stable. To better compare the performance of the three methods we also calculated the sensitivity (MCI-c predicted as AD) at a fixed specificity (MCI-s predicted as CTL). We set the specificity to that of the visual rating assessment and recalculated the sensitivity and specificity of the other two methods used.</p

Sensitivity/specificity and likelihood ratios for the different methods.

<p>Confidence intervals within parentheses, LR+ = positive likelihood ratio and LR− = negative likelihood ratio.</p

Subject characteristics.

<p>Data are represented as mean ± standard deviation. AD = Alzheimer's disease, MCI = Mild Cognitive Impairment, CTL = healthy control, Education in years, MMSE = Mini Mental State Examination, ADAS1 = Word list non-learning (mean), CDR = Clinical Dementia Rating.</p

Representations of ROIs included as candidate input variables in the multivariate OPLS model.

<p>(A) Regional volumes. (B) Regional cortical thickness measures.</p

OPLS cross validated score plots and MRI measures of importance for the separation between AD and CTL.

<p>(A) The scatter plot visualises group separation and the predictability of the AD vs. CTL model. Each black square represents an AD subject and each gray circle a control subject. Control subjects to the left of zero and AD subjects to the right of zero are falsely predicted. Q²(Y)>0.05 (statistically significant model). (B) Measures above zero have a larger value in controls compared to AD and measures below zero have a lower value in controls compared to AD. A measure with a high covariance is more likely to have an impact on group separation than a measure with a low covariance. Measures with jack knifed confidence intervals that include zero have low reliability.</p