Structural neuroimaging has been applied to the identification of individuals with Alzheimer’s disease (AD) and mild cognitive impairment (MCI). However, these methods are greatly impacted by age limiting their utility for detection of preclinical pathology. We built linear models for age based on multiple combined structural features using a large independent lifespan sample of 272 healthy adults across a wide age range from the Human Connectome Project Aging study. These models were then used to create a new support vector machine (SVM) training model in 136 CE and 268 control participants based on residues of fit from the expected age-effects relationship. Subsequent validation assessed the accuracy of the SVM model in new datasets. Finally, we applied the classifier to 276 individuals with MCI to evaluate prediction for early impairment and longitudinal cognitive change. The optimal 10-fold cross-validation accuracy was 93.07%, compared to 91.83% without age detrending. In the validation dataset, the classifier for AD obtained an accuracy of 84.85% (56/66), sensitivity of 85.36% (35/41) and specificity of 84% (21/25). Classification accuracy was improved when using the lifespan sample as opposed to the classification sample. Importantly, we observed cross-sectional greater AD specific biomarkers, as well as faster cognitive decline in MCI who were classified as more ‘AD-like’ (MCI-AD), and these effects were pronounced in individuals who were late MCI. The top five contributive features were volumes of left hippocampus, right hippocampus, left amygdala, the thickness of left and right middle temporal & parahippocampus gyrus. Linear detrending for age in SVM for combined structural features resulted in good performance for recognition of AD and AD-specific biomarkers, as well as prediction of MCI progression. Such procedures may be used in future work to enhance prediction in samples with atypical age distributions.
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