11C-PIB PET image analysis for Alzheimer's diagnosis using weighted voting ensembles

Alzheimer's Disease (AD) is one of the leading causes of death and dementia worldwide. Early diagnosis confers many benefits, including improved care and access to effective treatment. However, it is still a medical challenge due to the lack of an efficient and inexpensive way to assess cognitive function [1]. Although research on data from Neuroimaging and Brain Initiative and the advancement in data analytics has greatly enhanced our understanding of the underlying disease process, there is still a lack of complete knowledge regarding the indicative biomarkers of Alzheimer's Disease. Recently, computer aided diagnosis of mild cognitive impairment and AD with functional brain images using machine learning methods has become popular. However, the prediction accuracy remains unoptimistic, with prediction accuracy ranging from 60% to 88% [2,3,6]. Among them, support vector machine is the most popular classifier. However, because of the relatively small sample size and the amount of noise in functional brain imaging data, a single classifier cannot achieve high classification performance. Instead of using a global classifier, in this work, we aim to improve AD prediction accuracy by combining three different classifiers using weighted and unweighted schemes. We rank image-derived features according to their importance to the classification performance and show that the top ranked features are localized in the brain areas which have been found to associate with the progression of AD. We test the proposed approach on 11C-PIB PET scans from The Alzheimer's Disease Neuroimaging Initiative (ADNI) database and demonstrated that the weighted ensemble models outperformed individual models of K-Nearest Neighbors, Random Forests, Neural Nets with overall cross validation accuracy of 86.1% ± 8.34%, specificity of 90.6% ± 12.9% and test accuracy of 80.9% and specificity 85.76% in classification of AD, mild cognitive impairment and healthy elder adults.