A Novel Ensemble-Based Machine Learning Algorithm To Predict The Conversion From Mild Cognitive Impairment To Alzheimer’s Disease Using Socio-demographic Characteristics, Clinical Information And Neuropsychological Measures

Abstract

Background: Despite the increasing availability in brain health related data, clinically translatable methods to predict the conversion from Mild Cognitive Impairment (MCI) to Alzheimer's disease (AD) are still lacking. Although MCI typically precedes AD, only a fraction of 20-40% of MCI individuals will progress to dementia within 3 years following the initial diagnosis. As currently available and emerging therapies likely have the greatest impact when provided at the earliest disease stage, the prompt identification of subjects at high risk for conversion to full AD is of great importance in the fight against this disease. In this work, we propose a highly predictive machine learning algorithm, based only on non-invasively and easily in-the-clinic collectable predictors, to identify MCI subjects at risk for conversion to full AD. Methods:The algorithm was developed using the open dataset from the Alzheimer's Disease Neuroimaging Initiative (ADNI), employing a sample of 550 MCI subjects whose diagnostic follow-up is available for at least 3 years after the baseline assessment. A restricted set of information regarding sociodemographic and clinical characteristics, neuropsychological test scores was used as predictors and several different supervised machine learning algorithms were developed and ensembled in final algorithm. A site-independent stratified train/test split protocol was used to provide an estimate of the generalized performance of the algorithm. Results:The final algorithm demonstrated an AUROC of 0.88, sensitivity of 77.7%, and a specificity of 79.9% on excluded test data. The specificity of the algorithm was 40.2% for 100% sensitivity. Discussion:The algorithm we developed achieved sound and high prognostic performance to predict AD conversion using easily clinically derived information that makes the algorithm easy to be translated into practice. This indicates beneficial application to improve recruitment in clinical trials and to more selectively prescribe new and newly emerging early interventions to high AD risk patients.Keywords Alzheimer's disease · clinical prediction rule · machine learning · mild cognitive impairment · personalized medicine · precision medicine · neuropsychological tests 1