Evaluating conversion from mild cognitive impairment to Alzheimer's disease with structural MRI: a machine learning study

Alzheimer's disease is a disabling neurodegenerative disorder for which no effective treatment currently exists. To predict the diagnosis of Alzheimer's disease could be crucial for patients' outcome, but current Alzheimer's disease biomarkers are invasive, time consuming or expensive. Thus, developing MRI-based computational methods for Alzheimer's disease early diagnosis would be essential to narrow down the phenotypic measures predictive of cognitive decline. Amnestic mild cognitive impairment (aMCI) is associated with higher risk for Alzheimer's disease, and here, we aimed to identify MRI-based quantitative rules to predict aMCI to possible Alzheimer's disease conversion, applying different machine learning algorithms sequentially. At baseline, T1-weighted brain images were collected for 104 aMCI patients and processed to obtain 146 volumetric measures of cerebral grey matter regions [regions of interest (ROIs)]. One year later, patients were classified as converters (aMCI-c = 32) or non-converters, i.e. clinically and neuropsychologically stable (aMCI-s = 72) based on cognitive performance. Feature selection was performed by random forest (RF), and the identified seven ROIs volumetric data were used to implement support vector machine (SVM) and decision tree (DT) classification algorithms. Both SVM and DT reached an average accuracy of 86% in identifying aMCI-c and aMCI-s. DT found a critical threshold volume of the right entorhinal cortex (EC-r) as the first feature for differentiating aMCI-c/aMCI-s. Almost all aMCI-c had an EC-r volume <1286 mm3, while more than half of the aMCI-s patients had a volume above the identified threshold for this structure. Other key regions for the classification between aMCI-c/aMCI-s were the left lateral occipital (LOC-l), the middle temporal gyrus and the temporal pole cortices. Our study reinforces previous evidence suggesting that the morphometry of the EC-r and LOC-l best predicts aMCI to Alzheimer's disease conversion. Further investigations are needed prior to deeming our findings as a broadly applicable predictive framework. However, here, a first indication was derived for volumetric thresholds that, being easy to obtain, may assist in early identification of Alzheimer's disease in clinical practice, thus contributing to establishing MRI as a useful non-invasive prognostic instrument for dementia onset.