Detecting Amyloid Positivity Using Morphometric Magnetic Resonance Imaging

Background: Early detection of amyloid-β (Aβ) positivity is essential for an accurate diagnosis and treatment of Alzheimer’s disease (AD), but it is currently costly and/or invasive. Objective: We aimed to classify Aβ positivity (Aβ+) using morphometric features from magnetic resonance imaging (MRI), a more accessible and non-invasive technique, in two clinical population scenarios: one containing AD, mild cognitive impairment (MCI) and cognitively normal (CN) subjects, and another only cognitively impaired subjects (AD and MCI). Methods: Demographic, cognitive (Mini-Mental State Examination MMSE scores), regional morphometry MRI (volumes, areas, and thicknesses), and derived morphometric graph theory (GT) features from all subjects (302 Aβ+, age: 73.3±7.2, 150 male; 246 Aβ–, age: 71.1±7.1, 131 male) were combined in different feature sets. We implemented a machine learning workflow to find the best Aβ+ classification model. Results: In an AD+MCI+CN population scenario, the best-performing model selected 120 features (107 GT features, 12 regional morphometric features and the MMSE total score) and achieved a negative predictive value (NPVadj) of 68.4%, and a balanced accuracy (BAC) of 66.9%. In a AD+MCI scenario, the best model obtained NPVadj of 71.6%, and BAC of 70.7%, using 180 regional morphometric features (98 volumes, 52 areas and 29 thicknesses from temporal, parietal, and frontal brain regions). Conclusions: Although with currently limited clinical applicability, regional MRI morphometric features have clinical usefulness potential for detecting Aβ status, which may be augmented by a combination with cognitive data when cognitively normal subjects make up a substantial part of the population presenting for diagnosis.