Machine learning-enhanced non-amnestic Alzheimer's disease diagnosis from MRI and clinical features

Alzheimer's disease (AD), defined as an abnormal buildup of amyloid plaques and tau tangles in the brain can be diagnosed with high accuracy based on protein biomarkers via PET or CSF analysis. However, due to the invasive nature of biomarker collection, most AD diagnoses are made in memory clinics using cognitive tests and evaluation of hippocampal atrophy based on MRI. While clinical assessment and hippocampal volume show high diagnostic accuracy for amnestic or typical AD (tAD), a substantial subgroup of AD patients with atypical presentation (atAD) are routinely misdiagnosed. To improve diagnosis of atAD patients, we propose a machine learning approach to distinguish between atAD and non-AD cognitive impairment using clinical testing battery and MRI data collected as standard-of-care. We develop and evaluate our approach using 1410 subjects across four groups (273 tAD, 184 atAD, 235 non-AD, and 685 cognitively normal) collected from one private data set and two public data sets from the National Alzheimer's Coordinating Center (NACC) and the Alzheimer's Disease Neuroimaging Initiative (ADNI). We perform multiple atAD vs. non-AD classification experiments using clinical features and hippocampal volume as well as a comprehensive set of MRI features from across the brain. The best performance is achieved by incorporating additional important MRI features, which outperforms using hippocampal volume alone. Furthermore, we use the Boruta statistical approach to identify and visualize significant brain regions distinguishing between diagnostic groups. Our ML approach improves the percentage of correctly diagnosed atAD cases (the recall) from 52% to 69% for NACC and from 34% to 77% for ADNI, while achieving high precision. The proposed approach has important implications for improving diagnostic accuracy for non-amnestic atAD in clinical settings using only clinical testing battery and MRI.

Functional Brain Network Identification in Opioid Use Disorder Using Machine Learning Analysis of Resting-State fMRI BOLD Signals

Understanding the neurobiology of opioid use disorder (OUD) using resting-state functional magnetic resonance imaging (rs-fMRI) may help inform treatment strategies to improve patient outcomes. Recent literature suggests temporal characteristics of rs-fMRI blood oxygenation level-dependent (BOLD) signals may offer complementary information to functional connectivity analysis. However, existing studies of OUD analyze BOLD signals using measures computed across all time points. This study, for the first time in the literature, employs data-driven machine learning (ML) modeling of rs-fMRI BOLD features representing multiple time points to identify region(s) of interest that differentiate OUD subjects from healthy controls (HC). Following the triple network model, we obtain rs-fMRI BOLD features from the default mode network (DMN), salience network (SN), and executive control network (ECN) for 31 OUD and 45 HC subjects. Then, we use the Boruta ML algorithm to identify statistically significant BOLD features that differentiate OUD from HC, identifying the DMN as the most salient functional network for OUD. Furthermore, we conduct brain activity mapping, showing heightened neural activity within the DMN for OUD. We perform 5-fold cross-validation classification (OUD vs. HC) experiments to study the discriminative power of functional network features with and without fusing demographic features. The DMN shows the most discriminative power, achieving mean AUC and F1 scores of 80.91% and 73.97%, respectively, when fusing BOLD and demographic features. Follow-up Boruta analysis using BOLD features extracted from the medial prefrontal cortex, posterior cingulate cortex, and left and right temporoparietal junctions reveals significant features for all four functional hubs within the DMN.