Detecting Alzheimer’s Disease Stages and Frontotemporal Dementia in Time Courses of Resting-State fMRI Data Using a Machine Learning Approach

Early, accurate diagnosis of neurodegenerative dementia subtypes such as Alzheimer's disease (AD) and frontotemporal dementia (FTD) is crucial for the effectiveness of their treatments. However, distinguishing these conditions becomes challenging when symptoms overlap or the conditions present atypically. Resting-state fMRI (rs-fMRI) studies have demonstrated condition-specific alterations in AD, FTD, and mild cognitive impairment (MCI) compared to healthy controls (HC). Here, we used machine learning to build a diagnostic classification model based on these alterations. We curated all rs-fMRIs and their corresponding clinical information from the ADNI and FTLDNI databases. Imaging data underwent preprocessing, time course extraction, and feature extraction in preparation for the analyses. The imaging features data and clinical variables were fed into gradient-boosted decision trees with fivefold nested cross-validation to build models that classified four groups: AD, FTD, HC, and MCI. The mean and 95% confidence intervals for model performance metrics were calculated using the unseen test sets in the cross-validation rounds. The model built using only imaging features achieved 74.4% mean balanced accuracy, 0.94 mean macro-averaged AUC, and 0.73 mean macro-averaged F1 score. It accurately classified FTD (F1 = 0.99), HC (F1 = 0.99), and MCI (F1 = 0.86) fMRIs but mostly misclassified AD scans as MCI (F1 = 0.08). Adding clinical variables to model inputs raised balanced accuracy to 91.1%, macro-averaged AUC to 0.99, macro-averaged F1 score to 0.92, and improved AD classification accuracy (F1 = 0.74). In conclusion, a multimodal model based on rs-fMRI and clinical data accurately differentiates AD-MCI vs. FTD vs. HC.