UG-FedDA: Uncertainty-Guided Federated Domain Adaptation for Multi-Center Alzheimer's Disease Detection

Alzheimer's disease (AD) is an irreversible neurodegenerative disorder, and early diagnosis is critical for timely intervention. However, most existing classification frameworks face challenges in multicenter studies, as they often neglect inter-site heterogeneity and lack mechanisms to quantify uncertainty, which limits their robustness and clinical applicability. To address these issues, we proposed Uncertainty-Guided Federated Domain Adaptation (UG-FedDA), a novel multicenter AD classification framework that integrates uncertainty quantification (UQ) with federated domain adaptation to handle cross-site structure magnetic resonance imaging (MRI) heterogeneity under privacy constraints. Our approach extracts multi-template region-of-interest (RoI) features using a self-attention transformer, capturing both regional representations and their interactions. UQ is integrated to guide feature alignment, mitigating source-target distribution shifts by down-weighting uncertain samples. Experiments are conducted on three public datasets: the Alzheimer's Disease Neuroimaging Initiative (ADNI), the Australian Imaging, Biomarkers and Lifestyle study (AIBL), and the Open Access Series of Imaging Studies (OASIS). UG-FedDA achieved consistent cross-domain improvements in accuracy, sensitivity, and area under the ROC curve across three classification tasks: AD vs. normal controls (NC), mild cognitive impairment (MCI) vs. AD, and NC vs. MCI. For NC vs. AD, UG-FedDA achieves accuracies of 90.54%, 89.04%, and 77.78% on ADNI, AIBL and OASIS datasets, respectively. For MCI vs. AD, accuracies are 80.20% (ADNI), 71.91% (AIBL), and 79.73% (OASIS). For NC vs. MCI, results are 76.87% (ADNI), 73.91% (AIBL), and 83.73% (OASIS). These results demonstrate that the proposed framework not only adapts efficiently across multiple sites but also preserves strict privacy.