Higher-Order Domain Generalization in Magnetic Resonance-Based Assessment of Alzheimer's Disease

Despite progress in deep learning for Alzheimer's disease (AD) diagnostics, models trained on structural magnetic resonance imaging (sMRI) often do not perform well when applied to new cohorts due to domain shifts from varying scanners, protocols and patient demographics. AD, the primary driver of dementia, manifests through progressive cognitive and neuroanatomical changes like atrophy and ventricular expansion, making robust, generalizable classification essential for real-world use. While convolutional neural networks and transformers have advanced feature extraction via attention and fusion techniques, single-domain generalization (SDG) remains underexplored yet critical, given the fragmented nature of AD datasets. To bridge this gap, we introduce Extended MixStyle (EM), a framework for blending higher-order feature moments (skewness and kurtosis) to mimic diverse distributional variations. Trained on sMRI data from the National Alzheimer's Coordinating Center (NACC; n=4,647) to differentiate persons with normal cognition (NC) from those with mild cognitive impairment (MCI) or AD and tested on three unseen cohorts (total n=3,126), EM yields enhanced cross-domain performance, improving macro-F1 on average by 2.4 percentage points over state-of-the-art SDG benchmarks, underscoring its promise for invariant, reliable AD detection in heterogeneous real-world settings. The source code will be made available upon acceptance at https://github.com/zobia111/Extended-Mixstyle.

Distance Transform Guided Mixup for Alzheimer's Detection

Alzheimer's detection efforts aim to develop accurate models for early disease diagnosis. Significant advances have been achieved with convolutional neural networks and vision transformer based approaches. However, medical datasets suffer heavily from class imbalance, variations in imaging protocols, and limited dataset diversity, which hinder model generalization. To overcome these challenges, this study focuses on single-domain generalization by extending the well-known mixup method. The key idea is to compute the distance transform of MRI scans, separate them spatially into multiple layers and then combine layers stemming from distinct samples to produce augmented images. The proposed approach generates diverse data while preserving the brain's structure. Experimental results show generalization performance improvement across both ADNI and AIBL datasets.

Single Domain Generalization for Alzheimer's Detection from 3D MRIs with Pseudo-Morphological Augmentations and Contrastive Learning

Although Alzheimer's disease detection via MRIs has advanced significantly thanks to contemporary deep learning models, challenges such as class imbalance, protocol variations, and limited dataset diversity often hinder their generalization capacity. To address this issue, this article focuses on the single domain generalization setting, where given the data of one domain, a model is designed and developed with maximal performance w.r.t. an unseen domain of distinct distribution. Since brain morphology is known to play a crucial role in Alzheimer's diagnosis, we propose the use of learnable pseudo-morphological modules aimed at producing shape-aware, anatomically meaningful class-specific augmentations in combination with a supervised contrastive learning module to extract robust class-specific representations. Experiments conducted across three datasets show improved performance and generalization capacity, especially under class imbalance and imaging protocol variations. The source code will be made available upon acceptance at https://github.com/zobia111/SDG-Alzheimer.