Diffusion with a Linguistic Compass: Steering the Generation of Clinically Plausible Future sMRI Representations for Early MCI Conversion Prediction

Early prediction of Mild Cognitive Impairment (MCI) conversion is hampered by a trade-off between immediacy--making fast predictions from a single baseline sMRI--and accuracy--leveraging longitudinal scans to capture disease progression. We propose MCI-Diff, a diffusion-based framework that synthesizes clinically plausible future sMRI representations directly from baseline data, achieving both real-time risk assessment and high predictive performance. First, a multi-task sequence reconstruction strategy trains a shared denoising network on interpolation and extrapolation tasks to handle irregular follow-up sampling and learn robust latent trajectories. Second, an LLM-driven "linguistic compass" is introduced for clinical plausibility sampling: generated feature candidates are quantized, tokenized, and scored by a fine-tuned language model conditioned on expected structural biomarkers, guiding autoregressive generation toward realistic disease patterns. Experiments on ADNI and AIBL cohorts show that MCI-Diff outperforms state-of-the-art baselines, improving early conversion accuracy by 5-12%.

Multi-task Learning for Heterogeneous Multi-source Block-Wise Missing Data

Multi-task learning (MTL) has emerged as an imperative machine learning tool to solve multiple learning tasks simultaneously and has been successfully applied to healthcare, marketing, and biomedical fields. However, in order to borrow information across different tasks effectively, it is essential to utilize both homogeneous and heterogeneous information. Among the extensive literature on MTL, various forms of heterogeneity are presented in MTL problems, such as block-wise, distribution, and posterior heterogeneity. Existing methods, however, struggle to tackle these forms of heterogeneity simultaneously in a unified framework. In this paper, we propose a two-step learning strategy for MTL which addresses the aforementioned heterogeneity. First, we impute the missing blocks using shared representations extracted from homogeneous source across different tasks. Next, we disentangle the mappings between input features and responses into a shared component and a task-specific component, respectively, thereby enabling information borrowing through the shared component. Our numerical experiments and real-data analysis from the ADNI database demonstrate the superior MTL performance of the proposed method compared to other competing methods.

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.

XDementNET: An Explainable Attention Based Deep Convolutional Network to Detect Alzheimer Progression from MRI data

A common neurodegenerative disease, Alzheimer's disease requires a precise diagnosis and efficient treatment, particularly in light of escalating healthcare expenses and the expanding use of artificial intelligence in medical diagnostics. Many recent studies shows that the combination of brain Magnetic Resonance Imaging (MRI) and deep neural networks have achieved promising results for diagnosing AD. Using deep convolutional neural networks, this paper introduces a novel deep learning architecture that incorporates multiresidual blocks, specialized spatial attention blocks, grouped query attention, and multi-head attention. The study assessed the model's performance on four publicly accessible datasets and concentrated on identifying binary and multiclass issues across various categories. This paper also takes into account of the explainability of AD's progression and compared with state-of-the-art methods namely Gradient Class Activation Mapping (GradCAM), Score-CAM, Faster Score-CAM, and XGRADCAM. Our methodology consistently outperforms current approaches, achieving 99.66\% accuracy in 4-class classification, 99.63\% in 3-class classification, and 100\% in binary classification using Kaggle datasets. For Open Access Series of Imaging Studies (OASIS) datasets the accuracies are 99.92\%, 99.90\%, and 99.95\% respectively. The Alzheimer's Disease Neuroimaging Initiative-1 (ADNI-1) dataset was used for experiments in three planes (axial, sagittal, and coronal) and a combination of all planes. The study achieved accuracies of 99.08\% for axis, 99.85\% for sagittal, 99.5\% for coronal, and 99.17\% for all axis, and 97.79\% and 8.60\% respectively for ADNI-2. The network's ability to retrieve important information from MRI images is demonstrated by its excellent accuracy in categorizing AD stages.

End-to-end Cortical Surface Reconstruction from Clinical Magnetic Resonance Images

Surface-based cortical analysis is valuable for a variety of neuroimaging tasks, such as spatial normalization, parcellation, and gray matter (GM) thickness estimation. However, most tools for estimating cortical surfaces work exclusively on scans with at least 1 mm isotropic resolution and are tuned to a specific magnetic resonance (MR) contrast, often T1-weighted (T1w). This precludes application using most clinical MR scans, which are very heterogeneous in terms of contrast and resolution. Here, we use synthetic domain-randomized data to train the first neural network for explicit estimation of cortical surfaces from scans of any contrast and resolution, without retraining. Our method deforms a template mesh to the white matter (WM) surface, which guarantees topological correctness. This mesh is further deformed to estimate the GM surface. We compare our method to recon-all-clinical (RAC), an implicit surface reconstruction method which is currently the only other tool capable of processing heterogeneous clinical MR scans, on ADNI and a large clinical dataset (n=1,332). We show a approximately 50 % reduction in cortical thickness error (from 0.50 to 0.24 mm) with respect to RAC and better recovery of the aging-related cortical thinning patterns detected by FreeSurfer on high-resolution T1w scans. Our method enables fast and accurate surface reconstruction of clinical scans, allowing studies (1) with sample sizes far beyond what is feasible in a research setting, and (2) of clinical populations that are difficult to enroll in research studies. The code is publicly available at https://github.com/simnibs/brainnet.

Edge-boosted graph learning for functional brain connectivity analysis

Predicting disease states from functional brain connectivity is critical for the early diagnosis of severe neurodegenerative diseases such as Alzheimer's Disease and Parkinson's Disease. Existing studies commonly employ Graph Neural Networks (GNNs) to infer clinical diagnoses from node-based brain connectivity matrices generated through node-to-node similarities of regionally averaged fMRI signals. However, recent neuroscience studies found that such node-based connectivity does not accurately capture ``functional connections" within the brain. This paper proposes a novel approach to brain network analysis that emphasizes edge functional connectivity (eFC), shifting the focus to inter-edge relationships. Additionally, we introduce a co-embedding technique to integrate edge functional connections effectively. Experimental results on the ADNI and PPMI datasets demonstrate that our method significantly outperforms state-of-the-art GNN methods in classifying functional brain networks.

Latent Diffusion Autoencoders: Toward Efficient and Meaningful Unsupervised Representation Learning in Medical Imaging

This study presents Latent Diffusion Autoencoder (LDAE), a novel encoder-decoder diffusion-based framework for efficient and meaningful unsupervised learning in medical imaging, focusing on Alzheimer disease (AD) using brain MR from the ADNI database as a case study. Unlike conventional diffusion autoencoders operating in image space, LDAE applies the diffusion process in a compressed latent representation, improving computational efficiency and making 3D medical imaging representation learning tractable. To validate the proposed approach, we explore two key hypotheses: (i) LDAE effectively captures meaningful semantic representations on 3D brain MR associated with AD and ageing, and (ii) LDAE achieves high-quality image generation and reconstruction while being computationally efficient. Experimental results support both hypotheses: (i) linear-probe evaluations demonstrate promising diagnostic performance for AD (ROC-AUC: 90%, ACC: 84%) and age prediction (MAE: 4.1 years, RMSE: 5.2 years); (ii) the learned semantic representations enable attribute manipulation, yielding anatomically plausible modifications; (iii) semantic interpolation experiments show strong reconstruction of missing scans, with SSIM of 0.969 (MSE: 0.0019) for a 6-month gap. Even for longer gaps (24 months), the model maintains robust performance (SSIM > 0.93, MSE < 0.004), indicating an ability to capture temporal progression trends; (iv) compared to conventional diffusion autoencoders, LDAE significantly increases inference throughput (20x faster) while also enhancing reconstruction quality. These findings position LDAE as a promising framework for scalable medical imaging applications, with the potential to serve as a foundation model for medical image analysis. Code available at https://github.com/GabrieleLozupone/LDAE

GKAN: Explainable Diagnosis of Alzheimer's Disease Using Graph Neural Network with Kolmogorov-Arnold Networks

Alzheimer's Disease (AD) is a progressive neurodegenerative disorder that poses significant diagnostic challenges due to its complex etiology. Graph Convolutional Networks (GCNs) have shown promise in modeling brain connectivity for AD diagnosis, yet their reliance on linear transformations limits their ability to capture intricate nonlinear patterns in neuroimaging data. To address this, we propose GCN-KAN, a novel single-modal framework that integrates Kolmogorov-Arnold Networks (KAN) into GCNs to enhance both diagnostic accuracy and interpretability. Leveraging structural MRI data, our model employs learnable spline-based transformations to better represent brain region interactions. Evaluated on the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset, GCN-KAN outperforms traditional GCNs by 4-8% in classification accuracy while providing interpretable insights into key brain regions associated with AD. This approach offers a robust and explainable tool for early AD diagnosis.

PHGNN: A Novel Prompted Hypergraph Neural Network to Diagnose Alzheimer's Disease

The accurate diagnosis of Alzheimer's disease (AD) and prognosis of mild cognitive impairment (MCI) conversion are crucial for early intervention. However, existing multimodal methods face several challenges, from the heterogeneity of input data, to underexplored modality interactions, missing data due to patient dropouts, and limited data caused by the time-consuming and costly data collection process. In this paper, we propose a novel Prompted Hypergraph Neural Network (PHGNN) framework that addresses these limitations by integrating hypergraph based learning with prompt learning. Hypergraphs capture higher-order relationships between different modalities, while our prompt learning approach for hypergraphs, adapted from NLP, enables efficient training with limited data. Our model is validated through extensive experiments on the ADNI dataset, outperforming SOTA methods in both AD diagnosis and the prediction of MCI conversion.

Ensemble Survival Analysis for Preclinical Cognitive Decline Prediction in Alzheimer's Disease Using Longitudinal Biomarkers

Predicting the risk of clinical progression from cognitively normal (CN) status to mild cognitive impairment (MCI) or Alzheimer's disease (AD) is critical for early intervention in Alzheimer's disease (AD). Traditional survival models often fail to capture complex longitudinal biomarker patterns associated with disease progression. We propose an ensemble survival analysis framework integrating multiple survival models to improve early prediction of clinical progression in initially cognitively normal individuals. We analyzed longitudinal biomarker data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort, including 721 participants, limiting analysis to up to three visits (baseline, 6-month follow-up, 12-month follow-up). Of these, 142 (19.7%) experienced clinical progression to MCI or AD. Our approach combined penalized Cox regression (LASSO, Elastic Net) with advanced survival models (Random Survival Forest, DeepSurv, XGBoost). Model predictions were aggregated using ensemble averaging and Bayesian Model Averaging (BMA). Predictive performance was assessed using Harrell's concordance index (C-index) and time-dependent area under the curve (AUC). The ensemble model achieved a peak C-index of 0.907 and an integrated time-dependent AUC of 0.904, outperforming baseline-only models (C-index 0.608). One follow-up visit after baseline significantly improved prediction accuracy (48.1% C-index, 48.2% AUC gains), while adding a second follow-up provided only marginal gains (2.1% C-index, 2.7% AUC). Our ensemble survival framework effectively integrates diverse survival models and aggregation techniques to enhance early prediction of preclinical AD progression. These findings highlight the importance of leveraging longitudinal biomarker data, particularly one follow-up visit, for accurate risk stratification and personalized intervention strategies.