Alzheimer

Accurately predicting the temporal evolution of clinical biomarkers is crucial for the early diagnosis and management of neurodegenerative diseases such as Alzheimer's disease. However, this relies on longitudinal data to capture biomarker changes over time, which is often sparse and irregular due to the high cost, labor-intensive nature, and patient burden. To address these challenges, we propose ENC-ODE, an Event-level Neurodegenerative modeling in Continuous time with neural Ordinary Differential Equations. ENC-ODE predicts future biomarker evolution by modeling clinical events through diagnosis-conditioned continuous dynamics. A target-conditioned attention mechanism weights and aggregates event-level predictions for the target time and modality without history compression. Extensive experiments on Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset demonstrate that ENC-ODE outperforms representative sequence models while offering a scalable and neuroscientifically grounded solution for clinical support. The code is available at https://github.com/JardinDelSol/enc-ode.

Automatic mapping between disease classification systems, such as the International Classification of Diseases (ICD), is a challenging yet essential task for integrating health data and conducting longitudinal data analysis. Existing embedding-based methods primarily focus on \emph{one-to-one} mappings, overlooking more complex \emph{one-to-many} scenarios. The threshold-based and top-K methods offer natural extensions; however, they involve inherent trade-offs between \emph{precision}, \emph{recall} and \emph{mapping coverage} -- the proportion of source codes with at least one mapping to a target code. To address this challenge, we introduce a novel method, which is inspired by the \emph{blocking-and-matching} pipeline commonly used in \emph{entity resolution}. In particular, we first generate a block of candidate matches (\emph{blocking}) and then employ a large language model (LLM) to identify all valid mappings within each block (\emph{matching}). Empirically, we show that the proposed method achieves higher precision with comparable recall and broader coverage across multiple ICD version pairs (ICD-9-CM$\leftrightarrow$ICD-10-CM and ICD-10-AM$\leftrightarrow$ICD-11). Our source code and dataset is available at: https://tinyurl.com/46kyn7wp.

Echocardiography is the most widely used non-invasive cardiac imaging modality, providing essential information for cardiovascular diagnosis. Interpreting an echocardiogram requires synthesizing complementary evidence across multiple heart views to identify abnormalities and produce structured clinical reports. While recent efforts focus on improving classification performance, most models lack explicit diagnostic reasoning and spatially grounded anatomical evidence, limiting clinician trust. We present EchoSonar-R, a multi-view reasoning-enabled vision-language model that jointly performs multi-label disease classification and report generation from echocardiography studies. EchoSonar-R combines a spatiotemporal video encoder with a structure-aware cardiac detector that provides spatially grounded anatomical cues to improve interpretability and clinician trust during cross-view reasoning. EchoSonar-R is trained in two stages: supervised fine-tuning (SFT) on reasoning-annotated targets, followed by Group Relative Policy Optimization (GRPO) with task-specific rewards that jointly align classification and report generation within a unified reinforcement-learning framework. Across a private multi-view dataset and two public benchmarks, EchoSonar-R improves macro balanced accuracy by 17.1% on the private set and 6.1% on MIMICEchoQA over the strongest baseline, achieves a GREEN clinical faithfulness score of 0.800, and produces interpretable reasoning traces grounded in multi-view visual evidence.

Speech-based cognitive impairment detection offers a noninvasive, accessible alternative to costly biomarker assays, yet transformer-based models remain clinically uninterpretable. We propose a multi-stage explainability framework that translates black-box transformer predictions into clinically grounded narratives by integrating SHapley Additive exPlanations (SHAP)-based token attribution, theory-informed linguistic features, and a four-stage LLM reasoning pipeline using LLaMA-3.1-70B-Instruct. Built on the SpeechCARE-Adaptive Gating Network multimodal screening model (F1 = 72.11% on the NIA PREPARE benchmark), the framework maps model outputs to four cognitive-linguistic dimensions, including lexical richness, syntactic complexity, and semantic coherence. Physician evaluation on 70 stratified English samples demonstrated strong alignment with patient-level cognitive profiles, and a System Usability Scale score of 82/100 indicated high potential for clinical workflow integration.

Early detection of dementia enables timely intervention, and reflecting cognitive impairment, spontaneous speech offers a non-invasive screening modality. Conventional approaches often focus on a single representational dimension -- such as acoustic descriptors, pause modeling, automatic speech recognition (ASR) transcripts, or multimodal fusion -- limiting integrative reasoning across heterogeneous cognitive symptoms. We propose a low-rank adaptation (LoRA)-tuned large language model (LLM) that performs structured multi-view reasoning over four complementary speech-derived signals: ASR transcripts with pause markers, discourse-level topic cues, temporal fluency statistics, and phonological sequences. These cues are encoded within a unified prompt, enabling a single LLM to learn a coherent decision function without modality-specific encoders or late-stage fusion. On ADReSSo, our best model achieves an F1-score of 90.14%, and ablation confirms the complementary contribution of each view.

Early detection of dementia through speech analysis offers a non-invasive screening alternative, but capturing both acoustic and linguistic biomarkers remains challenging. We propose a multimodal framework leveraging Whisper for dual-purpose extraction: acoustic representations from encoder outputs and transcripts via automatic speech recognition (ASR). For the acoustic pathway, temporal networks with attention pooling aggregate variable-length sequences into fixed-dimensional embeddings. For the linguistic pathway, we prompt a large language model (LLM) to extract interpretable features spanning lexical diversity, syntactic complexity, semantic coherence, and discourse patterns. A gated fusion network integrates both modalities. On ADReSS and ADReSSo, our method achieves F1-scores of 89.47% and 90.14%, demonstrating effective integration of acoustic and LLM-augmented linguistic features. Ablation shows that multimodal fusion consistently outperforms either modality alone.

Early and scalable detection of mild cognitive impairment (MCI) remains an unresolved clinical challenge. Existing EEG-based screening approaches are constrained by handcrafted feature pipelines that discard neurophysiologically meaningful domain structure and deep learning classifiers that sacrifice interpretability for performance. No existing work unifies physiologically organized concept encoders, cross-concept interaction modeling, and nonlinear tabular classification in a sleep EEG-based MCI detection framework. This study proposes Concept-guided Polynomial-transformed Tabular learning using Kolmogorov-Arnold Network (CPTabKAN), which maps heterogeneous EEG-derived features into domain-informed concept representations, expands them via degree-2 polynomial transformation to expose first- and second-order interactions, and applies a Fourier-parameterized TabKAN classifier to learn nonlinear decision boundaries. CPTabKAN was evaluated on the Study of Osteoporotic Fractures cohort (372 subjects, overnight polysomnography), using 1,379 features organized into ten physiologically motivated concept groups. Under 10-fold cross-validation, CPTabKAN-Second Order achieved a weighted F1-score of 0.9038 (SD 0.034), outperforming GradientBoosting by 5.65 percentage points (t(9)=1.934,p=0.043, one-sided paired test), with advantages persisting under SMOTE-based balancing. Ablation analysis confirmed independent contributions from each component. Concept importance analysis revealed that power spectral density, multi-scale entropy, and Hjorth parameters dominated first-order weights, while cross-concept interactions involving Lempel-Ziv-Welch complexity, statistics, demographics, and slow oscillations exceeded all first-order scores. These results demonstrate that concept-structured, interaction-aware tabular learning surfaces physiologically coherent reasoning, supporting clinical trust.

Accurately predicting the spatiotemporal evolution of amyloid-$β$ and tau proteins at the individual level is critical for improving the diagnosis and treatment of Alzheimer's disease. We consider the problem of constructing patient-specific digital twins that model the propagation of these biomarkers on the cortical surface using reaction--diffusion dynamics. A major challenge is that the underlying nonlinear aggregation mechanisms are unknown and must be inferred from sparse, noisy, and heterogeneous longitudinal PET imaging data. To address this, we develop a data-driven framework that learns biomarker dynamics directly from clinical observations. The approach combines operator learning with reduced-order representations to infer governing equations of disease progression from data. Using this framework, we achieve predictive accuracies of 87% for amyloid-$β$ and 81% for tau. Building on the learned dynamics, we further formulate a PDE-constrained optimal control problem to design personalized therapeutic strategies that regulate pathological protein propagation. By integrating data-driven dynamical modeling with treatment optimization, the proposed digital twin framework provides an interpretable and predictive platform for understanding disease progression and enabling precision interventions in neurodegenerative disorders.

Longitudinal modelling of Alzheimer's disease progression is clinically useful only if it can describe not just the most likely next diagnosis, but how a patient may evolve over time and how reliable that forecast is. Most deep learning approaches reduce this problem to single-step classification, treating cognitively normal, mild cognitive impairment, and dementia as flat categories while providing limited insight into how uncertainty accumulates across future visits. We propose a probabilistic framework that combines ordinal diagnosis prediction, multi-horizon trajectory generation, and decomposed uncertainty estimation. A Temporal Fusion Transformer encoder is adapted with a CORAL ordinal output layer, asymmetric loss weighting, and converter oversampling to respect disease-stage ordering and improve sensitivity to MCI-to-dementia transitions. Conditioned on the learned patient-context representation, an autoregressive Mixture Density Network generates five-year probabilistic trajectories for diagnosis state, CDR Sum of Boxes, MMSE orientation, and hippocampal volume. On ADNI, the model outperforms linear, recurrent, and transformer baselines for next-visit diagnosis prediction, with the strongest gains on MCI-versus-dementia discrimination. Generated trajectories achieve near-nominal 90% credible interval coverage, widening uncertainty across the forecast horizon, and biomarker dynamics consistent with expected Alzheimer's disease progression. We further separate aleatoric from epistemic uncertainty using analytic mixture variance and a five-member bootstrap ensemble, which provides the strongest encoder diversity and output-level epistemic signal. Epistemic uncertainty is higher for rare progression archetypes, MCI and dementia patients, and under external evaluation on OASIS-3, where it increases alongside prediction error.

Dementia diagnosis requires integrating multi-modal clinical assessments from diverse informants and clinicians under incomplete and heterogeneous data conditions. Yet most AI-driven approaches remain Alzheimer's disease (AD)-centric, framing the problem as binary AD detection or three-stage AD progression modeling within well-curated research settings. This pathology-driven paradigm overlooks the broader, syndrome-level nature of dementia, which spans multiple stages, phenotypes, and etiologies. In this paper, we propose Dementia-Agents, a clinically aligned multi-agent framework for real-world dementia staging and phenotyping. The framework follows a three-step workflow: (1) a data agent translates structured clinical records into semantically faithful textual representations that preserve missing-data signals and routes them to domain-aligned experts; (2) five fine-tuned expert agents generate domain-level predictions; and (3) a coordinator agent performs probabilistic aggregation to produce final staging and phenotyping decisions. We develop and evaluate Dementia-Agents on a real-world clinical cohort of 1,066 patients from two cognitive neurology services. Compared with monolithic multi-modal large language models (MLLMs) and prior medical multi-agent systems, our approach achieves consistent improvements in diagnostic performance for real-world syndrome-level dementia staging and phenotyping, while preserving domain-level interpretability.

The evaluation of vision-language models (VLMs) for chest X-ray (CXR) analysis has largely been limited to disease-presence classification without visual grounding. Such evaluations fail to verify the expert-level lesion perception necessary to ensure the clinical reliability of VLMs. To address these limitations, we introduce CheXpercept, a sequential, multi-level perception benchmark that mirrors a radiologist's cognitive workflow across coarse-level detection, fine-level contour evaluation and revision, and semantic-level attribute extraction. To ensure high clinical fidelity at scale, we construct the dataset using a semi-automated generation pipeline paired with a review by six medical experts. CheXpercept contains 10,400 QA items derived from 2,100 CXRs, covering seven clinically critical pulmonary and cardiac lesions. To demonstrate the current landscape of VLM perception, we benchmark 14 general and medical VLMs on CheXpercept. The models achieve adequate performance only at the coarse level, with accuracy degrading precipitously on deeper visual tasks. Notably, medical VLMs show almost no perceptual advantage over their general-domain counterparts, highlighting a systemic flaw in current domain adaptation. The code and dataset will be publicly available.

Alzheimer's disease (AD) is an irreversible neurodegenerative disorder and a leading cause of death worldwide. Early diagnosis plays an important part especially at the Mild Cognitive Impairment stage, where timely intervention can help slow its progression before it advances to AD. Neuroimaging data, like Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET) scans, can help detect brain changes early by providing structural and functional brain changes related to the disease. Yet, many multimodal models still fuse MRI and PET with static concatenation and apply identical computation to all subjects, which limits robustness to patient/site heterogeneity and can waste computation. To address these limitations, we present the first study of combining 3D convolutional feature extractors with three fusion strategies - concatenation, Gated Multimodal Unit (GMU), and gated self-attention - and a sparsely gated Mixture-of-Experts (MoE) classifier that performs input-adaptive routing, activating only the most informative experts per case. Finally, we utilize Grad-CAM to visualize disease-related regions, ensuring model interpretability. Experiments are performed across three binary classification tasks (NC vs. MCI, MCI vs. AD, and NC vs. AD). Results show that GMU achieves accuracies of 80.46 % (NC vs. MCI) and 95.47 % (NC vs. AD), while gated self-attention attains 82.08 % on MCI vs. AD. Ablations show that removing the MoE consistently degrades accuracy across all tasks. These findings underscore the value of input-adaptive, multimodal modeling for AD diagnosis by leveraging the complementary nature of MRI and PET.

\noindent\textbf{Background and Objective:} Speech has emerged as a low-cost and non-invasive digital biomarker with considerable potential for cognitive impairment detection. However, limited labeled data and cross-dataset variability remain major challenges for robust speech-based screening systems. \par\noindent\textbf{Methods:} We developed a segment-level representation learning framework for speech-based cognitive impairment detection. Speech recordings were divided into short segments and converted into spectrogram representations. To improve robustness under limited-data conditions, offline and online augmentation strategies were combined with autoencoder-based representation learning and contrastive objectives to enhance discriminative latent representations. \par\noindent\textbf{Results:} Experiments conducted on four independent Mandarin Chinese speech datasets demonstrated stable and competitive performance in both binary and three-class classification tasks, with particularly notable improvements in the clinically challenging three-class setting. Ablation studies further supported the effectiveness of the proposed framework. \par\noindent\textbf{Conclusions:} The findings suggest that segment-level speech representation learning may provide a scalable and practical approach for cognitive impairment screening in resource-constrained clinical settings.

The retina offers a noninvasive window into neurodegenerative disease, capturing subtle structural patterns associated with a risk of future cognitive decline. Vision-language alignment frameworks such as REVEAL have shown that pairing retinal fundus images with structured clinical risk narratives improves early prediction of Alzheimer's disease (AD). A key design choice in these approaches is the use of phenotypic grouping, where individuals with similar risk profiles are treated as multi-positive pairs during contrastive learning. However, existing methods operationalize phenotypic similarity as a discrete construct, relying on hard group assignments that impose rigid supervision and decouple group formation from representation learning. We propose a continuous formulation of phenotypic structure within contrastive learning. Rather than assigning samples to fixed clusters, we model inter-subject similarity as a differentiable weighting function derived from intra-modality embedding similarities in both retinal images and risk profiles. These weights define soft multi-positive relationships through a continuous aggregation operator, enabling graded supervision that reflects the spectrum nature of disease risk. We further introduce a soft-target contrastive objective that jointly learns cross-modal alignment and phenotypic structure in an end-to-end manner. Evaluated on UK Biobank retinal imaging data for incident AD prediction, the proposed framework consistently outperforms discrete group-based contrastive learning and standard vision-language baselines. By treating phenotypic similarity as a learnable, continuous signal rather than a fixed grouping rule, our approach provides a principled and robust foundation for population-scale neurodegenerative risk modeling from multi-modal retinal and clinical data.

Family members caring for individuals with Alzheimer's disease and related dementias (AD/ADRD) provide the foundation of long-term care worldwide. In 2023, more than 11 million U.S. family and friends contributed 18 billion hours of unpaid care, often at the cost of their own physical and mental health. These informal caregivers -- also referred as the "invisible second patients" -- experience elevated rates of mental health problems. Yet research commonly reduces their complex psychosocial experiences to a single construct of caregiver burden, obscuring which specific needs are unmet or effectively supported. At the same time, digital and AI-enabled technologies are rapidly expanding, from smartphone apps and videoconferencing to sensor platforms and AI chatbots. However, the absence of shared frameworks across medicine, psychology, and technology research limits cumulative progress. This study introduces a Caregiver Mental Health and Technology Taxonomy that systematically links AD/ADRD caregiver needs with corresponding classes of technology-based interventions. Drawing from an interdisciplinary literature review and two qualitative studies with caregivers, the taxonomy identifies mismatches between caregiver priorities and existing technological support, highlights under-served domains such as relational strain and compassion fatigue, and proposes design directions for adaptive, responsive systems. The framework offers a shared vocabulary to guide clinicians, researchers, and technology designers in developing more person-centered and clinically grounded innovation in dementia care.

Early detection of cognitive impairment relies on neuropsychological tests to minimize subjectivity by assessing multiple cognitive domains. Speech-based evaluation can support diagnostics and improve accessibility, but transcription errors and the omission of nonverbal subtests (e.g., motor skills) limit accuracy. Beyond conventional test scores, speech-derived features can provide additional insights into cognitive status. This study investigates the speech-based evaluation of the German "Syndrom-Kurz-Test," a standardized dementia screening test comprising verbal and motor subtests. We train models that integrate transcript-derived scores and Whisper embeddings per verbal subtest to reduce scoring errors. To compensate for missing motor subtests, we then leverage these fused representations to approximate expert overall ratings. Despite omitting subtests, our models strongly correlate with expert ratings and efficiently and accurately discriminate between cognitive status groups.

Mild Cognitive Impairment (MCI) is a medical condition characterized by a noticeable decline in memory, language, or thinking abilities. MCI detection from spontaneous speech is promising for scalable screening. However, learned models often exploit demographic cues correlated with labels, resulting in a large performance gap across subgroups. We present a multimodal framework that combines (i) cross-model fusion between modalities (speech, text, and image), and (ii) unlearning using gradient reversal that discourages the shared embedding from encoding task-irrelevant demographic attributes. Evaluated on the multilingual benchmarks TAUKADIAL and PREPARE, our method outperforms the state-of-the-art multilingual and multimodal baseline in MCI classification while substantially reducing the performance gap across patient subgroups (sex and language). We further analyze transfer across datasets, showing that demographic unlearning helps learn more robust representations for MCI detection.

Recent advances in generative machine learning models have significantly improved medical imaging, offering promising solutions for data augmentation, privacy preservation, and improved model generalization. However, synthesizing high-quality structural MRI data for Alzheimer's Disease (AD) remains challenging due to the subtle, region-specific, and progressive anatomical changes associated with neurodegeneration. In this paper, we extend the Med-DDPM conditional diffusion model -- originally designed for brain tumor synthesis -- to generate 3D structural MRIs specifically tailored to AD. We adopted Med-DDPM due to its established stability and structural fidelity compared to other generative models, which makes it particularly suitable for capturing the subtle anatomical changes characteristic of AD. Our approach conditions the diffusion process on anatomical segmentation masks derived from the ADNI dataset, incorporating key AD-relevant brain structures into the generation process. We systematically evaluate the quality and utility of the synthetic images by training segmentation models on real, synthetic, and hybrid (mixed) datasets. Experimental results demonstrate that segmentation models trained exclusively on synthetic data achieve comparable Dice scores (0.6532) to those trained on real data (0.6513), while exhibiting significantly enhanced recall. Notably, models trained on hybrid datasets (mixing real and synthetic images) outperform both real and synthetic-only baselines, achieving a Dice score of 0.7244. These findings underscore the successful use of conditional diffusion models for generating anatomically accurate, AD-specific synthetic MRIs, and highlight their potential for enhancing training data availability, improving diagnostic accuracy, and promoting research reproducibility in neuroimaging studies.

Recent incidents involving LLMs used for mental-health support reveal a critical evaluation gap: surface-level safety scores do not capture how models behave across realistic, emotionally sensitive interactions over time. Existing benchmarks measure knowledge, safety, or static response quality, but miss whether LLM interactions help users keep reflecting, coping, and making decisions themselves. We formalize this missing dimension as COGNITIVE ATROPHY, a process-level behavioural measure in AI-mediated mental-health support distinct from safety and helpfulness. To measure it, we introduce COGNITIVE ATROPHY BENCH, a clinically grounded benchmark built from 1,576 fully human-generated counseling conversations, 15,680 turns, and 42,230 responses from five LLMs. Three clinical and neuropsychology experts developed a 20-attribute schema spanning user context, response behaviour, and global risk flags; six trained clinical reviewers applied it with span-grounded evidence, producing 5,324 reviewer judgments. We further introduce the User-Input Risk Index (UIRI), the Cognitive Atrophy Risk Index (ARI), and trajectory summaries. Across five LLMs, models show a consistent moderate-to-high level of atrophy-aligned behaviour across single and multi-turn settings. While models generally respond to overt safety cues, they adapt less reliably when users seek solutions or decisions. The dominant recurring patterns are directive advice, problem-solving, recommendation responses, topic shifts, and forms of validation that may reinforce dependence rather than reflection. Our work makes COGNITIVE ATROPHY measurable and provides a foundation for auditing model behaviour in sensitive LLM conversations.

Dementia and depression are the most prevalent neuropsychiatric disorders in geriatric populations, and their overlapping symptoms pose major challenges for differential diagnosis. In this study, we investigate open-weights Large Language Models (LLMs) for predicting dementia and depression severity from speech samples collected during standardized history taking interviews with 154 German-speaking subjects. We introduce an observer-based Global Depression Scale (GDS-D) aligned with the established Global Deterioration Scale (GDS), enabling parallel global staging of affective and cognitive symptoms. We compare three LLMs (Mistral 3.1, DeepHermes, Qwen3) in two settings: (1) zero-shot prediction and (2) LLM-based feature extraction for Support Vector Regression, using human and pause-enriched transcripts. Results show that LLMs effectively predict depression severity in zero-shot settings (best MAE of 0.60), while dementia assessment benefits substantially from structured feature extraction (best MAE of 0.78), reducing errors by up to 35% over zero-shot baselines. Pause-enriched transcripts achieve competitive performance with human transcriptions, demonstrating the viability of fully automatic screening pipelines for differential neuropsychiatric assessment.

Despite increasing adoption of multimodal approaches in Alzheimer's Disease (AD) research -- aimed at integrating molecular, structural, clinical, and genetic biomarkers to enhance disease characterization -- the relationships among these modalities remain poorly understood. A systematic analysis of their dynamic interaction is essential for improving disease modeling, identifying redundant assessments, and reducing patient burden and acquisition costs. In this paper, we present a quantitative analysis of multimodal AD biomarkers by integrating tau-PET, structural MRI, cognitive scores (MMSE and CDR), and APOE4 data from 789 subjects drawn from the ADNI dataset. In our analyses, we (A) quantify cross-modal mutual information and explained variance to assess redundancy and predictive dependencies; (B) examine associations between tau topologies and structural atrophy across brain regions to select informative ROIs; (C) perform a statistical decomposition of the tau-cognition association into atrophy-related and atrophy-independent components; (D) and identify a dominant neurodegenerative trajectory that aligns with cognitive decline. This study provides a systematic characterization of cross-modal relationships, improving the interpretability and selection of biomarkers in AD. Code is publicly available at: https://github.com/antonioscardace/Multimodal-AD.

Tau positron emission tomography (PET) is widely used for the in vivo characterization of disease stage and progression in Alzheimer's disease (AD). With the adoption of multiple tau PET tracers including AV-1451, PI-2620, MK-6240 with different binding behaviors in various large-scale studies, there is a great need of effective harmonization methods to enable the cross-tracer integration of tau PET datasets. While previous methods such as CenTauR were proposed to standardize scalar tau PET measures, they are limited in accounting for the heterogeneity of tau pathology. In this work, we propose Feynman-Kac Reweighted Schrödinger Bridge Matching (FKRSBM), a surface-based framework for cross-tracer tau PET harmonization. FKRSBM learns a direct stochastic transport between tracer domains using Schrödinger Bridge matching, avoiding the Gaussian-prior routing used in diffusion-based translation. To promote biologically consistent transport, FKRSBM introduces an endpoint penalty favoring bridge pairings with matched tau-pathology status and implements it through a Feynman-Kac reweighted endpoint proposal. To preserve cortical organization, FKRSBM uses a spherical convolutional network for vertex-level harmonization on cortical surface meshes. In our experiments, we demonstrate our method by harmonizing Tau PET images acquired with the AV-1451 (n=1480) and PI-2620 (n=2458) tracers from two large-scale datasets. Compared to previous methods including ComBat, CycleGAN, Diffusion Model(DF), and unregularized Schrödinger Bridge Model(DSBM), the proposed FKRSBM method outperforms these baselines in subgroup-level alignment, tau-positivity consistency, and diagnostic classification while preserving subject-specific cortical topography of tau pathology. The code is available at: https://github.com/jianweizhang17/FKRSBM.

Chest X-ray (CXR) interpretation often requires longitudinal comparison to assess disease progression. Existing approaches typically rely on temporal feature fusion or inter-study discrepancy modeling, yet remain limited in capturing subtle progression semantics and overlook the inherently directional nature of disease trajectories. In this paper, we propose ProTrans, a novel vision-language pretraining framework that formulates disease progression as a directional semantic transition between paired CXR studies. ProTrans leverages radiology reports to anchor individual CXR representations within interpretable disease states, and introduces a learnable progression feature map to explicitly encode semantic shifts between states, aligned with report-derived progression descriptions. To enforce direction-aware perception, ProTrans incorporates a reversed temporal modeling process and imposes bidirectional reconstruction consistency across states and transitions, thereby disentangling directional semantics and promoting coherent trajectory modeling. Extensive experiments on longitudinal downstream tasks, including disease progression classification and progression captioning, demonstrate that ProTrans consistently outperforms existing methods, establishing a unified pretraining framework for longitudinal CXR understanding. https://github.com/RPIDIAL/ProTrans

Alzheimer's disease (AD) progression is often described through the amyloid-tau-neurodegeneration, or AT(N), cascade. However, most longitudinal models represent this cascade either as a fixed sequence of biomarkers or as a black-box forecasting task. This makes it difficult to determine when biologically guided biomarker relationships influence future regional pathology. In this study, we introduce Bayesian Networks with Latent Time Embedding (BN-LTE), a Bayesian structural framework for stage-aware modeling of AD progression. BN-LTE estimates disease pseudotime from baseline biomarker profiles and constrains directed dependencies according to biologically plausible AT(N) ordering. Posterior spline-varying structural equations are then used to link initial multimodal measurements with future annualized regional tau-PET change. Across repeated subject-disjoint evaluations using ADNI data, BN-LTE shows strong spatial reconstruction of tau progression compared with the included forecasting baselines. Beyond spatial reconstruction, BN-LTE recovers posterior stage-varying AT(N)-constrained effects and identifies a mid-pseudotime window of amyloid sensitivity. This window is supported by model-implied g-formula contrasts, root-adjusted AIPW, mechanism-sensitive ablations, and robustness analyses across spline and prior specifications. Overall, these findings position BN-LTE as a Bayesian structural framework for forecasting tau progression while examining stage-dependent AT(N)-cascade mechanisms in observational longitudinal neuroimaging data. Our code is available at https://github.com/danleneurocom/BN-LTE.

This study proposes an overall deep learning architecture for multi-class classification of plant diseases from high-resolution leaf imagery, with a particular interest in investigating the behavior of ResNet-50 and a hybrid ResNet + Vision Transformer (ViT) design. A specially gathered image database with 15,200 training images and 3,800 validation images spanning 38 classes across multiple crops, including tomato, apple, grape etc. were subjected to preprocessing steps such as resizing, normalization, and data augmentation to enhance model robustness. Multiple architectures, including ResNet-50, MobileNetV2, and EfficientNet-B0, were trained and compared with the hybrid ResNet + ViT model. All models were fine-tuned using the AdamW optimizer and cross-entropy loss, with early stopping applied to prevent overfitting and ensure generalization. Furthermore, interpretability techniques such as Grad-CAM and saliency maps were implemented to indicate disease-relevant regions, while segmentation-based analysis was performed to identify the affected parts of a leaf. For every one of the considered architectures, ResNet-50 led to the highest accuracy of 98.74%, whereas the hybrid ResNet + ViT model achieved a competitive accuracy of 98.58%, showing that the hybrid architectures were effective in capturing both local and overall information. The experimental results showcase the promise of transformer-based models to achieve highly accurate, interpretable, and computationally efficient computer-based multi-class multi-disease classification systems, providing helpful assistance for cultivation management practices as well as for precision farming.

Alzheimer's Disease (AD) is a complex neurodegenerative disorder that continues to impact millions of people worldwide. Predicting AD conversion during the prodromal stage remains critical for disease understanding and patient care. As such, survival models are widely used for AD risk prediction, yet they are typically static predictors with limited interpretability and no capacity for natural language reasoning. In this work, we propose iLENS, an interpretable large language model (LLM) guided framework based on mixture-of-experts (MoE) for survival prediction in AD conversion. Our approach uses LLM to synthesize structured neuroimaging measurements and unstructured information to guide expert routing. Our framework demonstrates competitive predictive performance and capability in patient subtyping. Furthermore, our framework provides transparent, biologically grounded rationales for its routing decisions, bridging the gap between high-performance survival analysis and interpretable clinical decision support.

This paper presents a two-stage Hybrid Classical-Quantum (HCQ) pipeline for binary Alzheimer's disease (AD) classification from 3D T1-weighted structural MRI volumes, where the classical and quantum components are designed to complement each other rather than operate independently. A supervised 3D $β$-variational autoencoder (VAE) is trained end-to-end under voxel-wise reconstruction, KL-divergence, and focal classification losses that compress each 3D MRI volume (resized from 152 x 184 x 152 to 96 x 96 x 96) into a 64-dimensional latent code. Partial Least Squares (PLS) regression selects the six components in the latent code that best separate Alzheimer's Disease (AD) from cognitively normal (CN) subjects and rescales them into rotation angles, which are encoded onto a six-qubit register using the ZZ quantum feature map to give us the respective quantum states. The input to a precomputed-kernel Support Vector Machine (SVM) is an N x N Gram matrix (N = 308), created by calculating the overlap between every pair of quantum states. The novelty of this work lies in the fact that the quantum kernel operates directly on disease-aware features that are learned end-to-end by a supervised autoencoder, rather than on pre-extracted inputs. On 308 ADNI-1 subjects, consisting of 137 AD and 171 CN subjects, the baseline achieved 67.2% accuracy and 0.759 AUC, while the stability-enhanced variant reached 72.1% accuracy and 0.799 AUC with cross-fold variance halved. 3D Grad-CAM further helped validate our model's focus on brain regions linked to Alzheimer's. The HCQ pipeline could serve as a general-purpose framework for diagnostic classification across biomedical imaging domains that present similar challenges for classical approaches.

Alzheimer's Disease (AD) is a progressive neurodegenerative disorder that affects millions of older adults, with prevalence expected to rise significantly in the coming years. Early diagnosis, particularly during the mild cognitive impairment (MCI) stage, is critical for timely intervention. Structural Magnetic Resonance Imaging (sMRI) has emerged as a key modality for detecting AD-related brain changes, but traditional graph-based approaches often struggle with modality and inter-site heterogeneity, limiting diagnostic performance. In this paper, we propose Graph Matching Network for Alzheimer's Disease Diagnosis (GMN4AD), designed to model interactions between heterogeneous brain graphs derived from neuroimaging data. Unlike conventional methods that treat each brain graph independently, GMN4AD leverages graph matching to capture cross-graph relationships, enhancing diagnostic precision. Furthermore, we introduce a test-time domain adaptation strategy that combines contrastive learning to mitigate domain shifts during inference. Extensive experiments on three public AD datasets demonstrate that GMN4AD achieves superior performance compared to state-of-the-art methods, offering a robust and generalizable solution for AD diagnosis.

Alzheimer's disease (AD) is a fatal disorder that destroys memory and cognitive skills in the elderly population. Most treatments for AD are effective in the early stage, leading to an increasing demand for early AD diagnosis. AD diagnosis increasingly relies on multimodal data such as clinical assessments, structural Magnetic Resonance Imaging (MRI), and Positron Emission Tomography (PET) imaging. However, MRI and PET acquisition remain costly and not universally accessible, making full-modality inference impractical in real-world clinical workflows. We propose ProMUSE, a Progressive Multi-modal Uncertainty Guided Staged Evidential Network that adaptively determines when additional modalities are necessary, helping reduce the overall cost of data acquisition while maintaining accuracy. ProMUSE first performs evidential classification using low-cost clinical data and quantifies uncertainty via a Dirichlet-based subjective logic model. When uncertainty exceeds a learned threshold, ProMUSE progressively incorporates MRI or PET features, fusing modality-wise belief and uncertainty through Dempster-Shafer theory to obtain a calibrated multimodal prediction. This staged acquisition strategy enables accurate diagnosis while minimizing reliance on expensive imaging. Experiments on ADNI, AIBL, and OASIS across CN-AD, CN-MCI, and MCI-AD tasks demonstrate that ProMUSE achieves competitive or superior accuracy compared to full-modality baselines while reducing MRI/PET usage by 50-90%, yielding substantial cost savings. These results highlight ProMUSE as a practical, uncertainty-aware, and resource-efficient solution for real-world AD screening.

Despite advances in information extraction driven by deep learning and large language models, performance gaps remain in highly specialized biomedical fields, where domainspecific complexity poses challenges for generalist models. In this work, we focus on the domain of autoimmunity, where the main entities of interest are autoimmune diseases, autoantibodies (i.e., molecules that may mark or cause these diseases), their molecular targets, their location in the body, and their associated clinical signs. Herein, we present AAbAAC (AutoAntibodies and Autoimmunity Annotated Corpus), a corpus of 115 abstracts selected from PubMed, where we manually annotated entities and their relationships. First, AAbAAC was used to evaluate several methods on the task of named entity recognition (NER), and secondly, to fine-tune NER models. Our study demonstrates the utility of AAbAAC for information extraction in the domain of autoimmunity, showing expected improvement in NER performance after finetuning. This illustrates the value of small-scale annotation efforts for specialized domains and contributes to the computational study of autoimmunity. The AAbAAC corpus is available at https://github.com/f-maury/AAbAAC.

Voice-based screening offers a scalable and non-invasive way to assess neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD), but their staging remains challenging due to the difficulty of integrating heterogeneous data. This paper presents NeurMLLM, an efficient multimodal generative framework for neurodegenerative disease staging. NeurMLLM first encodes the spectrograms and Mel-frequency cepstral coefficients of audio data with vision transformers and projects their representations into the embedding space of a large language model (LLM), where they are concatenated with transcript and demographic instruction tokens as a single unified sequence. The LLM is then instruction-tuned via Low-Rank Adaptation using task prompts to autoregressively predict a constrained label token, enabling a generative classification. By evaluating on the Bridge2AI-Voice dataset for fine-grained staging of AD and PD, we observe that NeurMLLM achieves strong performance, consistently outperforming classical machine learning methods and existing LLM-based approaches. The results show the high potential of multimodal LLMs in neurodegenerative disease staging, improving staging accuracy and supporting accessible deployment.

Neurodegenerative diseases such as Alzheimer's disease (AD) require accurate and scalable tools for assessing disease severity, yet current clinical staging remains time-intensive and prone to variability. We propose an attention-enhanced multimodal machine learning framework with ordinal regression for automated and interpretable AD severity staging. The framework integrates T1-weighted MRI with demographic and genetic variables and compares unimodal and multimodal architectures using ordinal and non-ordinal prediction heads. Models were trained and validated using cohort-stratified splits derived from the ADNI, AIBL, and NIFD datasets. A strictly held-out test set was constructed using subjects excluded from all training, validation, preprocessing, and hyperparameter tuning procedures, with subject-level splitting employed throughout to prevent data leakage. Among unimodal approaches, the T1-weighted MRI model achieved slightly higher adjacent-stage accuracy (0.963) and agreement with clinical staging (QWK 0.444) than the tabular model (QWK 0.433). Integrating imaging, demographic, and genetic information improved overall performance. The multimodal non-ordinal baseline achieved the lowest prediction error (MAE 0.340), whereas the ordinal multimodal model achieved the highest adjacent-stage accuracy (0.970) and strongest agreement with clinical staging (QWK 0.549). These findings indicate that ordinal formulations better capture the ordered structure of the CDR scale and yield predictions more consistent with clinical staging. Explainability analyses using Grad CAM++ and SHAP demonstrated anatomically and clinically plausible model behavior, supporting transparent decision-making. Overall, attention-based multimodal learning with ordinal regression represents a robust, interpretable, and scalable approach for automated AD severity staging and AI-assisted clinical decision support.

Early detection of neurodegeneration remains a critical clinical challenge. This study investigates whether sleep EEG signal criticality, quantified via Multifractal Detrended Fluctuation Analysis (MFDFA), serves as a non-invasive biomarker for future cognitive decline. We analyzed longitudinal data from the National Sleep Research Resource (NSRR) Study of Osteoporotic Fractures (SOF) cohort, comparing baseline sleep EEG dynamics between women who remained cognitively normal and those who later progressed to dementia-related impairment ($3MS < 78$).Our results reveal significant group-level differences in Hurst exponent $H(q)$ distributions, particularly during non-REM stages N2 and N3. Cognitively healthy individuals exhibited signal dynamics significantly closer to an optimally critical state across all electrode locations ($p \leqslant 0.001$), supporting the Brain Criticality Hypothesis. Supervised UMAP projections confirmed clear spatial separation between groups throughout the overnight sleep architecture.The dementia group demonstrated a shift in DFA exponents toward $1.0$, suggesting that a reconfiguration of scale-free neural dynamics during sleep precedes clinical symptoms. These findings highlight the potential for MFDFA-derived measures to be integrated into automated, sleep-based screening tools, enabling earlier preventative interventions during the prodromal window of dementia.

Supervised fine-tuning with synthetic rationale data is widely assumed to improve language model performance on clinical prediction tasks by teaching models not just what to predict but why. We test this assumption on five-year Alzheimer's disease and related dementias (ADRD) prediction from longitudinal health histories. Across a large-scale controlled experiment of 504 configurations, we find that rationale-based SFT consistently and substantially hurts prediction performance relative to label-only fine-tuning. The degradation persists across model families and data scales, and is not resolved by using a reasoning-oriented base model. Crucially, the failure is not explained by poor rationale quality: human expert annotation confirms that the generated rationales are medically accurate and faithfully grounded in patient-specific evidence, and few-shot experiments show that the same rationales improve performance when used as inference-time demonstrations rather than training targets. We identify the root cause as a structural conflict between narrative plausibility and discriminative optimization. We hope our work paves the path toward a more precise understanding of when and how rationale-based supervision helps and when it does not, guiding the responsible development of language models for high-stakes clinical prediction.

Reduced facial expressivity is a common motor manifestation of Parkinson's disease (PD), often described as hypomimia or facial bradykinesia. This paper examines whether temporal motion descriptors extracted from facial-region keypoints can support in-the-wild PD-related video classification on the YouTubePD benchmark. Each video is represented using geometric descriptors from 14 predefined facial regions. Static geometry, normalized geometry, velocity-based descriptors, relative-velocity descriptors, and a GRU sequence baseline are compared under the same binary classification protocol. To assess stability and interpretability, the study includes seed-robustness analysis, region-level ablation, and permutation importance. The best result is obtained with normalized velocity descriptors and a Random Forest classifier, reaching a balanced accuracy of 0.826 and an AUROC of 0.855 on the held-out test split. Across 10 random seeds, this representation remains stable, with balanced accuracy of 0.810 +/- 0.018 and AUROC of 0.855 +/- 0.005. Overall, the results suggest that normalized facial-region motion is a lightweight and interpretable representation for YouTubePD video classification. The study is framed as a benchmark-level analysis and does not claim clinical severity assessment or MDS-UPDRS facial-expression scoring.

Alzheimer's disease (AD) progression is highly heterogeneous and is typically observed through sparse and irregular longitudinal data, posing challenges for prediction and personalised monitoring. Existing machine learning approaches have improved AD prediction using multimodal data, yet often focus on static classification or cohort-level risk estimation, providing limited support for subject-specific modelling and uncertainty-aware reasoning. To address these limitations, we present a personalised digital twin framework for AD prediction and scenario-based analysis using multimodal longitudinal data. The proposed approach integrates complementary modelling strategies to capture clinical transitions and temporal dependencies across visits. Using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), including cognitive assessments, clinical variables, and MRI-derived phenotypes, the framework predicts cognitive status and diagnostic categories while quantifying predictive uncertainty and enabling patient-specific what-if trajectory analysis. Evaluation on leak-free subject-level splits demonstrates strong performance in score forecasting and diagnosis classification. In this sparse and irregular ADNI setting, transition-based modelling of adjacent visits achieved higher predictive accuracy than the sequence-based branch, suggesting that local transition modelling may be more data-efficient. While sequence models remain valuable for uncertainty-aware trajectory forecasting, local transition modelling offers a more data-efficient and robust predictive strategy. These findings highlight the importance of aligning temporal modelling strategies with clinical data structure and suggest that transition-based digital twin formulations may provide a practical and interpretable approach for personalised disease forecasting in neurodegenerative disorders.

Parkinson's disease (PD) is a progressive neurodegenerative disorder that frequently causes speech impairments associated with hypokinetic dysarthria. As speech production relies on the precise coordination of complex neuromuscular mechanisms, speech analysis has emerged as a promising non-invasive and cost-effective biomarker for early PD detection. Recent deep learning approaches have shown encouraging results; however, most existing methods rely on a single speech representation, potentially overlooking complementary pathological information encoded across different feature spaces. In this work, we propose a multi-branch deep learning framework for automatic PD detection from speech. Each recording is segmented into 5-second chunks and represented using three complementary modalities: Log-Mel spectrograms, MFCCs, and HuBERT embeddings extracted from raw waveforms. The spectrograms are processed using a pre-trained ResNet-18 encoder, MFCC sequences are modeled through a BiLSTM network, and raw speech is encoded using a pre-trained HuBERT model. To effectively integrate these heterogeneous representations, we introduce a context-guided cross-modal attention mechanism that dynamically weights temporal HuBERT embeddings according to the global acoustic context derived from the spectrogram and MFCC branches. Experiments conducted on the publicly available Spanish PC-GITA corpus under strict speaker-independent 5-fold cross-validation demonstrate the effectiveness of the proposed approach. The proposed architecture achieves an accuracy of 91.51%, an F1-score of 91.24%, and an AUC of 95.97%. Furthermore, ablation studies confirm the contribution of both the proposed context-guided cross-modal attention mechanism and the integration of complementary speech representations. These findings highlight the potential of heterogeneous speech modeling for robust and clinically reliable PD detection.

Alzheimer's disease is a progressive neurodegenerative disorder, and its progression varies substantially across patients. Existing work aims to forecast patients' future cognitive state, with minimal focus on reconstructing the state from past visits. Furthermore, in current research, quantifying predictive uncertainty remains underexplored and relies on costly modalities such as MRI, PET, and CSF, limiting their deployment in resource-limited settings. In this research, our primary objectives are: First, bidirectional prediction of cognitive scores from irregular visits to present the complete disease trajectory. Second, to enable interpolation and extrapolation capabilities to assist clinicians in informed prognostic decision making, and third, to provide a well-calibrated uncertainty estimate for all predictions, and finally, to achieve the objectives using the modalities available during routine visits. We propose a unified framework, GNOVA: A GRU-Neural ODE Variational Autoencoder. The architecture combines a Gated Recurrent Unit encoder and a Neural ODE decoder within a variational autoencoder framework. In our work, we forecast the CDR-SB and MMSE Scores. The GRU encoder allows for any number of inputs at any time point. The Neural-ODE decoder performs continuous estimation, allowing interpolation and extrapolation at any desired time point. The Variational autoencoder allows for uncertainty estimation in predictions. We worked with 1,727 patients from the ADNI dataset over 10 years; the model achieved mean absolute errors of 1.35 and 2.28 for CDR-SB and MMSE scores, respectively, without requiring any neuroimaging or biomarker data. Feature-ablation studies revealed that age, BMI, and APOE4 status were strong predictors. The proposed framework enables the reconstruction of incomplete patient histories and the anticipation of future cognitive states.

Language models trained for clinical disease inference are trained on patient data, which may include sensitive and private information, and data owners may request the removal of their data from a trained model due to privacy or copyright concerns. However, exactly unlearning patient-specific data is intractable, and retraining with minor data removal is resource-intensive. While there exists several machine unlearning methods that can be used, their utility is generally restricted to non-medical domains. Moreover, the existing benchmarks for evaluating such unlearning methods primarily utilize synthetically curated datasets, which are not truly representative of real-world systems. Hence, the effectiveness of these unlearning methods in the medical domain is largely unclear. To this end, we introduce REMEDI, an extensive benchmark for machine unlearning tailored to multi-label and multiclass clinical disease inference, where label correlations, longitudinal structure, and safety constraints make unlearning particularly challenging. Unlike the existing benchmarks, REMEDI considers: (1) a relevant application domain (medical), (2) comprehensive unlearning setups involving diverse sets of forget instances, (3) challenging unlearning scenarios including multi-label and multi-class classification tasks, and (4) evaluation metrics involving performance both in terms of utility and extent of unlearning achieved. REMEDI is developed using the MIMIC-III clinical database that contains comprehensive clinical data of patients. Experiments with existing unlearning methods indicate that there exists a trade-off between utility and unlearning performance. They are also largely unsuited to multi-label classification tasks. To facilitate reproducibility, we make our benchmark publicly available.

Neurodegenerative disorders such as Alzheimer's disease exhibit highly organized patterns of regional brain vulnerability, yet the biological mechanisms underlying this spatial selectivity remain incompletely understood. Existing imaging-transcriptomic studies have largely relied on correlation-based analyses between gene expression and neuroimaging phenotypes, limiting their ability to model how molecular organization gives rise to neurodegeneration. Here, we introduce a cross-scale spatially-aware generative framework for modeling transcriptomic programs underlying cortical neurodegeneration. Regional transcriptomic profiles were derived from the Allen Human Brain Atlas using 910 landmark genes across 68 cortical regions. Neurodegenerative vulnerability maps were constructed from ADNI FreeSurfer cortical thickness measurements by computing regional cortical thinning differences between cognitively normal controls (NC = 926) and Alzheimer's disease subjects (AD = 426). A variational generative architecture was used to learn latent biological programs linking regional gene-expression organization to cortical degeneration while incorporating graph-based spatial smoothness regularization to preserve cortical organization. The proposed framework achieved strong prediction of regional neurodegenerative vulnerability, yielding an explained variance of 0.8604 and a significant spatial correlation between predicted and observed cortical degeneration profiles (r = 0.9439, p < 0.001). The learned latent representations revealed structured transcriptomic organization associated with distributed disease susceptibility. These findings demonstrate that biologically constrained generative modeling can bridge microscale molecular organization with macroscale neurodegeneration, providing a foundation for spatially-aware generative neurobiology and computational neuroscience.

The development of multilingual Alzheimer's Disease Dementia (AD) detection models presents significant challenges due to the resource-intensive and time-consuming nature of language-specific model training. We propose a novel solution using cross-language training to detect AD in languages beyond those used for model training. This study investigates multilingual deep learning models for detecting AD across different languages and cognitive impairment levels. Using datasets in English, Chinese, Arabic, and Hindi, we developed transformer-based models for binary AD classification. Our approach achieved F1 scores of 82% across all languages, demonstrating strong cross-linguistic generalization. The rapid inference time (0.5 seconds) supports potential real-time screening applications, while consistent performance across languages indicates feasibility for global deployment.

Early and accurate detection of Alzheimer's disease (AD) is important for timely intervention and disease management. Generalized Eigenvalue Proximal Support Vector Machine (GEPSVM) and its Universum-based variants have shown promising results for AD classification. However, existing methods treat Universum samples as independent points and do not consider the geometric relationships among them. This paper proposes two graph-guided Universum learning models, namely UG-GEPSVM and IUG-GEPSVM, for AD versus cognitively normal (CN) classification using structural MRI data. In the proposed framework, mild cognitive impairment (MCI) subjects are used as Universum data to provide intermediate information between AD and CN classes. A graph is constructed over the Universum samples using Gaussian similarity, Minimum Spanning Tree connectivity, and multi-hop propagation. From this graph, a Laplacian matrix is derived that captures the geometric structure of the MCI samples. This Laplacian-based regularization is incorporated into the learning process in place of the conventional independent Universum penalty term. UG-GEPSVM integrates this regularization into the generalized eigenvalue formulation, while IUG-GEPSVM extends the numerically stable improved GEPSVM framework using a standard eigenvalue formulation. Experiments on ADNI MRI dataset variants using ICA- and PCA-based features at five different noise levels show that both proposed models consistently outperform existing GEPSVM and Universum-based methods. UG-GEPSVM achieves the highest average AUC of 88.07% and maintains stable performance under increasing noise levels. Statistical tests further confirm the significance of the observed improvements.

Understanding how structural connections are associated with tau propagation in Alzheimer's disease (AD) remains a central open question, yet existing computational models either rely heavily on biophysical assumptions or lack neurobiologically interpretable pathway maps. We present SC-TauPath, a structural connectivity (SC) attribution framework that maps tau propagation pathways from in vivo neuroimaging data. SC-TauPath combines a Network Diffusion Model (NDM)-augmented multilayer perceptron with gradient $\times$ input attribution to score each SC edge's contribution to tau prediction, then translates these attribution scores into multi-scale pathway maps (backbone edges, high-traffic routes, and hub ROIs), which validates established Braak staging anatomy. Applied to 234 ADNI participants with paired DTI SC and 18F-Flortaucipir PET, SC-TauPath achieves strong cross-validated tau prediction and yields attribution-based pathway maps consistent with established Braak staging anatomy, demonstrating that SC encode spatially specific information about regional tau distribution in AD.

The graphical representation of the brain offers critical insights into diagnosing and prognosing neurodegenerative disease via relationships between regions of interest (ROIs). Despite recent emergence of various Graph Neural Networks (GNNs) to effectively capture the relational information, there remain inherent limitations in interpreting the brain networks. Specifically, convolutional approaches ineffectively aggregate information from distant neighborhoods, while attention-based methods exhibit deficiencies in capturing node-centric information, particularly in retaining critical characteristics from pivotal nodes. These shortcomings reveal challenges for identifying disease-specific variation from diverse features from different modalities. In this regard, we propose an integrated framework guiding diffusion process at each node by a downstream transformer where both short- and long-range properties of graphs are aggregated via diffusion-kernel and multi-head attention respectively. We demonstrate the superiority of our model by improving performance of pre-clinical Alzheimer's disease (AD) classification with various modalities. Also, our model adeptly identifies key ROIs that are closely associated with the preclinical stages of AD, marking a significant potential for early diagnosis and prevision of the disease.

Understanding complex interactions between brain regions is critical for early neurodegenerative disease classification such as Alzheimer's Disease (AD) and Parkinson's Disease (PD). While graph-based models are widely used to analyze brain networks, most existing approaches primarily focus on pairwise interactions between directly connected nodes, limiting their ability to capture higher-order dependencies across multiple regions. Although hypergraph-based methods have been proposed to model higher-order relations, many rely on predefined hyperedges or restrict learning to hyperedge weights, reducing flexibility and limiting their capacity to capture multi-resolution structural patterns. In this regard, we introduce an adaptive multi-scale hyperedge learning framework, i.e., MuHL, which constructs hierarchical node features and dynamically learns high-order interactions through continuous hyperedge construction over multi-resolution graph signals. Extensive experiments on multiple brain network benchmarks demonstrate that MuHL consistently improves disease classification performance across different stages, and further identifies key regions of interest (ROIs) and their group-wise interactions from the learned hyperedges that are associated with disease progression, highlighting its potential as a powerful tool for brain network analysis in neurodegenerative disorders.

Predicting whether an individual with Alzheimer's disease will experience mild or severe disease progression is essential for personalized treatment. Typically, practitioners seek to predict the distribution of a discrete disease score, conditional on an individual's current MRI volume and their historical disease trajectory. Classical statistical regression models and single-task neural networks are not well-suited for this purpose because fitting separate models is infeasible (since each individual typically has few observations), while ignoring individual-level correlation leads to poor generalization. Meta-learning, in contrast, provides a natural avenue to dynamically predict distributions without retraining and model nonlinear relationships between the outcome and covariates. Motivated by this, we propose a Bayesian meta-learner that is trained on multiple individuals but tailors the predictive disease score distribution to each individual's historical data. Our model predicts on unseen individuals without retraining, scales linearly with the number of historical observations, and is guaranteed to be less overconfident when predicting long-term disease scores compared to its deterministic counterpart. On real-world data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, our model achieves performance competitive with both single-task models and deterministic meta-learners, while substantially improving performance when predicting long-term disease progression.

Multimodal neuroimaging fusion of functional MRI (fMRI) and diffusion tensor imaging (DTI) provides complementary information for cognitive impairment analysis, but remains challenged by heterogeneous feature spaces and misaligned representations. We propose \textit{NeuroAlign}, a hierarchical framework for structured multimodal fusion. It introduces (1) \textit{Dual-Modal Hierarchical Alignment} (DMHA), which models multi-scale dynamic connectivity and aligns dynamic-static and functional-structural embeddings; and (2) \textit{Dual-Domain Hierarchical Interaction} (DDHI), which enables fine-grained modulation and global interaction between connectivity- and region-level features. To support feature-level inspection, we design \textit{Synergistic Activation Mapping} (SAM), a gradient-free, marker-oriented attribution method for DFC, SFC, ALFF, and FA. Evaluated on GUTCM, ADNI, and OASIS under five-fold validation, NeuroAlign achieves competitive MCI/SCD detection and preliminary cross-dataset transferability. Attribution analyses reveal modality-specific and partially consistent brain patterns, providing model-derived evidence for multimodal representation analysis.

Mild cognitive impairment (MCI) and subjective cognitive decline (SCD) are closely associated with the early Alzheimer's disease continuum, where accurate and explainable diagnosis is important for early risk assessment and intervention. Existing connectome-based deep learning models can improve classification performance but often provide limited insight into disease-related functional and structural connectivity changes. This paper proposes an atlas-knowledge-guided Generative Counterfactual Attention-guided Network (GCAN) for explainable cognitive decline diagnosis using multimodal brain connectomes. GCAN formulates diagnosis as a source-to-target counterfactual generation problem, where target-label connectomes are generated from source-label inputs and their differences are used to construct counterfactual attention maps. To preserve connectome topology, an Atlas-aware Bidirectional Transformer (AABT) performs network-level token encoding and decoding under brain-atlas constraints. The framework is further extended from functional connectivity (FC) to joint functional and structural connectivity (SC) modeling, enabling counterfactual analysis of complementary functional reorganization and structural topology changes. Experiments on hospital-collected and ADNI datasets show that GCAN achieves competitive performance across HC vs. SCD, HC vs. MCI, and SCD vs. MCI classification tasks. Visualization, circular connectome analysis, CAM-based comparison, ablation studies, and confidence interval analysis further support the interpretability and reliability of the proposed framework. Modality-specific FC and SC pre-trained classifiers are used to provide target-state priors for counterfactual generation while being separated from the downstream diagnostic classifier to prevent data leakage.

Financial exploitation is a growing concern for people with Alzheimer's disease, especially during periods of reduced cognitive stability. Conventional fraud detection systems usually rely on financial behavior alone and ignore clinically relevant factors that may alter vulnerability. This paper proposes a medication-aware framework that synchronizes medication adherence with transaction-level monitoring to improve detection of cognitively risky financial events. A hybrid simulation dataset was constructed for 180 patients across 45 days, producing 8,100 medication records and 30,855 transactions. The framework evaluates amount anomaly, vendor novelty, transaction frequency, time deviation, and medication adherence through financial-only, additive medication-aware, and interaction-aware logistic models. Results show that the financial-only baseline obtained the highest global F1-score of 0.5000, but the interaction-aware model improved recall during medication-induced vulnerability windows from 0.7442 to 0.9070 and achieved the highest average precision for ranked high-risk cases. The findings suggest that medication adherence is most useful as a contextual modifier of financial risk rather than as an isolated predictor.

Deep learning-based Major Depressive Disorder (MDD) detection using Electroencephalography (EEG) is fundamentally constrained by the "small-sample dilemma." Prevailing generative data augmentation methods not only incur heavy computational overhead but also risk introducing synthetic noise, thereby blurring classification boundaries. To challenge the traditional "data quantity first" convention, we propose a novel framework "Beyond Augmentation": Score-Guided Classification (SGC). SGC does not synthesize pseudo-samples; instead, it utilizes an unsupervised generative network architecture to model the structural and statistical anomaly degrees of samples, serving as the core "Pathological Prior". This prior, after robust normalization, is explicitly fused with deep feature representations, thereby precisely guiding the classifier's decision boundary. Furthermore, to dynamically adapt to varying channel configurations, we propose a Cross-Channel Spatial Adaptation module, utilizing a spatial mapping mechanism to effectively resolve the hardware heterogeneity of mismatched channels in multi-center datasets. Extensive experiments on the Mumtaz2016 and high-density MODMA datasets demonstrate the effectiveness and exceptional generalizability of our method under the challenging "zero data augmentation" setting and at "zero sample synthesis cost". Keywords: Electroencephalography (EEG), Depression Detection, Anomaly Score, Diffusion Models, Few-Shot Learning

AI-driven respiratory sound classification (RSC) is promising for automated pulmonary disease detection, yet multi-site deployment is hindered by inter-stethoscope variability. We introduce a federated domain generalization (FedDG) formulation for RSC in which clients hold recordings from different stethoscopes and the model is evaluated on an unseen device. Our empirical analysis shows that stethoscope-induced style and disease-relevant content are partially entangled, making deterministic style removal unreliable. In response, we propose BTS-CAFE, a framework combining (i) causality-inspired device-style interventions with constraints designed to limit content distortion, (ii) counterfactual metadata augmentation to relieve device and demographic shortcuts, and (iii) gradient alignment to promote device-invariant decision boundaries across clients. Built on BTS with CLAP, a multimodal language-audio pretraining model, BTS-CAFE improves the out-of-distribution ICBHI Score by 3.69 points on average over five held-out devices relative to its backbone, and outperforms conventional data augmentation and federated learning baselines in simulated device leave-out evaluations on the ICBHI and SPRSound datasets.

Language models are increasingly being deployed for conversational support in informal caregiving contexts, where interactions often extend beyond information-seeking: caregivers seek emotional reassurance, guidance, and help, while navigating uncertain, relationally complex care decisions. Yet most safety evaluations assess model behavior under generic prompts, leaving a critical question unexamined: does a model's safety profile change with its support role? We study this by operationalizing four expert-reviewed support roles grounded in social support theory: Inform, Coach, Relate, and Listen, and comparing them against two baseline controls: a basic prompting condition and a retrieval-augmented generation (RAG) condition. We evaluate across three language models (GPT-4o-mini, Llama-3.1-8B-Instruct, and MedGemma-1.5-4b-it) on 5,000 real-world queries from online Alzheimer's Disease and Related Dementias (ADRD) communities. We find that the LLM's support role systematically shapes both the prevalence and composition of interactional risks. Furthermore, a human evaluation study reveals a perceived quality--safety tension: more directive, information-oriented roles are rated as more helpful and trustworthy despite exhibiting elevated interactional risk profiles. We release ~90,000 support role-conditioned model responses with risk annotations as an ecologically grounded resource for research on safer LLM-mediated conversational support.

Predicting conversion from Mild Cognitive Impairment (MCI) to Alzheimer's Disease (AD) is critical for early intervention. Current deep learning paradigms predominantly rely on cross-sectional structural MRI, neglecting prognostic value in patient-specific anatomical trajectories. We introduce the Temporal Adaptive Fusion Network (TAF-Net), a hybrid CNN-Transformer architecture that models paired longitudinal 3D MRI scans. Central to TAF-Net is a Temporal Fusion Module governed by an Adaptive Temporal Gate, which learns patient-specific weightings to synthesize three spatiotemporal representations: explicit structural change, region-to-region temporal cross-attention, and bilateral feature concatenation. Evaluated on the Alzheimer's Disease Neuroimaging Initiative cohort for three-year MCI-to-AD conversion prediction, TAF-Net achieved the highest discriminative performance among all evaluated methods using only structural MRI, significantly outperforming the strongest baseline and approaching multimodal methods requiring PET, CSF, or genetic data. The architecture exhibited exceptional data efficiency, matching baseline performance with a fraction of training data. Ablation studies demonstrate that longitudinal fusion improves discrimination while reducing predictive variance by 48% compared to single-timepoint evaluation. Interpretability analyses reveal spatial attention aligned with established AD pathology in the medial temporal lobe and ventricles, while the gating mechanism prioritizes explicit volumetric change with strong positive correlation to conversion risk.

Confirming Alzheimer's disease (AD) typically relies on positron emission tomography (PET), which remains costly and invasive, motivating the use of structural MRI-based prescreening. Deep learning on non-Euclidean manifolds, particularly brain cortical surfaces, faces significant challenges due to the data's spherical topology. Recent surface models have enabled learning from cortical surface data; however, imposing face-based uniform patches often causes duplicate vertices at patch boundaries. In general, many surface-based models are limited in their awareness of the region of interest (ROI), which can result in non-cortical regions, such as the medial wall, being included. We propose a cortical surface tokenization that performs ROI-preserving, vertex-based, variable-sized patch partitioning. We refer to these cortical surface patches as cortical supervertices (CSVs). Building on this representation, we design the CSV Vision Transformer (CSV-ViT), a variable-size patch-tolerant Vision Transformer that uses padding and a mask-aware patch embedding. We used T1-weighted MRI and evaluated our framework by classifying AD-related status into three categories: AD diagnosis, amyloid positivity, and tau positivity. Across the experiments, CSV-ViT achieved higher classification performance than recent surface-based models. The results suggest that the proposed CSV-ViT may support MRI-based prediction of AD-related status prior to PET or CSF confirmation.

Dementia detection from spontaneous speech offers a scalable approach to cognitive screening, yet NLP systems remain predominantly English-centric. This limitation is especially acute in the Philippines, where Filipino-English code-switching is pervasive and no prior work has addressed NLP-based dementia detection. We present the first systematic evaluation of transformer-based dementia detection in Filipino speech and the first assessment of NeoBERT in a clinical NLP setting. To separate language from domain effects, we construct a parallel bilingual dataset of 4,000 DementiaBank-derived transcripts, with Filipino translations produced manually to preserve discourse-level markers of cognitive decline. We evaluate five model families, TF-IDF + LogReg, BERT, NeoBERT, XLM-R, and RoBERTa-Tagalog, under monolingual, zero-shot cross-lingual, and bilingual fine-tuning settings. We find that in-domain performance does not transfer across languages, with English-trained BERT dropping to Macro-F1 = 0.455 on Filipino, and that architectural modernization alone does not improve robustness. Bilingual fine-tuning, however, eliminates cross-lingual degradation across all transformer models, converging to Macro-F1 = 0.969-0.973. These results suggest that multilingual clinical NLP performance is driven primarily by linguistic coverage during training rather than model scale or architecture.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the leading cause of dementia, affecting memory, reasoning, communication, and daily functioning. Early diagnosis is particularly important, as timely intervention may help slow cognitive decline and improve patient care. Recent studies have demonstrated that spontaneous speech contains valuable linguistic and acoustic biomarkers associated with dementia. However, existing approaches often rely on independently trained modality-specific models, feature concatenation strategies, ensemble methods, or attention-based fusion mechanisms that do not explicitly maximize the dependency between speech and transcript representations. In this work, we propose a multimodal deep learning framework for automatic dementia detection that jointly exploits speech and transcript information in an end-to-end trainable manner. Specifically, speech recordings are divided into 10-second segments and passed through a pre-trained HuBERT model to extract contextualized acoustic representations. To better capture informative temporal speech characteristics, attentive statistics pooling is employed to aggregate frame-level acoustic embeddings. For the textual modality, transcripts are encoded using a pre-trained BERT model, where the [CLS] token representation is used as the linguistic embedding. The acoustic and textual representations are subsequently combined using an attention-based Audio-Text Fusion (AT-Fusion) mechanism. In addition, we introduce a MINE objective to maximize the mutual information between modalities and improve multimodal representation alignment. The fused multimodal representation is finally used for dementia classification. Experiments conducted on the publicly available ADReSS Challenge and PROCESS-2 dataset demonstrate the effectiveness and robustness of the proposed approach for speech-based dementia assessment.

Large audio and language models have recently demonstrated zero-shot reasoning capabilities across various domains. However, it remains unclear how the form of audio input, whether handcrafted acoustic features extracted from speech or the raw audio waveform itself, affects performance for Parkinson's disease (PD) detection across different languages. In this study, we systematically compare two input modalities for zero-shot PD detection: (i) handcrafted acoustic features extracted from speech recordings analyzed by a general-purpose LLM, and (ii) direct waveform input analyzed by audio-capable models. Experiments on PD speech datasets in four languages show that performance varies across input modalities, speech tasks, and languages. Handcrafted acoustic features provide more stable performance in a low-resource language (e.g., Bengali), whereas audio input yields dataset-dependent gains. These findings highlight the impact of input modality on zero-shot PD detection from speech.

No existing nested Archimedean copula tool handles all three of (a) arbitrary per-variable (right-)censoring in survival analysis, (b) arbitrary nesting trees, and (c) exact parameter gradients. Existing implementations handle only bivariate problems, low dimensional (i.e., $d \leq 10$) cases, two layers of nesting, or only hand-derived copula nestings. We present \textsc{acopula}, a JAX-native framework that, given any Archimedean generator -- classical or neural -- evaluates exact nested-copula likelihoods and parameter gradients under arbitrary censoring masks in polynomial time. The mechanism is polynomial powering of Taylor-mode automatic differentiation output, which replaces per-family hand-derived partial Bell polynomial tables with a single differentiable computation that any user-defined generator can drive. We conduct extensive simulations to verify the correctness of \textsc{acopula}. We then demonstrate (a) per-variable censoring on $85{,}229$ MIMIC-IV ICU admissions in high dimensions with $d{=}53$, fit by both classical Archimedean families and nested neural Archimedean copulas; (b) an 11-sector hierarchical model on S&P~500 daily returns at $d{=}98$; (c) family-agnostic censored MLE across ten families, five of them with no prior implementation, on a retinopathy study; and (d) a ${\sim}650\times$ per-density speedup over R's \texttt{nacLL} at $d{=}35$, scaling quadratically to $d{=}8{,}000$.

Von Economo neurons (VENs) are selectively lost in behavioural-variant frontotemporal dementia (bvFTD) and reduced in autism spectrum conditions (ASC), yet their computational role in social learning remains unexplained. We train a spiking neural network (the VENCircuit) embedding VEN-like projection neurons (K=40, 2% of total) in a recurrent pyramidal circuit across 50 matched random initialisations with and without VENs. The network is trained on a controlled binary classification task; we make no claim to model social cognition directly. VEN-intact networks converged in 49/50 cases (98%) versus 35/50 (70%) for VEN-ablated networks (Fisher's exact OR=21.0, 95% CI 2.7-167, p=8.7e-5). Failed ablated networks showed complete absence of learning, inconsistent with a speed-of-learning account. Phase-ablation experiments show VEN removal is most disruptive during mid-training (epochs 5-25), when a co-adaptive dependency forms in the pyramidal circuit. We derive a formal account showing VENs provide a direct gradient pathway immune to Jacobian instabilities affecting the recurrent circuit. Inference-time VEN ablation caused a significant performance drop (Wilcoxon p=0.022), ranging from no change (16/20 networks) to catastrophic collapse (0.989 to 0.620). VENs function as acquisition scaffolds whose developmental absence produces stochastic learning failure - a computational analogue of variable social skill acquisition in ASC - with falsifiable predictions for organoid and electrophysiology studies.

Rare diseases such as inborn errors of immunity (IEI) require early diagnosis to prevent end organ damage and improve quality of life. Hurdles in accessing and curating large scale electronic health record (EHR) data limit routine data driven analyses to remain on the forefront of IEI and other rare disease trends. Development of machine learning (ML) algorithms in IEI for pattern recognition as well as published methodology examining how to systematically process and integrate complex medical data is limited. Our proposed pipeline, including data curation and ML clustering algorithms, is designed to recognize novel rare disease patterns and extract IEI- associated features from a national data registry. Our methodology for EHR data formatting and processing presents the pipeline that transforms raw immunologic lab data into vectors. This is further combined with hyperparameter tuning for diseases pattern recognition via clustering. This study refines IEI feature awareness, develops data tool kits for rare disease populations analysis, and expands on transforming complex medical records in data structures interpretable by unsupervised ML.