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Multimodal AI for Alzheimer Disease Diagnosis: Systematic Review of Datasets, Models, and Modalities

Background: Early detection of Alzheimer disease (AD) is essential for timely intervention; yet, diagnostic performance varies widely across modalities and datasets. Recent multimodal artificial intelligence (AI) models have made significant progress, but the evidence base remains fragmented due to heterogeneous datasets, modeling frameworks, and reporting quality. Objective: This systematic review aimed to analyze studies on multimodal AI models for AD diagnosis, prognosis, and risk prediction over 5 years. We evaluated dataset characteristics, modality combinations, modeling strategies, performance metrics, and methodological limitations. We further discuss real-world implications and translational pathways. Methods: Following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 guidelines, we systematically searched PubMed, IEEE Xplore, Scopus, ACM Digital Library, Cochrane, and arXiv, with the final datasets last searched on November 15, 2025. Studies applying multimodal machine learning or deep learning to AD, mild cognitive impairment, and dementia outcomes were included, whereas studies using a single modality or lacking sufficient methodological detail were excluded. QUADAS-2 (Revised Quality Assessment of Diagnostic Accuracy Studies tool) assessed risk of bias. Extracted performance results were synthesized across 4 major multimodal dataset families. Results: A total of 66 studies met the inclusion criteria. Across datasets, multimodal models consistently outperformed single-modal baselines. Alzheimer’s Disease Neuroimaging Initiative–based diagnosis achieved an average accuracy of 92.5% (SD 3.8%), while mild cognitive impairment–conversion models achieved an average area under the curve (AUC) of 0.922 (SD 0.045), and several fusion architectures reported AUCs above 0.95. In contrast, UK Biobank risk-prediction studies reported an average AUC of 0.84 (SD 0.056), and this reflects performance in large, population-based datasets. DementiaBank speech-language studies achieved an average AUC of 0.813 (SD 0.042), and cross-lingual AD detection achieved an accuracy of 77% (SD 6.5%). Self-collected multimodal datasets demonstrated average accuracies around 96% (SD 2.4%), but their generalizability is limited due to small sample sizes and single-center designs. Conclusions: This systematic review demonstrates that multimodal AI models consistently outperform single-modal models for AD diagnosis, prognosis, and risk prediction by integrating complementary biological, clinical, and behavioral information. Unlike prior reviews, this review provides a unified synthesis across heterogeneous clinical, imaging, genetic, and linguistic datasets, enabling cross-domain comparison of modeling strategies and performance. However, the generalizability of reported performance was limited due to substantial heterogeneity in dataset composition, outcome definitions, and validation, and prevalent risks of bias. By evaluating these factors, this review clarifies where current evidence is robust and where caution is warranted. The findings highlight the need for standardized multimodal benchmarks, transparent evaluation protocols, and clinically grounded model design to enable reliable real-world deployment. Overall, this work advances the field by framing multimodal AI not only as a performance-driven tool but also as a translational framework for equitable, interpretable, and scalable AD diagnosis. Trial Registration: PROSPERO CRD420251241895;
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Suicidal Thoughts and Behaviors Among Chinese Adolescents in Relation to Negative Life Events, Internet Addiction, and Sexual Abuse: Cross-Sectional Study

Background: Increasing suicidal thoughts and behaviors (STB) among adolescents raise social concerns and have a well-recognized association with sexual abuse (SA). However, research regarding the mechanisms explaining the association between SA and STB remains limited. Objective: This study aims to examine the chained mediating effects of negative life events (NLE) and internet addiction (IA) between SA and STB among adolescents in China. Methods: This cross-sectional study used data from the Science Database of the People Mental Health survey conducted between March 2013 and December 2022 by the National Population Health Data Center of the National Research Institute for Family Planning. Through stratified sampling, 20,893 adolescents were recruited from 16 Chinese provinces. After excluding samples with missing relevant variables, 10,664 (55.89%; aged 16-17.9 y; n=5826, 54.63% women) adolescents were included in the final analysis. STB was the outcome variable, with NLE and IA as mediators, all assessed via a questionnaire that was uniformly administered by trained investigators in school settings. The Pearson χ test was used to analyze the association between SA and STB. Using a combination of multiple linear regression and bootstrap testing, the study constructed a chain mediation model to explore how SA influences STB in adolescents through NLE and IA. Results: The scores for SA, NLE, IA, and STB were 1.330 (SD 1.714), 51.960 (SD 23.822), 34.88 (SD 13.852), and 0.690 (SD 1.396), respectively. Multiple linear regression analysis indicated SA was associated with NLE (β=2.382, 95% CI 2.112‐2.653;
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Determinants of the Uptake and Frequency of Use of a Web Portal Digital Health Intervention in Patients With Type 2 Diabetes and/or Coronary Heart Disease: Secondary Analysis of a Randomized Controlled Trial

Background: The targeted application and design of digital health interventions (DHIs) require an understanding of usage determinants. Usage includes uptake (initial use) and frequency (extent of use), but it is unclear whether both components are driven by the same determinants. Objective: This study aimed to examine the determinants of uptake and frequency of use and assess whether they differ. Methods: The investigated DHI was a web portal provided in an intervention for improving disease-related self-management. This study is a secondary analysis of intervention group data from a parallel-group randomized controlled trial. Eligibility criteria were being an adult and being diagnosed with type 2 diabetes and/or coronary heart disease. Sociodemographic, psychological, and health-related variables were examined as determinants. Determinants were analyzed using simple and multiple regression models. Uptake was analyzed using logistic regression, and frequency was analyzed using negative binomial regression with robust SEs. Frequency was analyzed for those who used the DHI at least once. Except for sociodemographic variables, all other variables were standardized to a range from 0 to 1. For simple regression, inflation of the α error due to multiple testing was controlled via the approach of Benjamini and Hochberg, and for multiple regression, it was controlled via the significance of the complete multiple regression model. Results: Of 462 intervention group members, 199 (43.1%) used the web portal at least once. After controlling for inflation of the α error, simple regression for uptake yielded significant effects for higher education (B=0.56, 95% CI 0.18-0.95; =.004), openness (B=1.08, 95% CI 0.33-1.83; =.005), intention regarding physical activity (B=2.28, 95% CI 1.30-3.26;
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Improving Retrieval Augmented Generation for Health Care by Fine-Tuning Clinical Embedding Models: Development and Evaluation Study

Background: Embedding models are critical components of Retrieval Augmented Generation (RAG) systems for retrieving and searching unstructured medical data. However, existing models are predominantly trained on publicly available English datasets, limiting their effectiveness in non-English health care settings. More importantly, these models lack training on real-world clinical documents, leading to inaccurate context retrieval when integrated into RAG systems for health care applications. This gap is particularly pronounced in specialized medical documentation containing domain-specific terminology, abbreviations, and nuanced clinical language. Objective: This retrospective study aimed to develop and validate embedding models specifically trained on real-world clinical documents from multiple medical specialties to improve medical information retrieval (IR) and RAG system performance in both German and English language contexts. Methods: We fine-tuned embedding models, so-called sentence transformers, using the multilingual-e5-large architecture as a foundation. Training data consisted of approximately 11 million question-answer pairs synthetically generated from 400,000 diverse clinical documents from a large German tertiary hospital, spanning 163,840 patients and 282,728 clinical cases between 2018 and 2023. The large language model generated medically relevant questions and corresponding answers for each document. The dataset was additionally pseudonymized and translated into English to aim for broader applicability. Models were evaluated in 2 distinct scenarios: IR using questions with multiple relevant passages, and RAG system performance in both cross-patient and patient-centered contexts. Results: In the IR evaluation, the fine-tuned miracle model achieved a mAP@100 of 0.27, outperforming the multilingual-e5-large baseline (0.14) and state-of-the-art models such as bge-m3 (0.11). In the RAG evaluation, the model demonstrated robust performance comparable with the baseline in the constrained patient-centered scenario (BERTScore F1 0.781 vs 0.778) and showed moderate improvements in the unconstrained cross-patient setting (BLEURT 0.56 vs 0.53). Notably, the model trained on pseudonymized data achieved comparable retrieval performance (mAP@100 0.25) and the highest scores for patient-centered contextual precision (0.93). Performance gains were robust in the German dataset, while the translated English model demonstrated promising results as a proof of concept for cross-lingual transfer. Conclusions: By leveraging a comprehensive real-world dataset spanning multiple medical specialties and using large language models for synthetic question generation, we successfully created and validated domain-specific embedding models. These models can improve medical IR in large-scale search spaces and perform competitively in constrained RAG applications. By publishing the models trained on pseudonymized data, other health care institutions can integrate or adapt these embedding models to their needs. This work establishes a reproducible framework for developing domain-specific clinical embedding models, with the potential to improve data retrieval in medical settings.
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Robot-Assisted Therapy for Upper Limb Rehabilitation After Stroke: Umbrella Review

Background: Stroke is a leading cause of long-term upper limb disability, severely impacting patients’ independence and quality of life. Robot-assisted therapy (RAT) has emerged as a promising, high-intensity rehabilitation alternative. However, conclusions from existing systematic reviews on its efficacy are inconsistent and often lack a holistic framework, limiting their use for guiding personalized clinical decisions. Objective: This study aims to systematically synthesize recent evidence on RAT for upper limb rehabilitation after stroke. Guided by the International Classification of Functioning, Disability and Health framework, it moves beyond singular outcomes to provide a multidimensional evaluation across body function, activity, and participation levels. The review aims to provide stratified guidance for clinical decision-making based on patient- and intervention-specific characteristics, thereby supporting evidence-based practice and informing future research. Methods: This study included systematic reviews and meta-analyses published from January 1, 2019, to December 26, 2025, comparing RAT with conventional therapy for upper limb rehabilitation after stroke. Overall, 6 databases, including PubMed, Web of Science, and Embase, were searched. Two reviewers (XZ and LZ) independently performed study selection, data extraction, and quality assessment using the AMSTAR 2 tool. The synthesis integrated outcome measures and subgroup analyses derived from the included studies. Results: This umbrella review included 21 meta-analyses encompassing 535 randomized controlled trials and 27,598 patients across acute, subacute, and chronic stroke stages. According to AMSTAR 2, 17 reviews were high quality, 3 moderate, and 1 critically low. The synthesis demonstrated that RAT was superior in improving upper limb motor function, but no statistically significant advantages were observed in activities of daily living compared to conventional therapy. Subgroup analyses revealed that treatment effects were influenced by stroke stage, upper limb motor impairment level, and robot type. Conclusions: RAT is an effective intervention for improving upper limb motor function after stroke. However, its benefits are primarily observed at the level of body function, with limited evidence for long-term maintenance. The current evidence is constrained by significant outcome heterogeneity and methodological limitations inherent to umbrella reviews. Future research should validate these findings in broader clinical practice, focus on translating functional gains into sustained improvements in daily activities and participation, and include cost-effectiveness evaluations. Trial Registration: PROSPERO CRD42024497183; https://www.crd.york.ac.uk/PROSPERO/view/CRD42024497183
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Memory Bear AI Memory Science Engine for Multimodal Affective Intelligence: A Technical Report

arXiv:2603.22306v1 Announce Type: new Abstract: Affective judgment in real interaction is rarely a purely local prediction problem. Emotional meaning often depends on prior trajectory, accumulated context, and multimodal evidence that may be weak, noisy, or incomplete at the current moment. Although multimodal emotion recognition (MER) has improved the integration of text, speech, and visual signals, many existing systems remain optimized for short-range inference and provide limited support for persistent affective memory, long-horizon dependency modeling, and robust interpretation under imperfect input. This technical report presents the Memory Bear AI Memory Science Engine, a memory-centered framework for multimodal affective intelligence. Instead of treating emotion as a transient output label, the framework models affective information as a structured and evolving variable within a memory system. It organizes processing through structured memory formation, working-memory aggregation, long-term consolidation, memory-driven retrieval, dynamic fusion calibration, and continuous memory updating. At its core, multimodal signals are transformed into structured Emotion Memory Units (EMUs), enabling affective information to be preserved, reactivated, and revised across interaction horizons. Experimental results show consistent gains over comparison systems across benchmark and business-grounded settings, with stronger accuracy and robustness, especially under noisy or missing-modality conditions. The framework offers a practical step from local emotion recognition toward more continuous, robust, and deployment-relevant affective intelligence.
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Ca2+ transient detection and segmentation with the Astronomically motivated algorithm for Background Estimation And Transient Segmentation (Astro-BEATS)

arXiv:2603.22311v1 Announce Type: new Abstract: Fluorescence-based Ca$^{2+}$-imaging is a powerful tool for studying localized neuronal activity, including miniature Synaptic Calcium Transients, providing real-time insights into synaptic activity. These transients induce only subtle changes in the fluorescence signal, often barely above baseline, which poses a significant challenge for automated synaptic transient detection and segmentation. Detecting astronomical transients similarly requires efficient algorithms that will remain robust over a large field of view with varying noise properties. We leverage techniques used in astronomical transient detection for miniature Synaptic Calcium Transient detection in fluorescence microscopy. We present Astro-BEATS, an automatic miniature Synaptic Calcium Transient segmentation algorithm that incorporates image estimation and source-finding techniques used in astronomy and designed for Ca$^{2+}$-imaging videos. Astro-BEATS outperforms current threshold-based approaches for synaptic Ca$^{2+}$ transient detection and segmentation. The produced segmentation masks can be used to train a supervised deep learning algorithm for improved synaptic Ca$^{2+}$ transient detection in Ca$^{2+}$-imaging data. The speed of Astro-BEATS and its applicability to previously unseen datasets without re-optimization makes it particularly useful for generating training datasets for deep learning-based approaches.
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Dynamic Fusion-Aware Graph Convolutional Neural Network for Multimodal Emotion Recognition in Conversations

arXiv:2603.22345v1 Announce Type: new Abstract: Multimodal emotion recognition in conversations (MERC) aims to identify and understand the emotions expressed by speakers during utterance interaction from multiple modalities (e.g., text, audio, images, etc.). Existing studies have shown that GCN can improve the performance of MERC by modeling dependencies between speakers. However, existing methods usually use fixed parameters to process multimodal features for different emotion types, ignoring the dynamics of fusion between different modalities, which forces the model to balance performance between multiple emotion categories, thus limiting the model's performance on some specific emotions. To this end, we propose a dynamic fusion-aware graph convolutional neural network (DF-GCN) for robust recognition of multimodal emotion features in conversations. Specifically, DF-GCN integrates ordinary differential equations into graph convolutional networks (GCNs) to {capture} the dynamic nature of emotional dependencies within utterance interaction networks and leverages the prompts generated by the global information vector (GIV) of the utterance to guide the dynamic fusion of multimodal features. This allows our model to dynamically change parameters when processing each utterance feature, so that different network parameters can be equipped for different emotion categories in the inference stage, thereby achieving more flexible emotion classification and enhancing the generalization ability of the model. Comprehensive experiments conducted on two public multimodal conversational datasets {confirm} that the proposed DF-GCN model delivers superior performance, benefiting significantly from the dynamic fusion mechanism introduced.
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From Static Templates to Dynamic Runtime Graphs: A Survey of Workflow Optimization for LLM Agents

arXiv:2603.22386v1 Announce Type: new Abstract: Large language model (LLM)-based systems are becoming increasingly popular for solving tasks by constructing executable workflows that interleave LLM calls, information retrieval, tool use, code execution, memory updates, and verification. This survey reviews recent methods for designing and optimizing such workflows, which we treat as agentic computation graphs (ACGs). We organize the literature based on when workflow structure is determined, where structure refers to which components or agents are present, how they depend on each other, and how information flows between them. This lens distinguishes static methods, which fix a reusable workflow scaffold before deployment, from dynamic methods, which select, generate, or revise the workflow for a particular run before or during execution. We further organize prior work along three dimensions: when structure is determined, what part of the workflow is optimized, and which evaluation signals guide optimization (e.g., task metrics, verifier signals, preferences, or trace-derived feedback). We also distinguish reusable workflow templates, run-specific realized graphs, and execution traces, separating reusable design choices from the structures actually deployed in a given run and from realized runtime behavior. Finally, we outline a structure-aware evaluation perspective that complements downstream task metrics with graph-level properties, execution cost, robustness, and structural variation across inputs. Our goal is to provide a clear vocabulary, a unified framework for positioning new methods, a more comparable view of existing body of literature, and a more reproducible evaluation standard for future work in workflow optimizations for LLM agents.
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Bridging the Know-Act Gap via Task-Level Autoregressive Reasoning

arXiv:2603.22619v1 Announce Type: new Abstract: LLMs often generate seemingly valid answers to flawed or ill-posed inputs. This is not due to missing knowledge: under discriminative prompting, the same models can mostly identify such issues, yet fail to reflect this in standard generative responses. This reveals a fundamental know-act gap between discriminative recognition and generative behavior. Prior work largely characterizes this issue in narrow settings, such as math word problems or question answering, with limited focus on how to integrate these two modes. In this work, we present a comprehensive analysis using FaultyScience, a newly constructed large-scale, cross-disciplinary benchmark of faulty scientific questions. We show that the gap is pervasive and stems from token-level autoregression, which entangles task selection (validate vs. answer) with content generation, preventing discriminative knowledge from being utilized. To address this, we propose DeIllusionLLM, a task-level autoregressive framework that explicitly models this decision. Through self-distillation, the model unifies discriminative judgment and generative reasoning within a single backbone. Empirically, DeIllusionLLM substantially reduces answer-despite-error failures under natural prompting while maintaining general reasoning performance, demonstrating that self-distillation is an effective and scalable solution for bridging the discriminative-generative know-act gap
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MuQ-Eval: An Open-Source Per-Sample Quality Metric for AI Music Generation Evaluation

arXiv:2603.22677v1 Announce Type: new Abstract: Distributional metrics such as Fr\'echet Audio Distance cannot score individual music clips and correlate poorly with human judgments, while the only per-sample learned metric achieving high human correlation is closed-source. We introduce MUQ-EVAL, an open-source per-sample quality metric for AIgenerated music built by training lightweight prediction heads on frozen MuQ-310M features using MusicEval, a dataset of generated clips from 31 text-to-music systems with expert quality ratings. Our simplest model, frozen features with attention pooling and a two-layer MLP, achieves system-level SRCC = 0.957 and utterance-level SRCC = 0.838 with human mean opinion scores. A systematic ablation over training objectives and adaptation strategies shows that no addition meaningfully improves the frozen baseline, indicating that frozen MuQ representations already capture quality-relevant information. Encoder choice is the dominant design factor, outweighing all architectural and training decisions. LoRA-adapted models trained on as few as 150 clips already achieve usable correlation, enabling personalized quality evaluators from individual listener annotations. A controlled degradation analysis reveals selective sensitivity to signal-level artifacts but insensitivity to musical-structural distortions. Our metric, MUQ-EVAL, is fully open-source, outperforms existing open per-sample metrics, and runs in real time on a single consumer GPU. Code, model weights, and evaluation scripts are available at https://github.com/dgtql/MuQ-Eval.
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Can LLM Agents Generate Real-World Evidence? Evaluating Observational Studies in Medical Databases

arXiv:2603.22767v1 Announce Type: new Abstract: Observational studies can yield clinically actionable evidence at scale, but executing them on real-world databases is open-ended and requires coherent decisions across cohort construction, analysis, and reporting. Prior evaluations of LLM agents emphasize isolated steps or single answers, missing the integrity and internal structure of the resulting evidence bundle. To address this gap, we introduce RWE-bench, a benchmark grounded in MIMIC-IV and derived from peer-reviewed observational studies. Each task provides the corresponding study protocol as the reference standard, requiring agents to execute experiments in a real database and iteratively generate tree-structured evidence bundles. We evaluate six LLMs (three open-source, three closed-source) under three agent scaffolds using both question-level correctness and end-to-end task metrics. Across 162 tasks, task success is low: the best agent reaches 39.9%, and the best open-source model reaches 30.4%. Agent scaffolds also matter substantially, causing over 30% variation in performance metrics. Furthermore, we implement an automated cohort evaluation method to rapidly localize errors and identify agent failure modes. Overall, the results highlight persistent limitations in agents' ability to produce end-to-end evidence bundles, and efficient validation remains an important direction for future work. Code and data are available at https://github.com/somewordstoolate/RWE-bench.
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Learning What Matters Now: Dynamic Preference Inference under Contextual Shifts

arXiv:2603.22813v1 Announce Type: new Abstract: Humans often juggle multiple, sometimes conflicting objectives and shift their priorities as circumstances change, rather than following a fixed objective function. In contrast, most computational decision-making and multi-objective RL methods assume static preference weights or a known scalar reward. In this work, we study sequential decision-making problem when these preference weights are unobserved latent variables that drift with context. Specifically, we propose Dynamic Preference Inference (DPI), a cognitively inspired framework in which an agent maintains a probabilistic belief over preference weights, updates this belief from recent interaction, and conditions its policy on inferred preferences. We instantiate DPI as a variational preference inference module trained jointly with a preference-conditioned actor-critic, using vector-valued returns as evidence about latent trade-offs. In queueing, maze, and multi-objective continuous-control environments with event-driven changes in objectives, DPI adapts its inferred preferences to new regimes and achieves higher post-shift performance than fixed-weight and heuristic envelope baselines.
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PhySe-RPO: Physics and Semantics Guided Relative Policy Optimization for Diffusion-Based Surgical Smoke Removal

arXiv:2603.22844v2 Announce Type: new Abstract: Surgical smoke severely degrades intraoperative video quality, obscuring anatomical structures and limiting surgical perception. Existing learning-based desmoking approaches rely on scarce paired supervision and deterministic restoration pipelines, making it difficult to perform exploration or reinforcement-driven refinement under real surgical conditions. We propose PhySe-RPO, a diffusion restoration framework optimized through Physics- and Semantics-Guided Relative Policy Optimization. The core idea is to transform deterministic restoration into a stochastic policy, enabling trajectory-level exploration and critic-free updates via group-relative optimization. A physics-guided reward imposes illumination and color consistency, while a visual-concept semantic reward learned from CLIP-based surgical concepts promotes smoke-free and anatomically coherent restoration. Together with a reference-free perceptual constraint, PhySe-RPO produces results that are physically consistent, semantically faithful, and clinically interpretable across synthetic and real robotic surgical datasets, providing a principled route to robust diffusion-based restoration under limited paired supervision.
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CoMaTrack: Competitive Multi-Agent Game-Theoretic Tracking with Vision-Language-Action Models

arXiv:2603.22846v1 Announce Type: new Abstract: Embodied Visual Tracking (EVT), a core dynamic task in embodied intelligence, requires an agent to precisely follow a language-specified target. Yet most existing methods rely on single-agent imitation learning, suffering from costly expert data and limited generalization due to static training environments. Inspired by competition-driven capability evolution, we propose CoMaTrack, a competitive game-theoretic multi-agent reinforcement learning framework that trains agents in a dynamic adversarial setting with competitive subtasks, yielding stronger adaptive planning and interference-resilient strategies. We further introduce CoMaTrack-Bench, the first benchmark for competitive EVT, featuring game scenarios between a tracker and adaptive opponents across diverse environments and instructions, enabling standardized robustness evaluation under active adversarial interactions. Experiments show that CoMaTrack achieves state-of-the-art results on both standard benchmarks and CoMaTrack-Bench. Notably, a 3B VLM trained with our framework surpasses previous single-agent imitation learning methods based on 7B models on the challenging EVT-Bench, achieving 92.1% in STT, 74.2% in DT, and 57.5% in AT. The benchmark code will be available at https://github.com/wlqcode/CoMaTrack-Bench
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