Alzheimer

Pneumonia is difficult to diagnose in older long-term care residents; multimorbidity and atypical presentations obscure signs, motivating operationally efficient objective testing. We analyzed multi-channel digital stethoscope recordings from 185 Japanese residents (73 pneumonia, 112 symptomatic without), using radiologist-confirmed chest X-rays and clinician diagnoses as supervisory signals that train convolutional neural networks, multimodal fusion, and channel-based variants with time-domain Grad-CAM interpretability. Models were evaluated with repeated patient-level cross-validation showing models with X-ray supervision outperformed clinician supervision (F1 0.729, accuracy 0.783 vs. F1 0.637, accuracy 0.711). Additionally, a three-channel selection protocol maintained performance (F1 0.736; accuracy 0.803), with two mid-thoracic sites ranking highest and Grad-CAM attention overlapping adventitious sounds. These findings indicate automated multi-channel lung-sound analysis can aid long-term care pneumonia diagnosis, with X-ray supervision being more reliable than clinical, and fewer channels preserving performance while lowering acquisition times.

Clinical decision making heavily relies on predicting the disease progression trajectory by seeking to understand patient's health status which is characterised by multimodal medical data. AI holds great potential for learning useful representations from multimodal medical data to predict disease progression and aid clinical decision making. However, development of predictive AI models is constrained by missing modalities and incomplete tabular data frequently occurring in medical datasets. In addition, disease labels alone may only provide limited supervisory signals for learning representations from high-dimensional multimodal data. Here, we present MMAP, a novel Multimodal Missing-aware Alignment Pretraining method for learning image-tabular representations from incomplete data. An image encoder is pretrained with efficient sigmoid contrastive learning combined with generative reconstruction. A tabular encoder is built upon a tabular foundation model. A missing token generator enables the two encoders to take incomplete data as input, enabling the model to be robust against missing modalities, either with missing images or missing tabular data. We evaluate the clinical usefulness of the learnt multimodal representations on two challenging longitudinal clinical tasks for Alzheimer's disease: predicting disease stage conversion and predicting amyloid status. The proposed method outperforms strong multimodal and unimodal baselines.

Dynamic Time Warping (DTW) is the dominant approach for measuring similarity between time series, yet standard practice discards the optimal warping path after computing a single distance value, losing local alignment information most relevant to clinical diagnosis. We introduce DiaSeg, a framework that extracts diagonal segments from DTW paths with controlled breaks, characterizing each segment by five geometric features (effective length, interruption count, cost variation, temporal position, and path context), and enabling unsupervised pattern discovery without domain-specific feature engineering. Validated on 91 subjects across six clinical conditions (healthy aging, Parkinson's, Huntington's, ALS, brain tumor, and stroke), three findings emerge. First, diagonal segments form consistent unsupervised patterns (silhouette 0.33) aligned with biomechanical phase annotations, with label-based validation confirming near-perfect separation of healthy and pathological gait (ARI up to 0.986). Second, segments discriminate pathology at 69% (supervised) and 75% (patient-level clustering), with pathology manifesting through distributional shifts in segment length; combining segment and cycle-level features further improves classification to 91.7%. Third, while cycle-based methods achieve higher accuracy (91%), diagonal segments provide phase-specific interpretability unavailable in global representations, localizing where coordination breaks down within the gait cycle. DiaSeg thus transforms DTW from a black-box distance into a source of interpretable temporal features for neurodegenerative disease assessment.

Cortical hypometabolism measured by Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) is a highly sensitive biomarker for dementia diagnosis. However, high costs, radiation exposure, and limited accessibility constrain its clinical utility. While cross-modal synthesis from Magnetic Resonance Imaging (MRI) offers a promising alternative, existing volumetric generation methods do not explicitly account for the highly folded cortical geometry, where disease-related patterns predominantly reside. To address this, we introduce a novel surface-based diffusion bridge framework DB-SUiT for MRI-to-PET translation that operates natively on the cortical manifold. A conditional Spherical U-shaped vision Transformer (SUiT) is specifically designed to model the intricate cross-modal relationships while preserving surface topology. It combines spherical convolutional encoders for multi-scale surface feature extraction with bottleneck Transformers to capture long-range spatial dependencies, while incorporating demographic and subcortical conditions to refine the synthesis. Evaluated on two datasets, including subjects with different dementia types, DB-SUiT demonstrates high-fidelity synthesis that substantially outperforms other baselines. In automated dementia classification, synthesized PET surfaces improve performance over MRI by 14.2% and PET volumes by 11.3%, approaching the performance of real PET surfaces. In a blinded reader study, synthetic PET achieved 85.5% diagnostic accuracy, compared with 75.8% for MRI and 95.2% for real PET. This further demonstrates cross-cohort and cross-pathology generalization, as the model was evaluated without retraining on an external cohort that included a dementia subtype not represented during training. Our code is available at https://github.com/ai-med/DB-SUiT.

Representation learning from medical code sequences in electronic health records and medical claims data has been successful in various clinical applications, such as those regarding disease prediction. However, significant challenges remain in extending this approach to the discovery of scientific hypotheses. One reason is that many existing BERT-based models fail to adequately capture the hierarchical structure of medical codes and the complex interactions between diagnoses and treatments. To address these limitations, we propose a new unified pre-training framework that explicitly integrates hierarchical sub-token aggregation, partial masking, and cross-reference mechanisms. The proposed model consistently outperformed existing methods on both pre-training objectives and downstream clinical event prediction tasks, including the onset of dementia and hospitalization. We also conducted an in silico drug repositioning case study targeting Alzheimer's disease. In the hypothesis generation step, our approach successfully rediscovered known promising drugs in a data-driven manner without relying on such external knowledge sources as the literature. Subsequently, in the hypothesis prioritization step, we introduced a Task-Adaptive Representation Approach to alleviate the over-encoding of historical prescription information within diagnostic vectors, enabling the robust prioritization of generated hypotheses. This study establishes an exploratory screening workflow for hypothesis generation and prioritization based on observational associations. Importantly, this framework is not intended to provide causal evidence, but rather to identify promising candidates for subsequent rigorous causal inference. Overall, this study demonstrates that domain-informed representation learning combined with task-adaptive representation control can enable a practical hypothesis discovery workflow.

Spontaneous speech offers a scalable, noninvasive signal for respiratory health assessment, yet interpretable models that generalize across languages remain challenging because disease-related acoustic changes are confounded by language-specific phonetic variation. We present CL-DAF, a Cross-Lingual Disease-Alignment Framework that identifies acoustic dimensions whose disease effects remain consistent across languages. Using 201 English and 75 newly collected Bangla speakers, we construct a common 272-dimensional acoustic representation and quantify disease alignment using signed rank-biserial effects and the Language Invariance Score. We first show that spontaneous Bangla speech separates COPD from controls (AUC 0.85); however, 133 features reverse their disease direction across languages and the full representation transfers poorly (AUC 0.49 from Bangla to English). CL-DAF isolates 26 disease-aligned features that raise AUCs to 0.825 and 0.722 from English to Bangla and Bangla to English, respectively. These findings provide a foundation for multilingual clinical speech models emphasizing pathology over language-dependent variation.

Small clinical tabular datasets require interpretable machine learning because deep learning is often impractical and ensemble models can be difficult to inspect. A key pitfall is that statistical significance does not necessarily imply predictive utility. Using data from the Panama Aging Research Initiative--Health Disparities (PARI-HD) cohort (n=165), we implemented a leakage-safe threshold-likelihood Bernoulli/Categorical Naive Bayes (BNB/CNB) classifier. Within every training fold, each continuous predictor was reduced to a supervised chi-square-derived state, while income entered the model through a categorical likelihood. All data-dependent steps were performed within repeated stratified 10-fold cross-validation with 30 repeats. The demographic baseline achieved a ROC-AUC of 0.630 +/- 0.017. I-309 (CCL1) was the dominant incremental feature, increasing AUC by 0.110, with paired DeLong tests yielding p<0.05 in 100% of repeats. In the pre-specified primary analysis, I-309 produced a fixed-partition DeLong p=0.0018, with robustness assessed across 200 random partitions, where the median p-value was 0.0011. Within the exploratory family of 18 candidate markers, I-309 achieved a Benjamini-Hochberg-adjusted q=0.032 on the frozen partition and satisfied q<0.05 in 85% of random partitions, whereas no other marker demonstrated reliable incremental predictive value. Because the fitted model is an inspectable table of thresholds and class-conditional probabilities, these results identify I-309/CCL1 as an interpretable candidate feature for tabular prediction of cognitive impairment, pending external validation.

Deep networks trained on structural MRI for Alzheimer's disease (AD) staging often reach reasonable accuracy while attending to anatomically irrelevant regions, and multimodal models that add clinical tables frequently rely on variables that were used to assign the diagnostic label in the first place. We study both issues with a deliberately lightweight slice-based encoder (ResNet18 with a one-layer Transformer over slices) on 1,075 baseline T1-weighted scans from ADNI-1. First, we use FastSurfer segmentations as an anatomical reference: YOLOv8 models trained on segmentation-derived labels localize Alzheimer-relevant structures with mAP_50 above 0.96, and a Grad-CAM comparison shows that the image-only classifier frequently attends to the skull, orbits and background. Second, we adapt a CLIP-style image - tabular contrastive framework and organize ADNIMERGE variables along a label-leakage spectrum. Fusion with cognitive scores yields 87.3% three-way accuracy, which we treat as a leakage-driven upper bound rather than an imaging result; fusion with regional volumes yields 73.0%. We observe that the choice of contrastive target changes what the image encoder learns: on MCI vs. CN, the image-only head reaches 52.4% when the encoder is aligned to cognitive scores and 73.8% when aligned to volumes, although no tabular input is used at inference. Third, restricting the input to a per-subject crop of the medial temporal lobe raises image-only three-way accuracy from 58.7% to 65.1%. All results come from single runs on a small balanced test set, and we report confidence intervals and the protocol differences that prevent direct comparison with published numbers.

Dementia is a major and growing global health burden, with Alzheimer's disease (AD) accounting for most cases. Timely and accurate diagnosis is central to managing this burden and increasingly depends on integrating complementary clinical and imaging information. Multimodal deep learning can combine these modalities for AD diagnosis, but how its explanations behave across modalities, fusion strategies, and cohorts remains unclear. We developed an explainable multimodal framework pairing a 3D CNN encoder for T1-weighted MRI with a feedforward network for harmonized clinical and demographic data, comparing varied model setups on three-way and pairwise diagnostic tasks using 6,479 internal records from the ADNI and 1,703 independent records from the OASIS-3. On ADNI, the tabular-only model achieved the highest three-class AUC-ROC of 0.879 and best discriminated cognitively normal (CN) versus mild cognitive impairment (MCI; 0.903), while cross-attention performed best for MCI versus AD (0.861); CN versus AD was highly discriminative overall. On OASIS-3, the vision-only model performed best (three-class AUC-ROC 0.910); CN versus MCI remained difficult, and no fusion strategy consistently outperformed single modalities across tasks and cohorts. SHAP and Integrated Gradients identified the MMSE as the dominant tabular feature in both cohorts, with global feature rankings agreeing strongly in ADNI ($\rho=0.94$) and OASIS-3 ($\rho=0.96$); CAM-based explanations, however, changed with model configuration and cohort. These findings show that multimodal performance and explanations are task, modality, fusion, and cohort-dependent: a dominant cognitive signal persisted across cohorts, but feature contributions and CAM explanations did not, underscoring the need to evaluate explainability under cohort shift rather than as a stable, intrinsic property.

Early detection of cognitive decline from speech offers a scalable and non-invasive alternative to conventional clinical assessment. Verbal fluency tasks are particularly informative, but most automated approaches aggregate features across an entire recording, overlooking temporal speech dynamics. We propose the Cognitive Instability-Aware Cross-Modal Attention Network (CCMAN), a transfer learning framework that learns task-agnostic cognitive speech representations from multiple memory-probing tasks before fine-tuning on a minute-long semantic and phonemic verbal fluency task. CCMAN integrates semantic, acoustic, and linguistic information through bidirectional cross-attention, gated multimodal fusion, and transformer-based temporal modelling to derive interpretable biomarkers of cognitive decline. Experiments were conducted on 165.44 hours of speech from 843 participants (498 healthy controls, 245 with mild cognitive impairment, and 100 with dementia). CCMAN achieved Macro-F1 scores of 0.81 and 0.59 for binary and multiclass semantic fluency classification, and 0.77 and 0.53 for phonemic fluency, consistently outperforming strong static and temporal baselines. Statistical analyses showed that semantic drift variance and pause variance, but not mean semantic drift, were significantly elevated in both MCI and dementia relative to healthy controls, while pause duration increased progressively over the task with the steepest slope in dementia, supporting global and progressive temporal speech instability as interpretable biomarkers. Evaluation on the independent PROCESS-2 benchmark further demonstrated the generalisability of the proposed framework, improving the baseline Macro-F1 by up to 9%. These findings support temporal speech instability as a dynamic speech biomarker for robust, interpretable, and generalisable early detection of cognitive decline.

Speech-based automatic detection of Alzheimer's disease (AD) provides a non-invasive and scalable approach to early cognitive screening. AD affects both lexical-semantic organization and speech production, including atypical pauses and word elongations. However, existing methods have yet to fully integrate these paralinguistic cues with linguistic content. We propose LLM-Anchored Paralinguistic Enrichment (LAPE), which enriches LLM-derived linguistic representations with paralinguistic cues through three coordinated innovations. The first is prosodic event textualization, which enables the LLM to model pauses and elongations jointly with lexical content by encoding them as explicit markers with bounded duration-aware repetition. The second is lexico-prosodic unitization and chunking, which preserves event identity and magnitude in both modalities by pooling only consecutive word units. The third is text-anchored paralinguistic fusion, which integrates local and utterance-level speech features by using NormGate to normalize and dynamically scale them relative to text. We evaluate LAPE on ADReSS and ADReSSo using participant-level cross-validation and leave-one-subject-out evaluation. LAPE achieves state-of-the-art performance across all four primary settings. Code will be released upon acceptance.

Speech-based Alzheimer's disease (AD) detection has recently benefited from multimodal foundation-model representations that integrate complementary acoustic and linguistic information. However, conventional probability averaging over these complementary classifiers is unreliable, because their posterior probabilities exhibit mismatched scales: identical values may reflect different confidence levels across models. We propose a robust rank aggregation framework that aggregates normalized prediction ranks instead of posterior probabilities. Each subject is scored by its percentile within a fixed training-cohort distribution of out-of-fold predictions; since rank ordering is invariant to monotonic transformations, this avoids probability-scale mismatch while preserving classifier confidence ordering. A confidence-gated Random Forest further corrects residual errors using clinically interpretable linguistic features, overriding the rank prediction only when the two disagree and the RF is highly confident, without additional deep model training or explicit posterior-probability calibration. On ADReSS2020 and ADReSSo2021, the method achieves accuracies of 95.83% and 90.14%, respectively, comparing favorably with previously reported results.

This study investigates the classification of individuals as healthy or at risk of Parkinson's disease using machine learning (ML) models, focusing on the impact of dataset size and preprocessing techniques on model performance. Four datasets are created from an original dataset: DS_0, (normal dataset), DS_1 (DS_O subjected to Canny edge detection and Hessian filtering), DS_2 (augmented DS_0), and DS_3 (augmented DS_1). We evaluate a range of ML models-Logistic Regression (LR), Decision Tree (DT), Random Forest (RF), Gradient Boosting (GB), XGBoost (XBG), Naive Bayes (NB), Support Vector Machine (SVM), and AdaBoost (AdB)-on these datasets, analyzing prediction accuracy, model size, and prediction latency. The results show that while larger datasets lead to increased model memory footprints and prediction latencies, the Canny edge detection preprocessing supplemented by Hessian filtering (used in DS_1 and DS_3) degrades the performance of most models. In our experiment, we observe that Random Forest (RF) maintains a stable memory footprint of 61 KB across all datasets, while models like KNN and SVM show significant increases in memory usage, from 5.7-7 KB on DS_0 to 102-220 KB on DS_2, and similar increases in prediction time. Logistic Regression, Decision Tree, and Naive Bayes show stable memory footprints and fast prediction times across all datasets. XGBoost's prediction time increases from 180-200 ms on DS_0 to 700-3000 ms on DS_2 (truncated)

Cardiac, neural, behavioral, and speech measurements from wearable and mobile devices provide partial, noise-sensitive views of physiological state. BioSync combines these measurements into the \textbf{BioSync Index (BSI)}, a continuous composite digital biomarker defined under the BEST framework. The model applies multi-head self-attention to modality tokens and adds a linear branch whose hypothesis class includes standard feature concatenation. This architecture is motivated by latent-variable measurement theory and by the possibility that joint observations contain information unavailable from individual modalities. We evaluated BioSync on two literature-informed synthetic cohorts: a four-modality cognitive-decline cohort using HRV, EEG, actigraphy, and speech, and a metabolic-autonomic cohort structured around the public AI-READI wearable schema. In the cognitive cohort, BioSync and concatenation obtained AUCs of 0.928 and 0.926, respectively. In the metabolic cohort, BioSync obtained accuracy/F1 of 0.764/0.766, compared with 0.756/0.758 for concatenation. The BSI correlated with latent severity in both cohorts ($r=0.91$ and $r=0.68$). A pure-attention ablation obtained cognitive-cohort AUC 0.911, locating the increase to 0.928 in the combined wide-and-deep architecture. With matched modality-dropout training, BioSync led concatenation at five of six cognitive-cohort corruption rates and at the highest metabolic-cohort rate. Its cognitive-cohort AUC was also higher than five published digital-biomarker reference values, although differences in datasets and tasks preclude a controlled benchmark claim. Comparison with single-modality, early-fusion, and late-fusion designs across six prespecified criteria identifies the model's computational properties; validation on real cohorts remains necessary.

Sentence-level recognition of depression symptoms is challenging because similar expressions can differ in symptom relevance, and language-model inference is insufficiently grounded in diagnostic definitions. This study proposes a two-stage framework separating symptom-candidate generation from definition-grounded verification. A contrastively fine-tuned sentence encoder generates a symptom candidate per sentence, and a fine-tuned language model verifies whether the candidate is present or absent using the sentence, its context, and a candidate-specific diagnostic definition, checking its judgment against that definition before answering. Evaluated against encoder, inference-based, medical, and general LLM baselines and a matched single-stage supervised classifier, the proposed pipeline attains the best accuracy and F1 scores of all methods, with rationales matching expert-authored annotations. A preliminary clinical audit indicates moderate alignment with diagnostic definitions, with explanation quality strongly dependent on prediction correctness. The results support decomposing symptom recognition into candidate generation and definition-grounded verification, though performance remains limited for rare categories.

Speech-based Alzheimer's disease (AD) detection increasingly relies on speech-enhanced and curated versions of the Pitt Corpus, where speech enhancement, sample selection, and demographic balancing are often treated as beneficial preprocessing steps. However, whether these transformations improve real-world AD detection or instead affect model generalization and prediction behavior remains unclear. In this work, we revisit the role of speech preprocessing and dataset curation across widely used benchmarks for speech-based AD detection. We evaluate the speech quality of different datasets, the cross-dataset generalization of multiple deep learning models under matched and mismatched enhancement settings, and the behavior of several recent large audio-language models (LALMs). Experimental results show that across multiple supervised speech models, speech-enhanced datasets often improve in-domain performance while reducing robustness in cross-domain evaluation. Matched enhancement between training and test data alleviates, but does not eliminate, this degradation. LALMs show a similar sensitivity: enhanced datasets induce stronger class imbalance and prediction shifts than unprocessed data. These results suggest that speech preprocessing and dataset curation can substantially influence downstream AD detection behavior, indicating that ``cleaner'' speech datasets are not necessarily more reliable for real-world AD detection.

Depression and anxiety in older adults with Mild Cognitive Impairment (MCI) are frequently underdiagnosed due to limited access to care. Multimodal analysis of remote clinical interviews is a scalable screening approach, but existing methods have three limitations. First, they do not correct temporal misalignment across multimodal features extracted at different resolutions, inducing spurious cross-modal associations. Second, remote recordings exhibit uneven modality dropout, but missing values are often zero-filled, making them indistinguishable from valid near-zero measurements. Finally, they do not jointly attribute predictions to modalities, questions, and interview moments, limiting fine-grained clinical interpretation. We propose a Temporally-Aligned, Missingness-Aware, Interpretable (TAMI) multimodal fusion framework. TAMI aligns speech, language, facial, and physiological features within question-answer segments on a shared timeline, encodes modality-level missingness over time, and conditions fusion on question context. In interviews with 49 older adults with MCI, TAMI achieved area under the receiver operating characteristic curve (AUROC) scores of 0.68 (depression) and 0.69 (anxiety). Fine-grained temporal alignment of multimodal features produced the largest performance gain ($Δ{\geq}0.1$). Multi-level interpretability analysis revealed that depression classification relied on eyegaze and open-ended questions, while anxiety classification depended on eyegaze and head pose, with attribution uniformly distributed across questions. Using only responses to the open-ended questions (5.1min), the depression model achieved an AUROC score of 0.67, which was not significantly different from using the full interview (19min) ($p>0.05$). Our findings support designing interview protocols centered on open-ended questions for depression screening in older adults with MCI.

Recent offline reinforcement learning (RL) studies report policies that outperform physician decisions on clinical outcomes. We conduct a systematic, partially crossed evaluation of five offline RL algorithm families and 14 reward designs in 44,894 post-2018 acute ischemic stroke patients from a nationwide registry (N = 129,033). Standard Fitted Q-Evaluation (FQE) yields an apparent policy-improvement estimate of +0.0069; adding an Early Neurological Deterioration penalty increases it to +0.0101. We identify reward-embedded confounding, in which a proxy terminal reward encodes baseline severity and prognosis as well as treatment efficacy. A 2 x 2 factorial analysis finds that terminal reward confounding accounts for 218.6% of the observed signal change, so its removal overshoots the null. After DML-inspired GBM reward residualization, the FQE estimate attenuates to +0.0033 (p = 0.132), and full deconfounding yields +0.0025 (p = 0.291). FQE-based diagnostics, T-learner analyses, and direct recurrence analyses converge away from a clinically meaningful aggregate improvement. A 1-year mRS factorial analysis replicates the attenuation. We provide an empirically motivated six-step evaluation checklist. NIHSS-stratified heterogeneity is hypothesis-generating for prospective trial design; hospital-level disagreement does not persist after full reward deconfounding.

Electroencephalography (EEG) is a promising, non-invasive, and cost-effective modality for Alzheimer's disease (AD) detection, but deep learning methods are limited by small and imbalanced clinical datasets. Generative augmentation offers a solution, yet existing approaches rely on inefficient class-specific models or fail to capture complex spatial and temporal brain dynamics. To address this, we propose GraM-Diff, a unified classifier-guided Graph-Mamba diffusion framework for EEG synthesis. It embeds Graph Convolutional Networks within a diffusion U-Net to model inter-electrode connectivity and Bidirectional Mamba state-space blocks for linear-complexity long-range temporal modeling. Latent-space classifier guidance lets a single model generate both healthy and pathological EEG within a shared representation, avoiding fragmented per-cohort pipelines. Across four EEG-based AD benchmarks, synthetic augmentation improves classification, yields superior Context-FID and correlation scores over strong generative baselines, and enhances robustness in data-scarce settings.

Detecting infection-related behavioral changes in mosquitoes from video data is challenging because mosquitoes are small, move rapidly and irregularly, and are affected by environmental factors such as background, lighting, and shadows, which can make reliable feature extraction difficult. In this study, a YOLO- and Contrastive Language-Image Pre-training (CLIP)-based vision-language framework is proposed to classify mosquito flight frames of uninfected and Dengue virus serotype 2 (DENV2)-infected mosquitoes. First, YOLO is used to isolate mosquito regions from the background. Then, visual features extracted from video frames are aligned with biologically meaningful textual prompts in a shared embedding space. The multimodal model was fine-tuned using supervised bidirectional contrastive learning and evaluated through frame-level image-text similarity-based classification. The results show that the proposed method achieved 98.54% accuracy and 99.91% sensitivity at the frame level. After temporal aggregation of frame-level information, the model achieved complete video-level performance. The ablation results showed that fine-tuning and CLIP-based representations were essential for this domain, while the textual branch provided semantic image-text alignment rather than an accuracy advantage over the vision-only model. These findings suggest that vision-language models can provide a useful framework for analyzing infection-related biological behaviors from video data.

Alzheimer's disease is a leading cause of death with no cure. Therefore, early detection is critical to slow progression and preserve quality of life. Diagnosis relies on medical history, cognitive tests, physical exams, and MRI brain scans, making deep learning suitable for Alzheimer's classification. This work proposes a benchmark that evaluates ten different convolutional neural network (CNN) architectures (including ResNet, DenseNet, MobileNet, EfficientNet, and VGG family models) under the same held-out test split protocol. A two-stage transfer learning and full fine-tuning pipeline is introduced to perform training using a class-balanced subset (3,900 images) derived from the OASIS medical imaging dataset, comprising 86,437 single-view MRI brain scans labeled into four classifications of Alzheimer's disease: Non-Demented, Very Mild Dementia, Mild Dementia, and Moderate Dementia. The best results were achieved by VGG16, with a 0.9637 validation accuracy and a 0.9533 test accuracy score. A key finding documented in this work is the difficulty of classifying the transition from Non-Demented to Very Mild Demented stages, observed consistently across all ten architectures.

Parkinson's disease (PD) is the second most common neurodegenerative disorder. Typical machine learning screening methods require PD labels, but the available data is limited by privacy concerns and the need for expert annotation. We propose a label-free face-plus-voice PD screen built entirely on frozen pretrained encoders--a face-expression Vision Transformer and HuBERT--in which no PD label touches any fit; the reference is training controls only. The voice modality uses a synthetic-dysarthria contrastive activation addition (CAA) direction built from time-stretch and breathy degradation of healthy speech; the face modality uses a k-nearest-neighbor anomaly score to the control embedding cluster. We introduce the alignment principle, a post-hoc analysis showing that a synthetic-degradation CAA detector works when the cosine similarity between the synthetic and real disease directions exceeds zero. Measured on the YouTubePD benchmark, this cosine is +0.37 for voice (CAA works, AUROC 0.765) and -0.48 for face (CAA fails; anomaly succeeds, AUROC 0.751). Equal-weight late fusion reaches AUROC 0.802 (95% CI [0.70,0.89]) with NPV 0.95, supporting a rule-out triage interpretation. An overfitting audit shows the voice detector transfers cleanly, while the face-side--and thus fused--AUROC is potentially optimistic pending external validation.

Neuroimaging and genetic testing are two important clinical references for nervous system diseases, offering complementary diagnostic information. However, integrating genomic and neuroimaging data for precise disease diagnosis is challenging due to cross-modality heterogeneity. Existing imaging-genetics approaches mainly encode genetic information as hard-coded labels, which lose the local sequence context around disease-associated variants. To address this limitation, we propose GeneFuse, a multimodal learning framework that aligns genetic representations from pre-trained Genomic Language Models (GLMs) with features extracted from images. GeneFuse integrates two components: (1) Genotype-Conditioned Feature Modulation (GCFM), a FiLM-inspired module that uses genomic embeddings to modulate image feature maps; and (2) Uncertainty-aware Genomic Residual Fusion (U-GRF), a fusion strategy that uses imaging-derived predictive uncertainty to gate the contribution of genotypic features. We evaluate GeneFuse on early cognitive decline identification (NC vs. MCI) and dementia screening (NC vs. AD). In the APOE-centered setting, GeneFuse achieves AUROCs of 0.77 and 0.83, outperforming existing imaging-genetics fusion methods. These results indicate that GLM-derived genomic embeddings provide additional information to imaging.

Alzheimer's disease (AD) progression is a longitudinal process with subtle pathological cues in the early stages. Yet, computational constraints have limited most neuroimaging models to either compromise spatial information or limit the number of longitudinal scans. We aim to overcome this bottleneck and fully leverage high-resolution, variable-length T1w structural MRI (4D sMRI) scan sequences. We introduce Parcel2Progression (P2P), a Longitudinal Transformer Framework which tackles this challenge using an Atlas-guided Parcel Encoder that tokenizes 3D scans into a set of richer anatomically grounded representations. A Longitudinal Transformer then integrates irregular, arbitrary-length longitudinal visits with patient age. This synergy delivers two key advantages: (1) parcel-specific interpretability, and (2) computational tractability for long-term analysis, which scales linearly with the number of scans compared to a naive quadratic 4D ViT cost. P2P outperforms prior works and baselines in both MCI (Mild Cognitive Impairment) to AD conversion prediction and AD vs. CN (Cognitively Normal) classification tasks across ADNI, AIBL, and MIRIAD datasets. Leveraging longitudinal scans boosts performance over single-scan baselines by up to 5% and 7% in balanced accuracy for AD classification and MCI conversion prediction tasks, respectively. Interpretability analysis using parcel saliencies and attention rollouts reveals clinically consistent atrophy patterns in AD and MCI subjects. We also demonstrate the frameworks' reliability in anomaly detection using a synthetic dataset, and test the model's generalizability for other neurodegenerative diseases like Frontotemporal Dementia.

Early diagnosis of Alzheimer's disease (AD) is critical for enabling timely interventions that may slow disease progression and improve patient outcomes. There is a growing need for AD detection methods that are non-invasive and cost-effective, especially in real-world clinical settings with diverse patient populations and recording conditions. Speech-based screening addresses these needs by using natural speech collected without specialized equipment. Recent advances in large language models (LLMs) have improved speech analysis by providing rich linguistic representations and strong generalization. In this study, we propose LSEAD, a speech-based AD detection framework using pretrained open-source LLMs. Speech recordings are automatically transcribed, and text embeddings are extracted using locally deployed LLMs. Principal component analysis (PCA) is applied to reduce dimensionality before classification. Because the framework relies only on speech transcripts and locally deployed models, it supports privacy-preserving AD risk assessment without external data exchange. We evaluate LSEAD on the ADReSS20 and ADReSSo2021 benchmark datasets. Experimental results show that LLM-based embeddings generalize well across datasets and improve AD classification accuracy by up to 5 percent over existing methods, especially for early-stage detection. These results demonstrate that LSEAD provides a practical, secure, and scalable approach for early AD screening.

Changes in spontaneous speech provide an early signal of cognitive dysfunction in Alzheimer's disease (AD) that large language models (LLMs) can detect. However, detection alone cannot establish whether the underlying model representations contribute functionally to behavior. We introduce an activation-guided intervention framework using Qwen3-8B. The framework identifies feed-forward neurons with higher activation rates for AD than control transcripts and modulates their output contributions during generation by scaling the corresponding down-projection weights. This yielded nine edited variants differing in intervention direction, magnitude, and scope. The original and edited models completed the same 12-turn neuropsychological battery, assessed through blinded human ratings and computational linguistic measures. Amplifying AD-associated neurons produced graded impairments in story recall, verbal fluency, working memory, procedural discourse, scene construction, and coreference resolution. Attenuation largely preserved performance and selectively improved several outcomes. Amplification also reduced lexical surprisal, idea density, syntactic complexity, and discourse quantity, broadly paralleling changes reported in human AD speech. These findings show that neurons identified solely from clinical language differences can influence behavior across multiple cognitive domains, providing proof of concept for an AD-related computational phenotype and a controlled framework for experimentally examining links between language and broader cognitive dysfunction.

Access to holistic, multimodal data improves the performance of Artificial Intelligence (AI) in medical classification tasks compared to utilizing single modalities or data sources. However, the inherent heterogeneity and complexity of clinical real-world data pose significant challenges to structured data analysis and AI application. This heterogeneity includes missing values, multiple time points, diverse modalities, and inconsistent formats and semantics. Data harmonization prior to data integration tackles this challenge but remains resource-intensive and error-prone, limiting the scalability and reproducibility of holistic, AI-driven decision support on clinical real-world data. We therefore propose PatTree, a graph-based, holistic representation of patients that can be derived from real-world clinical data through the automated structuring of multimodal clinical data. PatTree enables early-stage data integration without relying on pre-standardized inputs. While representing heterogeneous clinical data within a unified knowledge graph, PatTree preserves the semantic relationships between data elements across modalities and data sources, facilitating interoperability and machine-interpretable data access. Using a subset of the ADNI-1 cohort (n = 763), we demonstrate that classification of patients is directly feasible on PatTree reaching state-of-the-art classification performance. In the three-class classification task distinguishing Alzheimer's disease, mild cognitive impairment, and cognitively normal individuals, we achieve a balanced accuracy of 98.5% and an F$_1$ score of 0.987 on the held-out test set. Our results show that assumption-free, automated structuring of multimodal medical data can serve as a scalable foundation for clinical AI pipelines bypassing tedious data preparation and standardization.

End-to-end autonomous driving (E2E AD) systems integrate perception, prediction, and planning into a single differentiable architecture. While these models show great promise, their standard training often relies on output-only supervision, which can lead to weak gradients for the hidden layers of increasingly complex models. Recent works have integrated vision-language model (VLM) supervision for latent features to address this, yielding substantial empirical gains, yet leaving the underlying theoretical mechanisms poorly understood. Our investigation into this methodology reveals that the resulting performance gains stem not from VLM reasoning capabilities, as previously assumed, but rather from the latent connections forged between the E2E AD model and ground-truth (GT) data during training. Building on this insight, we propose a probabilistic deep supervision framework that regularizes intermediate latent representations directly from GT data. By treating model latents as reparameterizable distributions, we optimize the architecture via the Evidence Lower Bound (ELBO). Our evaluations conducted on the nuScenes dataset demonstrate that supervising trajectory-related latents with future GT paths consistently improves planning performance. Using identical training data and E2E architectures, our method achieves an 8% reduction in planning L2 error and a 3% decrease in collision rates compared to competitive vectorized baselines, all while incurring negligible computational overhead.

Identifying reliable Alzheimer's disease (AD) markers typically requires manual, labor-intensive transcription and expert analysis, limiting its scale. We introduce an automated pipeline that extracts qualitative knowledge about potential AD progression indicators directly from audio recordings of verbal fluency tests. Our method uses pretrained foundation models to process raw audio and extract clinically relevant variables to construct a Bayesian Network (BN); this BN is used to reason about the AD progression markers and infer their qualitative relationships. Our system successfully recovers known clinical knowledge and identifies novel relationships between linguistic markers.

Early detection of mental health disorders is often limited by the lack of specialized resources in Spanish and the difficulty of analyzing long histories of social media posts. This paper addresses these challenges through three main contributions. First, we introduce three Spanish foundational models specifically adapted to the mental health domain through domain-specific pre-training. Second, we propose Incremental Context Expansion (ICE), an automatic relabeling methodology designed for early detection. ICE identifies the point at which cumulative messages provide enough evidence of a disorder, generating more informative training samples. Third, we provide a set of fine-tuned models using the samples generated with the ICE methodology for early risk detection tasks. Our results on three Spanish benchmarks show that combining these specialized models with ICE improves the state-of-the-art, reducing detection latency while maintaining high performance. All models are publicly available.

As populations age, cognitive decline from mild cognitive impairment (MCI) to dementia is a defining health challenge of the coming decades, yet routine assessment often misses its earliest signs. This article critically synthesizes recent technological advances for detecting and managing cognitive impairment in older adults, spanning neurophysiological signals (chiefly electroencephalography, EEG), structural and molecular neuroimaging (MRI and amyloid/tau PET), blood-based biomarkers, and digital markers, integrated through artificial intelligence (AI), machine learning (ML), and deep learning (DL). Beyond summarizing, it contributes a cross-disciplinary taxonomy, a methodological-rigor lens foregrounding subject- and site-independent validation, an integrative early-detection framework linking tiered screening to intervention, and comparison tables of detection methods, interventions, and risk and protective factors. EEG markers (alpha/theta changes, P300 latency) and deep models (CNNs, LSTM/BiLSTM, transformers, self-supervised EEG foundation models) report strong accuracy, yet many rest on small, single-site datasets unlikely to survive rigorous external validation. Elsewhere, gains are tangible: plasma p-tau217 has reached clinical utility, with the first blood test cleared to aid Alzheimer's diagnosis in 2025; anti-amyloid therapies (lecanemab, donanemab) are approved despite modest, contested benefits; and multidomain lifestyle prevention has matured. Wearable, remote, speech, and virtual-reality tools enable continuous, ecologically valid monitoring, and multimodal fusion improves sensitivity and specificity. Barriers remain: standardization, explainability, data privacy, and equitable, externally validated deployment. The field's near-term promise lies in trustworthy, multimodal, longitudinally validated systems linking early detection to actionable, personalized care.

Functional magnetic resonance imaging (fMRI) is a widely used technique for studying the brain. Recent methods that utilize graph neural networks (GNNs) for analysis of brain functional connectivity have shown great potential for the classification of brain disorders, such as Alzheimer's disease (AD). However, these methods often assume a preset number of functional modules across all subjects, which overlooks inter-subject variability. In addition, the discovered modules are rarely used to directly guide the learned connectivity patterns. Here, to address these issues, we propose a Meta Probabilistic Pooling GNN (MPP-GNN). We frame the model's task as a coupled, bilevel optimization that performs adaptive graph partitioning hierarchically to discover subject-specific modules and then uses the discovered brain modules as an explicit prior to guide edge refinement and representation learning. We validate MPP-GNN on two public datasets for AD classification, achieving the highest AUC in comparison to established baselines for both datasets. Furthermore, our analysis demonstrates that MPP-GNN shows significant alignment with the canonical functional-network organization defined by the Yeo brain atlas and reveals a network-level dedifferentiation pattern for AD.

EEG-based disease diagnosis requires one prediction per subject, yet common pipelines segment recordings into short instances, inherit the subject label for every instance, and train instance-level classifiers. This assumes that all instances provide equally reliable diagnostic evidence. Multiple instance learning (MIL) avoids inherited labels by treating each subject as a bag. However, EEG datasets contain far fewer subjects than instances, which can limit the quality of the representations learned by end-to-end MIL. We propose BridgeMIL, a two-stage framework that decouples instance representation learning from subject-level supervision. Stage 1 pretrains the encoder without inherited instance labels by aligning temporally nearby windows and independently sampled within-subject sub-bags. Variance and covariance regularization prevent collapse and reduce redundancy without negative pairs. Stage 2 transfers the encoder to an attention-based MIL aggregator, applies supervision only to subject predictions, and limits representation drift through feature retention. Across three EEG disease datasets and five representative backbones, BridgeMIL attains the highest mean accuracy in 14 of 15 dataset-backbone settings and an overall mean accuracy of 76.57%, 4.28 percentage points higher than the strongest baseline. Further analyses reveal substantial variation in inherited-label reliability across instances, greater performance sensitivity to subject scarcity than to instance scarcity, and a more structured representation space with distinct subject-wise clusters and improved separation between diagnostic classes. Together, these findings underscore the importance of aligning supervision with the subject-level prediction objective while learning from abundant EEG instances without assigning disease labels to individual instances.

Accurate identification of Alzheimers disease (AD) using resting-state functional magnetic resonance imaging (rs-fMRI) remains challenging due to the high dimensionality, noise, and complex inter-regional dependencies inherent in functional brain connectivity, which limit the effectiveness of traditional approaches based on handcrafted connectivity features or conventional machine learning models. In this work, we present an attention-based deep learning framework for Alzheimers disease classification that operates directly on rs-fMRI functional connectivity matrices by treating brain regions as tokens and employing a Transformer-inspired self-attention mechanism to model long-range and global functional dependencies across distributed brain networks. The proposed framework learns discriminative functional representations without reliance on manual feature engineering and is evaluated on a longitudinal cohort from the Alzheimers Disease Neuroimaging Initiative (ADNI) comprising cognitively normal and Alzheimers disease subjects with multiple visits. A subject-wise evaluation protocol is adopted to prevent information leakage across visits, and class-weighted optimization is incorporated to address mild class imbalance. Experimental results for binary AD versus cognitively normal classification demonstrate that the proposed attention- based rs-fMRI model achieves an accuracy of 88.95% and a ROC-AUC of 0.90, along with a favorable precision-recall balance, highlighting the effectiveness of self-attention-driven functional connectivity modeling as a robust and interpretable approach for Alzheimers disease detection using resting-state fMRI.

Acoustic biomarkers show promise for detecting Alzheimer's Disease (AD), yet whether the cues driving diagnostic AI align with those salient to human listeners is underexplored across languages and genders, where pathological markers and perceptual strategies differ. We train models to predict clinical AD status (pathology) and human perceptual scores across Mandarin and Greek, male and female speakers. Using SHAP for interpretability and statistical models for validation, we compare feature importance by subgroup. Results reveal a context-dependent divergence: pathological-perceptual alignment is significant for Mandarin and female speakers but disappears for Greek and male speakers, where pathology models did not exceed chance; this is a failure mode that population-specific auditing surfaces. Global Explainable AI (XAI) explanations can mask critical demographic divergences, highlighting the need for population-specific explainability auditing for equitable deployment of clinical speech AI.

Electroencephalography (EEG) is widely used to diagnose neurological conditions, but its analysis usually relies on either predefined spectral features or deep neural networks. Predefined features carry a strong bias, since they fix in advance what counts as informative, while deep neural networks and foundation models are hard to interpret and need large amounts of data and compute. We present bag-of-waves, an interpretable framework that learns a small dictionary of recurring EEG waveform templates, called atoms, using shift-invariant k-means without labels. The continuous EEG is then turned into a sequence of atom tokens, whose counts feed a simple downstream classifier or clustering step. We extend this representation in two ways: we add atom-to-atom transitions, which we call n- grams, to capture temporal structure, and we move from single-channel atoms to regional and cross-channel spatial atoms for the multichannel case. We test the method on three complementary datasets, each probing a different aspect: single-channel mouse genotype clustering with only sixteen animals (the low-data and temporal case), resting-state dementia classification (the spatial case), and the TUEV benchmark, a six-way classification of clinical EEG events (a high-data comparison against strong deep and foundation baselines). Across all three datasets, bag-of-waves achieves performance competitive with state-of-the-art deep and foundation models. Yet, it operates with a fraction of the parameter count and provides full interpretability: because every atom corresponds to an inspectable waveform, the method explicitly recovers known clinical morphologies that a neurophysiologist can directly validate. Its main advantage is that it works in the low-data regime where heavier models are a poor fit.

Although artificial intelligence (AI) has shown promising performance in several medical tasks, accurate dementia etiology diagnosis with AI remains challenging due to complex overlapping symptoms among diseases. Scaling up the dataset size by combining the cross-center samples may bring a gain in the pursuit of performance, while the inherent data heterogeneity across centers or populations induces the conflict. Conventional multi-task learning paradigms offer a promising framework; however, they fail to consider critical meta information (e.g., site-specific acquisition and modality availability) to combat the heterogeneity. To address this challenge, we propose a Collaborative Meta Knowledge Enhancement (COME) framework for dementia etiology diagnosis, which injects multi-center acquisition semantics, source identifiers, and modality indicators as heterogeneity-aware embeddings into a unified Transformer architecture for scale-up training, enabling explicit modeling of heterogeneity. Besides, a trust-region constrained optimization scheme is designed to regularize the model from spurious correlations during training through a reference model. Across seven independent cohorts, our method achieves state-of-the-art in-domain performance with a mean macro-averaged AUC of 85.62% and a 4.29-point gain over the strongest baseline, while maintaining superior out-of-domain generalization under both cross-center and cross-sequence evaluations. Extensive validation also confirms the alignment between model predictions and established biomarkers (amyloid, tau) and clinical severity, highlighting the potential of COME to enable robust and interpretable dementia diagnostics in real-world settings.

Cognitive impairment (CI) is a growing public health concern. Early and accurate diagnosis is critical for enabling timely intervention and improving patient outcomes. Speech-based CI detection has emerged as a promising non-invasive approach, as speech signals encode both linguistic and acoustic markers associated with cognitive decline. Recent advances in large language models (LLMs) further strengthen the potential of speech-based assessment by enabling more expressive representation learning and improved generalization across diverse speakers, recording devices, and clinical environments. Moreover, multimodal learning by jointly modeling linguistic and acoustic features allows for a more comprehensive characterization of cognitive and behavioral changes related to CI, leading to more reliable detection. In this work, we propose a multimodal CI detection framework based on open-source LLMs that integrates speech audio and corresponding transcripts while preserving patient privacy. Acoustic embeddings are extracted directly from speech signals, while textual embeddings are generated from automatically transcribed speech. These modality-specific embeddings are then concatenated to create a combined feature vector and used for downstream classification, without requiring access to raw or sensitive patient data. The proposed approach is evaluated on the ADReSS20 and ADReSSo21 benchmark datasets. Experimental results show that the proposed multimodal framework achieves an CI classification accuracy of 92.4% and consistently outperforms single-modality baselines. Our work establishes a new state-of-the-art for CI identification, with the proposed method demonstrating superior cross-dataset generalization. This advance highlights the power of an LLM-based multimodal framework that fuses linguistic and acoustic data to enable robust, scalable, and non-invasive screening.

More than a million people in the UK suffer from frailty or dementia, which severely compromise their ability to travel in urban environments. This paper presents SafeStep, an AI-driven travel system that assists elderly users with their journeys. At the core of SafeStep is a novel travel graph representation, which integrates route planning with predictive modelling. For each stage of a journey, the system (i) generates personalized failure scenarios using a combi-nation of LLMs and the Anticip8 behavioral prediction engine, (ii) proposes targeted interventions, and (iii) estimates the impact of interventions on out-come probabilities. This enables SafeStep to select interventions that maximize the likelihood of the person reaching their destination. SafeStep was evaluated through experiments on travel graph generation and a field study involving 26 real-world journeys. Results showed that combining Anticip8 for failure pre-diction with GPT-based models for intervention evaluation yields the most re-liable performance. User feedback indicated that SafeStep improves confidence and perceived safety during travel, although interface usability needs to be im-proved for the target demographic. In the future, we would like to improve and release SafeStep. The AI system that was developed for SafeStep could be ap-plied in other areas, such as mental health, career coaching and addiction treatment.

Diabetic retinopathy is a leading cause of preventable blindness; its early lesions are small, low contrast, and easily missed in manual screening. Most automated detectors handle the four non-proliferative DR lesions: microaneurysms, hemorrhages, hard exudates, and soft exudates, with a single multi-class model, even though these lesions differ sharply in size, color, morphology, and prevalence, so a shared model favors common, easy classes over rare, difficult ones. We present PRISM-DR, a lesion-specific pipeline that trains one single-class detector per lesion, each with its own configuration. From a raw fundus image, the pipeline applies region of interest cropping, fundus-specific preprocessing, four parallel YOLO detectors, tiling, per-lesion ensembling of five cross-validation folds, and an inter-lesion suppression step that resolves overlaps by physical lesion size and clinical priority rather than confidence. Per lesion, the best of five YOLO generations is selected, and augmentation is tuned by Bayesian optimization. Trained on IDRiD with stratified five-fold cross-validation, the system reaches a test mAP50 of 0.527 and F1 of 0.529, highest AP50 on hard exudates with 0.561. Without fine-tuning, the models transfer well where the imaging scale is close to IDRiD and degrade as field of view and resolution depart. These modest absolute results reflect a small single-source training set and a difficult task; however, treating each lesion as a separate detection problem is a practical alternative to a single multi-class model.

Real-time EEG classification on edge devices is bottlenecked by the floating-point arithmetic of conventional neural networks. We investigated Differentiable Logic Gate Networks (Diff-Logic) as a hardware-native alternative that compiles models into pure Boolean circuits executable via bitwise CPU operations. Through rigorous iso-parameter experiments across four EEG datasets spanning two classification tasks, binary dementia detection and 3-class emotion recognition, we compared Diff-Logic against matched-capacity Multi-Layer Perceptron (MLP) and Binarized Neural Network (BNN) baselines at four complexity tiers (50k-500k parameters). On dementia screening, Diff-Logic achieved 80.2% Macro F1, outperforming the MLP baseline by 6.8%. On emotion recognition, the MLP retained a moderate performance advantage but incurred a 2.3$\times$ higher latency and 14$\times$ larger model size when deployed on a power-constrained (7W) Nvidia Jetson Orin Nano CPU (Single-core). Critically, Diff-Logic inference time remained nearly constant across a 10$\times$ increase in model scale, achieving a peak speedup of 2.9$\times$ over MLPs at the largest complexity tier. Our results establish logic-based neural architectures as a practical paradigm for resource-constrained brain-computer interfaces, achieving competitive or superior performance while natively satisfying the latency and memory constraints of portable edge deployment. Code is available on GitHub: https://github.com/Shyamal-Dharia/eeg-difflogic

Background. Predicting conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD) is central to trial enrichment and care planning, yet existing models provide no individual-level uncertainty estimates and rarely include transparent leakage audits. We introduce the first application of persistent homology to longitudinal clinical trajectory point clouds for this task, and the first split-conformal individual risk guarantee for any AD-conversion model. Methods. We analysed 741 MCI subjects (240 converters, 32.4%) from ADNI with a uniform 4-year follow-up cap. Five leakage sources were corrected; without them a naive pipeline achieved AUC=0.934, inflated by +0.075. Vietoris-Rips persistent homology and sublevel-set proxies were combined with trajectory slopes and engineered features (76 total) in a stacking ensemble evaluated by 5-fold cross-validation. Results. Cox and Random Survival Forest models with TDA features achieved concordance C=0.799 and C=0.826 versus C=0.753 and C=0.812 without (+0.045 and +0.014). The primary nested AUC is 0.840 (same-fold bound 0.866); external AUC was 0.879 on a zero-overlap ADNI-2/GO/3 cohort. H0 persistence entropy was the top SHAP feature and significantly associated with APOE4 dosage (Spearman r=-0.191, p<0.0001, Bonferroni-corrected). Cross-conformal coverage was 90.4%+-2.2% (target 90%); empirical external coverage 96.9%. Maximum fairness gap in false-negative rate across seven subgroups was 0.092. Conclusions. We propose H0 persistence entropy as a topological biomarker of cognitive decline and demonstrate that a leakage-audited, conformally calibrated pipeline reaches competitive accuracy with individual-level uncertainty quantification not previously available for this task.

Speech recordings used for dementia detection inherently expose speaker identity, raising critical privacy concerns. Existing methods typically address only singular threats and fail to resolve the privacy--utility trade-off. We propose a multi-level framework designed to neutralize two distinct eavesdropping vectors. At the signal level, a Cumulative Signal Attack (CSA) concentrates perturbations in keyword-aligned regions to maximize transcription error (Word Error Rate WER = 1.00) while preserving vital prosodic biomarkers. At the feature level, a Gradient Reversal Layer (GRL) with Mutual Information (MI)-guided noise injection suppresses speaker-discriminative dimensions while retaining dementia-relevant diagnostic structure. Evaluated on the DementiaBank Pitt Corpus, our framework achieves near-chance speaker identification (Equal Error Rate EER = 0.59, F1 = 0.003) while maintaining strong dementia classification performance (F1 = 0.78, AUC = 0.86).

Mild Cognitive Impairment is a critical early stage of cognitive decline that frequently precedes Alzheimer's disease, yet its automated detection from neuropsychological drawing tests remains fundamentally constrained by data scarcity, class imbalance, and diagnostic ambiguity near clinical boundaries. Existing methodologies attempt to bypass these constraints using computationally expensive, fully fine-tuned hybrid architectures that relegate spatial explainability to a post-hoc approximation rather than an intrinsic model property. We propose a parameter-efficient framework utilizing frozen DINOv2-Small model adapted via three modality-specific learnable prompt tokens while Operating with 1.19 million trainable parameters, each token serves as a query in a shared cross-attention layer over the source image patch tokens. Crucially, spatial explainability is achieved directly through these attention maps; as a structural consequence of the architecture. Then task-conditioned embeddings fused via an attention module to quantify modality-level importance per subject. To handle boundary ambiguity, a MoCA-adapted focal loss introduced that integrates continuous cognitive scores into the training target, loss modulation, and adaptive sample weighting, strictly generalizing standard soft-label approaches. Under stratified five-fold cross-validation, the proposed architecture yields an MCI-class F1 of 0.641 and an AUC of 0.795, outperforming the computationally heavier ResViT baseline by 0.110 in MCI-class F1.

Per-subgroup fairness audits of medical image classifiers face a sample-size problem: minority subgroups in held-out test sets have so few samples that the resulting confidence intervals on per-subgroup performance are wider than the bias the audit is meant to detect. We argue that a demographically-conditioned synthetic generator can do both: mitigate bias on the training side and detect bias on the evaluation side. Working on COVID-19 chest CT classification with an end-to-end fine-tuned Stable Diffusion 2.1 generator, we make two findings. For bias mitigation (training), a demographically-balanced synthetic cohort is most useful as a pretraining prior, not as joint augmentation: with the same fixed data, sequential pretraining followed by fine-tuning substantially outperforms joint augmentation, and the resulting classifier surpasses the full-real baseline at \sim$$100\times real-data efficiency. For bias detection (evaluation), across five synthetic minority cohorts and five classifier seeds, the synthetic estimator reproduces the subgroup ranking of a well-powered real oracle (Spearman $ρ= 1.00$ on MCC and Recall) and gives the more reliable per-cell estimate where the small real test set runs out of samples. The synthetic cohort is therefore most useful in exactly the cells that fairness audits care about, as both a fix for and a measure of subgroup bias.

Amyotrophic lateral sclerosis (ALS) is a progressive and heterogeneous neurodegenerative disease in which predicting clinically meaningful milestones, such as assistive device use, remains challenging. We developed a time-to-event, digital-twin-inspired framework that integrates longitudinal ALS Functional Rating Scale-Revised (ALSFRS-R) trajectories with survival modeling to support individualized prediction of functional decline and assistive device utilization. We constructed a harmonized longitudinal dataset by integrating diagnosis records, ALSFRS-R assessments, activities of daily living, and demographic information, followed by preprocessing to ensure data quality, temporal alignment, and cohort consistency. Correlation-based clustering identified coherent functional domains spanning bulbar, upper limb, axial, lower limb, and respiratory systems. Generalized additive mixed models characterized nonlinear, domain-specific functional decline across all domains. In addition, a temporal machine learning model was developed to predict longitudinal functional decline and capture stage-dependent disease progression. Cox proportional hazards modeling further identified lower limb function, particularly walking and stair climbing, as the strongest predictors of earlier wheelchair access. Building on these results, we implemented a digital twin-inspired temporal machine learning-based time-to-event (TTE) model that generates individualized survival curves and dynamically predicts wheelchair-free survival. This framework provides a scalable, interpretable, and clinically actionable approach for linking ALS progression with personalized decision support, with applications in proactive care planning, clinical trial stratification, and precision medicine.

When labeled data are scarce, off-the-shelf diffusion models can augment training sets for few-shot medical image classification, but not all generated samples are equally useful for the downstream task. Existing approaches largely improve synthetic data by increasing realism, diversity, or domain adaptation, while overlooking a more fundamental question: how should sample usefulness for classification be measured and optimized? We address this with Class-Contrastive Influence (C2I), a criterion that quantifies a sample's usefulness through its gradient-based influence on the classifier. We find that effective samples exhibit a strong C2I gap: their loss gradients align with validation gradients from the same class and oppose those from other classes. Our analysis further suggests that such high-C2I samples are hard, boundary-proximal examples that help refine the decision boundary and improve robustness. Building on this insight, we fine-tune diffusion models with reinforcement learning using a C2I-based reward to steer generation toward class-informative samples. Across several few-shot medical imaging benchmarks, C2I-guided generation improves downstream accuracy and robustness over diffusion-based augmentation baselines, showing that synthetic augmentation is most effective when guided by task usefulness rather than image quality alone.

Accurate diagnostic classification and disease-severity prediction for Alzheimer's disease are hampered by the incompleteness and heterogeneity of real-world clinical data. Left unaddressed, these barriers prevent reliable disease modelling and hinder effective clinical evaluation. Conventional imputation strategies introduce systematic bias, distort inter-feature relationships, and yield overconfident predictions, limitations especially consequential in diagnostic settings. Here, we propose NITROGEN, an imputation-free transformer that jointly models within-patient feature dependencies and between-patient relational structure through masked and intersample attention, enabling robust multimodal learning directly from partially observed records. We trained NITROGEN on ADNI (N=7858 scans), and evaluated it on two independent cohorts: OASIS-3 (N=2675 scans) and AIBL (N=1286 scans). Across cohorts and diagnostic and cognitive score prediction tasks, NITROGEN showed robust calibration and uncertainty quantification advantages over tree-based ensemble methods, while maintaining competitive discriminative performance. Cross-cohort and cross-method analyses identified cortical thickness in the temporal pole, age, and APOE genotype as important, though not individually sufficient, features for AD classification. We further introduced a modality-aware uncertainty adjustment that augments predictive uncertainty proportionally to the importance of absent modalities, enabling calibrated confidence when diagnostic information is unavailable. Together, our results show that imputation-free attention learning preserved meaningful discrimination under cohort shift, revealing expected degradation on more distributionally different cohorts, and demonstrate that evaluating models along calibration, interpretability, and cross-cohort reliability, not accuracy alone, is essential for clinical deployment.

It is still hard to find Alzheimer's disease (AD) early, especially when neuroimaging is expensive or tools that depend on language are not available. Spontaneous speech provides a non-invasive signal; however, numerous current methodologies depend on transcripts/ASR or computationally intensive deep models. We offer a simple, audio-only baseline for detecting AD using 176 Cookie Theft recordings from the DementiaBank Pitt corpus (88 AD, 88 controls). WebRTC voice activity detection (VAD) is used to separate speech from non-speech. We take out 99 hand-crafted acoustic-temporal features, including pause and fluency statistics, spectral/prosodic descriptors, and MFCC summaries with Δ and ΔΔ. Evaluation is performed using a stringent speaker-independent GroupShuffleSplit,documenting performance across 30 iterations. A lightweight SVM with an RBF kernel gets an average AUC of 0.674 across runs. For example, a single split has an AUC of 0.742 and an accuracy of 0.657. We also present an exploratory compact-feature analysis utilizing a Top-20 subset ranked by Random Forest importance; since selection is not nested within training splits, these results may be overly optimistic and are not employed for primary conclusions (AUC 0.719). The results indicate that transcript-free spectro-temporal and fluency-related cues can facilitate speaker-independent Alzheimer's disease screening from raw audio, establishing a practical foundation for deployment-oriented research.

Multimodal medical models often degrade when inputs are missing, a common scenario in real-world clinical workflows. Separately, even when all modalities are present, modality dominance is observed during training, where optimization over-relies on a highly predictive modality and undertrains complementary sources, resulting in poor robustness under partial availability. While training-time modality knockout improves missing-modality robustness, existing approaches use static masking rates that cannot adapt to evolving modality utility during training. We introduce ShapKO (Shapley-Adaptive Modality Knockout), a dynamic training strategy that learns modality-specific knockout probabilities based on validation utility. ShapKO periodically evaluates performance across modality subsets, estimates modality importance via Shapley values, and updates masking probabilities to suppress dominant modalities more frequently. This adaptive process promotes complementary representations, while requiring no architectural modifications. We evaluate ShapKO on three datasets covering multitask clinical classification, survival prediction, and cancer detection. ShapKO consistently improves performance under modality absence and yields interpretable trajectories of learned masking behavior. Code is available at: https://github.com/sumona00/ShapKO

Diagnostic decision making often relies on a sequence of pathology tests that bridge patient symptoms and final disease diagnosis. Existing clinical decision-support systems typically focus on predicting single diseases and do not explicitly recommend sets of intermediate tests or model dependencies among them. In this paper, we formulate pathology test recommendation as a multi-label classification problem where each case is associated with multiple, interdependent tests. We propose an AI-based framework that applies classifier chains with logistic regression, decision trees, random forests, and their ensemble to capture label dependencies between tests. Experiments on an expert-curated dataset from a private pathology laboratory show that classifier-chain models outperform their independent counterparts, improving F1-score and reducing Hamming loss while maintaining high accuracy across common and rare tests. To enhance trust and transparency, we integrate SHAP-based explainable AI, providing symptom-level attributions that align with established clinical reasoning in most cases. The results demonstrate that classifier chains combined with SHAP offer an effective and interpretable approach for multi-label pathology test recommendation, with potential to support clinicians in selecting appropriate diagnostic tests at an early stage.

Quantifying variability in a target population relative to a reference population is central to many scientific and clinical problems (e.g., diseased vs. healthy). Yet, without paired data and in the presence of heterogeneous target variation, existing methods struggle to separate multiple modes of target-specific variation. We propose \textit{CASL-VAE}, a deep contrastive latent variable model that learns structured latent generative factors from unpaired data. CASL-VAE factorizes variation into continuous common latent factors shared across populations and hierarchical salient latent factors that model target-specific heterogeneity as discrete subtypes and continuous within-subtype variation. Using variational inference, we show how approximate joint likelihood optimization over reference and target domains can be performed using unpaired data, providing a principled basis for paired-sample generation and cross-domain analysis. We validate CASL-VAE on semi-synthetic neuroimaging data, demonstrating improved subtype recovery and paired-sample generation compared to baseline clustering and generative models. We also validate its ability to reveal biologically plausible heterogeneity in Alzheimer's disease.

Social robots offer a promising means of supporting cognitive therapies for dementia care by guiding structured conversation and therapeutic activities. However, little is known about the conversational dynamics that emerge during robot-delivered cognitive stimulation therapy (CST) sessions. This study analysed the interaction patterns from robot-delivered individual CST (iCST) sessions conducted with people living with dementia in home settings. Our Co-STAR (Cognitive Stimulation Therapy by an Autonomous Robot) system was deployed in the homes of eight PwDs for one week, who completed 30-minute sessions. Conversational metrics, including words per turn, speech production rate, response duration, response latency, and self-referential language, were analysed to examine how conversational engagement is shaped by prompt personalisation, interaction phase, and participant characteristics. The findings highlight three key interactional properties of robot-delivered iCST. First, personalised prompts significantly increase response duration, self-referential language, and overall engagement compared to generic prompts. Second, conversational behaviour changes within sessions, with a reduction in the verbal output and autobiographical engagement observed during later interaction phases, which suggests cognitive fatigue. Third, first-session conversational metrics were associated with long-term participation, while living situation influenced conversational engagement patterns. These findings provide empirical insights into the factors that shape conversational engagement in robot-delivered iCST. They inform the design of adaptive conversational robots for dementia therapy.

Alzheimer's disease (AD) is a common neurodegenerative disorder, and early diagnosis is of great significance for delaying disease progression and enabling timely intervention. Mild cognitive impairment (MCI), which represents an intermediate clinical stage between cognitively normal aging and AD. Structural magnetic resonance imaging (sMRI) provides detailed characterization of anatomical structures and plays an important role in AD-related brain analysis. However, existing sMRI-based brain network methods typically rely on a single graph construction strategy, limiting their ability to jointly capture spatial relationships and morphological similarities between brain regions. To address these issues, this paper proposes an sMRI-based multi-view masked graph neural network model (MVMGNN) for AD diagnosis. A joint node-edge masking mechanism is proposed to simultaneously select radiomics feature dimensions and structural connections, reducing redundancy during graph learning. Furthermore, a patient-level cross-view gated fusion mechanism is proposed to integrate multi-view representations. Experimental results on the ADNI dataset demonstrate that MVMGNN outperforms several competing approaches in AD classification. Interpretability analysis further demonstrates that MVMGNN is able to identify key brain regions associated with AD, providing useful insights into discriminative patterns in sMRI-based brain networks.Our implementation is publicly available at https://github.com/chenzhao2023/MVMGNN_AD

In longitudinal Alzheimer's disease (AD) diagnosis support, clinical and imaging information is often collected at irregular visits. Integrating these multimodal observations may improve diagnostic assessment, but naive fusion can degrade performance when MRI is noisy or intermittently unavailable. We propose AT-Attn, a temporal-aware multimodal framework that combines Change-and-Time encoding, time-biased asymmetric cross-attention, and gated fusion to integrate MRI with longitudinal clinical information. We evaluate AT-Attn on an MRI-retained ADNI cohort of 1,520 patients using structural MRI, six cognitive-scale trajectories, and seven static clinical variables under patient-level five-fold cross-validation. The main asymmetric AT-Attn model achieves accuracy 0.719+/-0.024, macro F1 0.721+/-0.023, ROC-AUC 0.873+/-0.013, and PR-AUC 0.783+/-0.018, outperforming unimodal and naive multimodal fusion baselines while remaining competitive with strong tabular baselines. These results suggest that a temporal-aware and constrained fusion strategy can help structural MRI contribute clinically relevant complementary information for patient-level AD diagnosis support.

Cognitive therapies have been shown to enhance the quality of life and well-being of people living with dementia (PwDs). However, their use remains limited due to a shortage of trained professionals and the significant time and training required of informal caregivers. To address this gap, we developed and deployed a social robot capable of autonomously delivering cognitive stimulation therapy (CST) in the home. Nine PwDs participated in a one-week ($7$ days) study that involved daily robot-led sessions. Participants engaged positively with the system, completing nearly half of the scheduled sessions, an adherence rate higher than typically observed in caregiver-led CST. Our findings also highlight the crucial role of family members, who often supported session initiation and occasionally joined the activities, enriching the interactions. This work demonstrates the feasibility and potential of socially assistive robots to deliver in-home cognitive therapy, offering a scalable approach to extend access to dementia care.

Online social media posts provide scalable signals for early depression screening, and recent studies mainly improve pre-classification evidence through risk-post selection, symptom grounding, and clinically informed feature construction. However, these screening-stage designs often leave final decisions to a single detector, overlooking how users heterogeneously express depressive risk after screening. A monolithic classifier must average across heterogeneous users, which may dilute localized evidence and cause misclassification, especially for non-self-disclosing users. To address this issue, we propose WPG-MoE, a weak-prior-guided dense mixture-of-experts framework built on a shared large language model (LLM) backbone. WPG-MoE derives user-level weak semantic priors to softly route users to experts matched to different evidence layouts. We formulate this process as learning using privileged information (LUPI): rich LLM-extracted structured evidence guides training-time routing, while inference retains only Patient Health Questionnaire-9 (PHQ-9) template screening and the deployable backbone. Experiments on Chinese and English datasets show that WPG-MoE outperforms strong baselines with interpretable routing behavior.

Alzheimers disease (AD) is a brain disorder that develops slowly and mainly affects memory, thinking, language, and daily activities. It is one of the most common causes of dementia and creates many difficulties for patients as well as their families. In the early stage, the symptoms are often mild and may look like normal ageing. For this reason, many people are diagnosed late, when the disease has already progressed. At present, there is no complete cure for AD. Still, early detection can help doctors manage the condition better and take suitable steps at the right time. In this study, a machine learning model is proposed to detect the early stages of Alzheimers disease using clinical details, neuropsychological test scores, and neuroimaging-related measures. The data used in this work is collected from the Alzheimers Disease Neuroimaging Initiative (ADNI). As the dataset has missing values, iterative imputation is applied to fill them. The dataset also has class imbalance, which is handled using Borderline SVM-SMOTE. After that, feature selection is carried out using wrapper-based and embedded methods so that only important features are used for training. The selected features are divided into training and testing sets, and feature scaling is applied. A stacking ensemble model is developed using Logistic Regression, Extra Trees, Bagging KNN, and LightGBM as base classifiers. Along with this, an artificial neural network is also trained on the same dataset. The performance of these models is compared using precision, recall, F1-score, and AUC-ROC. This study aims to find the best classifier and also identify important biomarkers that may help in the early diagnosis of Alzheimers disease.

INTRODUCTION: Accurate MRI-based identification of Alzheimer's disease (AD), mild cognitive impairment (MCI), and related dementias remains challenging because disease-related structural changes are often subtle and heterogeneous. We developed NeuroBridge, a clinically guided multi-task MRI framework for neurodegenerative disease diagnosis. METHODS: NeuroBridge integrates large-scale self-supervised MRI pretraining with hippocampal segmentation, hippocampal atrophy classification, and reconstruction objectives, followed by gated fusion fine-tuning. Performance was evaluated across ADNI and OASIS cohorts, including cross-cohort transfer, probability-based analysis, and opportunistic screening. RESULTS: NeuroBridge achieved the highest performance across evaluated classification tasks, reaching 88.17% accuracy for AD versus cognitively normal controls in ADNI and 82.78% in OASIS. The largest gains occurred in MCI-related and mixed-diagnosis settings. The framework demonstrated strong cross-cohort generalization, systematic associations between predicted-class probability and accuracy, and the feasibility of probability-based opportunistic screening. DISCUSSION: Clinically guided multi-task representation learning improves neurodegenerative MRI diagnosis beyond conventional single-task approaches. NeuroBridge provides a robust and scalable framework for dementia assessment and MRI-based opportunistic screening.

Spontaneous speech is a vital non-invasive biomarker for Alzheimer's Disease (AD), yet many systems overlook non-linear structural disruptions and clinical heterogeneity in pathological language. We propose a Multi-View Gated Graph Attention Network that transcribes audio via Automatic Speech Recognition (ASR) to construct semantic, dependency, and co-occurrence graphs, characterizing speech through a "content-structure-flow" framework. Notably, the co-occurrence graph leverages Pointwise Mutual Information (PMI) from a normative corpus to quantify narrative logic and linguistic deviation. To address symptomatic diversity, an adaptive gated fusion mechanism dynamically integrates these views. Evaluated on the ADReSSo dataset, our model achieves 90.00% accuracy. Ablation results confirm that the PMI-based graph and heterogeneity-aware gating are essential for robust classification across diverse clinical populations. Our source code is publicly available at https://github.com/opeacc/AD.