Alzheimer

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Parameter-efficient fine-tuning (PEFT) has emerged as a promising paradigm for adapting pretrained models under limited data conditions. However, most existing PEFT methods are designed for matrix-structured parameters and are not well suited for high-dimensional convolutional kernels in medical imaging models. Moreover, they typically rely on additive updates and lack mechanisms to preserve the geometric structure of pretrained parameters, while multiplicative (geometry-aware) updates are difficult to integrate within a unified framework. To address this issue, this paper proposes GLT-PEFT, a gated Lie-Tucker parameter-efficient fine-tuning framework for Alzheimer's disease (AD) diagnosis. The proposed approach transfers a hippocampal segmentation pretrained model to a downstream classification task. Tucker decomposition enables tensor-aware low-rank adaptation of 3D convolutional kernels, while Lie group-based transformations provide structure-preserving multiplicative updates. A gating mechanism further reconciles additive and multiplicative update forms, resulting in a unified and more stable fine-tuning strategy. Extensive experiments demonstrate that GLT-PEFT achieves effective cross-task transfer while significantly reducing trainable parameters, highlighting its effectiveness for efficient and robust adaptation in medical imaging models.

Accurate assessment of cognitive decline from spontaneous speech remains challenging due to limited dataset size and class imbalance. In this work, we propose a large language model (LLM)-driven data augmentation framework to improve the prediction of cognitive scores from speech. Experiments are conducted on a Japanese corpus in which each participant provides both a spontaneous oral narrative and a written response to the same clinical prompt. The written responses serve as semantic anchors to generate multiple oral-like monologues in different styles using GPT-5. We then predict Hasegawa Dementia Scale scores, a widely used cognitive screening tool in Japan, using a Partial Least Squares regression model trained on Sentence-BERT speech embeddings. We investigate two augmentation strategies: random class-balanced selection, which yields moderate but unstable improvements, and similarity-guided class-balanced selection. The latter prioritizes semantically close synthetic samples, leading to more consistent improvements and substantially reducing prediction error for minority low-score participants while maintaining performance for the majority group. Overall, our findings demonstrate the potential of semantically guided LLM-driven augmentation as a principled approach for addressing class imbalance and improving data efficiency in clinical speech analysis.

The detection of Alzheimers disease (AD) is considered crucial, as timely intervention can improve patient outcomes. Electroencephalogram (EEG)-based diagnosis has been recognized as a non-invasive, accessible, and cost-effective approach for AD detection; however, it faces challenges related to data availability, accuracy of modern deep learning methods, and the time-consuming nature of expert-based interpretation. In this study, a novel lightweight and high-performance model, DeepTokenEEG, was designed for the diagnosis of AD and the classification of EEG signals from AD patients, individuals with other neurological conditions, and healthy subjects. Unlike traditional heavy-weight models, DeepTokenEEG ultilizes spatial and temporal tokenizer that effectively captures AD-related biomarkers in both temporal and frequency domain with only 0.29 million paramaters. Trained in a combined dataset of 274 subjects, including 180 AD cases, and 94 healthy controls, the proposed method achieves a maximum recorded accuracy of 100% on specific frequency bands, representing an improvement of 1.41-15.35% over state-of-the-art methods on the same dataset. These results indicate the potential of DeepTokenEEG for early detection and screening of AD, with promising applicability for deployment due to its compact size.

Missing modalities are prevalent in real-world Alzheimer's disease (AD) assessment and pose a significant challenge to multimodal learning, particularly when the distribution of observed modality subsets differs between training and deployment. Such missingness pattern mismatch induces a conditional representation shift across modality subsets. Existing approaches that rely on implicit imputation or modality synthesis often fail to explicitly model modality availability and uncertainty, leading to overconfident dependence on synthesized features, reduced robustness, and miscalibrated uncertainty estimates. To address these limitations, we propose PRA-PoE, an incomplete multimodal learning framework that is equipped with Prototype-anchored Representation Alignment (PRA) and an Uncertainty-aware Product of Experts (UA-PoE) fusion mechanism. First, PRA uses learnable global prototypes and availability-conditioned tokens to encode modality availability, distinguish observed from missing modalities, re-synthesize features for missing modalities, and adaptively refine observed representations to align latent spaces across modality subsets, with the goal of reducing representation shift under varying missingness patterns. Second, UA-PoE models each modality as a Gaussian expert and performs closed-form Product of Experts fusion, where experts with higher uncertainty are automatically down-weighted via lower precision, improving uncertainty reliability. We evaluate PRA-PoE under a clinically realistic protocol by training with naturally missing data and testing on all non-empty modality combinations. PRA-PoE consistently outperforms the state-of-the-art across datasets, achieving a 5.4% relative improvement in average accuracy on ADNI and a 10.9% relative gain in average F1 on OASIS-3 over the strongest baseline across all non-empty modality subsets.

Reasoning-based end-to-end (E2E) autonomous driving has recently emerged as a promising approach to improving the interpretability of driving decisions as it can generate human-readable reasoning together with predicted trajectories. Such approaches commonly generate multiple trajectories to capture diverse future behaviors, and they fall into two categories: (1) multi-reasoning, where one reasoning sequence is generated per trajectory, and (2) single-reasoning, where a single reasoning is shared across all trajectories. The former offers richer diversity at the cost of redundant computation, while the latter is more efficient but is often assumed to sacrifice diversity. Alpamayo 1, a representative system, adopts the multi-reasoning approach and achieves competitive trajectory prediction performance. However, the efficiency of this design remains largely unexplored, making it a well-motivated subject for investigation. In this paper, we systematically analyze and improve Alpamayo 1 in two ways. First, we reduce inference latency while preserving trajectory diversity by redesigning Alpamayo 1 into a single-reasoning system. Through extensive experiments, we find that replacing multi-reasoning with single-reasoning does not meaningfully degrade trajectory diversity. Second, we accelerate diffusion-based action generation by eliminating inter-block overhead arising from unnecessary copy operations and inefficient kernel execution. Through closed-loop and open-loop experiments, we validate both optimizations, demonstrating a 69.23% reduction in inference latency while maintaining trajectory diversity and prediction quality. These results highlight the importance of jointly analyzing system architecture and runtime execution to improve the efficiency of reasoning-based E2E AD systems.

Deep learning models in medical imaging typically operate as parametric memory, diagnosing patients by recalling fixed knowledge learned during training. This contrasts sharply with clinical practice, where physicians employ analogical reasoning to diagnose new cases by referencing similar records from past exemplars. While In-Context Learning (ICL) frameworks such as Tabular Prior-Fitted Networks (TabPFN) offer a promising diagnosis-by-reference paradigm, they are designed with tabular-specific inductive priors and rely on non-differentiable preprocessing pipelines, leading to manifold mismatch and gradient fracture when applied to heterogeneous multimodal data. To address these limitations, we propose PromptDx, a novel diagnosis-by-reference framework that leverages a pre-trained TabPFN as an ICL engine while enabling seamless integration with multimodal representations. Our core contribution is a Differentiable Prompt Tuning (DPT) mechanism that aligns a Masked Multimodal Modeling module with the pre-trained ICL engine. By training a lightweight adapter as a differentiable surrogate for the engine's non-differentiable preprocessors, we enable an end-to-end optimization of multimodal prompts within the ICL paradigm. We validate our method on the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset using 3D MRI and tabular biomarkers. Experiments demonstrate that our approach outperforms traditional parametric baselines. Notably, our method achieves superior performance using only 1% context samples compared to 30% in standard ICL, demonstrating exceptional manifold condensation ability. We further validate the generalizability of our DPT framework across six tabular datasets with diverse scales. Overall, our method offers a more data-efficient and clinically aligned paradigm for Alzheimer's Disease diagnosis.

Individuals with Alzheimer's disease (AD) and Alzheimer's disease-related dementia (ADRD) experience memory and thinking changes that impact their ability to use digital daily management tools. For example, adding an event to a digital calendar requires multiple steps that may act as barriers to independent use for individuals with AD/ADRD. This paper presents AI-Care, a conversational agentic artificial intelligence (AI) layer built on top of a remote caregiving platform co-designed with people with AD/ADRD. AI-Care is designed to reduce the cognitive load on individuals with AD/ADRD when managing everyday tasks such as setting calendar reminders and organizing to-do lists through natural-language interaction with a voice-first chatbot. The system uses a LangGraph-based stateful orchestration approach in which each request passes through sanitization, intent classification, context loading, safety checks, deterministic slot collection, tool execution, and response composition. Safety-critical responses, particularly around medications and allergies, are grounded in caregiver-verified records rather than free-form model generation. The system does not make autonomous medical or treatment decisions. Incomplete or ambiguous requests are handled through controlled multi-turn clarification rather than silent failure or guessing. The system supports both typed and spoken input, with voice output through ElevenLabs text-to-speech. Longer responses are chunked before synthesis to avoid rushed playback. A preliminary pilot with four individuals with mild-to-moderate AD/ADRD showed that users found the system trustworthy, competent, and likable, and were able to complete the evaluated coordination tasks through conversation. We describe the design goals, system architecture, safety controls, and findings from this formative evaluation.

Medium-horizon Alzheimer's disease progression prediction is difficult because future clinical scores can remain tied to baseline severity, while biomarker histories are irregular and incompletely observed. We develop an anchor-based analysis of 24-month Clinical Dementia Rating Sum of Boxes (CDR-SB) change using harmonized Alzheimer's Disease Neuroimaging Initiative (ADNI) tables. Each labeled sample is anchored at a mild cognitive impairment visit, uses only clinical and biomarker history observed at or before that anchor, and defines the response as CDR-SB at the future visit closest to 24 months within an 18--30 month window minus anchor CDR-SB. The analytic cohort contains 2,600 labeled anchors from 858 participants and 7,276 longitudinal rows. We propose a residual gap-aware transformer that combines a mixed-effects statistical reference with transformer-based residual learning from pre-anchor clinical and biomarker histories. The model uses participant-level random intercepts in the mixed-effects reference, observation-level triplet tokenization for irregular histories, and a learned nonnegative time-gap penalty inside self-attention. We compare the proposed model with a Bayesian-information-criterion-selected linear mixed-effects baseline, GRU-D, and STraTS under repeated participant-level train--test splits. Across five participant-level random seeds, the proposed model achieves the best mean test performance across all reported metrics, reducing MSE by 13.1% and increasing prediction--observation correlation by 26.4% relative to the mixed-effects baseline. It also improves over both GRU-D and STraTS in mean error and correlation. These results show that statistical anchoring and gap-aware residual learning provide a useful structure for medium-horizon Alzheimer's disease progression prediction.

Fast prototyping of new SE(3) estimation objectives remains awkward in practice. Modern Lie-group frameworks -- GTSAM, manif, Sophus, SymForce, Ceres -- target first-order workloads through different code-generation and automatic-differentiation strategies, each optimized for a particular seam between hand-derived geometry and generic differentiation. The remaining gap is a compact, AD-safe path from these first-order primitives to exact Hessians, observed-information matrices, and higher-order derivative tensors: the quantities needed for exact Newton steps, observed-information covariance estimates, and covariance correction. This paper presents a hybrid analytical/AD recipe for SE(3) negative log-likelihoods. The practitioner writes the NLL gradient once, generic over a scalar type, and places the analytical/AD seam at the point-action interface y = Tx. Closed-form Lie-group Jacobians are used up to this interface; AD is applied only beyond it. The same source is then instantiated with ordinary floating-point scalars for gradients, vector-seeded dual numbers for exact Hessians in a single forward-mode pass, and nested dual numbers for higher-order derivative tensors. On a representative 6-DoF, 5-landmark SE(3) NLL, the advocated seeded-Hessian path is approximately 5x faster than finite-differencing the AD gradient on this benchmark while matching a nested-AD oracle to machine precision. The implementation adds roughly 70 lines of analytical-Jacobian code over an AD-only baseline. We also identify and fix a removable singularity in the standard SO(3)/SE(3) scalar basis that would otherwise produce NaNs at the origin under seeded AD, and we audit which Lie-group derivative tensors require this stabilized basis. The result is a practical path from rapidly written SE(3) objectives to exact higher-order derivatives, with predictable runtime and no finite-difference tuning.

The systemic, metabolic, lifestyle factors have established associations with Alzheimer's Disease (AD) through epidemiologic and AD-specific biomarker studies. Whether colored fundus photography (CFP) contains retinal structural signatures corresponding to these AD-related risk domains remains unclear. To determine whether deep learning (DL) models can predict 12 AD-related risk factors from CFP and to characterize the retinal structures underlying these predictions, thereby assessing whether CFP reflects pathways to AD vulnerability. Using 62,876 CFPs from 44,501 unique participants from the UK Biobank, DL models were trained to predict 12 factors linked to AD incidence: 6 categorical (sex, smoking, sleeplessness, economic status, alcohol use, depression) and 6 continuous (age, age at completing education, BMI, systolic, diastolic blood pressure, HbA1c). Model performance, model saliency, and saliency-derived scores (CAM-Score) were evaluated and compared to retinal morphometry. The scores were also compared between incident-AD cases (average 8.55 years before onset) and matched controls. Performance of DL ranged from AUROC= 0.5654-0.9480 for categorical and R2=-0.0291-0.7620 for continuous factors, outperforming most of the morphometry-machine learning models. Saliency-based score consistently highlighted biologically meaningful regions, particularly the optic nerve head and retinal vasculature. It also aligned with present morphometric variations. Several saliency-based scores differed significantly between incident AD and matched controls, suggesting potential overlap between retinal correlates of risk factors and preclinical AD-associated changes. CFP encodes retinal signatures linked to AD risk factors. Although not diagnostic, DL-derived retinal representations may uncover biologically meaningful risk-related structural changes mirroring the potential AD vulnerability.

Individualized Alzheimer's disease (AD) progression prediction requires models that use irregular visits, account for censoring, avoid diagnostic leakage, and provide calibrated horizon risks. We propose PROgression-aware MultI-horizon Survival Estimation for Alzheimer's Disease (PROMISE-AD), a leakage-safe survival framework for predicting conversion from cognitively normal (CN) to mild cognitive impairment (MCI) and from MCI to AD dementia using ADNI/TADPOLE tabular histories. PROMISE-AD converts pre-index visits into tokens with standardized measurements, missingness masks, longitudinal changes, time-normalized slopes, visit timing, and non-diagnostic categorical attributes. A temporal Transformer fuses global, attention-pooled, and latest-visit representations to estimate a progression score and latent discrete-time mixture hazards. Training combines survival likelihood, horizon-specific focal risk loss, progression ranking, hazard smoothness, and mixture-balance regularization, followed by validation-set isotonic calibration for 1-, 2-, 3-, and 5-year risks. In held-out testing across three seeds, PROMISE-AD achieved an integrated Brier score (IBS) of 0.085 $\pm$ 0.012, C-index of 0.808 $\pm$ 0.015, and mean time-dependent AUC of 0.840 $\pm$ 0.081 for CN-to-MCI conversion, yielding the lowest IBS among compared methods. For MCI-to-AD conversion, PROMISE-AD achieved the highest C-index (0.894 $\pm$ 0.018) and near-ceiling 5-year discrimination (AUROC 0.997 $\pm$ 0.003; AUPRC 0.999 $\pm$ 0.001), although some baselines had lower IBS. Ablations and interpretability supported longitudinal change features, fused temporal representations, mixture hazards, cognitive and functional measures, APOE4 status, and recent conversion-proximal visits. These findings suggest that progression-aware survival modeling can provide interpretable multi-horizon AD conversion risk estimates.

Accurate prediction of conversion from Mild Cognitive Impairment (MCI) to Alzheimers Diseases (AD) is essential for early intervention, however, developing reliable conversion predictive models is difficult to develop due to limited longitudinal data availability We evaluate TabPFN (Tabular Pre-Trained Foundation Network) against traditional machine learning methods for predicting 3 year MCI to AD conversion using the TADPOLE dataset derived from ADNI. Using multimodal biomarker features extracted from demographics, APOE4, MRI volumes, CSF markers, and PET imaging, we conducted an experimental comparison across varying training set sizes (N=50 to 1000) and models including XGBoost, Random Forest, LightGBM, and Logistic Regression. TabPFN achieved one the highest performance (AUC=0.892), outperforming LightGBM (AUC=0.860) and demonstrating advantages in low data settings. At N=50 training samples, TabPFN maintained strong AUC while the traditional machine learning models struggles at small training samples. These findings demonstrate that foundation models are promising for disease prediction in data limited scenarios, such as Alzheimers diseases.

Alzheimer's disease is a neurodegenerative disorder marked by progressive declines in memory and language that reduce independence in daily life, motivating socially assistive robotic support. This paper presents MEMOR-E, a mobile quadruped robot with an interactive tablet interface that assists patients and caregivers through medication reminders, routine guidance, memory oriented interactions, and companionship. We evaluated the feasibility of fine tuning large language models (LLMs) to emulate stage consistent cognitive behavior and interpret responses across standard neuropsychological language tasks, using audio transcriptions from 235 Alzheimer's patients and synthetically generated healthy controls. We also report findings on using in context learning (ICL) in LLMs, where a second LLM produced domain and severity level cognitive error summaries. Our results show that MEMOR-E can generate stage aware, non diagnostic cognitive summaries that support personalized assistive interactions, while explainable AI mechanisms translate model outputs into transparent, human readable evidence to enable caregiver oversight and trustworthy human robot interaction.

Predicting individual cognitive decline in Alzheimer's disease (AD) is difficult due to the heterogeneity of disease progression. Reliable clinical tools require not only high accuracy but also fairness across demographics and robustness to missing data. We present CognitiveTwin, a digital twin framework that predicts patient-specific cognitive trajectories. The model integrates multi-modal longitudinal data (cognitive scores, magnetic resonance imaging, positron emission tomography, cerebrospinal fluid biomarkers, and genetics). We use a Transformer-based architecture to fuse these modalities and a Deep Markov Model to capture temporal dynamics. We trained and evaluated the framework using data from 1,666 patients in the TADPOLE (Alzheimer's Disease Neuroimaging Initiative) dataset. We assessed the model for prediction error, demographic fairness, and robustness to missing-not-at-random (MNAR) data patterns. ognitiveTwin provides accurate and personalized predictions of cognitive decline. Its demonstrated fairness across patient demographics and resilience to clinical dropout make it a reliable tool for clinical trial enrichment and personalized care planning.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder and a major cause of dementia. Structural MRI is widely used to analyze AD-related brain atrophy; however, most deep learning methods rely on computationally expensive 3D convolutional neural networks (CNNs), limiting deployment in resource-constrained settings. This work introduces two main contributions. First, we propose a pipeline that converts T1-weighted MRI into anatomically informed 2D point clouds using Anatomical Priority Sampling (APS), producing ADNI-2DPC, the first neuroanatomically labeled MRI-derived point cloud dataset. Second, we present NeuroAPS-Net, a lightweight geometric deep learning model that incorporates anatomical priors via region-aware feature encoding and ROI token aggregation. Experiments on ADNI-2DPC demonstrate that NeuroAPS-Net achieves competitive classification accuracy while significantly reducing inference latency and GPU memory compared to state-of-the-art point cloud methods. These results highlight the potential of anatomically guided point cloud learning as an efficient and interpretable alternative to voxel-based CNNs for AD classification.

The retina provides a unique, noninvasive window into Alzheimer's disease (AD) and dementia, capturing early structural changes through morphometric features, while systemic and lifestyle risk factors reflect well-established contributors to disease susceptibility long before clinical symptom onset. However, current retinal analysis frameworks typically model imaging and risk factors separately, limiting their ability to capture joint multimodal patterns critical for early risk prediction. Moreover, existing methods rarely incorporate mechanisms to organize or align patients with similar retinal and clinical characteristics, constraining the learning of coherent cross-modal associations. To address these limitations, we introduce REVEAL (REtinal-risk Vision-Language Early Alzheimer's Learning), a framework that aligns color fundus photographs with individualized disease-specific risk profiles for predicting incident AD and dementia, on average 8 years before diagnosis (range: 1-11 years). Because real-world risk factors are structured questionnaire data, we translate them into clinically interpretable narratives compatible with pretrained vision-language models (VLMs). We further propose a group-aware contrastive learning (GACL) strategy that clusters patients with similar retinal morphometry and risk factors as positive pairs, strengthening multimodal alignment. This unified representation learning framework substantially outperforms state-of-the-art retinal imaging models paired with clinical text encoders, as well as general-purpose VLMs, demonstrating the value of jointly modeling retinal biomarkers and clinical risk factors. By providing a generalizable and noninvasive approach for early AD and dementia risk stratification, REVEAL has the potential to enable earlier intervention and improve preventive care at the population level.

Alzheimer disease (AD) is a neurodegenerative disease that lacks specific treatment options. Natural drugs have displayed neuroprotective effects; however, their high-throughput discovery is challenging because of the expense of experimental testing.The study proposed a machine learning approach to identify the anti-dementia activity of natural compounds based on molecular descriptors obtained from cheminformatics. The study used a set of active and inactive compounds obtained from public databases like ChEMBL and PubChem. Various molecular descriptors, including molecular weight, lipophilicity (LogP), topological polar surface area (TPSA), and hydrogen bonding descriptors, were calculated with RDKit. Data preprocessing and feature selection were applied, followed by the development of several classification models (Random Forest, XGBoost, Support Vector Machines, Logistic Regression) and their evaluation based on accuracy, precision, recall, F1-score and ROC-AUC. The outcome suggests that ensemble techniques, such as Random Forest, delivered the best predictive accuracy and ROC-AUC values. This study also highlights that critical physicochemical descriptors in particular lipophilicity, molecular weight and polarity are important in driving neuroprotective activity as identified by feature importance analysis. The integrated machine learning approach shows the potential of combining natural product research and machine learning in early drug discovery for dementia. They provide a means of rapidly exploring large datasets and selecting candidates for experimental confirmation, thus minimising costs and time in the development of drugs for neurodegenerative diseases.

Alzheimer's disease (AD) confirmation often relies on positron emission tomography (PET) or cerebrospinal fluid (CSF) analysis, which are costly and invasive. Consequently, structural MRI biomarkers such as cortical thickness (CT) are widely used for non-invasive AD screening. Multiscale structural mapping (MSSM) was recently proposed to integrate gray-white matter contrasts (GWCs) with CT from a single T1-weighted MRI (T1w) scan. Building on this framework, we propose MSSM+, together with surface supervertex mapping (SSVM) and a Supervertex Vision Transformer (SV-ViT). 3D T1w images from individuals with AD and cognitively normal (CN) controls were analyzed. MSSM+ extends MSSM by incorporating sulcal depth and cortical curvature at the vertex level. SSVM partitions the cortical surface into supervertices (surface patches) that effectively represent inter- and intra-regional spatial relationships. SV-ViT is a Vision Transformer architecture operating on these supervertices, enabling anatomically informed learning from surface mesh representations. Compared with MSSM, MSSM+ identified more spatially extensive and statistically significant group differences between AD and CN. In AD vs. CN classification, MSSM+ achieved a 3%p higher area under the precision-recall curve than MSSM. Vendor-specific analyses further demonstrated reduced signal variability and consistently improved classification performance across MR manufacturers relative to CT, GWCs, and MSSM. These findings suggest that MSSM+ combined with SV-ViT is a promising MRI-based imaging marker for AD detection prior to CSF/PET confirmation.

Longitudinal neuroimaging is essential for modeling disease progression in Alzheimer's disease (AD), yet irregular sampling and missing visits pose substantial challenges for learning reliable temporal representations. To address this challenge, we propose SDE-HGNN, a stochastic differential equation (SDE)-driven spatio-temporal hypergraph neural network for irregular longitudinal fMRI connectome modeling. The framework first employs an SDE-based reconstruction module to recover continuous latent trajectories from irregular observations. Based on these reconstructed representations, dynamic hypergraphs are constructed to capture higher-order interactions among brain regions over time. To further model temporal evolution, hypergraph convolution parameters evolve through SDE-controlled recurrent dynamics conditioned on inter-visit intervals, enabling disease-stage-adaptive connectivity modeling. We also incorporate a sparsity-based importance learning mechanism to identify salient brain regions and discriminative connectivity patterns. Extensive experiments on the OASIS-3 and ADNI cohorts demonstrate consistent improvements over state-of-the-art graph and hypergraph baselines in AD progression prediction. The source code is available at https://anonymous.4open.science/r/SDE-HGNN-017F.

Accurate extraction of Alzheimer's Disease and Related Dementias (ADRD) phenotypes from electronic health records (EHR) is critical for early-stage detection and disease staging. However, this information is usually embedded in unstructured textual data rather than tabular data, making it difficult to be extracted accurately. We therefore propose LLM-MINE, a Large Language Model-based phenotype mining framework for automatic extraction of ADRD phenotypes from clinical notes. Using two expert-defined phenotype lists, we evaluate the extracted phenotypes by examining their statistical significance across cohorts and their utility for unsupervised disease staging. Chi-square analyses confirm statistically significant phenotype differences across cohorts, with memory impairment being the strongest discriminator. Few-shot prompting with the combined phenotype lists achieves the best clustering performance (ARI=0.290, NMI=0.232), substantially outperforming biomedical NER and dictionary-based baselines. Our results demonstrate that LLM-based phenotype extraction is a promising tool for discovering clinically meaningful ADRD signals from unstructured notes.

Alzheimer's disease is a progressive neurodegenerative disorder in which mild cognitive impairment (MCI) precedes dementia. Structural MRI provides biomarkers but requires costly infrastructure, limiting population-scale deployment. Speech offers a non-invasive alternative, yet speech-only classifiers are developed independently of neuroimaging and lack biological grounding for CN-versus-MCI classification. We propose MINT (Multimodal Imaging-to-Speech Knowledge Transfer), a three-stage framework that transfers MRI-derived biomarker structure to speech during training. An MRI teacher defines a compact embedding space for CN-versus-MCI classification, while a residual projection head aligns speech representations to this space using a combined geometric loss. The frozen MRI classifier enables imaging-free inference. On ADNI-4, aligned speech achieves performance comparable to speech baselines, while multimodal fusion improves over MRI alone. Ablations identify dropout regularization and self-supervised pretraining as important design choices. To our knowledge, MINT is the first demonstration of MRI-to-speech knowledge transfer for early Alzheimer's screening without imaging at inference.

Tau positron emission tomography supports Alzheimer's disease staging but is difficult to scale because of tracer, scanner, and radiation constraints. Synthesis from structural MRI is therefore attractive, but it is a particularly difficult setting. T1-weighted and FLAIR MRI provide anatomy and disease correlated morphology, but they do not directly measure Tau-PET relevant signal. We introduce SFL-Net, a multi-input synthesis framework that predicts Tau-PET from T1-weighted and FLAIR MRI. SFL-Net factorizes the latent representation into shared, T1-specific, FLAIR-specific, and complementary pathways and preserves anatomical detail through latent structural conditioning rather than direct encoder-decoder connections. We evaluated SFL-Net and baseline models using 605 training and 83 validation subjects from ADNI-3 and OASIS-3 datasets. Evaluation included raw image fidelity, standardized uptake value ratio agreement, high uptake overlap, regional Bland-Altman bias, braak derived stage agreement, non-inferiority sensitivity analysis, and latent component Shapley attribution. SFL-Net performed competitively on both clinically relevant and reconstruction metrics, while also delivering explicit source level auditability that conventional UNet derived models lack.

Generative modeling frameworks have emerged as an effective approach to capture high-dimensional image distributions from large datasets without requiring domain-specific knowledge, a capability essential for disease progression modeling. Recent generative approaches have attempted to capture progression by mapping images to a latent space and guiding representations to generate follow-up images from previous time points. However, these methods impose constraints on distribution learning, resulting in latent spaces with limited controllability for generating follow-up images without paired subject-specific longitudinal guidance. In order to enable controlled movements in the latent representational space and generate progression images from a previous time-point image without subject-specific guidance, we introduce a conditionable Diffusion Auto-encoder framework that forms a compact latent space capturing high-level semantics and providing means to control generation. Our approach leverages this latent space to condition and apply controlled shifts to the representations of previous time-point images by isolating progression and subject identity information for generating follow-up images. The shifts are implicitly guided by correlating with progression attributes and constraining to Alzheimer's disease specific regions, without paired longitudinal guidance. We validate the generations through image quality metrics, volumetric progression analysis, and downstream tasks in Alzheimer's disease datasets from different sources. This demonstrates the effectiveness of our approach for Alzheimer's progression modeling and longitudinal image generation.

Dementia disorders such as Alzheimer's disease (AD) and frontotemporal dementia (FTD) exhibit overlapping electrophysiological signatures in EEG that challenge accurate diagnosis. Existing EEG-based methods are limited by full-band frequency analysis, which hinders the precise differentiation of dementia subtypes and severity stages. To address this limitation, we propose a Variational Mixture of Graph Neural Experts (VMoGE) framework that integrates multi-band EEG analysis with variational graph neural networks and a mixture-of-experts architecture. Each expert specializes in a specific EEG frequency band and models brain connectivity using a Gaussian Markov random field prior, while a variational gating mechanism adaptively integrates the expert outputs. This design enables the model to learn frequency-specific brain network representations while modeling latent uncertainty through variational inference. Experimental results on two EEG dementia datasets show that VMoGE achieves strong performance, with an AUC of 0.89 for HC vs. AD classification in the main comparison and competitive results across dementia subtyping and CDR staging tasks. Clinically, VMoGE offers three key translational values: the expert gating weights correlate with MMSE scores and CDR severity; slow-wave $δ$- and $θ$-band contributions are associated with AD-related EEG slowing and disease progression; and spatially localized activation maps reveal posterior $θ$- and $α$-band alterations and region-specific $β$-band changes, providing neurophysiologically interpretable markers aligned with known AD neuropathology.

Dementia affects over 55 million people worldwide, projected to reach 139 million by 2050, with Alzheimer's disease (AD) accounting for 60-70% of cases. AD is associated with disruptions in metabolic brain connectivity. Detecting these disruptions early is crucial for AD management. FDG-PET is a useful tool for identifying such impairments. However, most studies rely on group-level analyses or thresholding, potentially masking individual differences and overlooking weaker yet biologically critical brain connections. Moreover, AD prediction largely focuses on univariate rather than multivariate outcomes. To address this, we introduce explainable graph-theoretical machine learning (XGML), a framework for constructing individual metabolic brain graphs and identifying subgraphs most predictive of multivariate disease-related outcomes. Using Alzheimer's Disease Neuroimaging Initiative (ADNI) FDG-PET data, we compared six graph representations against three non-graph baselines, each with six machine learning models using repeated stratified 3-fold cross-validation (10 repeats). The best configuration combined kernel density estimation with Hellinger distance and random forest. Across eight cognitive scores, it reached an overall Fisher-z-averaged Pearson correlation of r=0.595, with strongest performance for ADAS13 (r=0.67), ADAS11 (r=0.65), and ADASQ4 (r=0.62). We identified key edges that were jointly but differentially predictive across outcomes, suggesting their potential as network biomarkers of cognitive decline. Preliminary external feasibility validation on an OASIS3 cohort yielded weak predictive performance for CDRSB (r=0.26) and MMSE (r=0.18), likely reflecting cohort, protocol, and diagnostic differences. Overall, our results suggest the promise of graph-theoretical machine learning for biomarker discovery, disease prediction, and understanding the neural mechanisms underlying AD.

Conversational speech reveals early signs of cognitive decline, including dementia and mild cognitive impairment (MCI). AI models show promise for speech-based screening, yet most research focuses on monolingual groups. In the UK, dementia is projected to rise fastest among Black and Asian communities, where multilingualism is common, making equity assessment critical. We recruited 1,395 participants (monolingual English speakers and multilingual speakers from Sheffield/Bradford) and collected over 263 hours of speech via the CognoMemory agent. Multilingual participants spoke English alongside Somali, Chinese, or South Asian languages (Hindi, Urdu, Punjabi, Mirpuri, Arabic). We evaluated ASR (Whisper, Wav2Vec 2.0, NeMo) and downstream AI models for cognitive classification and MMSE regression. ASR accuracy showed no significant differences across groups. However, downstream models exhibited systematic disparities: multilingual speakers were more often misclassified as impaired, especially in memory, fluency, and reading tasks. False-positive rates were substantially higher for multilingual (28 to 37%) than monolingual (12 to 16%) speakers, meaning multilingual individuals were approximately 2.5 times more likely to receive incorrect impairment labels. These biases worsened when models were trained on DementiaBank. This is the first large-scale analysis of false-positive bias in speech-based AI cognitive screening for UK multilingual ethnic minorities. Despite strong overall performance, current models show measurable disparities affecting multilingual speakers. Addressing these biases is essential for safe, equitable deployment in diverse healthcare settings.