Alzheimer's Disease
Momentum
3 papers in the last four weeks, with none the four weeks before. 0.0% of all new papers.
Latest papers 45
Cognitive decline is highly heterogeneous across individuals, which complicates prognosis, trial design, and treatment planning. We present the Personalized Cognitive Decline Assessment Digital Twin (PCD-DT), a multimodal and uncertainty-aware framework for modeling patient-specific disease trajectories from sparse, noisy, and irregular longitudinal data. The framework combines three methodological components: (1) latent state-space models for individualized temporal dynamics, (2) multimodal fusion for clinical, biomarker, and imaging features, and (3) uncertainty-aware validation and adaptive updating for robust digital twin operation. We also outline how conditional generative models can support data augmentation and stress testing for underrepresented progression patterns. As a preliminary feasibility study, we analyze longitudinal TADPOLE trajectories and show clear separation between cognitively normal and Alzheimer's disease cohorts in ADAS13, ventricle volume, and hippocampal volume over five years. We further conduct a multimodal next-visit prediction ablation using an LSTM sequence model on 3{,}003 visit-pair sequences derived from TADPOLE, where the combined cognitive plus MRI configuration achieves the lowest standardized RMSE for both ADAS13 (0.4419) and ventricle volume (0.5842), outperforming a Last Observation Carried Forward baseline. A Bayesian tensor modeling component for high-dimensional imaging fusion is also discussed. These results support the feasibility of the proposed architecture while also highlighting the need for stronger uncertainty calibration and longer-horizon predictive evaluation. The PCD-DT framework provides a principled starting point for personalized in silico modeling in neurodegenerative disease. This work positions PCD-DT as a foundational step toward clinically deployable, uncertainty-aware digital twin systems.
Evaluating TabPFN for Mild Cognitive Impairment to Alzheimer's Disease Conversion in Data Limited Settings
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.
MEMOR-E: In-Context and Fine-Tuned LLM Personalization for Alzheimer's Assistive Robotics
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.
Task-guided Spatiotemporal Network with Diffusion Augmentation for EEG-based Dementia Diagnosis and MMSE Prediction
Patients with dementia typically exhibit cognitive impairment, which is routinely assessed using the Mini-Mental State Examination (MMSE). Concurrently, their underlying neurophysiological abnormalities are reflected in Electroencephalography (EEG), providing a basis for joint modeling. However, traditional multi-task approaches suffer from feature entanglement, which leads to inter-task interference when handling heterogeneous objectives.To address this challenge, we propose a task-guided spatiotemporal network (TGSN) with diffusion augmentation for EEG-based dementia diagnosis and MMSE prediction. Specifically, TGSN integrates a multi-band feature fusion module to capture complementary spectral information from EEG. Meanwhile, a pre-trained data augmentation module utilizing a diffusion process is introduced toincrease sample diversity. To model the complex spatiotemporal patterns of EEG, we propose a gated spatiotemporal attention module that captures long-range spatial dependencies and temporal dynamics. Moreover, we design a task-guided query module to achieve task-specific feature extraction, thereby mitigating task interference. The effectiveness of TGSN is evaluated on the XY02 dataset. Experimental results demonstrate that the proposed network outperforms several state-of-the-art methods, achieving classification accuracies of 97.78% for Alzheimer's Disease (AD)/Frontotemporal Dementia (FTD) and 83.93% for AD/FTD/Vascular Cognitive Impairment (VCI), which exceed the best baselines by 16.39% and 8.28%, respectively. In parallel, it reduces the RMSE for MMSE prediction to 1.93 and 2.38, achieving significant error reductions of 1.44 and 1.43 compared to the best baselines. Additionally, validation on the DS004504 dataset demonstrates strong cross-dataset generalization...
TEMPO: Transformers for Temporal Disease Progression from Cross-Sectional Data
Event-Based Models (EBMs) infer biomarker progression from cross-sectional data but typically only as ordinal sequences and rely on rigid model assumptions. We propose \textsc{Tempo}, a Transformer architecture that learns both ordinal and continuous event sequences through simulation-based supervised learning. \textsc{Tempo} uses two Transformer modules: one treats biomarkers as tokens to infer event sequencing; the other treats patients as tokens, representing each by their per-biomarker abnormality profile, to infer patients' disease stages. On synthetic benchmarks, \textsc{Tempo} reduces normalized Kendall's Tau distance by 52.89% and staging MAE by 25.33% compared to state-of-the-art SA-EBM, with larger reductions in high-dimensional settings (58.88% and 61.10%). Applied to ADNI, \textsc{Tempo} recovers a biologically plausible Alzheimer's progression: early medial temporal atrophy, followed by amyloid accumulation and cognitive decline, and late-stage tau pathology with terminal acceleration of global neurodegeneration -- broadly consistent with established disease models. \textsc{Tempo} also eliminates the need to derive custom inference algorithms and enables rapid empirical comparison of generative hypotheses.
CognitiveTwin: Robust Multi-Modal Digital Twins for Predicting Cognitive Decline in Alzheimer's Disease
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.
REVEAL: Multimodal Vision-Language Alignment of Retinal Morphometry and Clinical Risks for Incident AD and Dementia Prediction
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.
Improved Multiscale Structural Mapping with Supervertex Vision Transformer for the Detection of Alzheimer's Disease Neurodegeneration
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.
SDE-Driven Spatio-Temporal Hypergraph Neural Networks for Irregular Longitudinal fMRI Connectome Modeling in Alzheimer's Disease
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.
LLM-MINE: Large Language Model based Alzheimer's Disease and Related Dementias Phenotypes Mining from Clinical Notes
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.
MINT: Multimodal Imaging-to-Speech Knowledge Transfer for Early Alzheimer's Screening
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.
Cross-Task Generalization in Handwriting-Based Alzheimer's Screening via Vision Language Adaptation
Alzheimer's disease (AD) is a prevalent neurodegenerative disorder for which early detection is critical. Handwriting, which can be disrupted by subtle motor and cognitive decline, provides a non-invasive and cost-effective window for AD screening. Existing handwriting-based AD studies mostly rely on online trajectories and hand-crafted features, while the influence of handwriting task type on diagnostic performance and cross-task generalization remains underexplored. Meanwhile, large-scale vision--language models have demonstrated strong transfer and adaptation ability in natural-image anomaly detection and several medical modalities, such as chest X-ray and brain MRI. However, handwriting-based disease detection remains unexplored within this paradigm. To address this gap, we introduce a lightweight Cross-Layer Fusion Adapter (CLFA) framework that repurposes Contrastive Language--Image Pre-training (CLIP) for handwriting-based AD screening. CLFA inserts multi-level adapters into a frozen visual encoder, combining cross-layer feature fusion with depthwise 2D convolution on patch grids to capture both local stroke irregularities and higher-level handwriting structure. This design progressively aligns pretrained vision--language representations with AD-related handwriting cues and supports transfer from supervised source tasks to task-disjoint unseen target tasks. On the Darwin dataset, under the subject-disjoint cross-task protocol, averaged over all 600 task-disjoint source-target pairs, CLFA achieves 74.63% AUC, 74.85% accuracy, and 73.72% F1 score, outperforming the best competing model by 2.15, 1.79, and 1.87 percentage points, respectively.
Variational Mixture of Graph Neural Experts for Alzheimer's Disease Recognition across Frequency Bands in EEG Brain Networks
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 - and -band contributions are associated with AD-related EEG slowing and disease progression; and spatially localized activation maps reveal posterior - and -band alterations and region-specific -band changes, providing neurophysiologically interpretable markers aligned with known AD neuropathology.
Achieving detailed medial temporal lobe segmentation with upsampled isotropic training from implicit neural representation
Imaging biomarkers in magnetic resonance imaging (MRI) are important tools for diagnosing, tracking and treating Alzheimer's disease (AD). Neurofibrillary tau pathology in AD is closely linked to neurodegeneration and generally follows a pattern of spread in the brain, with early stages involving subregions of the medial temporal lobe (MTL). Accurate segmentation of MTL subregions is needed to extract granular biomarkers of AD progression. MTL subregions are often imaged using T2-weighted (T2w) MRI scans that are highly anisotropic due to constraints of MRI physics and image acquisition, making it difficult to reliably model MTL subregions geometrically and extract morphological measures, such as thickness. In this study, we propose a segmentation framework for MTL subregions in isotropic space, in which an implicit neural representation is used to construct the isotropic training atlas from the anisotropic low-resolution T2w data, with T1w MRI as an auxiliary modality to support the INR and segmentation. In an independent test set, the morphological measures extracted using this isotropic model showed stronger effect sizes than those from models trained on anisotropic data in distinguishing participants with mild cognitive impairment (MCI) from cognitively unimpaired individuals. In the test-retest analysis, the morphological measures extracted using the isotropic model showed greater stability than those from the anisotropic segmentation. This study demonstrates improved reliability of MRI-derived MTL subregion biomarkers without additional atlas annotation effort, which may more accurately quantify and track the relationship between AD pathology and brain atrophy for monitoring disease progression.
Enhancing brain age estimation with structural MRI and synthesized cerebral blood volume maps
BrainAGE is a promising imaging-derived biomarker of neurobiological ageing and disease risk, yet current approaches rely predominantly on T1-weighted structural MRI, overlooking functional vascular changes that may precede tissue damage and cognitive decline. DeepCBV maps, synthesized from non-contrast MRI, offer a scalable alternative to contrast-enhanced perfusion imaging by capturing vascular information relevant to early neurodegeneration. We developed a multimodal BrainAGE framework that combines predictions from two separate three-dimensional convolutional neural networks: one trained only on structural MRI scans and another trained only on DeepCBV maps. Each model was trained and validated on 2851 scans from 13 open-source datasets and was evaluated for concordance with MCI and AD. The combined model achieved the most accurate brain age gap for CN controls, with a mean absolute error of 3.95 years, outperforming models trained on MRI or DeepCBV alone. Saliency maps revealed complementary modality contributions: MRI emphasized white matter and cortical atrophy, while DeepCBV highlighted vascular-rich and periventricular regions implicated in hypoperfusion and early cerebrovascular dysfunction, consistent with known patterns of normal ageing. Next, we observed that BrainAGE increased stepwise across diagnostic strata (CN < MCI < AD) and correlated with cognitive impairment. DeepCBV-based BrainAGE showed a particularly strong separation between stable versus progressive MCI, suggesting sensitivity to prodromal vascular changes that precede overt atrophy. Integrating structural MRI with deep learning-derived vascular measures substantially enhances BrainAGE estimation and improves sensitivity to MCI and AD progression, supporting its potential role in risk stratification, early detection and monitoring of therapeutic response.