Language-Based Digital Twins for Elderly Cognitive Assistance

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.

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.

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.