White matter hyperintensities (WMH) are key imaging markers in cognitive aging, Alzheimer's disease (AD), and related dementias. Although automated methods for WMH segmentation have advanced, most provide only global lesion load and overlook their spatial distribution across distinct white matter regions. We propose a deep learning framework for robust WMH segmentation and localization, evaluated across public datasets and an independent Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. Our results show that the predicted lesion loads are in line with the reference WMH estimates, confirming the robustness to variations in lesion load, acquisition, and demographics. Beyond accurate segmentation, we quantify WMH load within anatomically defined regions and combine these measures with brain structure volumes to assess diagnostic value. Regional WMH volumes consistently outperform global lesion burden for disease classification, and integration with brain atrophy metrics further improves performance, reaching area under the curve (AUC) values up to 0.97. Several spatially distinct regions, particularly within anterior white matter tracts, are reproducibly associated with diagnostic status, indicating localized vulnerability in AD. These results highlight the added value of regional WMH quantification. Incorporating localized lesion metrics alongside atrophy markers may enhance early diagnosis and stratification in neurodegenerative disorders.

Alzheimer's disease and related dementias (ADRD) affect one in five adults over 60, yet more than half of individuals with cognitive decline remain undiagnosed. Speech-based assessments show promise for early detection, as phonetic motor planning deficits alter acoustic features (e.g., pitch, tone), while memory and language impairments lead to syntactic and semantic errors. However, conventional speech-processing pipelines with hand-crafted features or general-purpose audio classifiers often exhibit limited performance and generalizability. To address these limitations, we introduce SpeechCARE, a multimodal speech processing pipeline that leverages pretrained, multilingual acoustic and linguistic transformer models to capture subtle speech-related cues associated with cognitive impairment. Inspired by the Mixture of Experts (MoE) paradigm, SpeechCARE employs a dynamic fusion architecture that weights transformer-based acoustic, linguistic, and demographic inputs, allowing integration of additional modalities (e.g., social factors, imaging) and enhancing robustness across diverse tasks. Its robust preprocessing includes automatic transcription, large language model (LLM)-based anomaly detection, and task identification. A SHAP-based explainability module and LLM reasoning highlight each modality's contribution to decision-making. SpeechCARE achieved AUC = 0.88 and F1 = 0.72 for classifying cognitively healthy, MCI, and AD individuals, with AUC = 0.90 and F1 = 0.62 for MCI detection. Bias analysis showed minimal disparities, except for adults over 80. Mitigation techniques included oversampling and weighted loss. Future work includes deployment in real-world care settings (e.g., VNS Health, Columbia ADRC) and EHR-integrated explainability for underrepresented populations in New York City.

Alzheimer's disease is a prevalent neurodegenerative disorder for which early detection is critical. Handwriting-often disrupted in prodromal AD-provides a non-invasive and cost-effective window into subtle motor and cognitive decline. Existing handwriting-based AD studies, mostly relying on online trajectories and hand-crafted features, have not systematically examined how task type influences diagnostic performance and cross-task generalization. Meanwhile, large-scale vision language models have demonstrated remarkable zero or few-shot anomaly detection in natural images and strong adaptability across medical modalities such as chest X-ray and brain MRI. However, handwriting-based disease detection remains largely unexplored within this paradigm. To close this gap, we introduce a lightweight Cross-Layer Fusion Adapter framework that repurposes CLIP for handwriting-based AD screening. CLFA implants multi-level fusion adapters within the visual encoder to progressively align representations toward handwriting-specific medical cues, enabling prompt-free and efficient zero-shot inference. Using this framework, we systematically investigate cross-task generalization-training on a specific handwriting task and evaluating on unseen ones-to reveal which task types and writing patterns most effectively discriminate AD. Extensive analyses further highlight characteristic stroke patterns and task-level factors that contribute to early AD identification, offering both diagnostic insights and a benchmark for handwriting-based cognitive assessment.

Accurate predictions of conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD) can enable effective personalized therapy. While cognitive tests and clinical data are routinely collected, they lack the predictive power of PET scans and CSF biomarker analysis, which are prohibitively expensive to obtain for every patient. To address this cost-accuracy dilemma, we design a two-stage machine learning framework that selectively obtains advanced, costly features based on their predicted "value of information". We apply our framework to predict AD progression for MCI patients using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Our framework reduces the need for advanced testing by 20% while achieving a test AUROC of 0.929, comparable to the model that uses both basic and advanced features (AUROC=0.915, p=0.1010). We also provide an example interpretability analysis showing how one may explain the triage decision. Our work presents an interpretable, data-driven framework that optimizes AD diagnostic pathways and balances accuracy with cost, representing a step towards making early, reliable AD prediction more accessible in real-world practice. Future work should consider multiple categories of advanced features and larger-scale validation.

Accurate diagnosis of Alzheimer's disease (AD) is essential for enabling timely intervention and slowing disease progression. Multimodal diagnostic approaches offer considerable promise by integrating complementary information across behavioral and perceptual domains. Eye-tracking and facial features, in particular, are important indicators of cognitive function, reflecting attentional distribution and neurocognitive state. However, few studies have explored their joint integration for auxiliary AD diagnosis. In this study, we propose a multimodal cross-enhanced fusion framework that synergistically leverages eye-tracking and facial features for AD detection. The framework incorporates two key modules: (a) a Cross-Enhanced Fusion Attention Module (CEF AM), which models inter-modal interactions through cross-attention and global enhancement, and (b) a Direction-Aware Convolution Module (DACM), which captures fine-grained directional facial features via horizontal-vertical receptive fields. To support this work, we constructed a synchronized multimodal dataset, including 25 patients with AD and 25 healthy controls (HC), by recording aligned facial video and eye-tracking sequences during a visual memory-search paradigm, providing an ecologically valid resource for evaluating integration strategies. Extensive experiments on this dataset demonstrate that our framework outperforms traditional late fusion and feature concatenation methods, achieving a classification accuracy of 95.11% in distinguishing AD from HC, highlighting superior robustness and diagnostic performance by explicitly modeling inter-modal dependencies and modality-specific contributions. Introduction Alzheimer's disease (AD), a progressive and irreversible neurodegenera-tive disorder, represents the primary cause of dementia in older adults [1]. It typically begins with mild memory loss and gradually progresses to severe impairments in executive and cognitive functions [2]. Within the global aging population, more than 150 million people worldwide will be affected by AD or other forms of dementia [3], imposing a substantial burden on both families and healthcare systems. Early and accurate identification of Alzheimer's disease is vital to initiate interventions that may slow progression and improve quality of life. Clinically, the diagnosis of AD primarily relies on biomarker analysis, neu-roimaging techniques, and neuropsychological assessments.

Early detection of Alzheimer's disease (AD) is crucial because its neurodegenerative effects are irreversible, and neuropathologic and social-behavioral risk factors accumulate years before diagnosis. Identifying higher-risk individuals earlier enables prevention, timely care, and equitable resource allocation. We predict cognitive performance from social determinants of health (SDOH) using the NIH NIA-supported PREPARE Challenge Phase 2 dataset derived from the nationally representative Mex-Cog cohort of the 2003 and 2012 Mexican Health and Aging Study (MHAS). Data: The target is a validated composite cognitive score across seven domains-orientation, memory, attention, language, constructional praxis, and executive function-derived from the 2016 and 2021 MHAS waves. Predictors span demographic, socioeconomic, health, lifestyle, psychosocial, and healthcare access factors. Methodology: Missingness was addressed with a singular value decomposition (SVD)-based imputation pipeline treating continuous and categorical variables separately. This approach leverages latent feature correlations to recover missing values while balancing reliability and scalability. After evaluating multiple methods, XGBoost was chosen for its superior predictive performance. Results and Discussion: The framework outperformed existing methods and the data challenge leaderboard, demonstrating high accuracy, robustness, and interpretability. SHAP-based post hoc analysis identified top contributing SDOH factors and age-specific feature patterns. Notably, flooring material emerged as a strong predictor, reflecting socioeconomic and environmental disparities. Other influential factors, age, SES, lifestyle, social interaction, sleep, stress, and BMI, underscore the multifactorial nature of cognitive aging and the value of interpretable, data-driven SDOH modeling.

We introduce scenario-based cognitive status identification in older drivers from naturalistic driving videos, leveraging large vision models. In recent times, cognitive decline including Dementia and Mild Cognitive Impairment (MCI), is often underdiagnosed due to the time-consuming and costly nature of current diagnostic methods. By analyzing real-world driving behavior captured through in-vehicle sensors, this study aims to extract "digital fingerprints" that correlate with functional decline and clinical features of dementia. Moreover, modern large vision models can draw meaningful insights from everyday driving patterns across different roadway scenarios to early detect cognitive decline. We propose a framework that uses large vision models and naturalistic driving videos to analyze driver behavior, identify cognitive status and predict disease progression. We leverage the strong relationship between real-world driving behavior as an observation of the current cognitive status of the drivers where the vehicle can be utilized as a "diagnostic tool". Our method identifies early warning signs of functional impairment, contributing to proactive intervention strategies. This work enhances early detection and supports the development of scalable, non-invasive monitoring systems to mitigate the growing societal and economic burden of cognitive decline in the aging population.

Understanding the relationship between mild cognitive impairment (MCI) and driving behavior is essential for enhancing road safety, particularly among older adults. This study introduces a novel approach by incorporating specific trip destinations-such as home, work, medical appointments, social activities, and errands-using geohashing to analyze the driving habits of older drivers in Nebraska. We employed a two-fold methodology that combines data visualization with advanced machine learning models, including C5.0, Random Forest, and Support Vector Machines, to assess the effectiveness of these location-based variables in predicting cognitive impairment. Notably, the C5.0 model showed a robust and stable performance, achieving a median recall of 0.68, which indicates that our methodology accurately identifies cognitive impairment in drivers 68\% of the time. This emphasizes our model's capacity to reduce false negatives, a crucial factor given the profound implications of failing to identify impaired drivers. Our findings underscore the innovative use of life-space variables in understanding and predicting cognitive decline, offering avenues for early intervention and tailored support for affected individuals.

Background: Alzheimer's disease and related dementias (ADRD) are progressive neurodegenerative conditions where early detection is vital for timely intervention and care. Spontaneous speech contains rich acoustic and linguistic markers that may serve as non-invasive biomarkers for cognitive decline. Foundation models, pre-trained on large-scale audio or text data, produce high-dimensional embeddings encoding contextual and acoustic features. Methods: We used the PREPARE Challenge dataset, which includes audio recordings from over 1,600 participants with three cognitive statuses: healthy control (HC), mild cognitive impairment (MCI), and Alzheimer's Disease (AD). We excluded non-English, non-spontaneous, or poor-quality recordings. The final dataset included 703 (59.13%) HC, 81 (6.81%) MCI, and 405 (34.06%) AD cases. We benchmarked a range of open-source foundation speech and language models to classify cognitive status into the three categories. Results: The Whisper-medium model achieved the highest performance among speech models (accuracy = 0.731, AUC = 0.802). Among language models, BERT with pause annotation performed best (accuracy = 0.662, AUC = 0.744). ADRD detection using state-of-the-art automatic speech recognition (ASR) model-generated audio embeddings outperformed others. Including non-semantic features like pause patterns consistently improved text-based classification. Conclusion: This study introduces a benchmarking framework using foundation models and a clinically relevant dataset. Acoustic-based approaches -- particularly ASR-derived embeddings -- demonstrate strong potential for scalable, non-invasive, and cost-effective early detection of ADRD.

Delirium represents a significant clinical concern characterized by high morbidity and mortality rates, particularly in patients with mild cognitive impairment (MCI). This study investigates the associated risk factors for delirium by analyzing the comorbidity patterns relevant to MCI and developing a longitudinal predictive model leveraging machine learning methodologies. A retrospective analysis utilizing the MIMIC-IV v2.2 database was performed to evaluate comorbid conditions, survival probabilities, and predictive modeling outcomes. The examination of comorbidity patterns identified distinct risk profiles for the MCI population. Kaplan-Meier survival analysis demonstrated that individuals with MCI exhibit markedly reduced survival probabilities when developing delirium compared to their non-MCI counterparts, underscoring the heightened vulnerability within this cohort. For predictive modeling, a Long Short-Term Memory (LSTM) ML network was implemented utilizing time-series data, demographic variables, Charlson Comorbidity Index (CCI) scores, and an array of comorbid conditions. The model demonstrated robust predictive capabilities with an AUROC of 0.93 and an AUPRC of 0.92. This study underscores the critical role of comorbidities in evaluating delirium risk and highlights the efficacy of time-series predictive modeling in pinpointing patients at elevated risk for delirium development.