Prediction of Alzheimer's disease progression within 6 years using speech: A novel approach leveraging language models.

INTRODUCTION: Identification of individuals with mild cognitive impairment (MCI) who are at risk of developing Alzheimer's disease (AD) is crucial for early intervention and selection of clinical trials. METHODS: We applied natural language processing techniques along with machine learning methods to develop a method for automated prediction of progression to AD within 6 years using speech. The study design was evaluated on the neuropsychological test interviews of n = 166 participants from the Framingham Heart Study, comprising 90 progressive MCI and 76 stable MCI cases. RESULTS: Our best models, which used features generated from speech data, as well as age, sex, and education level, achieved an accuracy of 78.5% and a sensitivity of 81.1% to predict MCI-to-AD progression within 6 years. DISCUSSION: The proposed method offers a fully automated procedure, providing an opportunity to develop an inexpensive, broadly accessible, and easy-to-administer screening tool for MCI-to-AD progression prediction, facilitating development of remote assessment. HIGHLIGHTS: Voice recordings from neuropsychological exams coupled with basic demographics can lead to strong predictive models of progression to dementia from mild cognitive impairment. The study leveraged AI methods for speech recognition and processed the resulting text using language models. The developed AI-powered pipeline can lead to fully automated assessment that could enable remote and cost-effective screening and prognosis for Alzehimer's disease.

Large Language Models in Neurology Research and Future Practice.

Recent advancements in generative artificial intelligence, particularly using large language models (LLMs), are gaining increased public attention. We provide a perspective on the potential of LLMs to analyze enormous amounts of data from medical records and gain insights on specific topics in neurology. In addition, we explore use cases for LLMs, such as early diagnosis, supporting patient and caregivers, and acting as an assistant for clinicians. We point to the potential ethical and technical challenges raised by LLMs, such as concerns about privacy and data security, potential biases in the data for model training, and the need for careful validation of results. Researchers must consider these challenges and take steps to address them to ensure that their work is conducted in a safe and responsible manner. Despite these challenges, LLMs offer promising opportunities for improving care and treatment of various neurologic disorders.

Development and validation of predictive models for COVID-19 outcomes in a safety-net hospital population.

OBJECTIVE: To develop predictive models of coronavirus disease 2019 (COVID-19) outcomes, elucidate the influence of socioeconomic factors, and assess algorithmic racial fairness using a racially diverse patient population with high social needs. MATERIALS AND METHODS: Data included 7,102 patients with positive (RT-PCR) severe acute respiratory syndrome coronavirus 2 test at a safety-net system in Massachusetts. Linear and nonlinear classification methods were applied. A score based on a recurrent neural network and a transformer architecture was developed to capture the dynamic evolution of vital signs. Combined with patient characteristics, clinical variables, and hospital occupancy measures, this dynamic vital score was used to train predictive models. RESULTS: Hospitalizations can be predicted with an area under the receiver-operating characteristic curve (AUC) of 92% using symptoms, hospital occupancy, and patient characteristics, including social determinants of health. Parsimonious models to predict intensive care, mechanical ventilation, and mortality that used the most recent labs and vitals exhibited AUCs of 92.7%, 91.2%, and 94%, respectively. Early predictive models, using labs and vital signs closer to admission had AUCs of 81.1%, 84.9%, and 92%, respectively. DISCUSSION: The most accurate models exhibit racial bias, being more likely to falsely predict that Black patients will be hospitalized. Models that are only based on the dynamic vital score exhibited accuracies close to the best parsimonious models, although the latter also used laboratories. CONCLUSIONS: This large study demonstrates that COVID-19 severity may accurately be predicted using a score that accounts for the dynamic evolution of vital signs. Further, race, social determinants of health, and hospital occupancy play an important role.

Redefining and Validating Digital Biomarkers as Fluid, Dynamic Multi-Dimensional Digital Signal Patterns.

"Digital biomarker" is a term broadly and indiscriminately applied and often limited in its conceptualization to mimic well-established biomarkers as defined and approved by regulatory agencies such as the United States Food and Drug Administration (FDA). There is a practical urgency to revisit the definition of a digital biomarker and expand it beyond current methods of identification and validation. Restricting the promise of digital technologies within the realm of currently defined biomarkers creates a missed opportunity. A whole new field of prognostic and early diagnostic digital biomarkers driven by data science and artificial intelligence can break the current cycle of high healthcare costs and low health quality that is being driven by today's chronic disease detection and treatment approaches. This new class of digital biomarkers will be dynamic and require developing new FDA approval pathways and next-generation gold standards.

Designing Metabolic Division of Labor in Microbial Communities.

Microbes face a trade-off between being metabolically independent and relying on neighboring organisms for the supply of some essential metabolites. This balance of conflicting strategies affects microbial community structure and dynamics, with important implications for microbiome research and synthetic ecology. A "gedanken" (thought) experiment to investigate this trade-off would involve monitoring the rise of mutual dependence as the number of metabolic reactions allowed in an organism is increasingly constrained. The expectation is that below a certain number of reactions, no individual organism would be able to grow in isolation and cross-feeding partnerships and division of labor would emerge. We implemented this idealized experiment using in silico genome-scale models. In particular, we used mixed-integer linear programming to identify trade-off solutions in communities of Escherichia coli strains. The strategies that we found revealed a large space of opportunities in nuanced and nonintuitive metabolic division of labor, including, for example, splitting the tricarboxylic acid (TCA) cycle into two separate halves. The systematic computation of possible solutions in division of labor for 1-, 2-, and 3-strain consortia resulted in a rich and complex landscape. This landscape displayed a nonlinear boundary, indicating that the loss of an intracellular reaction was not necessarily compensated for by a single imported metabolite. Different regions in this landscape were associated with specific solutions and patterns of exchanged metabolites. Our approach also predicts the existence of regions in this landscape where independent bacteria are viable but are outcompeted by cross-feeding pairs, providing a possible incentive for the rise of division of labor. IMPORTANCE Understanding how microbes assemble into communities is a fundamental open issue in biology, relevant to human health, metabolic engineering, and environmental sustainability. A possible mechanism for interactions of microbes is through cross-feeding, i.e., the exchange of small molecules. These metabolic exchanges may allow different microbes to specialize in distinct tasks and evolve division of labor. To systematically explore the space of possible strategies for division of labor, we applied advanced optimization algorithms to computational models of cellular metabolism. Specifically, we searched for communities able to survive under constraints (such as a limited number of reactions) that would not be sustainable by individual species. We found that predicted consortia partition metabolic pathways in ways that would be difficult to identify manually, possibly providing a competitive advantage over individual organisms. In addition to helping understand diversity in natural microbial communities, our approach could assist in the design of synthetic consortia.