Access to the right evidence does not guarantee that large language models (LLMs) will reason with it correctly. This gap between retrieval and reasoning is especially concerning in clinical settings, where outputs must align with structured protocols. We study this gap using Written Exposure Therapy (WET) guidelines as a testbed. In evaluating model responses to curated clinician-vetted questions, we find that errors persist even when authoritative passages are provided. To address this, we propose an evaluation framework that measures accuracy, consistency, and fidelity of reasoning. Our results highlight both the potential and the risks: retrieval-augmented generation (RAG) can constrain outputs, but safe deployment requires assessing reasoning as rigorously as retrieval.

Alzheimer's disease (AD) is a heterogeneous, multifactorial neurodegenerative disorder characterized by beta-amyloid, pathologic tau, and neurodegeneration. There are no effective treatments for Alzheimer's disease at a late stage, urging for early intervention. However, existing statistical inference approaches of AD subtype identification ignore the pathological domain knowledge, which could lead to ill-posed results that are sometimes inconsistent with the essential neurological principles. Integrating systems biology modeling with machine learning, we propose a novel pathology steered stratification network (PSSN) that incorporates established domain knowledge in AD pathology through a reaction-diffusion model, where we consider non-linear interactions between major biomarkers and diffusion along brain structural network. Trained on longitudinal multimodal neuroimaging data, the biological model predicts long-term trajectories that capture individual progression pattern, filling in the gaps between sparse imaging data available. A deep predictive neural network is then built to exploit spatiotemporal dynamics, link neurological examinations with clinical profiles, and generate subtype assignment probability on an individual basis. We further identify an evolutionary disease graph to quantify subtype transition probabilities through extensive simulations. Our stratification achieves superior performance in both inter-cluster heterogeneity and intra-cluster homogeneity of various clinical scores. Applying our approach to enriched samples of aging populations, we identify six subtypes spanning AD spectrum, where each subtype exhibits a distinctive biomarker pattern that is consistent with its clinical outcome. PSSN provides insights into pre-symptomatic diagnosis and practical guidance on clinical treatments, which may be further generalized to other neurodegenerative diseases.

Summary: Combining new wearable technology and artificial intelligence, researchers are better able to track motion and monitor the progression of movement disorders. A multi-disciplinary team of researchers has developed a way to monitor the progression of movement disorders using motion capture technology and AI. In two ground-breaking studies, published in Nature Medicine, a cross-disciplinary team of AI and clinical researchers have shown that by combining human movement data gathered from wearable tech with a powerful new medical AI technology they are able to identify clear movement patterns, predict future disease progression and significantly increase the efficiency of clinical trials in two very different rare disorders, Duchenne muscular dystrophy (DMD) and Friedreich's ataxia (FA). DMD and FA are rare, degenerative, genetic diseases that affect movement and eventually lead to paralysis. There are currently no cures for either disease, but researchers hope that these results will significantly speed up the search for new treatments.

Concussion has been shown to leave the afflicted with significant cognitive and neurobehavioural deficits. The persistence of these deficits and their link to neurophysiological indices of cognition, as measured by event-related potentials (ERP) using electroencephalography (EEG), remains restricted to population level analyses that limit their utility in the clinical setting. In the present paper, a convolutional neural network is extended to capitalize on characteristics specific to EEG/ERP data in order to assess for post-concussive effects. An aggregated measure of single-trial performance was able to classify accurately (85%) between 26 acutely to post-acutely concussed participants and 28 healthy controls in a stratified 10-fold cross-validation design. Additionally, the model was evaluated in a longitudinal subsample of the concussed group to indicate a dissociation between the progression of EEG/ERP and that of self-reported inventories.

In this work, we consider the problem of predicting the course of a progressive disease, such as cancer or Alzheimer's. Progressive diseases often start with mild symptoms that might precede a diagnosis, and each patient follows their own trajectory. Patient trajectories exhibit wild variability, which can be associated with many factors such as genotype, age, or sex. An additional layer of complexity is that, in real life, the amount and type of data available for each patient can differ significantly. For example, for one patient we might have no prior history, whereas for another patient we might have detailed clinical assessments obtained at multiple prior time-points. This paper presents a probabilistic model that can handle multiple modalities (including images and clinical assessments) and variable patient histories with irregular timings and missing entries, to predict clinical scores at future time-points. We use a sigmoidal function to model latent disease progression, which gives rise to clinical observations in our generative model. We implemented an approximate Bayesian inference strategy on the proposed model to estimate the parameters on data from a large population of subjects. Furthermore, the Bayesian framework enables the model to automatically fine-tune its predictions based on historical observations that might be available on the test subject. We applied our method to a longitudinal Alzheimer's disease dataset with more than 3000 subjects [23] and present a detailed empirical analysis of prediction performance under different scenarios, with comparisons against several benchmarks. We also demonstrate how the proposed model can be interrogated to glean insights about temporal dynamics in Alzheimer's disease.