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Deep learning (DL) models have shown significant potential in Alzheimer's Disease (AD) classification. However, understanding and interpreting these models remains challenging, which hinders the adoption of these models in clinical practice. Techniques such as saliency maps have been proven effective in providing visual and empirical clues about how these models work, but there still remains a gap in understanding which specific brain regions DL models focus on and whether these brain regions are pathologically associated with AD. To bridge such gap, in this study, we developed a quantitative disease-focusing strategy to first enhance the interpretability of DL models using saliency maps and brain segmentations; then we propose a disease-focus (DF) score that quantifies how much a DL model focuses on brain areas relevant to AD pathology based on clinically known MRI-based pathological regions of AD. Using this strategy, we compared several state-of-the-art DL models, including a baseline 3D ResNet model, a pretrained MedicalNet model, and a MedicalNet with data augmentation to classify patients with AD vs. cognitive normal patients using MRI data; then we evaluated these models in terms of their abilities to focus on disease-relevant regions. Our results show interesting disease-focusing patterns with different models, particularly characteristic patterns with the pretrained models and data augmentation, and also provide insight into their classification performance. These results suggest that the approach we developed for quantitatively assessing the abilities of DL models to focus on disease-relevant regions may help improve interpretability of these models for AD classification and facilitate their adoption for AD diagnosis in clinical practice. The code is publicly available at https://github.com/Liang-lt/ADNI.

With generative artificial intelligence (AI), particularly large language models (LLMs), continuing to make inroads in healthcare, it is critical to supplement traditional automated evaluations with human evaluations. Understanding and evaluating the output of LLMs is essential to assuring safety, reliability, and effectiveness. However, human evaluation's cumbersome, time-consuming, and non-standardized nature presents significant obstacles to comprehensive evaluation and widespread adoption of LLMs in practice. This study reviews existing literature on human evaluation methodologies for LLMs in healthcare. We highlight a notable need for a standardized and consistent human evaluation approach. Our extensive literature search, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, includes publications from January 2018 to February 2024. The review examines the human evaluation of LLMs across various medical specialties, addressing factors such as evaluation dimensions, sample types and sizes, selection, and recruitment of evaluators, frameworks and metrics, evaluation process, and statistical analysis type. Drawing on the diverse evaluation strategies employed in these studies, we propose a comprehensive and practical framework for human evaluation of LLMs: QUEST: Quality of Information, Understanding and Reasoning, Expression Style and Persona, Safety and Harm, and Trust and Confidence. This framework aims to improve the reliability, generalizability, and applicability of human evaluation of LLMs in different healthcare applications by defining clear evaluation dimensions and offering detailed guidelines.

Alzheimer's Disease (AD) is the most common form of dementia in the United States. Sleep is one of the lifestyle-related factors that has been shown critical for optimal cognitive function in old age. However, there is a lack of research studying the association between sleep and AD incidence. A major bottleneck for conducting such research is that the traditional way to acquire sleep information is time-consuming, inefficient, non-scalable, and limited to patients' subjective experience. A gold standard dataset is created from manual annotation of 570 randomly sampled clinical note documents from the adSLEEP, a corpus of 192,000 de-identified clinical notes of 7,266 AD patients retrieved from the University of Pittsburgh Medical Center (UPMC). We developed a rule-based Natural Language Processing (NLP) algorithm, machine learning models, and Large Language Model(LLM)-based NLP algorithms to automate the extraction of sleep-related concepts, including snoring, napping, sleep problem, bad sleep quality, daytime sleepiness, night wakings, and sleep duration, from the gold standard dataset. Rule-based NLP algorithm achieved the best performance of F1 across all sleep-related concepts. In terms of Positive Predictive Value (PPV), rule-based NLP algorithm achieved 1.00 for daytime sleepiness and sleep duration, machine learning models: 0.95 and for napping, 0.86 for bad sleep quality and 0.90 for snoring; and LLAMA2 with finetuning achieved PPV of 0.93 for Night Wakings, 0.89 for sleep problem, and 1.00 for sleep duration. The results show that the rule-based NLP algorithm consistently achieved the best performance for all sleep concepts. This study focused on the clinical notes of patients with AD, but could be extended to general sleep information extraction for other diseases.