BackgroundLarge language models (LLMs) have shown promising performance in various healthcare domains, but their effectiveness in identifying specific clinical conditions in real medical records is less explored. This study evaluates LLMs for detecting signs of cognitive decline in real electronic health record (EHR) clinical notes, comparing their error profiles with traditional models. The insights gained will inform strategies for performance enhancement. MethodsThis study, conducted at Mass General Brigham in Boston, MA, analysed clinical notes from the four years prior to a 2019 diagnosis of mild cognitive impairment in patients aged 50 and older. We developed prompts for two LLMs, Llama 2 and GPT-4, on Health Insurance Portability and Accountability Act (HIPAA)-compliant cloud-computing platforms using multiple approaches (e.g., hard prompting, retrieval augmented generation, and error analysis-based instructions) to select the optimal LLM-based method. Baseline models included a hierarchical attention-based neural network and XGBoost. Subsequently, we constructed an ensemble of the three models using a majority vote approach. Confusion-matrix-based scores were used for model evaluation. FindingsWe used a randomly annotated sample of 4,949 note sections from 1,969 patients (women: 1,046 [53.1%]; age: mean, 76.0 [SD, 13.3] years), filtered with keywords related to cognitive functions, for model development. For testing, a random annotated sample of 1,996 note sections from 1,161 patients (women: 619 [53.3%]; age: mean, 76.5 [SD, 10.2] years) without keyword filtering was utilised. GPT-4 demonstrated superior accuracy and efficiency compared to Llama 2, but did not outperform traditional models. The ensemble model outperformed the individual models in terms of all evaluation metrics with statistical significance (p<0.01), achieving a precision of 90.2% [95% CI: 81.9%-96.8%], a recall of 94.2% [95% CI: 87.9%-98.7%], and an F1-score of 92.1% [95% CI: 86.8%-96.4%]. Notably, the ensemble model showed a significant improvement in precision, increasing from a range of 70%-79% to above 90%, compared to the best-performing single model. Error analysis revealed that 63 samples were incorrectly predicted by at least one model; however, only 2 cases (3.2%) were mutual errors across all models, indicating diverse error profiles among them. InterpretationLLMs and traditional machine learning models trained using local EHR data exhibited diverse error profiles. The ensemble of these models was found to be complementary, enhancing diagnostic performance. Future research should investigate integrating LLMs with smaller, localised models and incorporating medical data and domain knowledge to enhance performance on specific tasks.