Uncovering hidden subtypes in dementia: An unsupervised machine learning approach to dementia diagnosis and personalization of care

Objective: Dementia represents a growing public health challenge, affecting an increasing number of individuals. It encompasses a broad spectrum of cognitive impairments, ranging from mild to severe stages, each of which demands varying levels of care. Current diagnostic approaches often treat dementia as a uniform condition, potentially overlooking clinically significant subtypes, which limits the effectiveness of treatment and care strategies. This study seeks to address the limitations of traditional diagnostic methods by applying unsupervised machine learning techniques to a large, multi-modal dataset of dementia patients (encompassing multiple data sources including clinical, demographic, gene expression and protein concentrations), with the aim of identifying distinct subtypes within the population. The primary focus is on differentiating between mild and severe stages of dementia to improve diagnostic accuracy and personalize treatment plans. Methods: The dataset analyzed included 911 individuals, described by 157 multi-modal characteristics, encompassing clinical, genomic, proteomic and sociodemographic features. After handling missing data, the dataset was reduced to 561 rows and 135 columns. Various dimensionality reduction techniques were applied to improve the feature-to-patient ratio, and unsupervised clustering methods were employed to identify potential subtypes. The major novelty in our methodology regards the combination of different techniques, bridging high-dimensional statistical inference, multi-modal dimensionality reduction and clustering analysis, to appropriately model the multi-modal nature of the data and ensure clinical relevance. Results: The analysis revealed distinct clusters within the dementia population, each characterized by specific clinical and demographic profiles. These profiles included variations in biomarkers, cognitive scores, and disability levels. The findings suggest the presence of previously unrecognized subgroups, distinguished by their genomic, proteomic, and clinical characteristics. Conclusion: This study demonstrates that unsupervised machine learning can effectively identify clinically relevant subtypes of dementia, with important implications for diagnosis and personalized treatment. Further research is required to validate these findings and investigate their potential to improve patient outcomes.