Abstract:In the complex realm of cognitive disorders, Alzheimer's disease (AD) and vascular dementia (VaD) are the two most prevalent dementia types, presenting entangled symptoms yet requiring distinct treatment approaches. The crux of effective treatment in slowing neurodegeneration lies in early, accurate diagnosis, as this significantly assists doctors in determining the appropriate course of action. However, current diagnostic practices often delay VaD diagnosis, impeding timely intervention and adversely affecting patient prognosis. This paper presents an innovative multi-omics approach to accurately differentiate AD from VaD, achieving a diagnostic accuracy of 89.25%. The proposed method segments the longitudinal MRI scans and extracts advanced radiomics features. Subsequently, it synergistically integrates the radiomics features with an ensemble of clinical, cognitive, and genetic data to provide state-of-the-art diagnostic accuracy, setting a new benchmark in classification accuracy on a large public dataset. The paper's primary contribution is proposing a comprehensive methodology utilizing multi-omics data to provide a nuanced understanding of dementia subtypes. Additionally, the paper introduces an interpretable model to enhance clinical decision-making coupled with a novel model architecture for evaluating treatment efficacy. These advancements lay the groundwork for future work not only aimed at improving differential diagnosis but also mitigating and preventing the progression of dementia.