Digital Twins are advent to revolutionize the healthcare systems. DT Models are most advanced applications of GenAI technology to simulate patient virtual avatars for early detection of degenerative diseases, Modern treatment response monitoring and planning to provide personalized treatment. These DT models are non-invasive simulated avatars of cognitive disease patients for monitoring, the disease progression, execution of optimized treatment plan and therapeutic interventions. DT Models also leverages integration of multi-modal datasets such as neuroimaging, genetic profiles, and clinical history for enabling the disease progression modelling, real-time decision support system and fostering personalized interventions. GenAI models (generative adversarial networks (GANs), variational autoencoders (VAEs), and diffusion models) are designated to generation of complex, synthetic data and simulations. The AI-generated models improved facilitating tailored interventions for conditions such as Alzheimer’s, Parkinson’s, and schizophrenia by analyzing genetic, neuroimaging data and behavioral data of patient. This chapter enlighten the current advancement and various application of digital twins in the field of cognitive disease and also handing technical and ethical challenges such as ensuring data privacy, avoiding algorithmic bias, maintaining patient autonomy and achieving seamless interoperability across healthcare systems. Furthermore, this chapter explore the integration of Generative AI models with digital twin’s models ability to provide more adaptive, dynamic and predictive digital twins that are capable to real-time AI—driven simulation and highly accurate medical decision-making.