Grant: Operating Grant: Alzheimer Society Research Program - NI Grants

Mixed dementia is the most common form of dementia. It occurs when Alzheimer’s disease (AD) combines with vascular disease, thereby also affecting our brain’s blood vessels and immune function. As this happens, more symptoms develop such as memory difficulties. However, current research has primarily focused on AD, and neglected blood vessel health and associated immune responses (inflammation). This limits our ability to detect and treat appropriately. Our first objective is to compare inflammation markers in persons with AD who also have vascular-related brain issues to those who do not. Second, we will look for specific groups of patients who show unique patterns of inflammation and vascular changes together, seeing if we can group patients based on these health markers. Finally, we will create a combined score of inflammation and vascular markers to help us understand its impact on cognitive health. We will use brain scans and blood samples of 982 participants in different disease stages from three large cohorts (two Canadian, one American). We will use an artificial intelligence (AI) model to predict how and when each of the inflammation and vascular markers start to change within the disease. Our method differs from previous studies by using AI and more advanced models, and by combining different types of health markers to get a clearer picture. Controlling vascular brain changes and vascular-associated immune responses could delay dementia from progressing. To do that, we first must understand how and when these vascular and immune processes manifest in the brain. Our AI model will help with identifying high-risk individuals and patient selection for clinical trials targeting these specific health markers. Our study represents a unique and more detailed model of AD progression. AD is highly complex, involving not only toxic proteins like amyloid and tau but also changes in blood vessel health and the immune system. This project aims to clarify how and when these vascular and immune changes contribute to mixed dementia. By understanding these factors better, we hope to improve predictions of who might benefit from treatments targeting blood vessel health, leading to more personalized and effective care.