Grant: Operating Grant: Mechanisms in Brain Aging and Dementia

Understanding how serious respiratory infections accelerate brain aging Having a serious respiratory infection such as influenza, pneumonia, or COVID-19 in mid- to late-life can accelerate cognitive decline and dementia, even in healthy people without pre-existing conditions. There are no medications, therapies, or treatments to prevent post-infection cognitive decline but if there were, we could reduce the number of people living with cognitive decline or slow the development of dementia. We think that inflammation caused by an infection contributes to cognitive decline because people who have higher than average levels of inflammation develop cognitive decline and dementia faster than those with low levels of inflammation, probably because inflammation impairs immune cells in the brain called microglia which stops them from doing their job cleaning up the 'wear and tear' of the brain. When older adults get infections the have a strong inflammatory response that takes longer to go away and probably impairs brain microglia for longer. The first aim of our study is to determine what parts of learning, memory and micoglia function are impaired by having high levels of inflammation. The second aim will investigate what parts of memory and learning are harmed by infection so we can understand what we can prevent by preventing infections. We will infect young and old mice with the bacteria that causes pneumonia and investigate immune changes in their brain, which expect will be worse in old mice. We will also look at hospital records to see if people who went to the hospital for pneumonia were more likely to go back for dementia than people who went to the hospital for other reasons. Lastly, we will test drugs that target inflammation in old mice after they have recovered from their infection in hopes that they will not develop cognitive decline. To our knowledge we are the only research group doing preclinical testing to prevent post-infection cognitive decline.