Project 454830

Poor blood flow to the brain results in cognitive deficits and increases the risk of developing dementia. Such deficits, especially in the early stages, may be reversed by improving blood flow to the brain with stimulatory treatments such as physical exercise and low voltage electrical current passed through electrodes attached to the scalp. However, these treatments are modestly effective in dementia - only half of those treated benefit. Cognition may not improve in some patients if the capacity of the brain to restore blood flow is impaired. In this study, I will determine whether brain blood flow before the start of treatment can predict therapeutic response in patients with early cognitive deficits due to heart disease (which affects blood flow to the brain) who will undergo physical exercise or low voltage electrical stimulation. I will also determine the likelihood of a single patient benefiting from treatment from the images of brain blood flow. In addition, as biological processes such as oxidative stress affect cognitive improvement to treatment in these patients, I will investigate whether these processes affect brain blood flow. As these processes are potentially modifiable and easily measured in blood, determining whether they affect brain blood flow will allow for personalized therapy by treating these processes before stimulation therapy. Together, this study will pave the way for a "precision" approach to determine whether an individual patient's cognition will improve with these novel therapies, and identify biological processes that can be targeted pharmacologically to enhance future treatments.