(BRACE) Brain Aging and Cognition in Epilepsy

The PI of this project was:

This project was funded by: University of California - San Diego

The term of this project was: July 2022 to August 2022

The number of subjects scanned during this project was: 36

Epilepsy is the fourth most common neurological disease, costing the healthcare system approximately $15.5 billion annually and negatively impacting quality of life. The incidence and prevalence of epilepsy peaks over the age of 55—a group that is particularly vulnerable to accelerated cognitive and brain aging, placing them at increased risk for progressive neurodegenerative disorders, including Alzheimer’s disease (AD). Given that the most rapidly growing segment of the U.S. population is adults over the age of 55, the number of older adults living with epilepsy will dramatically increase over the next several decades, presenting a major public health concern. Therefore, there is a critical need to characterize cognitive and brain aging in older adults with epilepsy, identify underlying mechanisms of accelerated aging, and target modifiable risk factors that would prevent or mitigate cognitive decline and progression to dementia. We propose the first longitudinal, multi-site investigation of cognitive and brain aging in older adults (55-90 years) with epilepsy in efforts to identify vascular, genetic, biomarker and demographic risk factors for accelerated aging. We will accomplish this goal by obtaining state-of-the-art neuroimaging, comprehensive neuropsychological, vascular risk, and genetic/biomarker data on 100 patients with temporal lobe epilepsy (TLE) and frontal lobe epilepsy (FLE) from three geographically and racially/ethnically diverse epilepsy centers. We will follow these patients longitudinally, examine their imaging and cognitive trajectories over 5 years, and compare their trajectories to 100 patients with mild cognitive impairment (MCI) and 100 normal aging controls. We will then examine the influence of vascular, genetic, and cerebrospinal fluid biomarker risk profiles on cognitive decline and identify baseline factors that increase risk for progression to dementia. Our scientific premise is that older adults with focal epilepsy will show age-accelerated cognitive and brain aging comparable to that seen in MCI. We propose that elevated vascular risk and the presence of AD-associated pathology will underlie the association between accelerated brain aging (i.e., regional atrophy, white matter injury, and hypoperfusion) and cognitive decline in vulnerable patients.