PET/MR Correlates of Accelerated Aging in Chronic Epilepsy

Epilepsy affects more than 2 million Americans and is the fourth most common neurological disorder. While many patients experience long-term remission, lifelong chronic epilepsy is associated with cognitive, psychiatric, and somatic comorbidities and a well-characterized neuroimaging burden. Recently, there has been much interest and concern regarding disorders of cognitive and brain aging in the general population; however, there has been little systematic study of this issue in aging persons with chronic epilepsy. We hypothesize that prolonged exposure to epilepsy and its myriad of complications accelerate brain and cognitive aging. Specific Aim 1: Characterize biomarkers suggestive of accelerated brain aging in chronic focal epilepsy using advanced PET/MR methods. We hypothesize that PET/MR biomarkers sensitive to brain aging (e.g., increased beta amyloid deposition, morphological changes, changes in functional and structural connectivity, reduced microstructural integrity, reduced metabolism (FDG-PET), and reduced vascular integrity) will be greater in a cohort of chronic focal epilepsy patients compared to age-matched controls, and thus indicative of age-accelerated brain aging. Specific Aim 2: Characterize other risk and resilience factors for accelerated brain and cognitive aging biomarkers in chronic epilepsy. We hypothesize that age-related neuroimaging biomarkers will predict the presence and severity of cognitive abnormalities in patients with chronic focal epilepsy. Furthermore, we expect risk factors for poor cognitive outcome, including vascular, socioeconomic, and lifestyle to be more prevalent in epilepsy and related to age-related cognitive and neuroimaging biomarkers. Specific Aim 3: Identify the temporal sequence of biomarkers in chronic TLE that are indicative of brain and cognitive aging allowing us to model the mechanistic cascade that leads to accelerated aging. We will provide important new mechanistic evidence characterizing the consequences of chronic TLE on brain and cognitive aging and identify the specific neuroimaging and behavioral profiles, risk and resilience factors that may be protective (or detrimental) to the aging process.