Determinants of Premature Brain Aging in Temporal Lobe Epilepsy
Abstract number :
2.235
Submission category :
6. Cormorbidity (Somatic and Psychiatric)
Year :
2023
Submission ID :
240
Source :
www.aesnet.org
Presentation date :
12/3/2023 12:00:00 AM
Published date :
Authors :
Presenting Author: Ezequiel Gleichgerrcht, MD, PhD – Emory University
Kathryn Davis, MD, MS – University of Pennsylvania; Rebecca Roth, rebecca.anne.roth@emory.edu – BA, Emory University; Sarah Newman-Norlund, BS, MA – University of South Carolina; Alexandra Parashos, MD – Medical University of South Carolina; Jennifer Cashwell, DO – Medical University of South Carolina; Neha Gandhi, MD – Texas Institute for Neurological Disorders; Samaneh Nemati, MS – University of South Carolina; Erik Kaestner, PhD – University of California San Diego; Carrie McDonald, PhD – University of California San Diego; Sigfus Kristinsson, PhD – University of South Carolina; Anto Bagić, MD, PhD – University of Pittsburgh; Daniel Drane, PhD – Emory University; Patricia Dugan, MD – New York University; Julius Fridriksson, PhD – University of South Carolina; Ruben Kuzniecky, MD – Northwell / Hofstra University; Leonardo Bonilha, MD, PhD – Emory University
Rationale: Temporal lobe epilepsy (TLE) is associated with advanced brain aging. Nonetheless, the factors related to advanced brain aging in TLE are not fully understood. Epilepsy is also associated with a higher prevalence of modifiable comorbidities, which are important determinants of advanced brain aging in the general population. Here, we evaluated the independent contribution of epilepsy-related variables and modifiable risk factors, as well as their interaction, on premature brain aging in epilepsy.
Methods: Brain age was estimated using a machine learning model from T1-weighted MR images obtained in 515 persons with TLE and 615 neurologically healthy controls (HC). The difference between the MRI-estimated brain age and chronological age (i.e., the brain age gap [BAG]) was computed for each participant. Complete risk factor data were available for 301 HC and 167 patients with TLE. Group-wise differences in BAG were determined, including voxel-wise comparisons of regional contributors to BAG specific to each group. Propensity score matching was used to balance the datasets based on demographic and risk factor profiles, and multiple linear regression with interaction terms was used to evaluate the contributions of epilepsy and comorbidities on BAG.
Results:
Compared with HC, TLE was associated with double the risk of advanced brain aging. Epilepsy was independently associated with 3.35 additional brain years. The most pronounced group differences in BAG were seen between 20-25 and 35-45 years old. Brain regions disproportionally affected in TLE contributing to advanced BAG were medial temporal, perisylvian, and subcortical areas. In TLE, high BAG was specifically exacerbated by earlier age of onset of epilepsy and male sex. Diabetes mellitus, hypertension, liver disease, solid tumors, stroke/TIA, and tobacco use were disproportionally more prevalent in TLE. An average increase of 0.97 years in BAG was observed per comorbidity, with an additional 0.83 BAG increase per comorbidity due to an interaction with epilepsy.
Conclusions:
Advanced brain aging is a pervasive phenomenon in TLE that is related to both epilepsy-specific and more general modifiable risk factors. This observation has direct public health relevance since attention to modifiable risk factors is not typically at the forefront of epilepsy care, but targeted interventions could directly affect brain health in epilepsy.
Funding: This study was funded by NINDS grant R01NS110347 and NINDC grant P50DC014664 as well NCATS KL2TR002381.
Cormorbidity (Somatic and Psychiatric)