Grant: Project Grant

Epilepsy is one of the most common neurological disorders. While antiepileptic drugs can control the seizures in many patients, 30-40% of patients are drug-resistant. Furthermore, many patients present with cognitive deficits, affecting functioning and wellbeing. Epilepsy surgery is currently the most effective treatment to control the seizures and to improve quality of life in drug-resistant patients. However, many do not undergo this procedure (as they are not offered surgery, or decide against it), and some only do so after decades. While epilepsy is still widely considered a 'static' disorder, mounting evidence indicates that the adverse clinical and cognitive effects of the disease aggravate over time. Our project will examine disease progression in temporal lobe epilepsy, the most common drug-resistant epilepsy in adults. Building on findings in brain tissue of patients that underwent epilepsy surgery, we will test the role of misfolded tau protein in disease progression. Accumulation of tau is commonly seen in Alzheimer's Disease, and closely associated with neurodegeneration and dementia. Our project will capitalize on novel neuroimaging techniques to measure tau in the brain. We will examine whether tau is elevated in epileptic patients compared to controls and assess relations to brain atrophy and cognitive decline. Patients and controls will be longitudinally re-assessed with the same protocols, and we will test whether increases in tau and atrophy in patients relate to cognitive trajectories. We will enroll drug-resistant and well-controlled patients, to ascertain the potential modulation of progression by seizures. Finally, we will assess whether tau measures predict future cognitive function in patients undergoing and not undergoing epilepsy surgery. Our project will provide novel insights into progressive brain changes in epilepsy, their contribution to cognitive decline, and the modulation of this process through seizures and tau accumulation.