Seizure, cognitive change and dementia: Understanding the use and safety of anti-seizure medications

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PROJECT SUMMARY Guidelines for anti-seizure medications in older adult populations are incomplete or non-existent, even though the risk of recurrent unprovoked seizures (epilepsy) in adults peaks at 80 years old. As a group, anti- seizure medications are generally thought to be equally efficacious and medication choice should be informed by the secondary effects of these drugs. Older adults are likely to be particularly vulnerable to cognitive adverse effects because they may have lower cognitive reserve, undetected/undiagnosed neurodegeneration, competing cognitive impairing disorders, and often take other CNS-active drugs. Despite the increased risk and abundance of new prescriptions in older adults, most evaluation of the safety and effects of anti-seizure medications on cognition have been done in short-term studies in younger cohorts. No anti-seizure medication prescribing guidelines exist for older adults with mild cognitive impairment (MCI) or Alzheimer’s Disease and related dementias (ADRD). Currently, little information exists regarding anti-seizure medication use including: whether and how drug titration occurs, therapeutic drug monitoring, or how use may differ in older adults with dementia. In order to improve care, we must understand how and why particular anti-seizure medications are prescribed. We currently have limited understanding of how prescribers make decisions, including weighing any possible cognitive adverse effects, when adding and removing anti-seizure medications in older adults. These knowledge gaps are barriers to developing safe, effective and evidence-based treatment strategies. This study will use a large representative study of older adults (the Health and Retirement Study linked to Medicare data) to (1) understand differences in current use, titration, continuation, and laboratory monitoring of anti-seizure medications in older adults with seizures, with and without ADRD, (2) examine the comparative effect of commonly prescribed anti-seizure medications on cognitive decline and incident dementia, and (3) recruit a national sample of prescribers (e.g. primary care, internal medicine, geriatrics, emergency medicine, neurology) to understand decision-making in the context of anti-seizure medication prescription in older adults. My long-term goal is to develop an independent program focused on health services research to improve the care for older adults with seizure and dementia. The completion of this project will lay the foundation for a career of translating best evidence into practice. This project will form the backbone of an integrated training plan that will refine my existing pharmacoepidemiologic and biostatistical skills. Further, it will allow me to develop new knowledge in qualitative methods, geriatrics and cognitive decline. The training plan, focused mentorship and proposed project will allow me to learn, develop and apply the skills necessary for a successful transition to become an independent health services and outcomes researcher, and lay the groundwork for a trial of a multimodality intervention to improve prescribing in older adults with seizure, cognitive impairment and dementia.