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AES 2022 | Comorbid seizures in dementia lead to worse clinical outcomes and higher mortality rates

Seizures are a common comorbidity in patients with dementia, with prevalence estimates ranging from 10-64%. Diagnostic challenges in patients with cognitive impairment mean seizures can be difficult to recognize and often remain undiagnosed. As previous studies have shown accelerated cognitive decline in patients with dementia and co-morbid seizures, Ifrah Zawar, MD, University of Virginia School of Medicine, Charlottesville, VA, and her team wanted to investigate the wider impact of seizures on clinical and mortality outcomes. Using longitudinal data from 39 Alzheimer’s disease centers across the US, cognitive, functional, clinical, and mortality outcomes were compared between those with and without active seizures. Overall, 1.4% of the ~26,000 patients had active seizures. Patients with active seizures were significantly younger at the onset of cognitive decline, performed worse on cognitive tests, had worse functional assessment scores, and were more likely to have a physical dependence compared to those without seizures. The mortality data showed that a higher proportion of patients with active seizures had died (OR 1.56) and they were younger at death. Even after adjustment for sex, disease duration, stroke, depression, dominant AD mutation status, and education status, patients with active seizures were a higher risk of dying younger. This interview took place at the American Epilepsy Society (AES) Annual Meeting 2022 in Nashville, TN.

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Transcript (edited for clarity)

So the burden of comorbid seizures in various studies have ranged from 1.5 to up to 64% and the relative risk of epilepsy among dementia patients is eight to 10 fold compared to the general population. So there are several studies that have in the recent past looked at the impact of seizures, clinical seizures on cognition in dementia and Alzheimer’s disease and other dementias. However, none of these studies have looked at the functional and mortality outcomes...

So the burden of comorbid seizures in various studies have ranged from 1.5 to up to 64% and the relative risk of epilepsy among dementia patients is eight to 10 fold compared to the general population. So there are several studies that have in the recent past looked at the impact of seizures, clinical seizures on cognition in dementia and Alzheimer’s disease and other dementias. However, none of these studies have looked at the functional and mortality outcomes. So our rationale for doing this study was to look at the mortality outcomes because the fact that the seizures do contribute to worsening cognition does raise a concern that they could impact the overall mortality and functional outcomes as well. That was the rationale behind the study. And then we looked at the data from 39 Alzheimer’s Disease research centers, which under the umbrella of National Institute of Aging, have worked over the past two, three decades to collect data longitudinally from dementia patients who visit these centers.

We had over 44,000 patients’ data. We included the patients who did have cognitive impairment at the initial visit and looked at their seizure status. So we compared the patients who did have seizures at the initial visit compared to patients who did not have seizures at the initial visit, and then followed them over time longitudinally to look at their mortality data. And that what we found was patients with seizures had earlier mortality. So the average age of death was around 72 years for seizure patients compared to patients who did not have seizures, who had average age of death around 79 years. And in the Cox regression analysis, we found that patients with seizures and cognitive impairment were dying sooner compared to patients without seizures and cognitive impairment. So it does appear that in dementia patients, the presence of active seizures, active uncontrolled seizures that are requiring medical treatment, can contribute to worsening functional and mortality outcomes.

The implications of this finding are that seizures need to be recognized early in this patient population and treated with anti-seizure medications. The difficulty is that often seizures tend to be under-recognized, leading to delayed diagnosis among dementia patients, because they have ongoing confusion as a part of their ongoing cognitive impairment, and often they can be missed. Seizures may be confused with just a manifestation of dementia and can be missed and the diagnosis can be delayed. And I imagine that that does contribute to worsening cognition, worsening overall outcomes. So the next step is really to look at the distinct findings that can help us identify these patients early on in the disease process so that we can intervene and provide seizure medications early on.

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