Late-Onset Seizures: Etiology and Demographics in US Tertiary Care Epilepsy Centers.

Despite the recognition of Sudden Unexpected Death in Epilepsy (SUDEP) and other risks of premature mortality in people with epilepsy (PWE), mortality in older PWE remains an understudied entity. This review provides a comprehensive overview of the multifaceted causes of premature mortality in older adults with epilepsy and emphasizes the need for targeted interventions to reduce mortality and enhance the quality of life in this vulnerable population. It underscores the heightened prevalence of epilepsy among older adults and the interplay of intrinsic and extrinsic factors contributing to their mortality. Further, this paper delves into the nuances of diagnosing SUDEP in older adults and the underestimation of its incidence due to misclassification and lack of standardized protocols. Factors such as frailty, comorbidities, and the bidirectional relationship between epilepsy and conditions such as dementia and stroke further compound the mortality risks. Key factors, including status epilepticus, comorbid conditions (such as cardiovascular diseases, cerebrovascular events, and neurodegenerative disorders), and external causes like accidents, falls, and suicide, are discussed. It also examines the implications of anti-seizure medications, particularly polypharmacy, and their adverse effects on this population. Future directions include implementing enhanced diagnostic protocols, developing treatment plans, and integrating real-time monitoring technologies to reduce the risk of sudden death and multifaceted premature mortality in this patient population. Increasing awareness among healthcare providers and families about the risks and management of epilepsy in older adults, along with fostering collaborative research efforts, is essential to improve mortality outcomes. PLAIN LANGUAGE SUMMARY: There is a heightened risk of mortality in older people with epilepsy due to many causes unique to their population. Despite the risk, Sudden Unexpected Death in Epilepsy and early mortality in older adults with epilepsy are underestimated. Unique contributing factors include comorbid conditions like dementia, stroke, and frailty, adverse effects from polypharmacy, and increased risks of cardiovascular complications and external injuries such as falls and suicide. A careful consideration of all these factors can help mitigate the mortality in older adults with epilepsy.

Neurologic diseases such as stroke are risk factors for new-onset epilepsy in older adults. Recent evidence suggests that psychiatric disorders independently predict epilepsy in older male veterans. Our aim was to examine the relationship between these disorders in a population-based study of older adults that also included women and minorities. We used a national 5% random sample of 2005 Medicare beneficiaries including all 50 US states and Washington, DC. Beneficiaries were 65 years of age or older, with continuous Medicare Part A and Part B coverage and not in managed care plans. Epilepsy cases were identified from claims for physician visits, hospitalizations, and outpatient procedures. We used logistic regressions for the overall sample and stratified by gender to determine whether risk of new-onset epilepsy was associated with prior history of psychiatric (i.e., depression, psychosis, bipolar disorder, schizophrenia, posttraumatic stress disorder (PTSD), adjustment disorder, and substance abuse/dependence) and neurologic conditions (i.e., cerebrovascular disease, dementia, traumatic brain injury, brain tumor, metastatic cancer). Preexisting psychiatric disorders were significantly associated with new-onset epilepsy in the study population as were the neurologic conditions evaluated. Five of the seven psychiatric disorders examined were independently associated with new-onset epilepsy; substance abuse, psychosis, bipolar disorder, schizophrenia, and depression. Gender interaction effects were found for substance abuse/dependence and brain tumors. Both neurologic and psychiatric factors significantly predicted new-onset epilepsy in a population-based sample of male and female older adults. These results support earlier findings and extend the understanding of risk models for new-onset epilepsy in broader older adult populations.

There are no clinical guidelines dedicated to the treatment of epilepsy in older adults. We investigated physician opinion and practice regarding the treatment of people with epilepsy aged 65 years or older. We also sought to study how our opinion and practice varied between geriatricians, general neurologists, and epilepsy neurologists (i.e., epileptologists). We initially piloted our survey to measure test-retest reliability. Once finalized, we disseminated the survey via two rounds of facsimiles, and then conventional mail, to eligible individuals listed in a national directory of Canadian physicians. We used descriptive statistics such as stacked bar charts and tables to illustrate our findings. One hundred forty-four physicians (104 general neurologists, 25 geriatricians, and 15 epileptologists) answered our survey in its entirety (overall response rate of 13.2%). Levetiracetam and lamotrigine were the preferred antiseizure medications (ASMs) to treat older adults with epilepsy. Two thirds of epileptologists and almost half of general neurologists would consider prescribing lacosamide in >50% of people aged >65 years; only one geriatrician was of the same opinion. More than 40% of general neurologists and geriatricians erroneously believed that none of the ASMs mentioned in our survey was previously studied in randomized controlled trials specific to the treatment of epilepsy in older adults. Epileptologists were more likely as compared to general neurologists and geriatricians to recommend epilepsy surgery (e.g., 66.6% vs. 22.9%-37.5% among older adults). Therapeutic decisions for older adults with epilepsy are heterogeneous between physician groups and sometimes misalign with available clinical evidence. Our surveyed physicians differed in their approach to ASM choice as well as perception of surgery in older adults with epilepsy. These findings likely reflect the lack of clinical guidelines dedicated to this population and the deficient implementation of best practices.

Epilepsy, a chronic neurological disorder characterized by recurrent seizures, is not limited to any specific age group. While often associated with children and younger adults, epilepsy also presents unique challenges in older adults. This review aims to explore the epidemiology, aetiology, clinical presentation, diagnosis, and management of epilepsy in older adults. The review discusses the complexities of diagnosing epilepsy in this population, considering comorbidities, medication interactions, and age-related changes in the central nervous system. Furthermore, the importance of a multidisciplinary approach to the management of epilepsy in older adults, encompassing pharmacological interventions, lifestyle modifications, and psychosocial support is highlighted. By understanding the specific needs and challenges faced by older adults with epilepsy, healthcare professionals can optimize their care and improve their quality of life.

There are limited studies on the prevalence of epilepsy and co-morbid conditions in older adults with an ID. To begin to address this prevalence of epilepsy was estimated for participants in the Intellectual Disability Supplement to the Irish Longitudinal Study on Ageing. Associations with demographic variables and co morbid health conditions were examined. It was found that prevalence was high (30.7%); but declined as people aged. Those with epilepsy were less likely to live with family, independently or in community settings, rates of refractory epilepsy were high and, despite medication over half of those with epilepsy still reported experiencing seizures. Given these findings, people with ID and their careers have considerable needs for information about epilepsy management, and for support from specialist ID and epilepsy services.

Epilepsy among older populations has emerged as a growing global health concern in recent decades. However, comprehensive analyses of epilepsy burden among older adults are limited. This study aimed to assess the global burden of idiopathic epilepsy in the population aged 60 and above from 1990 to 2021 and project trends through 2035. Using data from the Global Burden of Disease (GBD) study 2021, we analyzed epilepsy-related metrics including incidence, prevalence, mortality, and disability-adjusted life years (DALYs) across 204 countries and territories, stratified by age, sex, and Socio-demographic Index (SDI). Data analysis encompassed relative change calculations, as well as average annual percentage change (AAPC). Additionally, we performed a decomposition analysis to determine the contributions of population growth, aging, and epidemiological changes, and used Bayesian age-period-cohort (BAPC) modeling to project future burden through 2035. From 1990 to 2021, the global burden of idiopathic epilepsy in older adults increased substantially, with rises in age-standardized incidence (26.64%), prevalence (20.01%), mortality (4.45%), and DALYs (0.32%). Males consistently showed higher burden across metrics. Regional analysis revealed significant disparities, with Western Europe reporting the highest age-standardized incidence rate and Andean Latin America the highest prevalence rate in 2021. Higher SDI regions demonstrated better outcomes in mortality and DALYs, though showing unique increases in age-standardized rates. Population growth emerged as the primary driver of increased burden across regions. Projections through 2035 indicate continuing increases in incidence (AAPC: 1.64%) and prevalence (AAPC: 1.34%) rates, while mortality (AAPC: -1.29%) and DALY (AAPC: -0.12%) rates are expected to decline. The global burden of idiopathic epilepsy in older adults has increased significantly, with notable disparities across regions and socioeconomic levels.While projected declines in mortality and DALY rates suggest improving healthcare outcomes, rising incidence and prevalence rates highlight the need for enhanced prevention strategies and specialized geriatric epilepsy care, particularly in resource-limited settings.

1 R. Tallis ( 1 Emeritus Professor of Geriatric Medicine, University of Manchester, Manchester, UK ) Older adults are now the largest group of individuals presenting with epilepsy (Wallace H, Shorvon S, Tallis R. Age-specific incidence and prevalence rates of treated epilepsy in an unselected population of 2,052,922 and age-specific fertility rates of women with epilepsy. Lancet 1998;352:1970–3) which affects over 1% of people over 65 years of age (Purcell B, Gaitatzis A, Sander JW, Majeed A. Epilepsy prevalence and prescribing patterns in England and Wales, Office of National Statistics. Health Statistics Quarterly 2002;15:23–30). The impact of seizures, their misdiagnosis, or their mismanagement, on an elderly person cannot be exaggerated. It is a matter of the greatest concern, therefore, that seizures in old age are comparatively neglected both in the scientific literature and in clinical practice (Tallis RC. ‘Epilepsy’. In: Tallis RC, Fillit H (eds) Textbook of Geriatric Medicine and Gerontology. 6th ed. Edinburgh: (Churchill Livingstone, 2003;549–572). A recent survey in the United Kingdom showed a lack of training in the diagnosis and management of epilepsy by geriatricians (Epilepsy Action: Survey of Geriatricians in the United Kingdom, 2005 [http://www.epilepsy.org.uk/press/releases/2005/epilepsyaction_pr_epilepsyweek2005_medical.pdf]). There are many challenges facing a physician who wishes to provide good care for people with late-onset seizures: diagnosis; education and support to minimise the psycho-social impact of seizures; rational decisions about the use of antiepileptic drugs; the management of co-morbid conditions; and long-term monitoring of seizure control and the effects of medication. Diagnosis often presents the most difficult challenge (Rowan AJ. ‘Paroxysmal disturbances resembling seizures in the elderly’. In Kaplan PW, Fisher RS (eds) Imitators of Epilepsy. New York: Demos, 2005;111–119). The range of differential diagnoses is extensive and accurate diagnosis is often made more difficult by the lack of a detailed history. The most important differential diagnosis is syncope and physicians dealing with ‘blackouts’ in older people should provide, or have ready access to, a service for diagnosing and managing this very common condition. Diagnosis should include identification of the underlying cause. The close relationship between elderly-onset seizures and cerebrovascular disease is now more fully understood (Cleary P, Shorvon S, Tallis R. Late-onset seizures as a predictor of subsequent stroke. Lancet 2004;363:1184–6) and detection and treatment of cardiovascular risk factors should be a routine part of the service. At present, we are a long way off meeting the challenge of epilepsy in older adults.

Older adults represent a highly heterogeneous population, with multiple diverse subgroups. Therefore, an individualized approach to treatment is essential to meet the needs of each unique subgroup. Most comparative studies focusing on treatment of epilepsy in older adults have found that levetiracetam has the best chance of long-term seizure freedom. However, there is a lack of studies investigating other newer generation antiseizure medications (ASMs). Although a number of randomized clinical trials have been performed on older adults with epilepsy, the number of participants studied was generally small, and they only investigated short-term efficacy and tolerability. Quality of life as an outcome is often missing but is necessary to understand the effectiveness and possible side effects of treatment. Prognosis needs to move beyond the focus on seizure control to long-term patient-centered outcomes. Dosing studies with newer generation ASMs are needed to understand which treatments are the best in the older adults with different comorbidities. In particular, more high-level evidence is required for older adults with Alzheimer's disease with epilepsy and status epilepticus. Future treatment studies should use greater homogeneity in the inclusion criteria to allow for clearer findings that can be comparable with other studies to build the existing treatment evidence base.

Newer glucose‐lowering drugs (GLDs) protect against cerebrovascular, neurodegenerative, and neuroinflammatory pathologies. Therefore, we performed a meta‐analysis of randomized controlled trials (RCTs) comparing newer GLDs to placebo that assessed long‐term cardiovascular and renal outcomes to analyze their potential to prevent late‐onset seizures and epilepsy, separately and as a combined outcome. A comprehensive MEDLINE and CENTRAL databases search for DPP‐4 inhibitors, GLP‐1 receptor agonists, and SGLT2 inhibitor RCTs, which reported adverse effects, including seizures and epilepsy on clinicaltrials.gov, yielded 413 studies. Of them, 27 studies with almost 200 000 patients (mean age 64.9 years, 65.6% males) were included. We calculated relative risk (RR) and odds ratio (OR) using the Mantel–Haenszel method and Peto's method. Patients taking newer GLDs had a 24% lower risk of late‐onset seizures and epilepsy, combined, (RR: 0.76, 95% CI: 0.62–0.95) and 22% lower risk of late‐onset seizures only (RR = 0.78; 95% CI = 0.60–1.00), compared to patients on placebo. This seizure and epilepsy prevention benefit was only noted among patients taking GLP‐1 receptor agonists. Stroke incidence was comparable between newer GLDs and placebo group. GLP‐1 receptor agonists like Semaglutide significantly reduce late‐onset seizures and epilepsy, and their anti‐epileptogenic potential in older adults needs further exploration.Plain Language SummaryOur analysis 27 clinical trials and nearly 200 000 patients evaluated the potential of newer glucose‐lowering drugs (GLDs) to prevent late‐onset seizures and epilepsy in older adults. The study found that newer GLDs, especially GLP‐1 receptor agonists like Semaglutide, reduced the combined risk of seizures and epilepsy by 24% compared to placebo. These findings suggest that newer GLDs may offer prevention against the development of seizures and epilepsy in older adults. However, further research is needed to confirm their anti‐epileptogenic effects.

To determine the prevalence, incidence, and predictors of epilepsy among older adults in the Cardiovascular Health Study (CHS). We analyzed data prospectively collected in CHS and merged with data from outpatient Medicare administrative claims. We identified cases with epilepsy using self-report, antiepileptic medication, hospitalization discharge ICD-9 codes, and outpatient Medicare ICD-9 codes. We used Cox proportional hazards regression to identify factors independently associated with incident epilepsy. At baseline, 42% of the 5,888 participants were men and 84% were white. At enrollment, 3.7% (215 of 5,888) met the criteria for prevalent epilepsy. During 14 years of follow-up totaling 48,651 person-years, 120 participants met the criteria for incident epilepsy, yielding an incidence rate of 2.47 per 1,000 person-years. The period prevalence of epilepsy by the end of follow-up was 5.7% (335 of 5,888). Epilepsy incidence rates were significantly higher among blacks than nonblacks: 4.44 vs 2.17 per 1,000 person-years (p < 0.001). In multivariable analyses, risk of incident epilepsy was significantly higher among blacks compared to nonblacks (hazard ratio [HR] 4.04, 95% confidence interval [CI] 1.99-8.17), those 75 to 79 compared to those 65 to 69 years of age (HR 2.07, 95% CI 1.21-3.55), and those with history of stroke (HR 3.49, 95% CI 1.37-8.88). Epilepsy in older adults in the United States was common. Blacks, the very old, and those with history of stroke have a higher risk of incident epilepsy. The association with race remains unexplained.

BackgroundIn a globally ageing population, epilepsy in older adults has gained increased clinical relevance. This includes both individuals who have grown old with epilepsy and those who develop epilepsy later in life. Whether seizure outcomes and treatment patterns differ between these groups remains insufficiently characterised.MethodsIn this retrospective study, we included patients aged ≥ 65 years treated at three outpatient epilepsy clinics in Berlin between 2010 and 2025. Patients were categorised according to age at epilepsy onset. Early-onset persistent epilepsy (EOPE) was defined as onset < 40 years, and late-onset epilepsy (LOE) as onset ≥ 65 years. The primary endpoint was seizure freedom during the last 12 months. Secondary endpoints included markers of antiseizure medication burden, adverse effects and quality of life.ResultsA total of 243 patients were included (114 EOPE, 129 LOE). Seizure freedom was less frequent in EOPE compared to LOE (50.0% vs. 69.0%, p = 0.003). Patients with EOPE had a significantly higher drug load (median defined daily dose 1.00 vs. 0.67; p < 0.001). EOPE was independently associated with, among other variables, lower odds of seizure freedom (adjusted odds ratio (adjOR) 0.34, 95%CI 0.16–0.71) and more frequent use of first- or second-generation ASM (adjOR 5.99, 95%CI 2.47–14.54). The latter finding remained robust in a sensitivity analysis restricted to seizure-free patients.ConclusionsIn older adults, EOPE and LOE are associated with differing clinical characteristics. Patients with EOPE show lower seizure freedom and higher treatment burden as compared to LOE. In seizure-free patients with long-standing epilepsy, ASM simplification may be considered.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00415-026-13916-9.

This article reflects key themes and discussions from the American Epilepsy Society Annual Meeting 2025, Epilepsy and Aging Special Interest Group (SIG) session entitled "Multimodal Biomarkers of Epilepsy in Older Adults." The perspectives presented here are intended to highlight emerging priorities for the field. Epilepsy in older adults is the fastest-growing segment of the epilepsy population worldwide. Despite rising incidence, prevalence, and substantial morbidity, care for late-onset epilepsy (LOE) remains anchored to a seizure-centric framework that inadequately addresses the broader consequences of seizures in later life. Older adults with LOE face markedly increased risks of dementia, mortality, and stroke, yet are frequently excluded from epilepsy and Alzheimer's disease (AD) clinical trials. Patient-centered outcomes, including cognition, sleep, function, and quality of life, remain underprioritized. In this article, we argue that LOE requires multimodal biomarkers and multidisciplinary care. We contend that LOE should be reframed as a biologically meaningful warning signal of network vulnerability and overlapping brain pathology, rather than a late-life complication to be managed pragmatically. Cognitive dysfunction is common, heterogeneous, and often precedes overt neurodegenerative diagnoses, positioning cognition as an early clinical signal. Neuroimaging and electrophysiological evidence further place LOE along a continuum intersecting cardiovascular risk factors, sleep disruption, and AD biology, challenging traditional silos between epilepsy and dementia care. We argue for greater inclusion of older adults in antiseizure medication trials and for the inclusion of individuals with epilepsy in AD clinical trials. We propose a brain-health-centered framework for LOE that integrates longitudinal electroencephalography, particularly sleep-inclusive strategies, routine cognitive screening with targeted neuropsychological assessment, neuroimaging, vascular and sleep risk evaluation, and selective use of neurodegenerative biomarkers when clinically actionable. Together, these shifts move care beyond seizure counting toward a comprehensive brain-health model aligned with the realities of aging epilepsy.

The incidence of epilepsy is highest in the older adult age group. Seizures in older adults can be more difficult to diagnose because their presentation is often subtle and can easily be mistaken for other conditions. Fortunately, new-onset epilepsy in the older adult is often pharmaco-responsive, with as many as 80-85% of patients achieving remission, often with monotherapy at modest doses. Many physiological and pathological changes occur with aging that can alter the pharmacokinetics of antiseizure drugs (ASDs). For the majority of the old- and new-generation ASDs, a decrease in dose may be needed to maintain concentrations equivalent to those found in young adults. The risk of drug interactions with ASDs is substantial, as polypharmacy is common. The first-generation ASDs (carbamazepine, phenytoin, phenobarbital, and valproic acid) have the potential to interact with many drugs, but many newer ASDs either do not have significant interactions or are selective inhibitors and inducers of specific hepatic enzymes. The differences in adverse effects between younger and older adults are not just due to dosing and pharmacokinetics. Older adults are more susceptible to the gait, balance, and cognitive effects of ASDs. Overall, the improved tolerability and decreased drug interaction potential of the newer-generation ASDs, such as lamotrigine and levetiracetam, have demonstrated their superiority in the treatment of seizures in older adults and, as such, are clearly favored for new-onset epilepsy in older adults.

To determine the association between brain MRI abnormalities and incident epilepsy in older adults. Men and women (ages 45-64 years) from the Atherosclerosis Risk in Communities study were followed up from 1987 to 2018 with brain MRI performed between 2011 and 2013. We identified cases of incident late-onset epilepsy (LOE) with onset of seizures occurring after the acquisition of brain MRI. We evaluated the relative pattern of cortical thickness, subcortical volume, and white matter integrity among participants with incident LOE after MRI in comparison with participants without seizures. We examined the association between MRI abnormalities and incident LOE using Cox proportional hazards regression. Models were adjusted for demographics, hypertension, diabetes, smoking, stroke, and dementia status. Among 1251 participants with brain MRI data, 27 (2.2%) developed LOE after MRI over a median of 6.4 years (25-75 percentile 5.8-6.9) of follow-up. Participants with incident LOE after MRI had higher levels of cortical thinning and white matter microstructural abnormalities before seizure onset compared to those without seizures. In longitudinal analyses, greater number of abnormalities was associated with incident LOE after controlling for demographic factors, risk factors for cardiovascular disease, stroke, and dementia (gray matter: hazard ratio [HR]: 2.3, 95% confidence interval [CI]: 1.0-4.9; white matter diffusivity: HR: 3.0, 95% CI: 1.2-7.3). This study demonstrates considerable gray and white matter pathology among individuals with LOE, which is present prior to the onset of seizures and provides important insights into the role of neurodegeneration, both of gray and white matter, and the risk of LOE.

Demographics and care of epilepsy in older adults in Germany.