Cognitive Decline in Older Adults with Epilepsy: Mechanisms, Risk Stratification, and Therapeutic Implications.

Older adults with epilepsy (≥50 years) are at an increased risk for cognitive impairment and dementia, a challenge that spans two main clinical groups. The first group includes individuals with chronic epilepsy, diagnosed and treated long-term from childhood or earlier adulthood, who are twice as likely to develop cognitive decline as they age. The second group comprises those with late-onset epilepsy, diagnosed after age 50, in whom a similar twofold increased risk of cognitive deterioration has been observed. Such decline is often linked to underlying causes such as stroke, traumatic brain injury, or neurodegenerative conditions like Alzheimer’s disease.



Current evidence indicates that this elevated risk results from a convergence of multifactorial mechanisms. Notably, amyloid and tau pathology, blood-brain barrier dysfunction, neurovascular changes, and neuroinflammatory processes are implicated. Despite advances in the use of biomarkers and imaging for risk stratification, considerable gaps remain in understanding which factors most strongly predict cognitive trajectories in this population. A deeper exploration of these mechanisms is essential for improving risk assessment and developing interventions that target cognitive outcomes for older adults living with epilepsy.



The primary challenge addressed by this Research Topic is the insufficient understanding and management of cognitive decline in older adults with epilepsy. Although advances have been made in identifying at-risk individuals, current risk stratification tools are limited, and many cases of cognitive deterioration remain unexplained, particularly in those without obvious underlying lesions or neurodegenerative biomarkers. Furthermore, there is a lack of clarity regarding the long-term cognitive effects of antiseizure medications (ASMs), especially considering pharmacokinetic and pharmacodynamic changes associated with aging and comorbidities.



To address these gaps, this Research Topic aims to foster multidisciplinary research that:

-Illuminates the distinct and overlapping drivers of cognitive decline in both chronic and late-onset epilepsy;

-Evaluates both traditional and novel biomarkers (imaging, EEG, CSF/blood) and their role in patient stratification;

-Investigates the impact of pharmacological and non-pharmacological interventions on cognitive trajectories;

-Explores therapeutic strategies targeting neurodegenerative, neurovascular, and neuroinflammatory pathways.