What is late-onset epilepsy?
The population across the UK and worldwide is ageing, which has driven an increase in the prevalence of late-onset epilepsy, defined as the development of epilepsy in later life. Late-onset epilepsy is also strongly associated with worsened cognition, disrupted sleep, and other disorders of brain health.
There is an urgent need to understand the mechanisms underlying late-onset epilepsy, its links to other disorders, and the associated negative impacts on cognition and sleep, which can substantially reduce quality of life and independence. An essential goal of research into late-onset epilepsy is to move towards patient-centred diagnoses and care that go beyond simply treating seizures and instead address the underlying changes happening in the brain, which include disruptions to blood flow (known as vascular diseases), the build-up of harmful proteins, and other biological changes. By better understanding these root causes, researchers hope to develop more targeted and effective treatments for people living with late-onset epilepsy.
How do we understand the mechanisms of late-onset epilepsy?
An important way to understand the mechanism of late-onset epilepsy is the use of laboratory tools called “preclinical models” which can include animal models that mimic human diseases. During the symposium, Dr. Rob Wykes emphasised that these models must be carefully designed to be clinically relevant by including frequent seizures, constant monitoring, and other common health issues. He has developed an improved model specifically for post-stroke epilepsy to develop robust, translatable predictors of this disease. These realistic models are essential for testing potential treatments early in research.
What mechanisms can cause late-onset epilepsy?
The Symposium mainly discussed two common causes of late-onset epilepsy: (1) stroke and vascular diseases and (2) aggregation of harmful proteins in the brain.
During his talk, Mr Jamie Elliot explained that the build-up of harmful proteins in the brain can cause development of seizure activity in laboratory models. Dr Francesca Chaloner went on to discuss how the use of preclinical models of protein build-up can be used to develop interventions to improve seizures. Importantly, Dr. Xin You Tai highlighted that people with epilepsy who have protein build-up often experience faster declines in cognition. Understanding these root mechanisms is paving the way for more precise and effective epilepsy therapies.
What other diseases are associated with late-onset epilepsy?
Late-onset epilepsy is linked to other brain conditions like dementia and vascular disease, a key focus of the Symposium. Dementia is a syndrome characterised by impaired cognition and is fundamentally linked to specific types of late-onset epilepsy through shared processes including protein build-up and abnormal brain activity.
Dr. Alice Lam, Dr. Xin You Tai and Professor Matthias Koepp are investigating the link between the two conditions. An ongoing longitudinal observational study led by Dr. Alice Lam will develop tools to predict which patients with late-onset unexplained epilepsy are at greatest risk for developing dementia.
Work by Professor Hedley Emsley and Dr. Josie Mayer demonstrates how understanding ties between vascular disease and epilepsy have shown us which drug treatment options work best for specific patient groups.
What is the relationship between late-onset epilepsy and sleep?
Sleep emerged as a key factor linking late-onset epilepsy, cognitive decline, and dementia. Dr. Xin You Tai highlighted that epileptic activity during sleep may disrupt critical processes involved in memory processing. Sleep disruption may also increase epileptic activity and impair the brain’s ability to clear proteins linked to dementia.
Dr. Aravind Kumar Kamaraj further emphasised the important role that sleep and the body’s natural 24-hour clock play in the link between epilepsy and dementia. He explained that unusually high levels of brain activity appear to be a common feature of both conditions, and that targeting this overactivity could lead to better treatments.
These talks highlighted the need for long-term studies investigating how sleep influences dementia risk in epilepsy and positioned sleep as an important target for future research and clinical intervention.
How can we improve care and management of late-onset epilepsy?
A recurring theme was that late-onset epilepsy is a manifestation of broader changes in the ageing brain rather than an isolated condition, requiring treatment to be tailored to each individual.
Professor Hedley Emsley described late-onset epilepsy as a sign that the brain’s networks may be starting to fail. Rather than seeing it as an isolated condition, he argued that it should be viewed as an opportunity to identify underlying brain health problems early and intervene to improve long-term health. Professor Ley Sander further emphasised the diagnostic challenges of late-onset epilepsy, particularly when patients have multiple health conditions and are taking many medications and proposed potential solutions to improve diagnostic accuracy.
In Dr. Josie Mayer’s talk, she emphasised the importance of managing risk factors associated with late-onset epilepsy including hypertension, diabetes, smoking and sleep apnoea. Furthermore, Professor Matthias Koepp explained that epilepsy developing later in life may sit at the crossroads between the build-up of harmful proteins linked to dementia and abnormal brain activity, raising the question of whether treating these changes could slow or alter the course of the condition. Finally, Dr. Adam Noble stressed the need for new ways of delivering specialist care, particularly in care homes, where many residents may require specialist epilepsy support.
Combined with emerging approaches such as long-term brain activity monitoring and objective sleep measures, these advances would offer opportunities for more personalised and effective management of late-onset epilepsy.
Overall Outcomes, Conclusions and Future Thoughts
To summarise the key messages from the Symposium, late-onset epilepsy may represent a critical opportunity for early intervention to improve long-term brain health outcomes in older adults, including reducing risk of dementia and stroke. Late-onset epilepsy should be understood as a sign of broader network failure, reflecting overlapping vascular issues and processes linked to dementia, and offers a unique lens for studying the ageing brain.
Looking ahead, the CLOVER (Collaboration for Late-Onset Epilepsy and Vascular Epilepsy Research) network, co-led by Dr. Clare Gordon, Professor Hedley Emsley, and Dr. Sana Hannan, will provide an important platform for collaborative work in this space. As Dr. Clare Gordon highlighted during the Symposium, ongoing priority-setting efforts – including an upcoming survey following earlier workshops with patients, carers, clinicians and researchers – will help shape future research directions. Central to this is the involvement of people with lived experience, exemplified by Mrs. Christine Clarke’s personal reflection, ensuring their perspectives continue to shape advances in research and care.
