Epilepsy & Alzheimer’s Disease: Investigating the Links Between Epilepsy and Cognitive Decline
By Amanda Nascimento
Oct, 2024.
Introduction
Epilepsy and Alzheimer's disease (AD) are both neurological conditions that have a significant impact on brain function, yet they are often studied independently. Recent research suggests a complex relationship between these two disorders, where epilepsy can both result from and exacerbate the pathological processes in Alzheimer's disease. Understanding this connection is crucial for developing effective treatment strategies aimed at slowing cognitive decline in affected individuals.
Pathophysiological Links Between Epilepsy and Alzheimer's Disease
Epilepsy and Alzheimer's disease share several pathophysiological mechanisms that contribute to neuronal dysfunction. One of the key factors is neuroinflammation, which plays a significant role in both conditions. In Alzheimer's, chronic inflammation contributes to the formation of amyloid plaques and neurofibrillary tangles, leading to neurodegeneration. Similarly, inflammation in epilepsy is known to promote hyperexcitability and seizure activity (Vezzani et al., 2011).
Excitotoxicity is another shared mechanism where excessive glutamate activity leads to neuronal damage. In Alzheimer's, abnormal levels of glutamate can enhance amyloid-beta toxicity, which further triggers seizures in susceptible regions of the brain. Furthermore, evidence suggests that amyloid-beta and tau proteins—hallmarks of Alzheimer's pathology—can also disrupt normal synaptic transmission, increasing the risk of epileptic events (Busche & Hyman, 2020).
Clinical Evidence of Epilepsy in Alzheimer's Patients
Clinical studies have shown that individuals with Alzheimer's disease are at a higher risk of developing seizures compared to the general population. Approximately 10-22% of Alzheimer's patients experience epileptic seizures, with higher rates observed in early-onset forms of the disease (Pandis & Scarmeas, 2012). Seizures in these patients often present as focal (partial) seizures, which can be challenging to diagnose due to their subtle manifestations, such as brief episodes of confusion or unresponsiveness.
Research also indicates that early-onset seizures in Alzheimer's patients can be a marker of faster cognitive decline. These patients tend to show more rapid deterioration in memory, language, and executive function compared to those without seizures (Lam et al., 2017). This link between seizure activity and accelerated neurodegeneration highlights the importance of monitoring for epilepsy in Alzheimer's patients.
Impact of Epilepsy on Cognitive Decline in Alzheimer's Disease
Epileptic seizures can exacerbate cognitive decline in Alzheimer's patients by accelerating the neurodegenerative processes already in progress. Recurrent seizures cause further neuronal loss, especially in areas of the brain involved in memory and cognition, such as the hippocampus. This continuous cycle of seizure-induced damage can lead to a decline in cognitive abilities at a rate faster than would be expected from Alzheimer's disease alone (Sanchez et al., 2012).
The use of antiepileptic drugs (AEDs) in these patients is a subject of ongoing debate. While AEDs can control seizure activity, some of these medications have been linked to cognitive side effects that may worsen the cognitive decline seen in Alzheimer's disease. For instance, older-generation AEDs like phenobarbital and phenytoin are known to impair cognitive function, whereas newer drugs like levetiracetam may offer a better cognitive profile (Cumbo & Ligori, 2010).
Conclusion
The link between epilepsy and Alzheimer's disease is becoming increasingly evident, with seizures playing a significant role in accelerating cognitive decline. Understanding this relationship opens new avenues for early diagnosis, better management, and more effective treatment strategies. Further research is needed to explore the bi-directional relationship between these conditions and to develop therapies that can address both epilepsy and cognitive impairment simultaneously.
References
Busche, M. A., & Hyman, B. T. (2020). Synergy between amyloid-beta and tau in Alzheimer's disease. Nature Neuroscience, 23(10), 1183-1193. https://doi.org/10.1038/s41593-020-0687-6
Cumbo, E., & Ligori, L. D. (2010). Levetiracetam, lamotrigine, and phenobarbital in patients with epilepsy and Alzheimer's disease. Epilepsy & Behavior, 17(4), 461-466. doi: 10.1016/j.yebeh.2010.01.015.
Lam, A. D., et al. (2017). Silent hippocampal seizures and spikes identified by foramen ovale electrodes in Alzheimer's disease. Nature Medicine, 26(6), 784-792. doi: 10.1038/nm.4330
Pandis, D., & Scarmeas, N. (2012). Seizures in Alzheimer disease: clinical and epidemiological data. Epilepsy Currents, 12(5), 184-187. doi: 10.5698/1535-7511-12.5.184.
Sanchez, P. E., et al. (2012). Levetiracetam suppresses neuronal network dysfunction and reverses synaptic and cognitive deficits in an Alzheimer’s disease model. Proceedings of the National Academy of Sciences, 115(31), E7316-E7325. doi: 10.1073/pnas.1121081109.
Vezzani, A., et al. (2011). The role of inflammation in epilepsy. Nature Reviews Neurology, 7(1), 31-40. doi: 10.1038/nrneurol.2010.178.
