Individuals with a genetic predisposition for Alzheimer’s disease may face a higher risk of developing epilepsy, while those with a specific type of epilepsy may be at a higher risk of developing Alzheimer’s disease, according to a study published today in the online issue of Neurology.
The new findings suggest that “not only are people with Alzheimer’s disease more likely to develop epilepsy, but also that those with focal epilepsy, which accounts for more than half of all cases of epilepsy, were more likely to develop Alzheimer’s disease,” remarks study author Jiali Pu.
In this study, researchers conducted a comprehensive genome-wide association study to analyze the gene variation in 111,326 individuals with Alzheimer’s disease and 677,663 individuals without the disease. By comparing long stretches of DNA, they aimed to identify small genetic differences associated with Alzheimer’s disease.
To determine a causal relationship between genetic variations and epilepsy risk, the researchers utilized a study design called Mendelian randomization. They sought to establish whether the identified genetic variations were responsible for an increased risk of epilepsy.
The results revealed a significant correlation between Alzheimer’s disease and an increased risk of two types of epilepsy. Individuals with Alzheimer’s disease showed a 5.3% higher risk of developing generalized epilepsy, characterized by seizures originating from both halves of the brain. Additionally, there was a 1.3% elevated risk of focal epilepsy with hippocampal sclerosis, which involves recurrent seizures affecting one half of the brain.
Further analysis was conducted by comparing the genes of 15,212 individuals with epilepsy to the genes of 29,677 individuals without epilepsy. The study found that those with focal epilepsy and hippocampal sclerosis had nearly four times the risk of developing Alzheimer’s disease compared to those without epilepsy.
Moreover, the researchers examined the genes of 13,116 individuals who had data on the levels of a biomarker called amyloid, associated with Alzheimer’s disease, in their cerebrospinal fluid. Genes predicting lower levels of this biomarker were found to be associated with an increased risk of generalized epilepsy, indicating a potential connection between amyloid plaque deposition in the brain and epilepsy.
These findings provide valuable insights into the bidirectional relationship between Alzheimer’s disease and epilepsy. The study highlights the increased risk of epilepsy in individuals with Alzheimer’s genes and the heightened risk of Alzheimer’s disease in those with certain forms of epilepsy.
“More effort should be made to screen for seizures in people with Alzheimer’s disease and to understand the impact of seizures on those facing these two challenging neurologic conditions,” Pu comments.
It is important to acknowledge a limitation of the study, which primarily involved participants of European ancestry. Consequently, caution should be exercised when generalizing the results to individuals residing in other countries and belonging to diverse ethnic backgrounds.
Further investigations are needed to elucidate the underlying mechanisms and explore potential therapeutic interventions that target shared pathways between the two conditions.
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