Epilepsy Increases After the Onset of Alzheimer’s Disease in Adults With Down Syndrome
An international multicenter study led by the Neurobiology of Dementia Group at Sant Pau Research Institute (IR Sant Pau) and the Alzheimer-Down Unit at Sant Pau Hospital, in collaboration with the Biomedical Research Networking Centre in Neurodegenerative Diseases (CIBERNED), has analysed the natural history of epilepsy in adults with Down syndrome and its relationship with Alzheimer’s disease. The study, published in The Lancet, included 4,804 people from different countries and shows that epilepsy is closely related to the symptomatic onset of Alzheimer’s disease in this population, with its risk progressively increasing as the disease advances.
The research was led by Dr. Lucía Maure-Blesa, Dr. María Carmona-Iragui and Dr. Juan Fortea from IR Sant Pau and involved the participation of various national and international centers.
“This study shows that epilepsy and Alzheimer’s disease are very closely related in people with Down syndrome. We have observed that epileptic seizures do not occur simply because people grow older; rather, their risk increases clearly when Alzheimer’s symptoms begin and continues to rise as the disease progresses,” explains Dr. Lucía Maure-Blesa, a neurologist at the Alzheimer-Down Unit at Sant Pau Hospital and one of the IR researchers who led the study.
More Than Half Develop Epilepsy Nine Years Later
The observational, longitudinal study analysed seven international cohorts over an overall observation period from October 24, 2012, to July 28, 2025. All participants were adults with Down syndrome, with a mean age of 43 years.
The findings show that epilepsy becomes more frequent with age, but especially when symptoms of Alzheimer’s disease appear. At this stage, the most common epileptic seizures are myoclonic seizures, characterized by brief, sudden muscle jerks, and tonic-clonic seizures, which involve loss of consciousness associated with muscle stiffness and convulsive movements.
The cumulative incidence of epilepsy increases linearly after the symptomatic onset of Alzheimer’s disease. Approximately one in ten people has epilepsy at the time of an Alzheimer’s disease diagnosis, and nine years later, more than half have developed it. Specifically, the cumulative incidence rises from 9.5% at diagnosis to 56.9% after nine years.
“This increase in risk indicates that the onset of epileptic seizures is closely linked to the point at which Alzheimer’s disease begins to manifest clinically. Before that point, new seizures are far less frequent; afterward, the risk progressively increases,” notes Dr. Maure-Blesa.
The study also indicates that the risk of epilepsy increases with the time elapsed since an Alzheimer’s diagnosis, independently of age. In addition, it is associated with a higher risk in people with severe or profound intellectual disabilities and in carriers of the APOE4 allele.
Higher Mortality and Faster Cognitive Decline
One of the study’s most relevant findings is the prognostic impact of late-onset myoclonic epilepsy associated with Down syndrome.
The presence of this type of epilepsy is associated with higher mortality and faster cognitive decline. Specifically, the study identifies an association with a 2.10-fold higher risk of mortality.
“The onset of epilepsy marks an important change in the progression of the disease. People who develop epilepsy experience faster cognitive decline and higher mortality,” explains Dr. Carmona-Iragui.
However, the researcher stresses that these results do not establish a causal relationship: “This does not necessarily mean that seizures are the cause of this worsening. They could also be a sign that Alzheimer’s is more aggressive or is at a more advanced stage. Understanding which of these two possibilities is occurring is precisely one of the major questions raised by this study.”
Paying Closer Attention to the Onset of Epileptic Seizures
The results also have implications for the clinical follow-up of adults with Down syndrome and Alzheimer’s disease.
“The most immediate implication is that we need to pay much closer attention to the onset of possible epileptic seizures, especially from the moment a person with Down syndrome begins to show symptoms of Alzheimer’s disease. Some seizures may be very obvious, but others, such as small jerks especially in the morning, may go unnoticed,” explains Dr. Maure-Blesa.
An International Cohort of More Than 4,800 People
Of the 4,804 participants included in the study, 3,238 (67.4%) remained cognitively stable; 267 (5.6%) had non-degenerative cognitive impairment; 321 (6.7%) had prodromal Alzheimer’s disease; and 978 (20.3%) had Alzheimer’s disease dementia.
Regarding the degree of intellectual disability, 1,020 participants had mild intellectual disability, 2,352 had moderate intellectual disability, and 779 had severe or profound intellectual disability.
To be considered to have active epilepsy, participants had to have an epilepsy diagnosis together with ongoing anti-seizure treatment or have experienced at least one seizure in the previous five years.
The authors conclude that the increase in epilepsy after the onset of Alzheimer’s symptoms and its relationship with shorter survival and faster cognitive decline reinforce the need to develop new prevention and treatment strategies.
Reference Article:
Maure-Blesa L, Carmona-Iragui M, Barroeta I, et al. Natural history and clinical impact of epilepsy in adults with Down syndrome: a multicentre clinical study. The Lancet. 2026. doi:10.1016/S0140-6736(26)00980-3.
