Epilepsy in Down Syndrome: Timing, Seizures, and Alzheimer’s Disease

What was studied

Researchers conducted a multicentre, observational, longitudinal study of 4,804 adults with Down syndrome from seven international cohorts. Participants were age 18 or older, had a mean age of 43 years, and had at least one longitudinal clinical assessment. About two-thirds were cognitively stable; others had non-degenerative cognitive decline, prodromal Alzheimer's disease, or Alzheimer's disease dementia.

The study examined how often active epilepsy occurred, when it appeared relative to symptomatic Alzheimer's disease, and whether it was associated with survival and cognitive trajectories. Active epilepsy meant an epilepsy diagnosis plus ongoing antiseizure medication or at least one seizure within the previous 5 years. Researchers also assessed EEG abnormalities.

What they found

Epilepsy became more common with age and increased sharply after symptomatic Alzheimer's disease began. The estimated cumulative incidence rose from 9.5% at Alzheimer's disease diagnosis to 56.9% after 9 years. With symptomatic Alzheimer's disease, epilepsy presented mostly as myoclonic or tonic-clonic seizures.

The likelihood of epilepsy was higher with more time since Alzheimer's disease diagnosis, severe-to-profound intellectual disability, and APOE ε4 carriership, independently of age. Late-onset myoclonic epilepsy in Down syndrome was associated with approximately twice the mortality rate and with faster cognitive decline. EEG abnormalities between seizures had little diagnostic utility.

The abstract reports an overall active epilepsy prevalence of 145.2 “per adults with Down syndrome,” but it does not specify a denominator, so this value cannot be clearly interpreted.

Limits of the evidence

This was an observational study, so it identifies associations but cannot establish that epilepsy causes faster cognitive decline or reduced survival. Alzheimer's disease stages were assigned by clinical consensus. The abstract does not describe seizure treatments, seizure control, individual follow-up durations, or the handling of missing data. It also does not specify the denominator for the reported overall epilepsy prevalence.

For families and caregivers

The findings indicate that seizures become increasingly frequent after symptomatic Alzheimer's disease begins in adults with Down syndrome, with myoclonic jerks and tonic-clonic seizures being the main reported types. Late-onset myoclonic epilepsy was associated with reduced survival and faster cognitive decline, but the study does not show whether preventing or treating seizures changes these outcomes.

What to watch next

Further prospective and interventional studies could test whether earlier recognition, prevention, or treatment of seizures and related brain hyperexcitability affects cognition, daily function, or survival.

Terms in this summary

symptomatic Alzheimer's disease

Alzheimer's disease that has begun to cause clinically noticeable cognitive symptoms.

LOMEDS

Late-onset myoclonic epilepsy in Down syndrome, which often emerges with symptomatic Alzheimer's disease.

myoclonic seizure

A seizure involving brief, sudden muscle jerks.

tonic-clonic seizure

A seizure that can cause body stiffening, rhythmic jerking, and loss of awareness.

cumulative incidence

The percentage of people who develop a condition over a stated period.

APOE ε4

A genetic variant that, in this study, was associated with a higher likelihood of epilepsy.

hazard ratio

A comparison of the rate at which an outcome occurs between groups. A hazard ratio of 2.10 indicates approximately twice the rate during follow-up.

interictal EEG

A recording of the brain's electrical activity taken between seizures.