Neurologists scrutinize the brain's capabilities, looking for clues to its functioning, not only when there is disease, but before. This allows us to find common spaces that some pathologies share. For some time, the close relationship between Down syndrome, Alzheimer's disease and the appearance of epilepsy has been studied. In fact, people with Down syndrome have a very high risk of developing dementia due to triplication of chromosome 21.
Now, an international multicenter study published in The Lancet this week, with 4,804 adults with Down syndrome, from seven European cohorts, reveals that late-onset epilepsy is not a coincidence, but an intrinsic part of Alzheimer's.
Lucía Maure, neurologist at the Hospital de la Santa Creu i Sant Pau (one of the participating centers), comments that "our data show that, once the symptoms of the neurodegenerative disease begin, the risk of presenting epileptic seizures increases markedly and increases as the disease progresses." This expert and one of the main authors attributes it to the biology of Alzheimer's disease, "since it triggers this neuronal hyperexcitability and is therefore part of the disease itself, not a coincidence."
To address the interrelation, the x-ray that appears after the study shows that 67.4% were cognitively stable, 5.6% had non-degenerative deterioration, 6.7% had early-stage Alzheimer's, and 20.3% had dementia. Intellectual disability was mild in 24.6%, moderate in 56.7%, and severe or profound in 18.8%. Regarding the prevalence of active epilepsy, it was present at 14.5%. In those over 60 years of age, 12.1% were asymptomatic, compared to 45.9% in symptomatic patients. The incidence rate in people over 60 years of age with Alzheimer's was 109.6 per 1,000 person-years compared to 6.9 in asymptomatic people. The cumulative risk of seizures throughout life rises from 3.3% at age 40 to 61.3% at age 70.
Late-onset epilepsy arises around the onset of Alzheimer's (one year before clinical diagnosis). Its cumulative incidence goes from 9.5% in the year of diagnosis to 56.9% after nine years. Its appearance implies that it doubles mortality and accelerates cognitive loss.
Early treatment after the first attacks is key, since the progression is 18.7% after three years in treated patients compared to 80.2% in untreated patients. For this, there is a wide medicine cabinet, ranging from levetiracetam, valproate and lamotrigine to other antiepileptics. Regarding this, Maure admits that they know that "crises trigger once the disease begins, often as small sudden jerks of the arms, especially when waking up, or as seizures, and that they worsen both the cognitive and survival prognosis." And according to this, the next step is to "now study if we can prevent their appearance with antiepileptic drugs from the beginning of the disease and if, by avoiding them, we can slow down cognitive deterioration and prolong survival."
Monitor for signs of the onset of epilepsy over time
Before reaching treatment, detection is key. In these cases, the conventional electroencephalogram (EEG) is used, but as the specialist points out, it does not help to "rule out epilepsy in these patients" and recommends "doing this test in a regulated and early manner, as soon as the patient enters the period of greatest risk, that is, when cognitive deterioration begins." To do this, he recommends longer exams that include periods of rest, sleep and waking up.
Also in the work, independent risk factors for active epilepsy have been measured, such as severe or profound intellectual disability and the presence of the alteration of the APOE-4 allele. Given the magnitude of the general risk, the co-author advises that this type of epilepsy be "integrated as one of the most frequent manifestations of Alzheimer's disease in this population and that it be actively searched for from the moment they are diagnosed."
At the same time, Maure adds that families and caregivers should be informed about this high risk to maintain a certain level of vigilance for any signs of suspicion and begin treatment as soon as crises appear.
