Abstract
With the aging of the general population, the number of patients with late-onset epilepsy is steadily increasing. This phenomenon is of particular relevance because current evidence suggests that a proportion of these cases may be associated with neurodegenerative diseases, especially Alzheimer’s disease (AD) (1). Beta-amyloid (A?) and tau proteins, which are hallmark pathologies of AD and are present years before the onset of clinical symptoms, may play a role in the development of neuronal hyperexcitability.
The risk of epileptic seizures is higher in patients with autosomal dominant AD. A seizure frequency of 47.7% has been reported after a mean follow-up of 8.4 years in patients with AD carrying pathogenic mutations in presenilin (PSEN)1, PSEN2, and amyloid precursor protein (APP), or duplications thereof. A meta-analysis showed that the apolipoprotein E ?4 allele is a risk factor for epilepsy. Moreover, it has been demonstrated that younger patients with AD are more likely to experience unprovoked seizures, with up to an 87-fold increase in the 50–59-year age group compared with the general population of the same age. Therefore, epilepsy is a frequent comorbidity in early-onset AD. In addition, patients with AD have an increased risk of developing epilepsy during the course of the disease, and several studies indicate that late-onset epilepsy may represent the first clinical manifestation of AD.
Depending on the degree of cognitive impairment, different forms of epilepsy have been described within the AD spectrum (Figure 1). The so-called “epileptic variant” of AD has generated growing clinical and research interest, and refers to cases in which epileptic seizures occur even when cognitive impairment is absent or minimal—namely, when neuropsychological evaluation reveals no deficits. In this regard, it is sometimes considered a “non-cognitive” presentation of AD, in which epileptic seizures constitute the initial and isolated clinical sign.
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