Affiliations: [a] Department of Neurology, San Gerardo Hospital, Monza, Italy
| [b] School of Medicine and Surgery and Milan Center for Neuroscience (NeuroMi), University of Milano-Bicocca, Monza, Italy
| [c] Department of Neuroscience, IRCCS-Institute for Pharmacological Research “Mario Negri”, Milan, Italy
Correspondence:
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Correspondence to: Jacopo C. DiFrancesco, MD, PhD, Department of Neurology, San Gerardo Hospital, Laboratory of Neurobiology, Milan Center for Neuroscience, School of Medicine and Surgery, University of Milano-Bicocca, Via Pergolesi, 33-20900 Monza (MB), Italy. E-mails: [email protected]; [email protected].
Abstract: Background:The prevalence of epilepsy with onset in adulthood increases with age, mainly due to the accumulation of brain damage. However, a significant proportion of patients experience seizures of unknown cause. Alzheimer’s disease (AD) is associated with an increased risk of seizures. Seizure activity is interpreted as a secondary event related to hyperexcitability caused by amyloid-β aggregation. Objective:Since neurodegenerative processes begin several years before clinical symptoms, epilepsy could be more frequent in the presymptomatic stages of dementia. Methods:We retrospectively reviewed the prevalence of epilepsy of unknown origin with adult onset before cognitive decline in a large cohort of AD patients (EPS-AD) recruited based on clinical and neuropsychological data. Data of patients with epilepsy followed by AD were compared with two control groups: patients with AD without seizures (no EPS-AD) and a large reference population (RP). Results:In AD patients, the prevalence of epilepsy of unknown origin, with onset in the adulthood before cognitive decline is 17.1 times higher compared with the RP (95% CI: 10.3–28.3). In EPS-AD, seizures begin on average 4.6 years (median 2.0) before the onset of cognitive symptoms and cognitive decline starts 3.6 years earlier compared with noEPS-AD. Conclusions:Neurodegenerative processes of dementia could play a key role in the pathogenesis of epilepsy in a subgroup of individuals intended to develop cognitive decline. Adult-onset epilepsy of undefined cause could thus represent a risk factor for the ongoing neurodegenerative damage, even preceding by years the onset of clinical symptoms of dementia.
