Predictive Value of Biomarkers of the Alzheimer's Disease (AD) in Elderly Patients With New-onset Epilepsy

Predictive Value of Biomarkers of the Alzheimer's Disease (AD) in Elderly Patients With New-onset Epilepsy

Beyond 60 years, the prevalence of epilepsy is estimated at approximately 1% and increases with age. In these patients, the etiology of epilepsy is unknown in 25% of cases, even up to 55% after 65 years. Although new-onset epilepsy in the elderly is associated with a vascular disease in 50% of cases, the hypothesis of an ongoing neurodegenerative process, including an Alzheimer's disease (AD), is also common. However, investigators do not have any marker that might help to identify the patients who develop epilepsy after 60 years and who might be, despite a normal cognitive functioning, already engaged in the pathophysiological process of AD.

A number of data suggest a link between the pathophysiological process of AD and epileptogenesis:

(i) a third of patients with epilepsy develops MA, (ii) the occurrence of epilepsy in AD is an aggravating factor for cognition, (iii) in animal models of AD, the relationship between neuronal hyperexcitability and amyloid deposits is bidirectional, the amyloid protein has a pro-seizure effect and the presence of epilepsy increases the amyloid deposits, (iv) in these models, the administration of an antiepileptic drug protects from deterioration of cognition, (v) the close relationship between amyloid and neuronal hyperexcitability might be mediated by the inflammatory processes associated with AD, and particularly the microglial activation which role in epileptogenesis has been shown elsewhere.

Investigators hypothesize that in a subgroup of patients who develop epilepsy after 60 years, the occurrence of epilepsy might reflect the presence of an ongoing amyloid pathology. Our goal is to identify through biomarkers of AD in the cerebrospinal fluid of patients who develop an epilepsy after 60 years with normal MRI and normal cognition those at high risk of later developing clinically defined AD.

Identifying patients with amyloid pathology which would be expressed through epilepsy before the onset of cognitive dysfunction might help to adapt both the management of seizures and of the cognitive dysfunction.

Inclusion Criteria:

• Age ≥ 60 years
• Patients with newly diagnosed epilepsy according to the latest criteria of the International League against Epilepsy.
• MMSE ≥ 28/30.
• Patients with or without cognitive complaints.
• Patients whose brain MRI did not reveal significant abnormalities outside slight cortical atrophy.
• Patients in whom the lumbar puncture did not revealed abnormalities suggestive of an infectious disease or a limbic encephalitis.
• Patient with adequate visual and auditory skills, an oral and written language in French available to clinical and neuropsychological assessment.
• Patient who have given its written consent.

Exclusion Criteria:

• Previous history of epilepsy before age 60 years.
• Patient with against-indication to MRI (pacemaker, ferromagnetic clips, mechanical heart valves, intra-cochlear implants, intraocular foreign body, skin or other) or refusing MRI.
• Presence of an abnormality in brain MRI.
• Patients with diagnostic criteria for dementia of Alzheimer's disease, vascular dementia, mixed dementia or frontotemporal lobar degeneration.
• Patients with autoimmune encephalitis.
• Patients under legal protection measure