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

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.

Study Overview

• Status: Completed
• Conditions: Epilepsy
• Intervention / Treatment: Biological: profile of CSF biomarkers of AD

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Bron, France, 69500
    • Hospices Civils de Lyon
  • Clermont-Ferrand, France
    • CHU Gabriel- Montpied
  • Grenoble, France
    • CHU des Alpes
  • Saint-Étienne, France
    • CHU Hôpital Nord

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Presence of biomarkers of AD in cerebrospinal fluid; Patients older than 60 years, with normal brain MRI and with normal cognitive functioning who demonstrate a profile of CSF biomarkers of AD suggestive of biological AD	Biological: profile of CSF biomarkers of AD; dosage of biomarker of AD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The primary endpoint was the number of patients in a population of subjects older than 60 years with new-onset epilepsy but without cognitive impairment whose profile of the CSF biomarkers of the AD is suggestive of an AD.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
changes in episodic verbal memory at 2 years	Evolution of RL/RI-16 score between inclusion and 2 years of follow-up	2 years
changes in visual recognition memory at 2 years	Evolution of DMS 48 score between inclusion and 2 years of follow-up	2 years
Evolution of DO 80 score	Evolution of semantic memory at 2 years: Evolution of DO 80 score between inclusion and 2 years follow-up	2 years
Evolution of categorical influences	Evolution of semantic memory at 2 years: Evolution of categorical influences between inclusion and 2 years follow-up	2 years
Evolution of TOP 10 score	Evolution of semantic memory at 2 years: Evolution of TOP 10 score between inclusion and 2 years follow-up	2 years
Changes in monthly frequency of seizures at 2 years	Evolution of monthly frequency of seizures between inclusion and 2 years of follow-up	2 years

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon
• Investigators: Study Director: Aurélie RICHARD-MORNAS, Doctor, Hospices Civils de Lyon

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2017
• Primary Completion (Actual): March 16, 2023
• Study Completion (Actual): March 16, 2023

Study Registration Dates

• First Submitted: July 4, 2016
• First Submitted That Met QC Criteria: August 5, 2016
• First Posted (Estimate): August 10, 2016

Study Record Updates

• Last Update Posted (Actual): March 23, 2023
• Last Update Submitted That Met QC Criteria: March 22, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: biomarkers; epilepsy; Alzheimer; predictive value
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Epilepsy; Alzheimer Disease
• Other Study ID Numbers: 69HCL16-0041; 2016-A00563-48 (Other Identifier: ID-RCB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No