Epileptiform Activity During REM Sleep in Alzheimer's Disease

  • End date
    Jun 26, 2022
  • participants needed
  • sponsor
    University Hospital, Toulouse
Updated on 5 February 2021


Recent clinical data showed that patients with Alzheimer Disease (AD) might present epilepsy at early stages of the disease (Cretin et al., 2016, Vossel et al., 2016). In mice models of Alzheimer disease, preclinical researchers observed an increase of epileptic events during Rapid Eye Movement (REM) sleep, which is very unusual. This study aims at testing if patients with AD present an exacerbation of epileptic events during REM sleep, which could constitute an early biomarker of the disease. Investigators will evaluate the incidence of epilepsy during each sleep stage in 40 patients with early or moderate forms of AD and in 40 healthy subjects. Investigators will also look for a link between epilepsy during sleep in AD participants and memory performances, brain damage (by using MRI scans) and in the case of patients, the phenotype of the Apolipoprotein E(ApoE) gene.


Preclinical researchers discovered that Tg2576 mouse model of Alzheimer Disease (AD) present epileptiform activity specifically during sleep, with a prominent increase during REM-sleep. This phenotype is specific to AD mice since REM-sleep usually prevents seizures and epileptiform activity in animal models of epilepsy. preclinical researchers also evidenced that this epileptic phenotype occurs at very early age in Tg2576 mice, far before the onset of cognitive impairments. Thus, preclinical researchers hypothesized that patients with AD might present subclinical epileptiform events during sleep which might worsen during REM-sleep. If so, it could be used as a specific and early biomarker of AD. Since sleep is involved in the consolidation of memory, preclinical researchers also hypothesized that epileptiform events during sleep might participate to cognitive dysfunction in AD patients.

In order to test this hypothesis, preclinical researchers designed a monocentric clinical study aiming at evaluating seizures and subclinical epileptiform activity during sleep in 40 patients at early to moderate stages of AD and 40 matched healthy participants. A blood sample will be collected of each patient for genetic testing of the Apolipoprotein E before they undergo a high-resolution MRI scan and a neuropsychological evaluation including episodic memory tests before an overnight polysomnography. Healthy subjects will undergo the same procedures except for the blood test from which they will be exempted. Then, all subjects (patients and healthy participants) will be tested for the memories acquired before the polysomnography in order to evaluate sleep related memory consolidation.

This should allow to evidence sleep related epileptic events, to precise their incidence in AD patients as well as in healthy participants, and to correlate these events to anomalies in brain structure and functional resting state connectivity (MRI) and/or sleep disturbances and/or cognitive decline.

Condition Alzheimer's Disease
Treatment Blood sample, neuropsychological evaluation, Overnight polysomnography, high-resolution MRI scan
Clinical Study IdentifierNCT03923569
SponsorUniversity Hospital, Toulouse
Last Modified on5 February 2021


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Inclusion Criteria

Is your age between 50 yrs and 90 yrs?
Gender: Male or Female
Do you have any of these conditions: Do you have Alzheimer's Disease??
For all participants
age from 50 to 75 years old
affiliated to the French health care system
For AD patients
meeting International Working Group (IWG)-2 criteria for diagnosis
Mini-Mental State Examination (MMSE) 20 (Greco version)
For healthy volunteers
Dubois 5 words test 9

Exclusion Criteria

For all participants
people not able to give consent
contraindication for MRI (metallic body parts, claustrophobia)
aphasia, apraxia or agnosia
neurological (other than AD) or any other serious disease (cancer, addiction, systemic disease)
non treated sleep apnea
major depression or anxiety for more than 3 months (Beck>10) or psychiatric disease
documented epilepsy
use of neuroleptics (more than one dose per day)
use of antiepileptics
use of benzodiazepines at a dose superior or equal to two intakes per day
use of antidepressants
restless leg syndrome treated by dopaminergic agonists
For AD patients
other causes of dementia
non-degenerative neurological lesions
white matter hypersignals
acute cognitive deficits
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