Effects of Donepezil and Memantine on Cognitive Functions After a Sleep Deprivation Challenge in Healthy Volunteers

Inclusion Criteria:

Demography

1. Healthy male subjects aged between 25 and 40 years-old inclusive

2. BMI between 18 kg/m2 to 27 kg/m2

   Health status

3. The subjects is in good health on the basis of the medical interview (medical history, symptoms) and the physical examination, vital signs and the results of blood chemistry and hematology.
4. ECG (12 leads) normal (120 < PR < 200 ms; QRS < 120ms; QTcF < 450ms) and/or without clinically relevant impairments as judged by investigator.
5. The subject does not smoke or smokes a maximum of 5 cigarettes per day and is able to stop during the days of the study.
6. No claustrophobia (fMRI)

7. The subject has normal visual and auditory abilities

   Specific to the study

8. Habitual good sleeping: sleeping on average 6,5 to 9 hours each night in the past month assessed by the Pittsburgh Quality Index.
9. Regular sleeping hours whereby they sleep no later than 1 am and rise before 9 am in the past month assessed by the Pittsburgh Quality Index.
10. The subject can complete the neuropsychological test battery during the training session
11. The subject corresponds to an extravert personality according to the Eysenck Personality Inventory

12. The subject is right-handed (Edinburgh Handedness Inventory, Imaging measurement condition).

    Regulations

13. The subjects is able to read and understand the Information Form and comply with the protocol instructions and restrictions
14. Subjects are covered by a social insurance
15. Subjects have provided written informed consent

Exclusion Criteria:

Medical history and clinical status

1. History or presence of psychiatric illness assessed by a psychiatric interview with the Mini-International Neuropsychiatric Interview (M.I.N.I-DSM IV).
2. History or presence of neurologic illness or others illnesses (general medical interview)
3. The subject has caffeine intake of greater than 5 drinks per day or excessive energy drink type intake.

4. The subject has an orthostatic blood pressure reduction > 20 mm Hg, based on a difference of systolic blood pressure between supine and after standing for 3 minutes.

   General conditions

5. The patient, in the opinion of the investigator, is unlikely to comply with the study protocol or is unsuitable for any other reason

6. The subject participates to another clinical trial or is still being within a washout period of a previous clinical trial, or subjects who received more than 4500 euros in the previous 12 months.

   Specific to the study

7. History or presence of daytime sleepiness with the Epworth scale (score > 10, pathological sleepiness).
8. History of obstructive sleep apnea assessed by the Berlin questionnaire.
9. History of periodic leg movements assessed by Restless Legs Syndrome questionnaire.
10. Extreme chronotypes: score at the Horne Ostberg scale (< 31 or > 69).
11. Jet lag > 2 hours in the last two weeks.
12. No time-shifted work during the last month.