Effects of Auditory Brain Stimulation by Pink Noise on Memory Capacities in Alzheimer's Disease: Proof of Concept Study

Study Overview
=================
Brief Summary
-----------------
Alzheimer's disease (AD) is a neurodegenerative disorder affecting almost 6% of the world's population over the age of 65. This disease, in its most typical sporadic form, is characterized by an episodic memory impairment linked to a deficit in consolidation. Many studies indicate that sleep promotes this consolidation stage during the deep slow sleep stage by facilitating the transfer of information between the hippocampus and the neocortex. A method of acoustic brain stimulation at night by pink noises has been recently developed and has shown its effectiveness in strengthening memory consolidation in healthy volunteers. Actually, there is no study observing the effect of this new stimulation method on populations with neurodegenerative pathologies, in particular in AD for which this technique could potentially become a therapeutic option. The hypothesis is that of a strengthening of the memory consolidation capacities in subjects with AD as has been shown in healthy subjects.

Detailed Description
-----------------
Alzheimer's disease (AD) is a neurodegenerative disorder affecting almost 6% of the world's population over the age of 65. This disease, in its most typical sporadic form, is characterized by an episodic memory impairment linked to a deficit in consolidation. Many studies indicate that sleep promotes this consolidation stage during the deep slow sleep stage by facilitating the transfer of information between the hippocampus and the neocortex. A method of acoustic brain stimulation at night by pink noises has been recently developed and has shown its effectiveness in strengthening memory consolidation in healthy volunteers. Actually, there is no study observing the effect of this new stimulation method on populations with neurodegenerative pathologies, in particular in AD for which this technique could potentially become a therapeutic option. The hypothesis is that of a strengthening of the memory consolidation capacities in subjects with AD as has been shown in healthy subjects.

Official Title
-----------------
Effects of Auditory Brain Stimulation by Pink Noise on Memory Capacities in Alzheimer's Disease: Proof of Concept Study

Conditions
-----------------
Alzheimer's Disease (AD)

Intervention / Treatment
-----------------
* Device: Dreem headband
* Device: Dreem headband


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria common to all participants: Age> 50 years at the inclusion Patient with regular sleep patterns Patient having given written consent Patient affiliated to a social security regimen Inclusion criteria for subjects with Alzheimer's disease: Patient with a beginning Alzheimer's disease defined according to the criteria of the National Institute on Aging-Alzheimer's Association or carriers of a prodromal Alzheimer's disease defined according to the criteria of the International Working Group IWG-2; the diagnosis must be supported by brain imaging and a blood test carried out in routine care MMSE score ≥ 24 Inclusion criteria for healthy volunteers: Absence of neurodegenerative pathologies Matched in age (+/- 5 years) and in sex with a patient Non-inclusion criteria common to all participants: Psychiatric pathologies (except depression or anxiety disorders stabilized for more than 3 months) History of pathology which may have consequences on cognitive functioning and / or sleep: brain tumor, constituted stroke, epilepsy, head trauma (with clinical or parenchymal sequelae objectified on brain imagery), brain surgery Any significant comorbidity likely to constitute a confounding factor according to the clinician Psychotropic treatments introduced or modified <3 months before inclusion Hypnotic and / or sedative treatments Chronic consumption of alcohol or drugs Legal incapacity and / or other circumstance rendering the patient unable to understand the nature, objective or consequences of the study Major under guardianship or curatorship Patient not French-speaking by birth or illiterate Exclusion Criteria common to all participants: Sleep disorders defined by a score> 5 on the Pittsburg sleep quality index (PSQI) A score> 10 on the Epworth sleepiness index

Ages Eligible for Study
-----------------
Minimum Age: 50 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ON-Stim<br>acoustic stimulation | Device: Dreem headband<br>* acoustic stimulation<br>|
| Sham Comparator: OFF-Stim<br>no acoustic stimulation | Device: Dreem headband<br>* acoustic stimulation<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| difference between morning and eve of the number of reminders found between the ON-stimulation condition and the OFF-stimulation condition, on the memory task of word matching. | gross variation of the difference between morning and eve of the number of reminders found between the ON-stimulation condition and the OFF-stimulation condition, on the memory task of word matching. | Day 7 | 
| difference between morning and eve of the number of reminders found between the ON-stimulation condition and the OFF-stimulation condition, on the memory task of word matching. | gross variation of the difference between morning and eve of the number of reminders found between the ON-stimulation condition and the OFF-stimulation condition, on the memory task of word matching. | Day 8 | 
| difference between morning and eve of the number of reminders found between the ON-stimulation condition and the OFF-stimulation condition, on the memory task of word matching. | gross variation of the difference between morning and eve of the number of reminders found between the ON-stimulation condition and the OFF-stimulation condition, on the memory task of word matching. | Day 14 | 
| difference between morning and eve of the number of reminders found between the ON-stimulation condition and the OFF-stimulation condition, on the memory task of word matching. | gross variation of the difference between morning and eve of the number of reminders found between the ON-stimulation condition and the OFF-stimulation condition, on the memory task of word matching. | Day 15 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of reminders found between the ON-stimulation condition and the OFF-stimulation condition, on the ecological memory task. | gross variation of the difference between morning and eve of the number of reminders found between the ON-stimulation condition and the OFF-stimulation condition, on the ecological memory task. | Day 7 | 
| Number of reminders found between the ON-stimulation condition and the OFF-stimulation condition, on the ecological memory task. | gross variation of the difference between morning and eve of the number of reminders found between the ON-stimulation condition and the OFF-stimulation condition, on the ecological memory task. | Day 8 | 
| Number of reminders found between the ON-stimulation condition and the OFF-stimulation condition, on the ecological memory task. | gross variation of the difference between morning and eve of the number of reminders found between the ON-stimulation condition and the OFF-stimulation condition, on the ecological memory task. | Day 14 | 
| Number of reminders found between the ON-stimulation condition and the OFF-stimulation condition, on the ecological memory task. | gross variation of the difference between morning and eve of the number of reminders found between the ON-stimulation condition and the OFF-stimulation condition, on the ecological memory task. | Day 15 | 
| The memory complaint for Mc Nair's Questionnaire | score from 0 to 156.156 control of a bad score. The variation between J0 and J15 will be studied. | Baseline | 
| Psychoaffective aspects (Depression) for MADRS (Montgomery Asberg Depression Rating Scale) | score from 0 to 60.60 control of a bad score. The variation between J0 and J15 will be studied. | Baseline | 
| Psychoaffective aspects (Anxiety) for HAMA (Hamilton Anxiety) | score from 0 to 56.56 control of a bad score. The variation between J0 and J15 will be studied. | Baseline | 
| Quality of sleep for Pittsburgh Index (PSQI) | It is more an index of tolerance than efficiency. If the score is higher, the tolerance is lower. | Baseline | 
| The memory complaint for Mc Nair's Questionnaire | score from 0 to 156.156 control of a bad score. The variation between J0 and J15 will be studied. | Day 15 | 
| Psychoaffective aspects (Depression) for MADRS (Montgomery Asberg Depression Rating Scale) | score from 0 to 60.60 control of a bad score. The variation between J0 and J15 will be studied. | Day 15 | 
| Psychoaffective aspects (Anxiety) for HAMA (Hamilton Anxiety) | score from 0 to 56.56 control of a bad score. The variation between J0 and J15 will be studied. | Day 15 | 
| Quality of sleep for Pittsburgh Index (PSQI) | It is more an index of tolerance than efficiency. If the score is higher, the tolerance is lower. | Day 15 | 
| amplitude of slow waves in deep slow sleep between the ON-stimulation condition and the OFF-stimulation condition | gross variation in the amplitude of slow waves in deep slow sleep between the ON-stimulation condition and the OFF-stimulation condition, on an ambulatory EEG device | Day 7 | 
| amplitude of slow waves in deep slow sleep between the ON-stimulation condition and the OFF-stimulation condition | gross variation in the amplitude of slow waves in deep slow sleep between the ON-stimulation condition and the OFF-stimulation condition, on an ambulatory EEG device | Day 8 | 
| amplitude of slow waves in deep slow sleep between the ON-stimulation condition and the OFF-stimulation condition | gross variation in the amplitude of slow waves in deep slow sleep between the ON-stimulation condition and the OFF-stimulation condition, on an ambulatory EEG device | Day 14 | 
| amplitude of slow waves in deep slow sleep between the ON-stimulation condition and the OFF-stimulation condition | gross variation in the amplitude of slow waves in deep slow sleep between the ON-stimulation condition and the OFF-stimulation condition, on an ambulatory EEG device | Day 15 |