Sleep Impairment in Subjects at Risk of Developing Alzheimer's Disease

Study Overview
=================
Brief Summary
-----------------
Alzheimer's disease (AD) is characterised by a progressive loss of memory and cognitive function. In the early stages of AD, there is a progressive accumulation of molecules: β-amyloid peptides (Aβ) in the brain. There is a link between the accumulation of Aβ peptides and the deterioration of sleep, but current knowledge does not confirmed this link. The objective of this study is to define whether there is a link between cognitive decline and sleep disorders. If a correlation is found, this could allow earlier treatment of sleep disorders in the longer term in order to slow the development of AD. Treatment protocols in the field of Alzheimer's disease (AD) are directed towards participants at risk of developing the disease, such as those who carry at least one ε4 allele on apolipoprotein E (APOE ε4). An individual with 2 ε4 copies has a 30-55% risk of developing AD with an age of onset around 68 years and a dose effect of the allele on risk and age of onset of symptoms.

Official Title
-----------------
Objective Sleep Impairment in APOEε4/ε4 Subjects at Risk of Developing Alzheimer's Disease: Risk Factor for Cognitive Decline?

Conditions
-----------------
Neuropathology, Cognitive Decline, Sleep Disorder

Intervention / Treatment
-----------------
* Procedure: Polysomnography
* Behavioral: Neuropsychological assessment
* Behavioral: Questionnaires on sleep and behavioural problems
* Procedure: Actimetrics
* Other: Biomarker assay


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis of mild Alzheimer's disease with a MMS between 21-30 Without anticholinesterase and/or memantine treatment or on stable doses for at least 3 months No antidepressant or anxiolytic treatment or stopped for at least 15 days The presence of a family carer to complete neuropsychological scales, questionnaires and sleep diaries Signed informed consent Able to carry out all visits and follow study procedures Affiliation to the French social security system Exclusion Criteria: Genetic form of alzheimer's disease Insufficient clinical and paraclinical information for the diagnosis of AD Patient living in a nursing home Illiteracy or inability to perform psycho-behavioural tests Major physical or neurosensory problems that may interfere with the tests Patient deprived of liberty, by judicial or administrative decision; Major depression according to Diagnostic and Statistical Manual of Mental Disorders (DSM-5) Major protected by law; Short-term life-threatening conditions

Ages Eligible for Study
-----------------
Minimum Age: 50 Years
Maximum Age: 85 Years

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

Accepts Healthy Volunteers
-----------------
No

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

Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single arm<br>Prodromal Alzheimer's patients | Procedure: Polysomnography<br>* Polysomnography will be performed for 24 hours at inclusion and 24 months<br>Behavioral: Neuropsychological assessment<br>* A full neuropsychological assessment will be performed at inclusion, 12 and 24 months<br>Behavioral: Questionnaires on sleep and behavioural problems<br>* Questionnaires on sleep and behavioural problems<br>Procedure: Actimetrics<br>* Measurement of actimetrics for 14 days at inclusion and at 24 months<br>Other: Biomarker assay<br>* Determination of the biomarkers Aβ42, Aβ40, Tau and P-Tau in blood and in the cerebrospinal fluid<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the Alzheimer's Disease Cooperative Study - Preclinical Alzheimer Cognitive (ADCS-PACC) scale score | The ADCS-PACC scale will be based on scores from the Mini Mental State Examination (MMSE), the Free Recall/Indicated Recall Test, the Digit Substitution Symbol Test, the Wechsler Intelligence Scale for Adults (WAIS-IV), and the 2-minute Verbal Fluency Test | From inclusion to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the Alzheimer's Disease Cooperative Study - Preclinical Alzheimer Cognitive (ADCS-PACC) scale score | The ADCS-PACC scale will be based on scores from the Mini Mental State Examination (MMSE), the Free Recall/Indicated Recall Test, the Digit Substitution Symbol Test, the Wechsler Intelligence Scale for Adults (WAIS-IV), and the 2-minute Verbal Fluency Test | From inclusion to 12 months | 
| Cognitive decline in ADCS-PACC composite score | The ADCS-PACC composite score is used to assess cognitive decline | At inclusion and at 12 months | 
| Concentration of proteins involved in Alzheimer disease | Determination of Aβ42, Aβ40, Tau and P-Tau proteins in serum and cerebrospinal fluid | At inclusion and at 24 months | 
| Sleep time at stage 1-2 during polysomnography | Time spent in stage 1-2 sleep measured in hours and minutes during polysomnography | At inclusion and at 24 months | 
| Sleep time at stage 3 during polysomnography | Time spent in stage 3 sleep measured in hours and minutes during polysomnography | At inclusion and at 24 months | 
| Time spent in Rapide Eye Movement (REM) sleep during polysomnography | Time spent in REM in hours and minutes during polysomnography | At inclusion and at 24 months | 
| Apnea Hypopnea index | The Apnea-Hypopnea Index is calculated from the number of apneas and hypopneas per hour of sleep (AHI = number of apneas + number of hyopneas / number of hours of sleep) during polysomnography | At inclusion and at 24 months | 
| Noctural oxygene saturation (SaO2) | The noctural SaO2 is an average of SaO2 values taken during the night. The value is expressed as a percentage and is measured during polysomnography | At inclusion and at 24 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
cognitive composite score, sleep, biomarkers, cognitive decline