Sleep Impairment in Subjects at Risk of Developing Alzheimer's Disease (WAVE-APOE4)

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Sleep Disorder; Cognitive Decline; Neuropathology
• Intervention / Treatment: Procedure: Polysomnography; Behavioral: Neuropsychological assessment; Behavioral: Questionnaires on sleep and behavioural problems; Other: Biomarker assay; Procedure: Actimetrics

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yves Dauvilliers, MD; Phone Number: +33467335219; Email: y-dauvilliers@chu-montpellier.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 48 years to 83 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

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

Experimental: Single arm; Prodromal Alzheimer's patients

Procedure: Polysomnography; Polysomnography will be performed for 24 hours at inclusion and 24 months; Behavioral: Neuropsychological assessment; A full neuropsychological assessment will be performed at inclusion, 12 and 24 months; Behavioral: Questionnaires on sleep and behavioural problems; Questionnaires on sleep and behavioural problems; Other: Biomarker assay; Determination of the biomarkers Aβ42, Aβ40, Tau and P-Tau in blood and in the cerebrospinal fluid; Procedure: Actimetrics; Measurement of actimetrics for 14 days at inclusion and at 24 months

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
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
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
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

Collaborators and Investigators

• Sponsor: University Hospital, Montpellier
• Collaborators: Institut National de la Santé Et de la Recherche Médicale, France
• Investigators: Principal Investigator: Karim BENNYS, MD, University Hospital, Montpellier

Study record dates

Study Major Dates

• Study Start (Anticipated): February 1, 2023
• Primary Completion (Anticipated): August 1, 2027
• Study Completion (Anticipated): December 1, 2027

Study Registration Dates

• First Submitted: November 9, 2022
• First Submitted That Met QC Criteria: December 5, 2022
• First Posted (Estimate): December 14, 2022

Study Record Updates

• Last Update Posted (Estimate): December 14, 2022
• Last Update Submitted That Met QC Criteria: December 5, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: sleep; biomarkers; cognitive composite score; cognitive decline
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Cognition Disorders; Sleep Wake Disorders; Alzheimer Disease; Cognitive Dysfunction
• Other Study ID Numbers: RECHMPL22_0392

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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