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

NCT05649514 — Not applicable, Recruiting, 50 participants, University Hospital, Montpellier

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

Registry	NCT05649514, acronym WAVE-APOE4
Status	Recruiting
Phase	Not applicable
Study type	Interventional; na, single group, masking: none, diagnostic
Enrollment	50 (Estimated)
Sponsor	University Hospital, Montpellier (Other); collaborators: Institut National de la Santé Et de la Recherche Médicale, France
Conditions	Neuropathology, Cognitive Decline, Sleep Disorder
Interventions	Polysomnography, Neuropsychological assessment, Questionnaires on sleep and behavioural problems, Actimetrics, Biomarker assay (Procedure, behavioral, other)
Dates	start 2025-02-05, primary completion 2027-08-01 (estimated), completion 2027-12-01 (estimated), first posted 2022-12-14, last updated 2025-06-27
Locations	1 site in France

-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.

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+Arms and interventions

Arm	Type	Interventions	Description
Single arm	Experimental	Procedure: Polysomnography; Behavioral: Neuropsychological assessment; Behavioral: Questionnaires on sleep and behavioural problems; Procedure: Actimetrics; Other: Biomarker assay	Prodromal Alzheimer's patients

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

+Outcome measures

Primary outcomes

Change in the Alzheimer's Disease Cooperative Study - Preclinical Alzheimer Cognitive (ADCS-PACC) scale score [From inclusion to 24 months]: 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

Secondary outcomes

Change in the Alzheimer's Disease Cooperative Study - Preclinical Alzheimer Cognitive (ADCS-PACC) scale score [From inclusion to 12 months]: 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
Cognitive decline in ADCS-PACC composite score [At inclusion and at 12 months]: The ADCS-PACC composite score is used to assess cognitive decline
Concentration of proteins involved in Alzheimer disease [At inclusion and at 24 months]: Determination of Aβ42, Aβ40, Tau and P-Tau proteins in serum and cerebrospinal fluid
Sleep time at stage 1-2 during polysomnography [At inclusion and at 24 months]: Time spent in stage 1-2 sleep measured in hours and minutes during polysomnography
Sleep time at stage 3 during polysomnography [At inclusion and at 24 months]: Time spent in stage 3 sleep measured in hours and minutes during polysomnography
Time spent in Rapide Eye Movement (REM) sleep during polysomnography [At inclusion and at 24 months]: Time spent in REM in hours and minutes during polysomnography
Apnea Hypopnea index [At inclusion and at 24 months]: 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
Noctural oxygene saturation (SaO2) [At inclusion and at 24 months]: 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

+Eligibility

Sex: All, ages: 50 Years to 85 Years

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

+Locations (1)

Facility	City	Country	Status
CHU de Montpellier	Montpellier, Hérault	France	Recruiting

+Investigators

Karim BENNYS, MD, Principal investigator, University Hospital, Montpellier