Biomarkers of Sleep-wake Cycle in Prodromal Alzheimer's Disease: Role in Cognitive Decline? (ALZ-OREX)

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.

Study Overview

• Status: Recruiting
• Conditions: Neuropathology
• Intervention / Treatment: Procedure: Polysomnography; Behavioral: Neuropsychological assessment; Behavioral: Questionnaires on sleep and behavioural problems; Procedure: Actimetry; Diagnostic test: Fractional diuresis; Procedure: Internal temperature measurement; Other: Biomarker assay

• Study Type: Interventional
• Enrollment (Estimated): 132
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yves Dauvilliers, MD; Phone Number: +33467335219; Email: y-dauvilliers@chu-montpellier.fr
• Study Contact Backup: Name: Claire Denis; Phone Number: +33467333162; Email: claire-denis@chu-montpellier.fr

Study Locations

• France
  • Montpellier, France
    • Recruiting
    • University Hospital, Montpellier
    • Contact: Karim BENNYS, MD
    • Principal Investigator: Karim BENNYS, MD
  • Poitiers, France
    • Not yet recruiting
    • University hospital of Poitiers
    • Contact: Marc PACCALIN, MD
    • Principal Investigator: Marc PACCALIN
  • Toulouse, France
    • Not yet recruiting
    • University Hospital of Toulouse
    • Contact: Rachel DEBS, MD
    • Principal Investigator: Rachel DEBS, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of mild Alzheimer's disease with a Mini Mental State (MMS) between 21-30
• The presence of a family carer to complete neuropsychological scales, questionnaires and sleep diaries
• Having a neurological assessment and/or follow-up requiring blood and cerebrospinal fluid (CSF) sampling with biomarkers for diagnostic purposes
• Patient who had a lumbar puncture less than one year ago or patient with a scheduled lumbar puncture as part of care
• 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
• Anticholinesterase and/or memantine treatment or on stable doses for at least 3 months
• Use of antidepressants, anxiolytics, hypnotics, neuroleptics, 15 days before inclusion
• 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
• Initial contraindication to diagnostic lumbar puncture (LP) (spinal surgery, skin infection, haemostasis abnormality, intracranial hypertension, severe coagulation disorders, curative anticoagulant therapy, severe liver failure)
• Refusal to perform a diagnostic lumbar puncture
• Contraindication to the use of E-Celsius: people weighing less than 40 kg, with intestinal disorders, with known swallowing disorders
• Patient deprived of liberty, by judicial or administrative decision;
• Major protected by law;
• Patient in a period of relative exclusion from another protocol or for whom the maximum annual compensation of €4500 has been reached;
• Refusal to participate in the protocol.

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; Alzheimer

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; Procedure: Actimetry; Measurement of actimetrics for 14 days at inclusion and at 24 months; Diagnostic test: Fractional diuresis; Split diuresis from 7pm-7am, 7am-12am and 12pm-19pm during polysomnography at inclusion inclusion and 24 months to measure melatonin concentration; Procedure: Internal temperature measurement; eCelsius capsule to measure internal temperature at inclusion and 24 months; Other: Biomarker assay; Determination of the biomarkers Aβ42, Aβ40, Tau and P-Tau in blood and in the cerebrospinal fluid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the Free and Cued Selective Reminding Test (FCSRT) scale score	The FCSRT test evaluates memory, the score obtained is between 0 and 48, higher score mean a better outcome	From inclusion to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the Free and Cued Selective Reminding Test (FCSRT) scale score	The FCSRT test evaluates memory, the score obtained is between 0 and 48, higher score mean a better outcome	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 24 months
Cognitive decline in the Alzheimer's Disease Cooperative Study- Preclinical Alzheimer Cognitive Composite (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
Concentration of orexinA/hypocretin	Determination in serum and cerebrospinal fluid	At inclusion and at 24 months
Changes in sleep duration	Average sleep duration (in hours and minutes) over a 14-day period from inclusion to M24 measured by actimetry	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 Rapid eye movement (REM) sleep during polysomnography	Time spent in stage 3 sleep measured 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 hypopneas / number of hours of sleep) during polysomnography	At inclusion and at 24 months
Nocturnal oxygen saturation (SaO2)	The nocturnal 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
Urinary melatonin concentration	Fractional diuresis	At inclusion and at 24 months
Internal temperature	The internal temperature will be measured with an e-Celsius capsule 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 (Actual): April 17, 2023
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027

Study Registration Dates

• First Submitted: October 28, 2022
• First Submitted That Met QC Criteria: November 17, 2022
• First Posted (Actual): November 29, 2022

Study Record Updates

• Last Update Posted (Estimated): October 7, 2025
• Last Update Submitted That Met QC Criteria: October 2, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: sleep; biomarkers; cognitive composite score; cognitive decline
• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction; Behavioral Disciplines and Activities; Psychological Tests; Neuropsychological Tests
• Other Study ID Numbers: RECHMPL18_0061

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No