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

Not Applicable
Recruiting
Conditions
Neuropathology
Interventions
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
Registration Number
NCT05629871
Lead Sponsor
University Hospital, Montpellier
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
132
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 & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Single armPolysomnographyAlzheimer
Single armQuestionnaires on sleep and behavioural problemsAlzheimer
Single armActimetryAlzheimer
Single armInternal temperature measurementAlzheimer
Single armFractional diuresisAlzheimer
Single armBiomarker assayAlzheimer
Single armNeuropsychological assessmentAlzheimer
Primary Outcome Measures
NameTimeMethod
Change in the Free and Cued Selective Reminding Test (FCSRT) scale scoreFrom inclusion to 24 months

The FCSRT test evaluates memory, the score obtained is between 0 and 48, higher score mean a better outcome

Secondary Outcome Measures
NameTimeMethod
Cognitive decline in ADCS-PACC composite scoreAt inclusion and at 24 months

The ADCS-PACC composite score is used to assess cognitive decline

Sleep time at stage 3 during polysomnographyAt inclusion and at 24 months

Time spent in stage 3 sleep measured in hours and minutes during polysomnography

Time spent in Rapid eye movement (REM) sleep during polysomnographyAt inclusion and at 24 months

Time spent in stage 3 sleep measured in hours and minutes during polysomnography

Change in the Free and Cued Selective Reminding Test (FCSRT) scale scoreFrom inclusion to 12 months

The FCSRT test evaluates memory, the score obtained is between 0 and 48, higher score mean a better outcome

Concentration of proteins involved in Alzheimer diseaseAt inclusion and at 24 months

Determination of Aβ42, Aβ40, Tau and P-Tau proteins in serum and cerebrospinal fluid

Concentration of orexinA/hypocretinAt inclusion and at 24 months

Determination in serum and cerebrospinal fluid

Changes in sleep durationAt inclusion and at 24 months

Average sleep duration (in hours and minutes) over a 14-day period from inclusion to M24 measured by actimetry

Urinary melatonin concentrationAt inclusion and at 24 months

Fractional diuresis

Cognitive decline in the Alzheimer's Disease Cooperative Study- Preclinical Alzheimer Cognitive Composite (ADCS-PACC) composite scoreAt inclusion and at 12 months

The ADCS-PACC composite score is used to assess cognitive decline

Sleep time at stage 1-2 during polysomnographyAt inclusion and at 24 months

Time spent in stage 1-2 sleep measured in hours and minutes during polysomnography

Apnea Hypopnea IndexAt 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 hypopneas / number of hours of sleep) during polysomnography

Nocturnal oxygen saturation (SaO2)At inclusion and at 24 months

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

Internal temperatureAt inclusion and at 24 months

The internal temperature will be measured with an e-Celsius capsule during polysomnography

Trial Locations

Locations (3)

University Hospital, Montpellier

🇫🇷

Montpellier, France

University Hospital of Poitiers

🇫🇷

Poitiers, France

University Hospital of Toulouse

🇫🇷

Toulouse, France

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