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

Overview

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.

Interventions

• 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

Primary outcome measures

• Change in the Free and Cued Selective Reminding Test (FCSRT) scale score [Time frame: From inclusion to 24 months]

Secondary outcome measures (12)

• Change in the Free and Cued Selective Reminding Test (FCSRT) scale score [Time frame: From inclusion to 12 months]
• Cognitive decline in ADCS-PACC composite score [Time frame: At inclusion and at 24 months]
• Cognitive decline in the Alzheimer's Disease Cooperative Study- Preclinical Alzheimer Cognitive Composite (ADCS-PACC) composite score [Time frame: At inclusion and at 12 months]
• Concentration of proteins involved in Alzheimer disease [Time frame: At inclusion and at 24 months]
• Concentration of orexinA/hypocretin [Time frame: At inclusion and at 24 months]
• Changes in sleep duration [Time frame: At inclusion and at 24 months]
• Sleep time at stage 1-2 during polysomnography [Time frame: At inclusion and at 24 months]
• Sleep time at stage 3 during polysomnography [Time frame: At inclusion and at 24 months]
• Time spent in Rapid eye movement (REM) sleep during polysomnography [Time frame: At inclusion and at 24 months]
• Apnea Hypopnea Index [Time frame: At inclusion and at 24 months]
• Nocturnal oxygen saturation (SaO2) [Time frame: At inclusion and at 24 months]
• Urinary melatonin concentration [Time frame: At inclusion and at 24 months]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Diagnostic

Study locations

France · 3 centers

• University Hospital, Montpellier — Montpellier
• University Hospital of Poitiers — Poitiers
• University Hospital of Toulouse — Toulouse

Identifiers

NCT: NCT05629871 · RECHMPL18_0061

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗