Neuropathology
Conditions
Keywords
cognitive composite score, sleep, biomarkers, cognitive decline
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.
Interventions
PROCEDUREPolysomnography
Polysomnography will be performed for 24 hours at inclusion and 24 months
BEHAVIORALNeuropsychological assessment
A full neuropsychological assessment will be performed at inclusion, 12 and 24 months
Questionnaires on sleep and behavioural problems
PROCEDUREActimetry
Measurement of actimetrics for 14 days at inclusion and at 24 months
DIAGNOSTIC_TESTFractional diuresis
Split diuresis from 7pm-7am, 7am-12am and 12pm-19pm during polysomnography at inclusion inclusion and 24 months to measure melatonin concentration
PROCEDUREInternal temperature measurement
eCelsius capsule to measure internal temperature at inclusion and 24 months
OTHERBiomarker assay
Determination of the biomarkers Aβ42, Aβ40, Tau and P-Tau in blood and in the cerebrospinal fluid
Sponsors
Institut National de la Santé Et de la Recherche Médicale, France
University Hospital, Montpellier
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
50 Years to 85 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in the Free and Cued Selective Reminding Test (FCSRT) scale score | From inclusion to 24 months | The FCSRT test evaluates memory, the score obtained is between 0 and 48, higher score mean a better outcome |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cognitive decline in ADCS-PACC composite score | At inclusion and at 24 months | The ADCS-PACC composite score is used to assess cognitive decline |
| Cognitive decline in the Alzheimer's Disease Cooperative Study- Preclinical Alzheimer Cognitive Composite (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 |
| Concentration of orexinA/hypocretin | At inclusion and at 24 months | Determination in serum and cerebrospinal fluid |
| Changes in sleep duration | At inclusion and at 24 months | Average sleep duration (in hours and minutes) over a 14-day period from inclusion to M24 measured by actimetry |
| 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 |
| Change in the Free and Cued Selective Reminding Test (FCSRT) scale score | From inclusion to 12 months | The FCSRT test evaluates memory, the score obtained is between 0 and 48, higher score mean a better outcome |
| Time spent in Rapid eye movement (REM) sleep during polysomnography | At inclusion and at 24 months | Time spent in stage 3 sleep measured 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 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 |
| Urinary melatonin concentration | At inclusion and at 24 months | Fractional diuresis |
| Internal temperature | At inclusion and at 24 months | The internal temperature will be measured with an e-Celsius capsule 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 |
Countries
France
Contacts
Primary ContactClaire Denis
Backup ContactYves Dauvilliers, MD
Outcome results
None listed