Clinical trial NCT01400542: Sleep Apnea in Early to Mid-Stage Alzheimer's Disease
Official title: Sleep Apnea in Early to Mid-Stage Alzheimer's Disease: What Impact of Treatment on the Cognitive Functions of Elderly Patients With Memory Loss?
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Early Onset Alzheimer Disease
Alzheimer Disease
Obstructive Sleep Apnea Syndromes
Keywords: Early Onset Alzheimer Disease
Alzheimer Disease
Sleep Apnea Syndromes
Obstructive Sleep Apnea Syndromes
Cognitive functions
Continuous Positive Airway Pressure (CPAP) treatment
Lead sponsor: Centre Hospitalier Universitaire de Saint Etienne
Sponsor class: OTHER
Collaborators: name: Association Lyonnaise de Logistique Posthospitalière
First posted: 2011-07-22
Enrollment: 22
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Elderly patients with a early or mid-Stage Alzheimer's disease with or without SAOS.

Brief summary: Obstructive sleep apnea (OSA) is much more common in the elderly than in the young; the latest studies show prevalence between 45% and 62% in individuals over 60. It is even higher in patients with dementia such as Alzheimer patients.

Several trials in elderly patients showed modified cognitive functions, particularly executive and attentional functions, in patients with respiratory sleep disorder. However the benefit of CPAP (Continuous Positive Airway Pressure) ventilation for Alzheimer patients is still controversial, as there are few studies documenting its effects on dementia patients' cognitive abilities, and clinicians appear reluctant to prescribe this type of treatment.

The investigators must keep in mind that Alzheimer patients suffer significant sleep disorders; advanced- stage patients spend 40% of the night awake and are drowsy a large part of the day. In dementia patients, sleep disorder is a major cause of hospitalization and institutionalization. The prevalence of obstructive sleep apnea (OSA) in this population is estimated at over 50%, and appears to be higher the more advanced the dementia. Trials on obstructive sleep apnea syndromes in Alzheimer patients show significatively improved scores on the apnea-hypopnea index (AHI), as well as satisfactory treatment tolerance. However, any impact on cognitive abilities has yet to be demonstrated.

In addition, cardiovascular pathologies such as arterial hypertension, cardiac arrhythmias, and strokes are strongly correlated to OSA. In light of its consequences on morbidity and mortality, OSA should be considered a public health issue.

In this context, the investigators wish to address the impact of CPAP treatment implementation on the cognitive parameters of patients diagnosed with OSA, particularly on their executive functions. This should provide evidence for mid-term assessment of the benefits of CPAP in caring for elderly patients with dementia.

In light of the prevalence of obstructive sleep pathologies in elderly patients reported in various studies and of the potential impact of CPAP treatment on cognitive abilities, the investigators propose a study to evaluate the impact of OSA treatment on elderly Alzheimer patients' cognitive abilities, particularly on their executive functions.

Executive functions are a rather heterogenous group of high-level cognitive processes which enable individuals to adopt a flexible, context-appropriate behavior. They also include planning abilities, working memory, cognitive control, abstract thought, rule learning, selective attention, motor response selection, etc... Executive functions are mainly associated to the functioning of the brain's frontal lobes, although subcortical structures also play a role. When the executive functions are affected by disease, daily life is significantly impeded as the individual becomes unable to perform complex tasks or regulate his/her behavior. Many tests can help evaluate these functions in dementia patients. A number of "ecological" tests, such as the zoo map test from the Behavioural Assessment of the Dysexecutive Syndrome (BADS) arsenal, are quite relevant for evaluating executive functions.

This project aims to improve the daily life of Alzheimer patients with sleep apnea by improving their executive cognitive functions through CPAP treatment.

According to the Paquid's trial, there are 12,400 Alzheimer patients in the French Loire department. \[27\] The study population will therefore be recruited in the "La Charité" center of CHU Saint-Etienne. The target population is older individuals (≥ 65) suffering from cognitive disorders similar to Alzheimer's disease.

OSA will be diagnosed based on polysomnography, on an outpatient basis. Apnea patients will receive CPAP treatment for 4 months, which is the minimum duration required to implement and accept treatment, and to measure its impact on patients' neurocognitive abilities.

Detailed description: This study's originality lies in that the target population is elderly and has been diagnosed with both Alzheimer's disease and sleep apnea, and in that it focuses on the impact of treatment on these patient's cognitive abilities, particularly on their executive abilities.We aim to provide practitioners with evidence-based arguments for screening and treating sleep apnea in dementia patients in order to care for these patients, whose treatment options are often scarce.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of Alzheimer-type dementia confirmed by the study's memory specialist.
* MMS comprised between 20 and 28 (inclusive)
* One main caregiver with full mental capacity, living under the same roof, present at all medical visits
* Patient covered by compulsory health insurance
* Patient signed the informed consent form

Exclusion Criteria:

* Prior diagnosis of sleep apnea or patients already benefitting from respiratory assistance equipment- History of COPD (Chronic Obstructive Pulmonary Disease), treated with bronchodilators or corticoids
* Patients with severe heart failure (stages III and IV of the NYHA Functional Classification)
* Patients with a recent history of stroke or myocardial infarction (within the last three months)
* Recently initiated or modified anticholinergic treatment (within the last two months)
* Patients under guardianship
* Behavioral disorders (pacing, agitation)
* Patients with severe dementia
* Patient with potentially low tolerance to treatment (latex allergies, claustrophobia, prior CPAP treatment which was badly tolerated)
* Serious bullous lung disease
* Pneumothorax
* Arterial hypotension
* Dehydration
* Cerebrospinal fluid effusion, recent concussion, or cranial surgery

Primary outcomes:
measure: Impact of the CPAP treatment on cognitive functions
timeFrame: At 4 Months
Secondary outcomes:
measure: Rate of apnea/hypopnea events per hour (AHI/h)
timeFrame: Each month from Day 1 to Month 4
measure: Impact of CPAP treatment on neuropsychological evaluation parameters
timeFrame: At 4 months
measure: Impact of the CPAP treatment on Quality of Life
timeFrame: At 4 months
Other outcomes:
Locations:
city: Saint-etienne
country: France
facility: CHU de Saint-Etienne
Study officials:
affiliation: CHU de Saint-Etienne
name: Emilie ACHOUR, MD
role: PRINCIPAL_INVESTIGATOR
References: