The Effect of Anticholinesterase Drugs on Sleep in Alzheimer's Disease Patients

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine the effects of the anticholinesterase drug donepezil on sleep in Alzheimer disease patients. Sleep structure and respiratory parameters will be analyzed by polysomnography.

Detailed Description
-----------------
Central acting cholinesterase inhibitors are the first primary pharmacological treatment approved for Alzheimer disease, of which donepezil is the most frequently used. Multicenter studies have found little toxicity, and its side effects (diarrhea, nausea, vomiting, nightmares, among others) are mild and transient. According to the literature, cholinergic active drugs may be expected to affect REM (rapid eye movement) sleep. Another possible effect is related to respiratory parameters in patients with Alzheimer disease and obstructive sleep apnea. In fact, cholinergic activity influences the upper airway opening via central and peripheral mechanisms. Intervention: Patients will be administered donepezil or placebo. The study has a randomized, double-blind placebo-controlled design. Complete polysomnography with REM sleep EEG spectral analysis and ADAS-cog scoring will be performed at baseline and after 3 and 6 months.

Official Title
-----------------
The Effect of Anticholinesterase Drugs on Sleep in Alzheimer's Disease Patients

Conditions
-----------------
Alzheimer Disease, Sleep Apnea, Obstructive

Intervention / Treatment
-----------------
* Drug: donepezil
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis of Alzheimer's disease based on the probability criteria of the Alzheimer's Disease and Related Disorders Association Rated 1 and 2 (mild to moderate level) on the Brazilian version of the Clinical Dementia Rating Exclusion Criteria: Other causes of dementia Other severe medical or psychiatric disease Clinical indication of psychoactive drugs other than experimental drug

Ages Eligible for Study
-----------------
Minimum Age: 50 Years
Maximum Age: 90 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>Donepezil treated Alzheimer patients | Drug: donepezil<br>* donepezil 5 mg 1 p / day for 1 month and 2p / day for 5 months on.<br>|
| Placebo Comparator: B<br>Placebo treated Alzheimer patients | Drug: Placebo<br>* Placebo 1p / day for 1 month and 2 / day for 5 months on<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Polysomnography parameters: sleep structure, respiratory, limb movements |  | onset, 3 and 6 months of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brain magnetic resonance imaging |  | onset | 
| laboratory tests: hematological evaluation, creatinine, vitamin B12-folic acid, thyroid hormones, GOT, GPT, GGT, bilirubin, fasting glycemia, venereal disease research test and urine sediment |  | onset | 
| electroencephalogram |  | onset | 
| Mini-mental state examination |  | onset | 
| IDATE |  | onset | 
| Frequency bands of scalp EEG areas: overall (average of all electrodes), frontal (F3, F4, F7, F8, Fz), temporal (T3, T4, T5, T6), parietal (P3, P4, Pz), central (C3, C4, Cz), and occipital (O1, O2, Oz). |  | onset, 3 and 6 months of treatment | 
| ADAS-cog scores |  | onset, 3 and 6 months of treatment | 
| Clinical Dementia Rating |  | onset | 
| EEG slowing ratio |  | onset, 3 and 6 monthes of treatment | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Alzheimer, polysomnography, REM sleep, donepezil, sleep apnea, oxygen saturation