Obstructive Sleep Apnea Clinical Trial
Official title:
Effects of Exercise Training on Structure and Cerebral Metabolism, Cognition and Neurovascular Control in Individuals With Obstructive Sleep Apnea
Abstract
Obstructive sleep apnea syndrome (OSA) is characterized by complete or partial collapse of a
narrowed pharynx and it's associated with reduction in cerebral blood flow, cardiovascular
disease, and neuropsychological deficits and reduces survival. In patients with AOS
structural, metabolic and hypoperfusion cerebral were associated not only with physiological
functions but also with attention and executive function. There is a higher association
between apnea hypopnea index and Mini-Mental State Examination in individuals with the exon 4
of APO E gene, indicating that exon 4 of APO E gene confers an increased risk for cognitive
decline in individuals with sleep apnea. The analysis of presence and consequences of OSA in
cerebral structure, inflammation and neurovascular control can permit a better investigation
of abnormalities in these individuals and implement interventions to reduce the risk of
development of cognitive and cardiovascular impairment. The non-pharmacological intervention
through exercise training can represent an important strategy for improvement in cerebral
alterations, cognition and reduction in sleep apnea index. The purpose of present study is
investigate the volume and metabolism cerebral, neurovascular control, cognition and exon 4
of APO E gene and their
The investigators recruited both male and female sedentary individuals between 40 to 65 years
from sleep laboratory that had recently performed sleep study. All non-menopause women were
studied between the first and the fifth day after the onset of menstruation, since hormonal
variability during the regular menstrual cycle may affect blood pressure (BP) or stress
perception. Hypertension was carefully excluded in the groups. All subjects had at least
three office BP measurements made by one of the study investigators, in addition three out of
office BP measurements. Study subjects who had a body mass index (BMI) > 30 kg/m2,
cardiopulmonary disease, chronic renal disease, diabetes mellitus, atrial fibrillation,
pacemaker, hypertension, renal failure, echocardiographic evidence of impaired left
ventricular function (ejection fraction >45%), history of psychiatric disorders, dementia or
other neurodegenerative disorders, a history of smoking or alcohol abuse (2 or more drinks
per day), any sleep apnea treatment, story of circadian desynchrony (e.g. shift workers),
incomplete 2 years of formal education, resting blood pressure lower than 140/90 mmHg, body
mass index (BMI) greater than 30 kg/m2. The study was approved by the institutional committee
on human research and all subjects gave written, informed consent.
Daytime sleepiness. The chance of falling asleep in different situations was assessed by
means of Epworth Sleepiness Scale.
Screening of Cognitive Functions. Brief cognitive functions were assessed by means of Mini
Mental State Examination test (Folstein et al., 1975).
Intelligence Quotient. Intelligence was estimated by means of Kaufman Brief Intelligence Test
using vocabulary and matrices subtests (Wagner et al., 2010).
Depression. Symptoms and depressive attitudes were assessed by means of Beck Depression
Inventory that consists of 21 items, whose intensity varies from 0 to 3. Individuals with
cutoffs < 10 (no or minimal depression) were included in the protocol (Beck et al., 1961).
Perception of Anxiety. Self-evaluation on the perception of anxiety was assessed by means of
Beck Depression Anxiety Inventory (Beck et al., 1988).
Psychiatric Mental State. Current mental state was assessed by means of Self Reporting
Questionnaire (SRQ-20). Individuals with cutoffs < 8 were included of the protocol.
Experimental Design. All subjects were healthy as confirmed by medical history and physical
examinations, blood profile, echocardiographic evaluation and were not taking medications.
All subjects abstained from caffeine for 24 hours before the study. All studies were
performed in the post-absorptive state with exception of blood sample collection.
Microneurography was performed in a quiet, temperature-controlled room on morning at
approximately the same time of day. The right leg was positioned for microneurography. After
an adequate nerve recording site was obtained, the subject rested quietly for 10 minutes.
Baseline muscle sympathetic nerve activity, blood pressure, and heart rate were then recorded
continuously for 4 minutes. Acute Color Word Stroop Test was then performed for 3 minutes.
After 10 minutes of recovery all patients completed 30% hand grip isometric contraction
followed by 2 minutes of brachial occlusion.
Sleep Study. All participants underwent overnight polysomnography as previously described
(Ueno et al., 2009; Drager et al., 2009; Garcia et al., 2013). Sleep stages, apneas,
hypopneas and arousals was defined and scored as previously described (Drager et al., 2009;
Garcia et al., 2013).
The apnea-hypopnea index (AHI) was calculated by total number of respiratory events (apneas
and hypopneas) per hour of sleep. Obstructive sleep apnea (OSA) was defined as a cessation of
respiratory airflow for 10 seconds with thoracoabdominal effort, which was detected by Piezo
respiratory effort sensor. Individuals with >70% of obstructive events were defined as
individuals with OSA.
Muscle Sympathetic Nerve Activity. Muscle sympathetic nerve activity (MSNA) was directly
recorded from the peroneal nerve using the technique of microneurography (Roveda et al.,
2003; Ueno et al., 2009). Muscle sympathetic bursts were identified by visual inspection by a
single investigator, blinded to the study protocol, and were expressed as burst frequency
(bursts per min) and burst per 100 heart beats.
Heart rate and blood pressure. Heart rate (HR) was beat-by-beat continuously measured during
the test obtained in a computer-recorded electrocardiographic tracing. Blood pressure (BP)
was monitored noninvasively from an automatic leg blood pressure cuff (nondominant leg) using
automated oscillometric device (Dixtal Biomedics, DX 2022). The systolic, diastolic and mean
blood pressures were registered every minute of protocol.
Mental stress. Mental stress was elicited using modified version of CWST (During this test,
subjects were shown a series of names of colors written in a different color ink from the
color specified. Subjects were asked to identify the color of the ink, not read the word.
Throughout each mental stress test, subjects were urged to work more quickly and gently
chastised for incorrect answers.
Cardiopulmonary Exercise Test. Maximal exercise capacity was determined by means of a maximal
progressive cardiopulmonary exercise test (SensorMedics - Vmax Analyzes Assembly, Encore 29S)
on an electromagnetically braked cycle ergometer (Ergoline - Via Sprint 150 P), with
work-rate constant increment (5 to 20W/min) at 60 to 70 rpm until exhaustion as previously
described (Ueno et al., 2009). Peak VO2 was defined as the maximum attained VO2 at the end of
the exercise period in which the subject could no longer maintain the cycle ergometer
velocity at 60 rpm.
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