Inflammation and Neurocognitive Damage Markers in Elderly People With Obstructive Sleep Apnea

Inflammation Clinical Trial

Official title:

Inflammation and Neurocognitive Damage Markers in Elderly People With Obstructive Sleep Apnea

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04882020
• Other study ID #: 2019-0529
• Status: Active, not recruiting
• Start date: August 21, 2019
• Est. completion date: June 11, 2021

Study information

• Verified date: May 2021
• Source: Hospital de Clinicas de Porto Alegre
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The aging process tends to promote an overall increase in inflammation compromising the immunologic system regulation, sleep/wakefulness pattern, and neurocognitive performance. In elders, there is an increase in repetitive arousals during sleep, secondary to breathing interruption by pharynx collapse, generating a transient reduction in oxygen delivery to the brain known as obstructive sleep apnea. This lack in oxygen supply results in an inflammatory process producing brain damage. Some substances present in the blood seem to be associated to neurocognitive damage, like S100β protein, cortisol, interleukin 1-β,6 and TNF-α. In the other way, a substance called brain-derived neurotrophic factor (BDNF) enhances cognitive function, and memory consolidation improvement.

Description:

An intermittent hypoxia in obstructive sleep apnea induces the production of reactive oxygen species (ROS), oxidative damage and inflammation generating pro-inflammatory cytokines, reactive gliosis and neuronal damage. The increase in oxidative damage seems to be associated to age, contributing to the progress of neurodegeneration. Transient hypoxemia leads to autonomic excitation causing hyperactivity of the sympathetic nervous system (SNS), and activation of the hypothalamic-pituitary-adrenal (HPA) axis, causing immunological changes and increased risk of damage to mental functions. Night awakenings caused by OSA are associated with changes on the HPA axis, resulting in increased serum cortisol levels. The fluctuation in serum cortisol levels at night is intrinsically related to sleep, and increases with advancing age. BDNF is responsible for increasing the growth of neurites, and synaptogenesis, preventing programmed cell death in adults, and is involved in stress responses on the HPA axis. Low BDNF levels are associated to cognitive impairment, less memory consolidation, depression, and OSA. There is a positive correlation between levels of BDNF and cortisol related to physiological regulation of brain activities. The increase in oxidative damage caused by intermittent hypoxia during obstructive sleep apnea increases serum levels of the s100β protein promoting reactive gliosis or astrogliosis being associated to depression in the elderly. Obstructive sleep apnea syndrome is associated with development of cardiovascular and neurological diseases by activating pro-inflammatory pathways. However, in elderly individuals, regardless of other specific pathologies, they already have a pro-inflammatory state secondary to loss of regulation of the immune system.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 76
• Est. completion date: June 11, 2021
• Est. primary completion date: April 30, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 65 Years to 80 Years

Eligibility

Inclusion criteria:

• Individuals aged 65 to 80;
• both sexes;
• free and informed consent form previously signed for participation in the MEDIDAS cohort study;
• previous performance of outpatient polysomnography with adequate technical quality
• AHI = 5 or = 30 events/hour;
• previous blood collection between 7-9 am; questionnaires.

Exclusion criteria:

• Have had treatment for sleep apnea;
• suffer from rheumatic or chronic diseases such as diabetes mellitus, heart failure, coronary artery disease, chronic renal failure or nephropathy (creatinine> 1.8 mg / dL), liver disease, history of stroke, aortic aneurysm, marked elevation in blood arterial pressure (> 180/110 mmHg), assessed by 24-hour ambulatory blood pressure monitoring (ABPM);
• cognitive deficit verified in the Mini Mental State Examination;
• diagnosis of Alzheimer's and Parkinson's.

Related Conditions & MeSH terms

• Apnea
• Apnea, Obstructive
• Inflammation
• Inflammatory Response
• Neurocognitive Disorders
• Neurodegenerative Diseases
• Obstructive Sleep Apnea
• Obstructive Sleep Apnea Syndrome
• Sleep Apnea
• Sleep Apnea Syndromes
• Sleep Apnea, Obstructive

Intervention

Diagnostic Test:
• cortisol, BDNF, s100B, IL-1B, IL-6, IL-10, TNF-alpha
compare both groups and evaluate the severity of obstructive sleep apnea modulates serum levels of inflammatory and neurocognitive markers in elederly.

Locations

Country	Name	City	State
Brazil	Hospital de Clínicas de Porto Alegre	Porto Alegre	Rio Grande Do Sul

Sponsors (2)

Lead Sponsor	Collaborator
Hospital de Clinicas de Porto Alegre	Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul, Brazil

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Serum level of Brain derived neurotrophic factor	Serum of brain-derived neurotrophic factor will be analyzed in the plasma of elderly volunteers using the Sandwich ELISA method.	Baseline
Secondary	Serum level of s100B protein	Serum of s100B protein will be analyzed in plasma in elderly volunteers using ELISA method.	Baseline
Secondary	Inflammatory markers	The serum levels of cytokines (IL-1b, IL-6, IL-10 and TNF-alpha) will be analyzed in the plasma of elderly volunteers. The serum level of cytokines using a unit multiplex assay in pg/mL.	Baseline
Secondary	Serum Cortisol levels	Serum cortisol levels will be analyzed in the plasma of elderly volunteers. The serum level of cortisol will be quantified by chemiluminescence microparticle immunoassay (CMIA) with reference values for blood collection performed in the morning shift from 3.7 to 19.4 ug / dL.	Baseline
Secondary	Neurocognitive Damage	Neurocognitive damage will be measured by the Mini Mental State Examination adapted for the Brazilian population. The maximum score for this scale is 30 points, indicating better cognitive performance. A score of 0-9 points indicates severe cognitive loss; 10-20 points of moderate cognitive loss; 21-26 points mild cognitive loss, 27-30 points without cognitive loss.	Baseline
Secondary	Depression	Depression will be measured by the Beck Depression Inventory. A score of 0-9 points indicates that the individual is not depressed; 10-18 points mild depression; 19-29 points moderate depression; 30-36 points severe depression.	Baseline
Secondary	Quality of life Score	Quality of life will be measured using the World Health Organization's Quality of Life questionnaire, which has assessments in the domains: physical, psychological, social relations and the environment. The evaluation of each domain is expressed as a percentage, where the higher the result (100%) indicates the better quality of life in the respective domain. The general quality of life is given by the average of the scores of the four domains, whose scores vary from 0 to 5 points. 1-2.9 points the quality of life needs to improve; 3-3.9 regular quality of life; 4-4.9 good quality of life; 5 very good quality of life.	Baseline