Clinical trial NCT05433883: The Relationship Between Obstructive Sleep Apnea and Alzheimer's Disease: Evidence and Effectiveness
Official title: The Relationship Between Obstructive Sleep Apnea and Alzheimer's Disease: Evidence and Effectiveness
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Obstructive Sleep Apnea of Adult
Mild Cognitive Impairment
Keywords: Alzheimer's disease
Obstructive Sleep Apnea
Lead sponsor: Chang Gung Memorial Hospital
Sponsor class: OTHER
First posted: 2022-06-27
Enrollment: 60
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The research plan to enroll 15 simple snoring patients (apnea/hypopnea \<5, control group), 30 severe OSA patients (apnea/hypopnea \>30, treatment group), and 15 mild cognitive impairment patients (comparative group). All patients complete Mini-Mental State Examination, peripheral blood sample for plasma Aβ42, Aβ40, Aβ42/Aβ40, Tau, NfL; amyloid deposit in18F-florbetapir PET; and Taiwan smell identification test. Thirty severe OSA patients (AHI\>30, treatment group) receive comprehensive upper airway surgery with/without bariatric surgery and repeat postoperative assessment in polysomnography and aforementioned examinations 1 year later.
Primary purpose: TREATMENT

Brief summary: The research plan to enroll 15 simple snoring patients (apnea/hypopnea \<5, control group), 30 severe OSA patients (apnea/hypopnea \>30, treatment group), and 15 mild cognitive impairment patients (comparative group). All patients complete Mini-Mental State Examination, peripheral blood sample for plasma Aβ42, Aβ40, Aβ42/Aβ40, Tau, NfL; amyloid deposit in18F-florbetapir PET; and Taiwan smell identification test. Thirty severe OSA patients (AHI\>30, treatment group) receive comprehensive upper airway surgery with/without bariatric surgery and repeat postoperative assessment in polysomnography and aforementioned examinations 1 year later.

Detailed description: Obstructive sleep apnea and Alzheimer's disease are both highly prevalent and age-related chronic disease with significant impacts on global public health. The link between OSA and AD showed an inter-dependent relationship. Our genetic study showed the expressions of AD-associated genes (CCL2, IL6, CXCL8, HLA-A, IL1RN) in severe OSA patients. Our epidemiological study revealed OSA patients were significantly associated with a higher incidence of AD (adjusted hazard ratio: 2.12) in comparison to non-OSA subjects and treated OSA patients exhibited a significantly reduced risk of AD (incidence rate ratio: 0.23) compared with non-treated OSA patients. Possible mechanisms of OSA in contributing to AD are sleep fragmentation, intermittent hypoxia, intrathoracic swings, and olfactory dysfunction. The cognitive decline in AD seems progressive and irreversible, by contrast, OSA sharing similar cognitive impairment is treatable. The purposes of this study are (1) to explore the relationship and mechanism between OSA and AD, and establish an alarm system as early stage of AD in OSA patients, (2) to testify the improvement of OSA can feedback to ameliorate cognitive impairment and modify the process of AD.

The research plan to enroll 15 simple snoring patients (apnea/hypopnea \<5, control group), 30 severe OSA patients (apnea/hypopnea \>30, treatment group), and 15 mild cognitive impairment patients (comparative group). All patients complete Mini-Mental State Examination, peripheral blood sample for plasma Aβ42, Aβ40, Aβ42/Aβ40, Tau, NfL; amyloid deposit in18F-florbetapir PET; and Taiwan smell identification test. Thirty severe OSA patients (AHI\>30, treatment group) receive comprehensive upper airway surgery with/without bariatric surgery and repeat postoperative assessment in polysomnography and aforementioned examinations 1 year later.

The data from the study can be used to explore the association between polysomnography and AD-related examinations, to compare the perioperative changes in polysomnography and AD-related examinations, to correlate the perioperative changes between polysomnography and AD-related examinations. The contributions of the study are to clarify the hypothesis: severe OSA is early stage and one of the etiology contributing to the development of AD, and sleep surgery improves OSA and consequently modify the process of AD, early detection of cognition and olfactory function in OSA patients can contribute to diagnosis of early stage AD and consequently early treatment to modify the development of AD.

Eligibility criteria: Inclusion Criteria:

1. age \>50 years
2. control group, AHI\<5 (n=15)
3. treatment group, AHI\>30 (n=30)
4. Comparative group, mild cognitive impairment (n=15)

Exclusion Criteria:

The exclusion criteria were definite neurologic disorders affecting brain structure (e.g., stroke, traumatic head injury or epilepsy), unstable medical diseases involving the heart, lungs, liver or kidneys, chronic insomnia, allergic rhinitis/paranasal sinusitis and alcohol or substance abuse/dependence currently or in the past one year.

Primary outcomes:
measure: polysomnography
timeFrame: one year
Secondary outcomes:
measure: Mini-Mental State Examination
timeFrame: one year
measure: peripheral blood sample for plasma Aβ42, Aβ40, Aβ42/Aβ40, Tau, NfL
timeFrame: one year
measure: amyloid deposit (18F-florbetapir PET)
timeFrame: one year
measure: Taiwan smell identification test
timeFrame: one year
Other outcomes:
Locations:
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital
Study officials:
affiliation: Chang Gung Memorial Hospital
name: professor
role: STUDY_CHAIR
References: