Role of Sleep Apnea in the Neuropsychological Function in Down Syndrome People

This is the first study about Neuropsychological function and OSAS in Taiwan. Although the correlation between OSAS and neuropsychological abnormalities had been reported, it is worth to understand more about the detailed domains that involved in our cohort. After this, investigators can dissect the cause of mental retardation in DS and help for further treatment strategies.

Study Overview

• Status: Completed
• Conditions: Down Syndrome
• Intervention / Treatment: Device: CPAP

Detailed Description

Down Syndrome (DS) is the most common cause of mental retardation with incidence of 1 in 848 (Lin, Hu et al. 1991). Although prenatal Down syndrome and Amniocentesis had been applied for years, in the survey of 2005, current birth incidence of DS is 1.6 in 10,000 live birth, meaning a 30-50 new cases per year (Jou, Kuo et al. 2005). Patients with DS will have multisystemic manifestations including short stature, mental retardation, dysmorphism, congenital heart disease, congenital anomaly of gastrointestinal and genitourinary tract, abnormal endocrine function, leukemia and leukemoid reaction. Beside mental retardation, other anomalies could be treated or controlled by current medical care. The IQ of DS is around 20-80 with significant cognitive, language, and behavior problems (Dierssen, Ortiz-Abalia et al. 2006).

In addition, obstructive sleep apnea syndrome (OSAS) had been observed in DS people with prevalence about 45-79% in the literature (de Miguel-Diez, Villa-Asensi et al. 2003; Dyken, Lin-Dyken et al. 2003; Shott, Amin et al. 2006; Fitzgerald, Paul et al. 2007), which is much higher than the 1-3% prevalence rate in general population (Holmes 1993; Gislason and Benediktsdottir 1995). The reasons of DS people prone to have OSAS are due to the combination of anatomical and physiological factors. In DS people, facial dysmorphism (midfacial hypoplasia, mandibular hypoplasia), macroglossia, small hypopharynx, pharyngeal hypotonia, tonsil and adenoid enlargement, obesity, laryngomalacia, and tracheomalacia contributed to upper airway obstructions in DS people (Trois, Capone et al. 2009; Pandit and Fitzgerald 2012). In addition, DS people has increased incidence of lower respiratory tract diseases including gastroesophageal reflux, immunological dysfunction, tracheal bronchus, airway malacia, congenital heart disease, and pulmonary hypoplasia, which will predispose to OSAS. While growing up, DS people still have generalized hypotonia with increasing risk of developing hypothyroidism and obesity, which are also risk factors for OSAS (Trois, Capone et al. 2009).

It has been noted that sleep disordered breathing is associated with neurocognitive deficit, particularly of memory, learning, attention, hyperactivity, executive functioning, cognitive capacity, and poor school performance (Beebe 2006; Pandit and Fitzgerald 2012). And a number of studies have reported improved attention, executive functioning, analytical thinking, verbal functioning, memory and academic progress at 6-12 months post- adenotonsillectomy (Chervin, Ruzicka et al. 2006). In DS, study demonstrated that a higher number of apneic episodes on polysomnography was correlated to the decreased visuoperceptual skill in DS (Andreou, Galanopoulou et al. 2002). Similarly, presence of snoring in DS was associated with a much higher rate of disruptive school behavior than without snore (Carskadon, Pueschel et al. 1993). Although learning disability and memory defect had been globally known in DS, the behavior, cognitive, and developmental impairment caused by OSAS is especially concerning because it might adversely affect their ability, even the social adaptation (Rihtman, Tekuzener et al. 2010) . Therefore, investigators would like to know the correlation between severity of OSAS and Neurocognitive and behavior in DS people in Taiwan. Also, investigators would like to follow the Neurocognitive and behavior changes in those who had been treated for OSAS, including tonsillectomy or Bilevel Positive Airway Pressure.

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Diagnosed with Down's syndrome by chromosome test, over 6 years old and IQ> 40.
2. Participants and caregiver who are willing and comply with study.

Exclusion Criteria:

1. Known to have uncontrolled heart, stomach, kidney or neurological / psychiatric disorders.
2. Cannot comply with study。

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Continuous Positive Airway Pressure (CPAP) Therapy	Device: CPAP; If following patients are suffering from sleep apnea and agree to receive treatment,; older than 18 years, AHI> 15 and present obvious symptoms or; less than 18 years, AHI still> 5 after tonsillectomy and present obvious symptoms. Investigators will process CPAP treatment for 3 months, and do neuropsychological assessment and sleep examination after treatment for 6 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Assessed the sleep apnea level with Apnoea-Hypopnoea Index (AHI) score.	3 months
Assessed neuropsychological functions with Wechsler Preschool and Primary Scale of Intelligence (WPPSI-R) vocabulary subdomain score.	3 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Assessed the memory domain that subtest of Sentence (WPPSI-R) .	3 months
Assessed the memory domain that forward memory (Leiter International Performance Scale-Revised) .	3 months
Evaluation of participants's Visuospatial functions with Geometric Design (WPPSI-R).	3 months
Evaluation of participants's Visuospatial functions with Block Design (WPPSI-R).	3 months
The Executive domain was assessed with TOWER (Developmental NEuroPSYchological Assessment, NEPSY)	3 months
Assessed the Language domain with Vocabulary subtest	3 months
Assessed the Sensorimotor domain with Visuomotor Precision-train and car	3 months
Measurement the effectiveness of therapy before and after treatment with Apnoea-Hypopnoea Index (AHI).	12 months
Measurement the effectiveness of therapy before and after treatment with Oxygen Desaturation Index (ODI).	12 months

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Investigators: Principal Investigator: Ni-Chung Lee, M.D, Ph.D, National Taiwan University Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 1, 2012
• Primary Completion (ACTUAL): December 1, 2016
• Study Completion (ACTUAL): December 1, 2016

Study Registration Dates

• First Submitted: August 17, 2017
• First Submitted That Met QC Criteria: August 28, 2017
• First Posted (ACTUAL): August 30, 2017

Study Record Updates

• Last Update Posted (ACTUAL): September 5, 2017
• Last Update Submitted That Met QC Criteria: August 31, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Disease; Congenital Abnormalities; Genetic Diseases, Inborn; Intellectual Disability; Abnormalities, Multiple; Chromosome Disorders; Syndrome; Down Syndrome
• Other Study ID Numbers: 201208075RIC

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No