Sleep, Aging and Risk for Alzheimer's Disease

NCT01962779 | Completed DMC

• 2 other identifiers: 12-03068R01HL118624
• Study Type: interventional
• Target: 235
• Locations: 1 country
• Sites: 2

Brief Summary

Our preliminary data show for in cognitively-normal elderly, that Sleep Disordered Breathing (SDB) is associated with the increase of cerebrospinal fluid (CSF) phosphorylated-Tau (P-Tau) and total-Tau (T-Tau), decreases in medial temporal lobe glucose uptake (FDG-PET) and volume (MRI) and progressive memory decline, all of which have been shown to be useful in predicting future dementia in older adults. These findings raise the question as to whether Alzheimer's disease (AD) tissue damage causes SDB in the elderly, or alternatively, if SDB acts as a risk factor for AD neurodegeneration. In the proposed study, we will investigate these mechanistic hypotheses in cognitively normal elderly by examining the longitudinal associations between SDB and cognitive decline, novel MR neuroimaging and CSF biomarkers for neurodegeneration; while our secondary goal is to launch a pilot treatment study to aid in interpreting the mechanistic hypotheses and to examine the effects of nasal continuous positive airway pressure (CPAP) on cognitive decline and neurodegeneration.

Conditions

Sleep Disordered Breathing; Alzheimer's Disease

Keywords

Sleep Disordered Breathing; Cognitively normal elderly; Alzheimer's disease; Prevention; Continuous positive airway pressure (CPAP)

Outcome Measures

Primary Outcomes (3)

• Observational. Cerebrospinal fluid (CSF) biomarkers of risk for Alzheimer's disease (AD) in sleep disordered breathing (SDB) subjects.

  At cross section, levels of CSF P-Tau, T-Tau and Aβ42 (in pg/mL) in subjects with SDB

  Baseline

• Observational. Structural MRI hippocampal volume in SDB subjects.

  At cross section, hippocampal volume (in mm3) in subjects with SDB

  Baseline

• Observational. MRI-ASL vasoreactivity response to CO2 challenge in subjects with SDB

  At cross-section, MRI-ASL measured vasoreactivity responses to CO2 (% of brain vasoreactivity to hypercapnia) in subjects with SDB

  Baseline

Secondary Outcomes (3)

• Interventional CPAP Clinical Trial, memory changes after CPAP treatment

  Change from baseline in memory tests at 6 months

• Interventional CPAP Clinical Trial, CSF biomarker changes after CPAP treatment

  Change from baseline in CSF biomarkers at 6 months

• Interventional CPAP Clinical Trial, MRI biomarker changes

  Change from baseline in MRI biomarkers at 6 months

Other Outcomes (3)

• Observational. 2-year longitudinal cognitive memory outcomes

  Change from baseline in memory tests at 24 months

• Observational. 2-year longitudinal AD-biomarker CSF outcomes

  Change from baseline in CSF biomarkers at 24 months

• Observational. 2-year longitudinal MRI structural and functional outcomes

  Change from baseline in MRI biomarkers at 24 months

Study Arms (2)

Continuous positive airway pressure

EXPERIMENTAL

Moderate to severe SDB subjects will be offered a 6-month therapy with continuous positive airway pressure (CPAP).

Other: Continuous positive airway pressure (CPAP)

No intervention

NO INTERVENTION

Subjects that refuse treatment with CPAP or that have a poor long-term compliance will be considered controls.

Interventions

Continuous positive airway pressure (CPAP) OTHER

Continuous positive airway pressure (CPAP). CPAP typically is used for people who have breathing problems, such as sleep apnea.

Continuous positive airway pressure

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female subjects with normal cognition and \>50 years of age will be enrolled. Younger subjects are not included as the risk for cognitive impairment is too low. Moreover, by selecting this age-range we minimize the possibility of including early-onset genetic forms of neurodegenerative diseases such as Alzheimer's disease and Frontotemporal Dementia.
• Normal subjects will be within normal limits on neurological and psychiatric examinations. All subjects enrolled will have both a Clinical Dementia Rating = 0 and Global Deterioration Scale \< 3.
• All subjects will have had a minimum of 12 years education.The education restriction reduces performance variance on cognitive test measures and improves the sensitivity for detecting pathology and disease progression using the robust norms available at NYU School of Medicine.
• All subjects will have an informed family member or life partner interviewed to confirm the reliability of the subject interview. All subjects will agree to the MRI imaging, the lumbar puncture, apolipoprotein E (ApoE) genotyping and DNA banking

You may not qualify if:

• History of brain tumor.
• Any radiation or chemotherapy anywhere in the body in the past 3-years.
• Significant history of alcoholism or drug abuse.
• History of psychiatric illness (e.g., schizophrenia, mania, PTSD, or life long history of major depression).
• Hamilton Depression Scale \>16 only with history of life long depressive episodes. Otherwise not excluded.
• Physical impairment of such severity as to adversely affect the validity of psychological testing.
• Hostility or refusal to cooperate.
• Any prosthetic devices (e.g., pacemaker or surgical clips) that constitutes a hazard for MRI imaging.
• History of a first-degree family member with early onset (before age 65) dementia.
• Antidepressants with anti-cholinergic properties.
• Regular use of narcotic analgesics (\>2 doses per week).
• Use of neuroleptics with anti-cholinergic properties.
• Other medications with central nervous system anticholinergic activity.
• Use of Anti-Parkinsonian medications.
• At the baseline individuals taking physician ordered or off-label memory or other cognitive enhancing medications (e.g. cholinesterase inhibitors or memantine) are excluded. At the follow-up these medications are allowed. Also excluded at baseline are individuals taking physician ordered, but off-label memory enhancements. Individuals taking over the counter memory enhancing or protecting medications (e.g. ginkgo biloba, vitamins) are not excluded.

Sponsors & Collaborators

• NYU Langone Health: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (2)

NYU Sleep Disorders Center

New York, New York, 10016, United States

Location

NYU Center for Brain Health

New York, New York, 11222, United States

Location

Related Publications (1)

• Osorio RS, Ducca EL, Wohlleber ME, Tanzi EB, Gumb T, Twumasi A, Tweardy S, Lewis C, Fischer E, Koushyk V, Cuartero-Toledo M, Sheikh MO, Pirraglia E, Zetterberg H, Blennow K, Lu SE, Mosconi L, Glodzik L, Schuetz S, Varga AW, Ayappa I, Rapoport DM, de Leon MJ. Orexin-A is Associated with Increases in Cerebrospinal Fluid Phosphorylated-Tau in Cognitively Normal Elderly Subjects. Sleep. 2016 Jun 1;39(6):1253-60. doi: 10.5665/sleep.5846.

  PMID: 26951396 DERIVED

MeSH Terms

Conditions

Sleep Apnea Syndromes; Alzheimer Disease

Interventions

Continuous Positive Airway Pressure

Condition Hierarchy (Ancestors)

Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Dementia; Brain Diseases; Central Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Positive-Pressure Respiration; Respiration, Artificial; Airway Management; Therapeutics; Respiratory Therapy

Study Officials

• Ricardo S Osorio, MD

  Research Assistant Professor

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 27, 2013
• First Posted: October 14, 2013
• Study Start: July 31, 2013
• Primary Completion: May 3, 2017
• Study Completion: May 3, 2017
• Last Updated: July 21, 2020

Record last verified: 2020-07

Locations

US (2)