Sleep Apnea in Elderly

Pathophysiology-Guided Therapy for Sleep Apnea in the Elderly

Sleep-disordered breathing (SDB or sleep apnea) is very common among elderly Veterans and leads to increased morbidity and mortality in this population. The proposal aims to identity whether oxygen, finasteride and acetazolamide can be effective in reducing unstable breathing and eliminating sleep apnea in the elderly via different mechanisms. This proposal will enhance the investigators' understanding of the pathways that contribute to the development of sleep apnea in the elderly. The investigators expect that the results obtained from this study will positively impact the health of Veterans by identifying new treatment modalities for sleep apnea. A cumulative effect of the investigators' research will fulfill the long-term goal of improving the quality of life of elderly Veterans suffering from sleep apnea and its potential life-threatening complications.

Sleep apnea-hypopnea syndrome (SAHS) has a high prevalence and is associated with adverse cardiovascular consequences in elderly Veterans. Positive airway pressure therapy is deemed cumbersome and often associated with non-adherence to therapy. This proposal will investigate whether alternative therapies can be developed by modulating specific physiologic mechanisms of ventilatory control. Specifically, the investigators will study whether interventions with sustained hyperoxia (Aim 1), finasteride (Aim 2) and acetazolamide (Aim 3) will reduce breathing instability during sleep by reducing chemoresponsiveness and/or increasing cerebrovascular reactivity (CVR) in order to alleviate sleep disordered breathing in the elderly with sleep apnea. The proposed aims will also allow us to delineate key mechanisms of breathing instability in the elderly. The investigators envision that the results obtained from this project will ultimately allow us to develop novel alternative therapies for sleep apnea in the elderly. The investigators will also compare CVR in young vs older adults

Inclusion Criteria:

• Adults with mild to moderate sleep apnea with Apnea-Hypopnea Index (AHI)>/=5 to 20/hour with central, obstructive, mixed apneas and hypopneas
• For the finasteride protocol elderly men with above criteria will be enrolled

Exclusion Criteria:

• Patients with severe sleep apnea (Apnea-Hypopnea Index (AHI)>20/hour)

• Patients with history of prostate cancer

• Males with hypogonadism

• History of cardiac disease, including myocardial infarction

• Bypass surgery

• Atrial and ventricular tachy-bradycardias

• Systolic congestive heart failure and Cheyne-Stokes respiration

• Current unstable angina

• Stroke

• Schizophrenia

• Untreated hypothyroidism

• Seizure disorder

• Preexisting renal failure and liver disorders

• Failure to give informed consent.

• Patients with significant pulmonary diseases by history and abnormal pulmonary function testing, including moderate obstructive/restrictive lung/chest wall disorders with resting oxygen saturation of <96% or on supplemental oxygen

• Patients on certain medications including:

  • study drugs
  • sympathomimetics/parasympathomimetics or their respective blockers
  • narcotics
  • antidepressants
  • anti-psychotic agents
  • other central nervous system (CNS) altering medications
  • current alcohol, tobacco or recreational drug use

• Patients with Body mass index (BMI)>34 kilograms per square meter (kg/m2) will be excluded to avoid the effects of morbid obesity on pulmonary mechanics and ventilatory control

• Elderly with unstable gait or mobility issues that may preclude safe participation

• Individuals with allergy to finasteride or acetazolamide will be excluded from the specific protocol

• Pregnant women