The Relationship Between OSA and Mood Disorders, Cognitive Impairment

Obstructive sleep apnea (OSA) is associated with a range of comorbid conditions, including psychiatric disorders and cognitive dysfunction. Common comorbidities in OSA such as cardiovascular disease and metabolic abnormalities may confer a higher risk for the development of mental and cognitive impairment in patients with OSA compared with the general population.¹ However, the pathophysiology of psychiatric disorders and the medications used to treat them may increase the risk for OSA. Accumulating evidence supports a multifaceted relationship between these conditions.

In a study published in JAMA Otolaryngology Head & Neck Surgery, researchers examined the risk of developing affective disorders in 197 patients with OSA during a 9-year period compared with a propensity-matched sample.² After adjustment for sociodemographic factors, comorbidities, and disability, the hazard ratio (HR) for affective disorders in patients with OSA was 2.04 (95% CI, 1.53-2.70).

Adjusted HRs (aHRs) for depressive and anxiety disorders were 2.90 (95% CI, 1.98-4.24) and 1.75 (95% CI, 1.26-2.44), respectively. In addition, women with OSA demonstrated a higher risk for prospective development of these disorders (aHRs 3.97 [95% CI, 1.54-10.19] and 2.42 [95% CI, 1.17-5.02], respectively) compared with men with OSA (aHRs, 2.74 [95% CI, 1.80-4.17] and 1.64 [95% CI, 1.13-2.39], respectively).

These findings align with those of previous studies, including a 2018 retrospective investigation that demonstrated a high prevalence of OSA in a sample of 413 individuals receiving treatment at an outpatient psychiatry clinic, particularly in individuals with major depressive disorder (MDD; 37.8%), posttraumatic stress disorder (PTSD; 35.5%), and bipolar disorder (16.7%).³

Multiple studies have also revealed associations between OSA and psychological disorders such as MDD and PTSD, including among samples of veterans.^4,5 Certain findings have demonstrated various implications pertaining to treatment outcomes. For example, study results published in 2017 reported lower adherence to continuous positive airway pressure (CPAP) therapy in patients with PTSD and OSA (regular use: g = -0.658; 95% CI, -0.856 to -0.460; time of average use per night: g = -0.873; 95% CI, -1.550 to -0.196) vs patients with only OSA.⁶

Other results have shown that MDD and PTSD symptoms improve with CPAP therapy for comorbid OSA.^7,4 In 2017, researchers found that low CPAP compliance led to increased scores on the PTSD checklist among veterans with subclinical PTSD and that poor compliance “may lead to overt PTSD if the OSA remains undertreated,” as stated in the paper.⁷

In addition, “[c]ase study reports and clinical trials both suggest that the treatment of OSA with CPAP can help to reduce the need for psychopharmaceuticals, and to help clarify which symptoms originate from the primary psychiatric illness” wrote the authors of a 2015 review published in the Journal of Clinical Sleep Medicine.⁴

Along with the increased prevalence of mental health disorders in patients with OSA, numerous cognitive deficits have been noted in this population, including impairments in executive function; attention; and episodic, visual, and verbal memory.¹ “Although the cognitive impairment in individuals with OSA is largely recognized as mild cognitive impairment, OSA [is] also recognized as [a] modifiable risk for dementia, neuropsychiatric disorders and stroke,” according to Otero et al.¹

Researchers have also observed a substantially elevated risk of developing OSA among individuals with psychiatric illness. A study published in the Journal of Clinical Medicine examined this relationship in a sample of 110 patients with psychiatric disorders (66 with MDD, 34 with bipolar disorder, and 10 with schizophrenia).⁸ Approximately 87% of patients were found to have an intermediate to high risk for OSA based on the STOP-BANG (Snoring, Tiredness, Observed Apnea, Blood Pressure, Body Mass Index, Age, Neck Circumference, and Male Gender) questionnaire, and approximately 71% reported daytime tiredness or sleepiness.

The researchers suggested that psychotropic drugs may represent one of the factors influencing the pathophysiology of OSA in psychiatric disorders, possibly via effects on metabolic and respiratory function. “Screening for OSA is mandatory in this medical population, as psychiatric patients have significantly poorer physical health than the general population and the coexistence of the two diseases can further negatively impact several health outcomes,” they concluded.

To learn more about the connection between OSA and mental and cognitive disorders, including proposed mechanisms and clinical implications, Pulmonology Advisor interviewed Yonatan Greenstein, MD, assistant professor of medicine in the Division of Pulmonary & Critical Care and Allergic & Immunologic Diseases at Rutgers New Jersey Medical School in Newark; and Adriane Soehner, PhD, assistant professor of psychiatry at the University of Pittsburgh School of Medicine in Pennsylvania.

Pulmonology Advisor: What is known about links between OSA and mental and cognitive impairment? 

Dr Greenstein: This is a fascinating topic with observational and basic science research to guide us. I like to think of OSA as a disease of sleep fragmentation and intermittent hypoxia. With this in mind, we can extrapolate data from other studies and disorders to help piece this puzzle together.

I will start first with cognitive impairment. In 2015, Osorio and colleagues at the New York University School of Medicine analyzed patient data from the Alzheimer’s Disease Neuroimaging Initiative.⁹ They found that patients with sleep-disordered breathing had a younger age at onset of mild cognitive impairment or Alzheimer dementia. In certain subsets, CPAP use delayed the age of mild cognitive impairment onset.

Anyone who has had to work a shift of 24 hours or longer or has had a few consecutive days of poor sleep, would not be surprised to hear that OSA is strongly linked to mood disorders. A recent study by Jackson and colleagues in Australia found that 23% of patients recently diagnosed with OSA had clinical depression.¹⁰ The prevalence of PTSD and anxiety is also thought to be elevated in patients with OSA.

Dr Soehner: OSA is strongly associated with mood and cognitive impairments. OSA is hypothesized to affect mood and cognition through sleep fragmentation and intermittent hypoxia. Estimated rates of depression among patients with OSA vary widely depending on study methodology, but generally indicate a higher prevalence relative to the general population, with 1 meta-analysis estimating that 36% of patients with MDD and 24% with BPD experienced OSA.¹¹

Studies of cognitive impairment in OSA indicate that the disorder can have an effect on vigilance, concentration, executive function, and memory. Some studies indicate that effective treatment of OSA can improve mood and cognitive outcomes, although some patients may experience persistent deficits. 

Pulmonology Advisor: What are believed to be the mechanisms underlying these associations? 

Dr Greenstein: Current hypotheses linking sleep-disordered breathing to cognitive impairment are numerous. Mak Daulatzai, MD, MSc, PhD, penned a great review article that focuses on the effects of intermittent hypoxia.¹² Take home points from this paper are that, in rat models, intermittent hypoxia increases cerebral amyloidogenesis and tau phosphorylation, which are prominent features of Alzheimer disease. In addition, hypoxia triggers neuronal and axonal degeneration in the brain.

Rosenzweig and colleagues wrote another excellent review that focuses on sleep-disordered breathing and the brain.¹³ In addition to the intermittent hypoxia effects, neuroinflammatory effects and ischemic preconditioning play a role in increasing the prevalence of various mood disorders.

Purported mechanisms are many and are an active area of research today.