Lower Oxygen Levels in Obstructive Sleep Apnea Associated With Worsening Mild Cognitive Impairment and Alzheimer Disease

Reena Mehra, MD, MS

In a recent study, findings demonstrated an association of worsening mild cognitive impairment (MCI) and Alzheimer disease (AD) with lower oxygen levels in patients with obstructive sleep apnea (OSA). These results suggest that changes in oxygen levels during sleep have a direct correlation between Montreal Cognitive Assessment (MOCA) scores in patients with MCI and AD.¹

In the study, researchers observed that patients with a lower MOCA score were older (71.4 ± 8.7 vs. 68.1 ± 9.4; P = .002), predominantly Black (17.8% vs. 10.8%; P = .013), had lower weight in pounds (median, 80.5 [IQR, 69.2-94.0] vs. 86.2 [IQR, 74.0-99.0]; P = .023), and had less prevalence of ADHD, anxiety, depression, gastroesophageal reflux disease and headache (P = .034; P = .024; P = .013; P = .016; and P = .040, respectively).

"MCI is considered a transitional stage between normal aging and dementia. Studies have demonstrated an association with rate of progression of MCI and dementia in individuals with OSA compared to those without OSA," senior author Reena Mehra, MD, MS, director of the Sleep Disorders Research Program at Cleveland Clinic Lerner College of Medicine, and colleagues wrote.^{1 "}The varying degree of hypoxia, sleep fragmentation, and poor quality of sleep in OSA patients have been associated with increased risk of stroke, memory impairment, cardiac arrhythmias, dyslipidemia, hypertension, obesity, and glucose intolerance."

Presented at the 2023 SLEEP Annual Meeting, held June 3-7, in Indianapolis, Indiana, Mehra and colleagues compared patients' MOCA score at the time of the sleep study as well as analyzed the comparison with multiple macro- and microvariables tested during the study. The data were presented in the 25th and 75th percentiles for the mean (±SD) or median with the continuous variables and N (with percentage) for the categorical variables.

Between the baseline of the MOCA groups (0-17 vs. 18-30), comparisons were conducted using 2-sample T-test or Wilcoxon rank sum test for the continuous variables according to distribution. Also, a χ-square test or Fisher exact test was performed on the categorical variables. Additionally, a linear regression assessed the relationship between baseline MOCA and sleep measures before and after adjustment for the covariates which included age, gender, race, and BMI.

After adjustment of the covariates, researchers observed that when the percentage of sleep time with arterial oxygen saturation (SaO₂) less than 90% in patients increased to 10%, the MOCA score would decrease to 0.24 (coefficient, –0.21; 95% CI, –0.41 to –0.01; P = .043). Similarly, when the sleep stage %N1 increased to 1% for patients, the MOCA score would decrease to 0.04 (coefficient, –0.04; 95% CI, –0.08 to –0.01; P = .011). Notably, when SaO₂ nadir increased to 10% in patients, the MOCA score would increase to 0.68 (coefficient, 0.68; 95%CI, 0.05-1.32; P = .035). The investigators noted that the decline in the MOCA scores was associated directly with the degree of hypoxia observed during the sleep studies.

This study is supported by previous findings from a systematic review that examined OSA and cognition, MCI, and AD/AD biomarkers which included the treatment effects of continuous positive airway pressure (CPAP).² Those findings revealed that OSA is associated often with mild impairment in attention, memory, and executive function in middle-aged adults. Although results did not show OSA associated with any particular pattern of cognitive impairment in older adults, it was associated with the development of MCI or AD in symptomatic patients.

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REFERENCES
1. Khan W, Pao W, Mehra R. Association of MOCA scores in individuals with Mild Cognitive Impairment-Alzheimer Disease and Obstructive Sleep Apnea. Presented at: 2023 SLEEP Annual Meeting; June 3-7; Indianapolis, Indiana. Abstract 0456.
2. Bubu OM, Andrade AG, Umasabor-Bubu OQ, et al. Obstructive sleep apnea, cognition and Alzheimer's disease: A systematic review integrating three decades of multidisciplinary research. Sleep Med Rev. 2020;50:101250. doi:10.1016/j.smrv.2019.101250