Age-Dependent Risk for Neurodegenerative Disorder Identified in Obstructive Sleep Apnea

A pilot study using sleep biomarkers in a clinical cohort of patients with varying severity of obstructive sleep apnea (OSA) revealed that neurodegenerative disorder (NDD) risk was largely age-dependent and not significantly influenced by the severity of untreated OSA. These findings suggest the need for longitudinal studies to compare NDD risk among patients with untreated OSA to controls who do not have sleep disordered breathing.¹

These findings were presented at the 2024 SLEEP Annual Meeting, held June 1 to 5, in Houston, Texas, by lead author Gandis Mažeika, MD, FAASM, sleep medicine specialist at Sound Sleep Health, and colleagues. Among 67 patients in the cohort, 37% had mild OSA, 34% had moderate OSA, and 29% had severe OSA (40% women, aged 63 to 84 years old [SD, 7.4 years]). Of these, 43% of patients had self-reported comorbid insomnia and depression.

Investigators screened consecutive in-home multi-night Sleep Profiler records in patients older than 54 years from a community sleep clinic. The researchers excluded cases with comorbid restless leg syndrome, hypersomnia, missing Apnea-Hypopnea Index (AHI), and AHI less than 5 or single-night recordings. Authors assigned NDD risk by utilizing a machine-learning algorithm that combined age and 9 sleep biomarkers to assign group probabilities for Alzheimer disease (AD), Lewy body disease, prodromal synucleinopathy and controls (CG).

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The sleep biomarkers researchers used included time-REM, non-REM hypertonia, autonomic-activation index, spindle-duration, atypical-N3, time-supine, sleep-efficiency, relative-theta, and theta/alpha. The patients who had a CG probability score higher than 70% classified as “Probably-normal,” and those scored between 45% and 70% classified as “Likely-normal”. Authors used insomnia severity higher than 14 and a Patient Health Questionnaire score higher than 5 as cutoffs for clinical insomnia and depression. In addition, the researchers used Mann-Whitney U-tests to assess the group differences.

Notably, 73% of patients classified as “Probably-normal”, 16% “Likely-normal”, and 11% as “Likely-NDD” or “Probable-NDD”. The “Probably-normal” group was younger compared with the rest of the cohort (62 [SD, 6.2] years vs. 68 [SD, 8.6 years]; P <.01). Of the “Probably-normal” classified (n = 49), OSA was mild in 16 patients, moderate in 17 patients and severe in 16 patients. Additionally, the mean AHI was notably higher in the “Probably-normal” group compared with those who had elevated NDD risk (29 [SD, 23.9] vs. 19 [SD, 13.6] events/h; P = .085).

In a previous literature review study published in Current Sleep Medicine Reports, findings showed a strong indication that OSA plays a major role in neurodegenerative processes.² In the review, authors noted reports of associations between OSA and alterations in grey and white matter, brain diffusivity, and deficits in memory, attention, and executive control observed in studies.

The results in the literature review also showed that OSA correlated with higher risks of AD and Parkinson disease and associated pathophysiology. Moreover, researchers noted reports that treatment alleviated but did not reverse some of the damage done to the brain. Thus, the evidence shows OSA as a promising target to slow neurodegeneration and delay the onset of related disorders.

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REFERENCES
 1. Mazeika G, Cho Y, Anderson J, et al. Relationship Between OSA and Sleep Biomarker Based Neurogenerative Disorder Risk in a Clinical Cohort. Presented at: 2024 SLEEP Annual Meeting; June 1-5; Houston, Texas. Abstract 0753.
2. Weihs, A., Frenzel, S. & Grabe, H.J. The Link Between Obstructive Sleep Apnoea and Neurodegeneration and Cognition. Curr Sleep Medicine Rep 7, 87–96 (2021). https://doi.org/10.1007/s40675-021-00210-5