Insular cortex metabolite changes in obstructive sleep apnea

Abstract

Study objective: Adults with obstructive sleep apnea (OSA) show significant autonomic and neuropsychologic deficits, which may derive from damage to insular regions that serve those functions. The aim was to assess glial and neuronal status from anterior insular metabolites in OSA versus controls, using proton magnetic resonance spectroscopy (PMRS), and thus to provide insights for neuroprotection against tissue changes, and to reduce injury consequences.

Design: Cross-sectional study.

Setting: University-based medical center.

Participants: Thirty-six patients with OSA, 53 controls.

Interventions: None.

Measurements and results: We performed PMRS in bilateral anterior insulae using a 3.0-Tesla magnetic resonance imaging scanner, calculated N-acetylaspartate/creatine (NAA/Cr), choline/creatine (Cho/Cr), myo-inositol/creatine (MI/Cr), and MI/NAA metabolite ratios, and examined daytime sleepiness (Epworth Sleepiness Scale, ESS), sleep quality (Pittsburgh Sleep Quality Index, PSQI), and neuropsychologic status (Beck Depression Inventory II [BDI-II] and Beck Anxiety Inventory [BAI]). Body mass index, BAI, BDI-II, PSQI, and ESS significantly differed between groups. NAA/ Cr ratios were significantly reduced bilaterally, and left-sided MI/Cr and MI/NAA ratios were increased in OSA over controls. Significant positive correlations emerged between left insular MI/Cr ratios and apnea-hypopnea index values, right insular Cho/Cr ratios and BDI-II and BAI scores, and negative correlations appeared between left insular NAA/Cr ratios and PSQI scores and between right-side MI/Cr ratios and baseline and nadir change in O2 saturation.

Conclusions: Adults with obstructive sleep apnea showed bilaterally reduced N-acetylaspartate and left-side increased myo-inositol anterior insular metabolites, indicating neuronal damage and increased glial activation, respectively, which may contribute to abnormal autonomic and neuropsychologic functions in the condition. The activated glial status likely indicates increased inflammatory action that may induce more neuronal injury, and suggests separate approaches for glial and neuronal protection.

Keywords: N-acetylaspartate; anxiety; autonomic; choline; creatine; depression; magnetic resonance spectroscopy; myo-inositol.

Figure 1

Left insular spectra from one obstructive sleep apnea (age 44.7 y; male) and one age- and sex-matched control subject (age 45.7 y; male). Peaks of NAA at 2.02 ppm, Cr at 3.02 ppm, Cho at 3.2 ppm, and MI at 3.56 ppm are shown; spectra are processed with Java-based magnetic resonance spectroscopy software (jMRUI, V 3.0) for display. OSA, obstructive sleep apnea; Cr, creatine; Cho, choline; MI, myoinositol; NAA, N-acetylaspartate.

Figure 2

Correlations between PMRS-derived metabolite ratios with OSA severity, sleep quality, oxygen saturation variables, and neuropsychologic scores in OSA subjects. Significant positive correlations appeared between the left insular MI/Cr ratios and AHI values (A). A significant negative correlation emerged between the left insular NAA/Cr ratios and PSQI scores (B). A significant positive correlation appeared between right insular Cho/Cr ratios and BDI-II scores (C), and right insular Cho/Cr ratios and BAI values (D). A significant negative correlation appeared between right insular MI/Cr ratios and baseline oxygen saturation (E) and oxygen saturation nadir change indices (F). AHI, apnea-hypopnea index; BAI, Beck Anxiety Inventory; BDI-II, Beck Depression Inventory II; Cho, choline; Cr, creatine; MI, myo-inositol; NAA, N-acetylaspartate; OSA, obstructive sleep apnea; PMRS, proton magnetic resonance spectroscopy; PSQI, Pittsburgh Sleep Quality Index.