Evaluation of nocturnal apnea and airflow limitation as indicators for cognitive dysfunction in patients with chronic obstructive pulmonary disease/obstructive sleep apnea hypopnea syndrome overlap syndrome

Abstract

Objective: The aim of this study is to investigate how much intermittent hypoxemia and airflow limitation contribute to cognitive impairment in overlap syndrome (OS), which is the coexistence of two common diseases, obstructive sleep apnea hypopnea syndrome (OSAHS) and chronic obstructive pulmonary disease (COPD).

Methods: We conducted a cross-sectional study of patients with OSAHS, COPD or OS, compared with normal controls, to determine the association between sleep apnea/pulmonary function-related indicators and cognitive dysfunction in individuals with OSAHS, COPD or OS.

Results: A total of 157 participants were recruited. Both OSAHS and OS presented lower adjusted Montreal cognitive assessment (MoCA) scores compared with COPD group. In addition, the MoCA score was significantly lower in COPD group compared with control group. The incidence of cognitive impairment was 57.4% in OSAHS group, and 78% in OS group, which were significantly higher than COPD group (29%) and control group (8.8%). Furthermore, a broader range of cognitive domains were affected in OS group compared with OSAHS group. Elevated levels of oxygen desaturation index (ODI) and/or apnea hypopnea index (AHI) were positively correlated with increased Epworth sleeping scale (ESS) in OSAHS and OS. Forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1) and peak expiratory flow (PEF) were positively correlated with cognitive scores in OSAHS but not in OS. Serum level of hypoxia-inducible factor-1α (HIF-1α) was significantly higher in OS. Logistic regression identified ODI as an independent risk factor for cognitive impairment in OS, while severity of snoring and PEF were independent risk factors in OSAHS.

Discussion: This study revealed significant cognitive impairment in OS, OSAHS and COPD. Sleep-related indicators are warranted in OS patients for detection, differentiation and grading of cognitive impairment, whereas pulmonary functions are warranted in OSAHS patients for detection and early intervention of cognitive impairment.

Keywords: Obstructive sleep apnea hypopnea syndrome; brain-derived neurotrophic factor; chronic obstructive pulmonary disease; cognitive impairment; hypoxia-inducible factor-1α; overlap syndrome.

Figure 1.

Comparison of sleep-related parameters across groups. (a) Epworth sleepiness scale (score); (b) apnea hypopnea index (events/hr); (c) oxygen desaturation index (events/hr); (d) mean arterial oxygen saturation (%); (e) lowest arterial oxygen saturation (%); (f) TS90% (%) of each group was indicated as mean ± SD. *, p < .05; **, p < .01, ***, p < .001.

Figure 2.

Comparison of biomarkers across groups. (a) HIF-1α (pg/mL); (b) BDNF (ng/mL) of each group was indicated as mean ± SD. *, p < .05.

Figure 3.

ROC curve for predicting cognitive impairment with two biomarkers in total cohort. Curve in blue indicates HIF-1α, curve in green indicates BDNF, and curve in red is reference.