18F-FDG PET, cognitive functioning, and CSF biomarkers in patients with obstructive sleep apnoea before and after continuous positive airway pressure treatment

Abstract

Introduction: Dysregulation of cerebral glucose consumption, alterations in cerebrospinal fluid (CSF) biomarkers, and cognitive impairment have been reported in patients with obstructive sleep apnoea (OSA). On these bases, OSA has been considered a risk factor for Alzheimer's disease (AD). This study aimed to measure cognitive performance, CSF biomarkers, and cerebral glucose consumption in OSA patients and to evaluate the effects of continuous positive airway pressure (CPAP) treatment on these biomarkers over a 12-month period.

Methods: Thirty-four OSA patients and 34 controls underwent ¹⁸F-fluoro-2-deoxy-D-glucose positron emission tomography (¹⁸F-FDG PET), cognitive evaluation, and CSF analysis. A subgroup of 12 OSA patients treated with beneficial CPAP and performing the 12-month follow-up was included in the longitudinal analysis, and cognitive evaluation and ¹⁸F-FDG PET were repeated.

Results: Significantly reduced glucose consumption was observed in the bilateral praecuneus, posterior cingulate cortex, and frontal areas in OSA patients than controls. At baseline, OSA patients also showed lower β-amyloid₄₂ and higher phosphorylated-tau CSF levels than controls. Increased total tau and phosphorylated tau levels correlated with a reduction in brain glucose consumption in a cluster of different brain areas. In the longitudinal analysis, OSA patients showed an improvement in cognition and a global increase in cerebral ¹⁸F-FDG uptake.

Conclusions: Cognitive impairment, reduced cerebral glucose consumption, and alterations in CSF biomarkers were observed in OSA patients, which may reinforce the hypothesis of AD neurodegenerative processes triggered by OSA. Notably, cognition and brain glucose consumption improved after beneficial CPAP treatment. Further studies are needed to evaluate the long-term effects of CPAP treatment on these AD biomarkers.

Keywords: Cerebrospinal fluid; Cognition; Continuous positive airway pressure; Obstructive sleep apnoea; Positron emission tomography.

Fig. 1

Flow chart of the recruitment and selection process

Fig. 2

Frontal (a), upper (b) and lateral (c) view of the three-dimensional (3D) rendering showing the results of SPM comparisons between 18 F-FDG uptake in OSA patients as compared to the control group. The significance values above a chosen threshold and the “T value” in this voxel for a given contrast is represented by use of a colour intensity code. OSA patients show a significant reduction of brain glucose consumption in left and right frontal, parietal and in right limbic cortex. Details are provided in Table 3. R: right; L: left

Fig. 3

3D rendering showing the results of SPM comparisons between 18 F-FDG uptake in patients OSA patients undergoing the longitudinal evaluation. At the 12-month follow-up, a significant increase of cortical glucose consumption is detectable in right and left frontal and parietal cortex and in in OSA patients. R: right; L: left