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.

Treatment of hypertension and obstructive sleep apnea counteracts cognitive decline in common neurocognitive disorders in diagnosis-related patterns

“…Similar to the above-mentioned link between Alzheimer’s pathology and AH, there are also reports on associations of OSA with amyloid pathology 43 , 85 contributing to the understanding of the pathophysiological consequences of OSA linked to hypoxia-induced dysfunctions 86 . Another aspect in this context is sleep fragmentation as an OSA-related factor resulting into cognitive decline 21 .…”

“…Neuroimaging studies indicated not only functional brain alterations in OSA 39 but also recovery after CPAP-treatment in brain regions which were affected by hypoxic damage 40 i.e. the hippocampus 41 , 42 , the frontal gyri 43 , and the default mode network 44 , 45 .…”

Assessment of Alzheimer’s disease-related biomarkers in patients with obstructive sleep apnea: A systematic review and meta-analysis

“…The Aβ42 contributes to cerebral amyloid angiopathy in AD and decreased concentrations of Aβ42 in CSF have all proven to be useful in the diagnosis of AD ( McKhann et al, 2011 ). Currently, increasing studies have linked OSA to decreased concentrations of Aβ42 in CSF ( Ju et al, 2016 ; Liguori et al, 2017 , 2019 ; Sharma et al, 2018 ; Diáz-Román et al, 2021 ; Fernandes et al, 2022 ). However, there were also studies indicating no significant difference of Aβ42 levels in CSF of OSA patients ( Osorio et al, 2014 ; Diáz-Román et al, 2021 ).…”

“…Increased levels of p-tau and t-tau in CSF could reflect cortical tangle formation and axonal degeneration or injury and can be used as a general marker in AD ( Kazim et al, 2022 ). Many studies have reported increased CSF t-tau and p-tau levels in OSA patients ( Diáz-Román et al, 2021 ; Fernandes et al, 2022 ). Nevertheless, several studies show no significant difference in CSF t-tau and p-tau levels in OSA patients ( Osorio et al, 2014 ; Ju et al, 2016 ; Liguori et al, 2017 , 2019 ).…”

“…Recently, increasing evidence suggests that OSA is not only a frequent diagnosis in Alzheimer’s disease (AD) patients but also raises the risk of developing MCI and AD, indicating that OSA may also be a risk factor for AD neurodegeneration ( Lim and Pack, 2014 ; Liguori et al, 2017 ). However, in contrast to other proven risk factors for the development of AD, symptoms of OSA can be significantly improved in clinical practice ( Fernandes et al, 2022 ). Thus, it is necessary to figure out whether OSA may promote AD pathology.…”