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

Wenqi Cui, Zhenghao Duan, Zijian Li, Juan Feng, Wenqi Cui, Zhenghao Duan, Zijian Li, Juan Feng

Abstract

Increasing evidence links Alzheimer's disease (AD) to various sleep disorders, including obstructive sleep apnea (OSA). The core AD cerebrospinal fluid (CSF) biomarkers, including amyloid-β 42 (Aβ42), total tau (t-tau), and phosphorylated tau (p-tau), can reflect key elements of AD pathophysiology before the emergence of symptoms. Besides, the amyloid-β (Aβ) and tau burden can also be tested by positron emission tomography (PET) scans. Electronic databases (PubMed, Embase, Web of Science, and The Cochrane Library) were searched until August 2022 to assess the AD-related biomarkers measured by PET scans and CSF in OSA patients. The overall analysis showed significant differences in Aβ42 levels (SMD = -0.93, 95% CI:-1.57 to -0.29, P < 0.001) and total tau (t-tau) levels (SMD = 0.24, 95% CI: 0.01-0.48, P = 0.308) of CSF, and Aβ burden (SMD = 0.37, 95% CI = 0.13-0.61, P = 0.69) tested by PET scans between the OSA and controls. Furthermore, CSF Aβ42 levels showed significant differences in patients with moderate/severe OSA compared with healthy control, and levels of CSF Aβ42 showed differences in OSA patients with normal cognition as well. Besides, age and BMI have influences on heterogeneity. Our meta-analysis indicated abnormal AD-related biomarkers (CSF and PET scans) in patients with OSA, supporting the current hypothesis that OSA, especially moderate/severe OSA, may start the AD neuropathological process.

Systematic review registration: [https://www.crd.york.ac.uk/PROSPERO/], identifier [CRD42021289559].

Keywords: Alzheimer’s disease; PET scans; amyloid-β 42 (Aβ42); obstructive sleep apnea; phosphorylated tau (p-tau); total tau.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2022 Cui, Duan, Li and Feng.

Figures

FIGURE 1
FIGURE 1
Flowchart of search strategy and study selection.
FIGURE 2
FIGURE 2
Forest plot comparing levels of cerebrospinal fluid (CSF) and positron emission tomography (PET) biomarkers in subjects with obstructive sleep apnea (OSA) and controls: (A) CSF Aβ42 level; (B) CSF t-tau level; (C) CSF p-tau level; (D) PET Aβ burden.
FIGURE 3
FIGURE 3
Funnel plot analysis used to detect publication bias: (A) CSF Aβ42 level (P = 0.072 in Begg’s test); (B) Cerebrospinal fluid (CSF) t-tau level (P = 0.452 in Begg’s test).
FIGURE 4
FIGURE 4
Sub-group analysis: (A) Cerebrospinal fluid (CSF) Aβ42 level based on age; (B) CSF Aβ42 level based on BMI; (C) CSF t-tau level based on BMI; (D) CSF p-tau level based on BMI; and (E) CSF Aβ42 level based on cognition status.
FIGURE 5
FIGURE 5
Forest plot of cerebrospinal fluid (CSF) Aβ42 level: (A) Mild obstructive sleep apnea (OSA) compared with healthy control; (B) Moderate/severe OSA compared with healthy control; (C) Mild OSA compared with moderate/severe OSA.

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