Cerebrospinal Fluid Biomarkers for Alzheimer's Disease in Sleep Deprived Patients: A Systematic Review and Meta-analysis
Giovanni Berton1, Marcus Moreira2, Amanda Cyntia Lima Fonseca Rodrigues3, Isabelle Batista Donadon4, Flavia Dreon Calza1, Érica Menegat1, Isabella Brkanitch1, Nicole Mattei1, Raul Hanel Dias1, Giancarlo Guerra1, Fabiana Tonial1
1Department of Medicine, University of Passo Fundo, 2Department of Medicine, Potiguar University, 3Department of Medicine, Positivo University, 4Department of Medicine, University of Buenos Aires
Objective:
To analyze whether cerebrospinal fluid (CSF) biomarkers, such as total tau (t-Tau), phosphorylated tau (p-Tau), and amyloid-β42 (Aβ42), increase with sleep deprivation (SD).
Background:
Several studies have assessed CSF biomarkers associated with Alzheimer's disease (AD) that could increase with SD; however, the results remain conflicting.
Design/Methods:
We conducted a prognostic systematic review and meta-analysis of randomized and non-randomized studies evaluating SD of any type versus regular sleep patterns in patients without AD. This study was registered with PROSPERO (CRD42023453244). There were no restrictions on follow-up or age. We calculated the mean differences (MD) with 95% confidence intervals (CI) to compare continuous endpoints between the intervention and control arms. Cochran’s Q test and I² statistics were used to evaluate heterogeneity. We defined low heterogeneity as p > 0.10 and I² < 25%, moderate heterogeneity as I² between 25%-75%, and high heterogeneity as I² > 75%. The DerSimonian Laird random effects model was used to calculate the pooled effect estimates. Statistical significance was set at p ≤ 0.05. We conducted the statistical analyses using Review Manager 5.4 (Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, Denmark).
Results:
We searched PubMed, Embase, and Cochrane Library and found 27 studies. After screening and selection, following the Cochrane and PRISMA recommendations, 5 studies with 177 patients were included. Our analysis showed that SD increased p-Tau levels (MD 1.01, 95% CI 0.29 to 1.74, p=0.06, I² = 0%). However, SD was not associated with changes in Aβ42 (MD -9.57, 95% CI -89.92 to 70.78, p=0.815, I² = 61%) or t-Tau levels (MD 16.29, 95% CI -9.20 to 41.78, p=0.210, I² = 35%).
Conclusions:
Sleep deprivation increased p-Tau, but not t-Tau nor Aβ42 in patients without AD.