Association Between Obstructive Sleep Apnea, Its Treatment, and Alzheimer's Disease: Systematic Mini-Review

Kuo, Chih-Yun; Hsiao, Hung‐Ta; Lo, Ing-Hsien; Nikolai, Tomáš

doi:10.3389/fnagi.2020.591737

Cited by 14 publications

(10 citation statements)

References 27 publications

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“…Circadian rhythm disturbances have been suggested as biomarkers for clinical stage AD [43]. The ndings of our genetic analyses were highly consistent, generally supporting the observational positive associations between AD with insomnia [3] and snoring [44], and the negative associations with sleep duration [45]. We also observed AD was positively associated with napping (r g = 0.16, p = 1.61×10 − 2 ), but this signi cance disappeared after Bonferroni correction.…”

Section: Discussionsupporting

confidence: 83%

Sleep and Alzheimer’s Disease: Shared Genetic Risk Factors, Drug Targets, Molecular Mechanisms, and Causal Effects

Chen

Wang

Jia

et al. 2021

Preprint

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Background: Alzheimer’s disease (AD) was associated with sleep-related phenotypes (SRPs). Whether they share common genetic etiology remains largely unknown. We explored the shared genetics and causality between AD and SRPs by using high-definition likelihood (HDL), cross phenotype association study (CPASSOC), transcriptome wide association study (TWAS), and bidirectional Mendelian randomization (MR) in summary-level data for AD (n = 79145) and summary-level data for seven SRPs (sample size ranges from 345552 to 386577). Results: AD shared strong genetic basis with insomnia (rg = 0.20; P = 9.70×10-5), snoring (rg = 0.13; P = 2.45×10-3), and sleep duration (rg = -0.11; P = 1.18×10-3). CPASSOC identifies 31 independent loci shared between AD and SRPs, including four novel shared loci. Functional analysis and TWAS showed shared genes were enriched in liver, brain, breast, and heart tissues, and highlighted the regulatory role of immunological disorders, very-low-density lipoprotein particle clearance, triglyceride-rich lipoprotein particle clearance, chylomicron remnant clearance and positive regulation of T cell mediated cytotoxicity pathways. Protein-protein interaction analysis provided three potential drug target genes (APOE, MARK4 and HLA-DRA) that interacted with known FDA-approved drug target genes. CPASSOC and TWAS demonstrated three regions 11p11.2, 6p22.3 and 16p11.2 may account for the shared basis between AD and sleep duration or snoring. MR showed AD had causal effect on sleep duration (βIVW = -0.056, PIVW = 1.03×10-3). Conclusion: Our findings provide strong evidence of shared genetics and causation between AD and sleep, and advance our understanding the genetic overlap between them. Identifying shared drug targets and molecular pathways can be beneficial to treat AD and sleep disorders more efficiently.

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Section: Discussionsupporting

confidence: 83%

Sleep and Alzheimer’s Disease: Shared Genetic Risk Factors, Drug Targets, Molecular Mechanisms, and Causal Effects

Chen

Wang

Jia

et al. 2021

Preprint

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“…Circadian rhythm disturbances have been suggested as biomarkers for clinical stage AD ( Liguori et al, 2020 ). The findings of our genetic analyses were highly consistent, generally supporting the observational positive associations between AD with insomnia ( Sadeghmousavi et al, 2020 ) and snoring ( Kuo et al, 2020 ) and the negative associations with sleep duration ( Lutsey et al, 2018 ). We also observed that AD was positively associated with napping ( r g = 0.16, p = 1.61 × 10 –2 ), but this significance disappeared after Bonferroni correction.…”

Section: Discussionsupporting

confidence: 79%

Sleep and Late-Onset Alzheimer’s Disease: Shared Genetic Risk Factors, Drug Targets, Molecular Mechanisms, and Causal Effects

et al. 2022

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Late-onset Alzheimer’s disease (AD) is associated with sleep-related phenotypes (SRPs). The fact that whether they share a common genetic etiology remains largely unknown. We explored the shared genetics and causality between AD and SRPs by using high-definition likelihood (HDL), cross-phenotype association study (CPASSOC), transcriptome-wide association study (TWAS), and bidirectional Mendelian randomization (MR) in summary-level data for AD (N = 455,258) and summary-level data for seven SRPs (sample size ranges from 359,916 to 1,331,010). AD shared a strong genetic basis with insomnia (rg = 0.20; p = 9.70 × 10–5), snoring (rg = 0.13; p = 2.45 × 10–3), and sleep duration (rg = −0.11; p = 1.18 × 10–3). The CPASSOC identifies 31 independent loci shared between AD and SRPs, including four novel shared loci. Functional analysis and the TWAS showed shared genes were enriched in liver, brain, breast, and heart tissues and highlighted the regulatory roles of immunological disorders, very-low-density lipoprotein particle clearance, triglyceride-rich lipoprotein particle clearance, chylomicron remnant clearance, and positive regulation of T-cell–mediated cytotoxicity pathways. Protein–protein interaction analysis identified three potential drug target genes (APOE, MARK4, and HLA-DRA) that interacted with known FDA-approved drug target genes. The CPASSOC and TWAS demonstrated three regions 11p11.2, 6p22.3, and 16p11.2 may account for the shared basis between AD and sleep duration or snoring. MR showed insomnia had a causal effect on AD (ORIVW = 1.02, PIVW = 6.7 × 10–6), and multivariate MR suggested a potential role of sleep duration and major depression in this association. Our findings provide strong evidence of shared genetics and causation between AD and sleep abnormalities and advance our understanding of the genetic overlap between them. Identifying shared drug targets and molecular pathways can be beneficial for treating AD and sleep disorders more efficiently.

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“…CPAP users had lower odds of incident diagnoses of AD (odds ratio [OR] = 0.78, 95% confidence interval [95% CI] = 0.69 to 0.89) and mild cognitive impairment (OR = 0.82, 95% CI = 0.66 to 1.02) [ 35 ]. A related systematic review indicated that receiving CPAP intervention for OSA treatment reduced the risk of AD [ 36 ]. Collectively, the results indicate that employing CPAP intervention to alleviate OSA symptoms and improve sleep quality can indirectly prevent neurodegenerative diseases by reducing neurochemical biomarker levels.…”

Section: Discussionmentioning

confidence: 99%

Continuous Positive Airway Pressure Reduces Plasma Neurochemical Levels in Patients with OSA: A Pilot Study

Liu

Huang

Hung

et al. 2023

Life

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Obstructive sleep apnea (OSA) is a risk factor for neurodegenerative diseases. This study determined whether continuous positive airway pressure (CPAP), which can alleviate OSA symptoms, can reduce neurochemical biomarker levels. Thirty patients with OSA and normal cognitive function were recruited and divided into the control (n = 10) and CPAP (n = 20) groups. Next, we examined their in-lab sleep data (polysomnography and CPAP titration), sleep-related questionnaire outcomes, and neurochemical biomarker levels at baseline and the 3-month follow-up. The paired t-test and Wilcoxon signed-rank test were used to examine changes. Analysis of covariance (ANCOVA) was performed to increase the robustness of outcomes. The Epworth Sleepiness Scale and Pittsburgh Sleep Quality Index scores were significantly decreased in the CPAP group. The mean levels of total tau (T−Tau), amyloid-beta-42 (Aβ42), and the product of the two (Aβ42 × T−Tau) increased considerably in the control group (ΔT−Tau: 2.31 pg/mL; ΔAβ42: 0.58 pg/mL; ΔAβ42 × T−Tau: 48.73 pg2/mL2), whereas the mean levels of T−Tau and the product of T−Tau and Aβ42 decreased considerably in the CPAP group (ΔT−Tau: −2.22 pg/mL; ΔAβ42 × T−Tau: −44.35 pg2/mL2). The results of ANCOVA with adjustment for age, sex, body mass index, baseline measurements, and apnea–hypopnea index demonstrated significant differences in neurochemical biomarker levels between the CPAP and control groups. The findings indicate that CPAP may reduce neurochemical biomarker levels by alleviating OSA symptoms.

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Association Between Obstructive Sleep Apnea, Its Treatment, and Alzheimer's Disease: Systematic Mini-Review

Cited by 14 publications

References 27 publications

Sleep and Alzheimer’s Disease: Shared Genetic Risk Factors, Drug Targets, Molecular Mechanisms, and Causal Effects

Sleep and Alzheimer’s Disease: Shared Genetic Risk Factors, Drug Targets, Molecular Mechanisms, and Causal Effects

Sleep and Late-Onset Alzheimer’s Disease: Shared Genetic Risk Factors, Drug Targets, Molecular Mechanisms, and Causal Effects

Continuous Positive Airway Pressure Reduces Plasma Neurochemical Levels in Patients with OSA: A Pilot Study

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