Self-reported obstructive sleep apnea, amyloid and tau burden, and Alzheimer's disease time-dependent progression

Omonigho M Bubu; Ogie Q Umasabor-Bubu; Arlener D Turner; Ankit Parekh; Anna E Mullins; Korey Kam; Madeline K Birckbichler; Fahad Mukhtar; Alfred K Mbah; Natasha J Williams; David M Rapoport; Mony de Leon; Girardin Jean-Louis; Indu Ayappa; Andrew W Varga; Ricardo S Osorio; and Alzheimer's Disease Neuroimaging Initiative

doi:10.1002/alz.12184

Self-reported obstructive sleep apnea, amyloid and tau burden, and Alzheimer's disease time-dependent progression

Alzheimers Dement. 2020 Oct 8:10.1002/alz.12184. doi: 10.1002/alz.12184. Online ahead of print.

Authors

Omonigho M Bubu^{1

2}, Ogie Q Umasabor-Bubu³, Arlener D Turner¹, Ankit Parekh⁴, Anna E Mullins⁴, Korey Kam⁴, Madeline K Birckbichler⁵, Fahad Mukhtar⁶, Alfred K Mbah⁶, Natasha J Williams², David M Rapoport⁴, Mony de Leon⁷, Girardin Jean-Louis², Indu Ayappa⁴, Andrew W Varga⁴, Ricardo S Osorio^{1

8}; and Alzheimer's Disease Neuroimaging Initiative¹

Affiliations

¹ Center for Sleep and Brain Health, Department of Psychiatry, NYU Grossman School of Medicine, New York, New York, USA.
² Center for Healthful Behavior Change, Department of Population Health, New York Grossman School of Medicine, New York, USA.
³ Department of Epidemiology and Infection Control, State University New York Downstate Medical Center, Brooklyn, New York, USA.
⁴ Division of Pulmonary, Critical Care and Sleep Medicine at the Icahn School of Medicine at Mount Sinai, New York, New York, USA.
⁵ Department of Applied Health Sciences, Wheaton College, Wheaton, Illinois, USA.
⁶ Department of Epidemiology and Biostatistics, College of Public Health, University of South Florida, Tampa, Florida, USA.
⁷ Brain Health Imaging Institute, Department of Radiology, Weill Cornell Medicine, New York, New York, USA.
⁸ Nathan S. Kline Institute for Psychiatric Research, Orangeburg, New York, USA.

Abstract

Introduction: Obstructive sleep apnea (OSA) is associated with Alzheimer's disease (AD) biomarkers in cognitively normal (CN) and mild cognitive impaired (MCI) participants. However, independent and combined effects of OSA, amyloid beta (Aβ) and tau-accumulation on AD time-dependent progression risk is unclear.

Methods: Study participants grouped by biomarker profile, as described by the A/T/N scheme, where "A" refers to aggregated Aβ, "T" aggregated tau, and "N" to neurodegeneration, included 258 CN (OSA-positive [OSA+] [A+TN+ n = 10, A+/TN- n = 6, A-/TN+ n = 10, A-/TN- n = 6 and OSA-negative [OSA-] [A+TN+ n = 84, A+/TN- n = 11, A-/TN+ n = 96, A-/TN- n = 36]) and 785 MCI (OSA+ [A+TN+ n = 35, A+/TN- n = 15, A-/TN+ n = 25, A-/TN- n = 16] and OSA- [A+TN+ n = 388, A+/TN- n = 28, A-/TN+ n = 164, A-/TN- n = 114]) older-adults from the Alzheimer's Disease Neuroimaging Initiative cohort. Cox proportional hazards regression models estimated the relative hazard of progression from CN-to-MCI and MCI-to-AD, among baseline OSA CN and MCI patients, respectively. Multi-level logistic mixed-effects models with random intercept and slope investigated the synergistic associations of self-reported OSA, Aβ, and tau burden with prospective cognitive decline.

Results: Independent of TN-status (CN and MCI), OSA+/Aβ+ participants were approximately two to four times more likely to progress to MCI/AD (P < .001) and progressed 6 to 18 months earlier (P < .001), compared to other participants combined (ie, OSA+/Aβ-, OSA-/Aβ+, and OSA-/Aβ-). Notably, OSA+/Aβ- versus OSA-/Aβ- (CN and MCI) and OSA+/TN- versus OSA-/TN- (CN) participants showed no difference in the risk and time-to-MCI/AD progression. Mixed effects models demonstrated OSA synergism with Aβ (CN and MCI [β = 1.13, 95% confidence interval (CI), 0.74 to 1.52, and β = 1.18, 95%CI, 0.82 to 1.54]) respectively, and with tau (MCI [β = 1.31, 95% CI, 0.87 to 1.47]), P < .001 for all.

Discussion: OSA acts in synergism with Aβ and with tau, and all three acting together result in synergistic neurodegenerative mechanisms especially as Aβ and tau accumulation becomes increasingly abnormal, thus leading to shorter progression time to MCI/AD in CN and MCI-OSA patients, respectively.

Keywords: Alzheimer's disease; amyloid beta42; brain amyloid‐positron emission tomography; cerebrospinal fluid biomarkers; longitudinal study; obstructive sleep apnea; p‐tau; t‐tau.

Abstract

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