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

TitleSelf-reported obstructive sleep apnea, amyloid and tau burden, and Alzheimer's disease time-dependent progression.
Publication TypeJournal Article
Year of Publication2020
AuthorsBubu OM, Umasabor-Bubu OQ, Turner AD, Parekh A, Mullins AE, Kam K, Birckbichler MK, Mukhtar F, Mbah AK, Williams NJ, Rapoport DM, de Leon M, Jean-Louis G, Ayappa I, Varga AW, Osorio RS
Corporate Authorsand Alzheimer's Disease Neuroimaging Initiative
JournalAlzheimers Dement
Date Published2020 Oct 08
ISSN1552-5279
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.

DOI10.1002/alz.12184
Alternate JournalAlzheimers Dement
PubMed ID33090679
PubMed Central IDPMC8026765
Grant ListR01 AG022374 / AG / NIA NIH HHS / United States
T32 HL129953 / HL / NHLBI NIH HHS / United States
K23 HL125939 / HL / NHLBI NIH HHS / United States
R25 HL105444 / HL / NHLBI NIH HHS / United States
R01 AG066870 / AG / NIA NIH HHS / United States
R01 HL118624 / HL / NHLBI NIH HHS / United States
K24 HL109156 / HL / NHLBI NIH HHS / United States
R21 AG049348 / AG / NIA NIH HHS / United States
R21 AG055002 / AG / NIA NIH HHS / United States
L30 AG064670 / AG / NIA NIH HHS / United States
R21 AG059179 / AG / NIA NIH HHS / United States
P30 AG059303 / AG / NIA NIH HHS / United States
R01 AG056682 / AG / NIA NIH HHS / United States
R01 AG056531 / AG / NIA NIH HHS / United States
R01 AG056031 / AG / NIA NIH HHS / United States
K07 AG052685 / AG / NIA NIH HHS / United States
Related Institute: 
Brain Health Imaging Institute (BHII)

Weill Cornell Medicine
Department of Radiology
525 East 68th Street New York, NY 10065