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Obstructive Sleep Apnea and Longitudinal Alzheimer's Disease Biomarker Changes
70 Pages Posted: 8 Oct 2018
More...Abstract
Objective: To determine the effect of self-reported clinical diagnosis of Obstructive Sleep Apnea (OSA) on longitudinal changes in brain amyloid-PET and CSF-biomarkers (Aβ42, T-tau and P-tau) in cognitively normal (NL), mild cognitive impairment (MCI) and Alzheimer's Disease (AD) elderly.
Methods: Longitudinal study with mean follow-up time of 2.52±0.51 years. Data was obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Participants included 516 NL, 798 MCI and 325 AD elderly. Main Outcomes were annual rate-of-change in brain amyloid-burden (i.e. longitudinal increases in florbetapir-PET uptake or decreases in CSF-Aβ42 levels); and tau-protein aggregation (i.e. longitudinal increases in CSF total-tau (T-tau) and phosphorylated-tau (P-tau)). Adjusted multi-level mixed effects linear regression models with randomly varying intercepts and slopes was used to test whether the rate-of-biomarker-change differed between participants with and without OSA.
Results: In NL and MCI groups, OSA subjects experienced faster annual increase in florbetapir uptake (B=.06, 95% CI .02, .11 and B=.08, 95% CI .05, .12 respectively) and decrease in CSF-Aβ42 levels (B=-2.71, 95% CI -3.11, -2.35 and B=-2.62, 95% CI -3.23, -2.03, respectively); as well as increases in CSF T-tau (B=3.68, 95% CI 3.31, 4.07 and B=2.21, 95% CI 1.58, 2.86, respectively) and P-tau (B=1.221, 95% CI, 1.02, 1.42 and, B=1.74, 95% CI 1.22, 2.27, respectively); compared to OSA- participants. No significant variations in the biomarker changes over time were seen in the AD group.
Interpretation: In both NL and MCI elderly, clinical interventions aimed to treat OSA may slow the progression of cognitive impairment due to AD.
Funding: This work was supported by grants from the NIH/NIA/NHLBI (T32HL129953, R01HL118624, R21AG049348, R21AG055002, R01AG056031, R01AG022374, R21AG059179, R01AG056682 and P30AG008051); Foundation for Research in Sleep Disorders; American Sleep Medicine Foundation, the American Thoracic Society Foundation, the Friedman Brain Institute. I.R. is supported by the Wellcome Trust (103952/Z/14/Z).
Declaration of Interest: All authors report no disclosures.
Ethical Approval: The Institutional Review Board at each of the ADNI participating centers approved the ADNI study. Written informed consent was obtained from all patients participating in ADNI.
Suggested Citation: Suggested Citation