EFFECT OF OBSTRUCTIVE SLEEP APNEA (OSA) ON RATE OF CHANGE OF AD BIOMARKERS IN COGNITIVELY NORMAL, MCI AND AD ELDERLY: FINDINGS FROM THE ALZHEIMER’S DISEASE NEUROIMAGING INITIATIVE (ADNI) COHORT

Abstract

We examined the effect of OSA on longitudinal changes in brain amyloid deposition, and AD Cerebrospinal fluid (CSF) biomarkers. Data from 1639 subjects (516 Cognitive Normal (CN), 798 Mild Cognitive Impairment (MCI) and 325 AD, mean ages = 74.4 ± 5.8; 73.4 ± 7.4 and 75.1 ± 7.8 respectively), in the ADNI database was used. OSA was self-reported and participants were labeled OSA positive, or OSA negative (mean ages = 72.3 ± 7.1; and 73.9 ± 7.3 respectively). AD biomarkers included CSF Aβ-42, TAU, PTAU and brain florbetapir-PET Aβ burden. Separate multi-level mixed effects linear regression models were used to examine the relationship between OSA and the rate of change of AD biomarkers over time (mean = 2.52 ± 0.51 years) in each group (CN, MCI and AD). The final models were adjusted for sex, BMI, and CPAP status. No significant difference existed between OSA groups for APOE e4 status, age and history of cardiovascular disease. Cross-sectional analyses showed associations between OSA and CSF Aβ-42 levels ONLY in the MCI, and AD groups (P <0.05 for all). OSA was associated with TAU levels ONLY in MCI patients (P =0.02). Furthermore, significant OSA associations were observed with Aβ-42 levels only in CN and MCI participants (P =0.02 for all). Longitudinal analyses revealed significant variations in the change in Aβ-42 volumes over time and the covariance between baseline Aβ-42 and Aβ-42 change over time showed that OSA subjects experienced faster increase in Aβ-42 over time (p < .0001 for all) in both the CN and MCI groups. Significant variations were observed in CSF Aβ-42, TAU and PTAU levels over time and the covariance parameters between the baseline CSF Aβ-42, TAU and PTAU volume change over time indicated that OSA participants experienced a faster decrease in CSF Aβ-42 and increases in TAU and PTAU volumes over time (p < .0001 for all) in both the CN and MCI groups. OSA possibly accelerates longitudinal changes in brain amyloid deposition, and CSF biomarkers burden, both in elderly cognitive normal and MCI individuals. Further research examining mechanisms underlying these observed effects are needed.