0885 Alzheimer’s disease progression risk in Cognitive Normal Older Adults with Obstructive Sleep Apnea using NIA-AA Research Framework

Abstract Introduction We determined risk profiles of strata-specific cognitive-normal (NL) older-adults with obstructive sleep apnea (OSA) characterized by their Aβ, P-Tau & T-tau (ATN) burden, on prospective AD stage-transition Methods Longitudinal study utilizing data from 167 community-dwelling NL older-adults participating in NYU studies on memory, sleep and aging. Subjects had baseline CSF AD-biomarker data and at least two follow-up clinical and neuropsychological data. OSA was defined using AHI4%. Using the NIA-AA Research Framework, data-driven, clinically relevant thresholds for CSF-Aβ42 (≤375pg/ml), P-tau (≥53.7pg/ml) and T-tau (≥367 pg/ml) indicated ATN status respectively. Twenty-four participants with suspected non-AD pathologic change defined as A-T+ were excluded leaving 143 for the analysis. Main outcome was AD stage-transition (i.e., change from Global Deterioration Scale (GDS) 1 or 2 [NL] at baseline to ≥3 [≥ MCI] during follow-up). Logistic mixed-effects models with random intercept and slope were used to assess associations between ATN characterized OSA subjects, and longitudinal AD stage transition, controlling for age-at-baseline, sex, APOE4-status, years-of-education, and their interactions with time. Results Of the 143 participants, 91 (63.8%) were women. The mean (SD) age was 69.6 (7.3) years and follow-up time was 4.73 (3.45) years. Sixteen (11.2%) were OSA+/A+/TN-, and 21 (14.7%) were OSA-/A+/TN-. Ninety-two (64.3%) had normal AD biomarkers (OSA+/A-/T- [n=45] and OSA-/A-/T- [N=47]). To generate strata-specific risks, subjects were combined into groups: (i) OSA subjects with AD pathologic change OSA+/A+/TN [n=25] consisting of OSA+/A+/TN+ [n=9] plus OSA+/A+/TN- [n=16] (ii) non-OSA subjects with AD pathologic change OSA-/A+/TN [n=26]) consisting of OSA-/A+/TN+ [n=5] and OSA-/A+/TN- [n=21] Fourteen subjects (9.8%) transitioned from NL to MCI (i.e., OSA+/A+/TN [6/25], OSA-/A+/TN [3/26], OSA+/A-/TN- [4/45] and OSA-/A-/TN- [3/47]). OSA+/A+/TN subjects were at higher risk of AD stage-transition relative to OSA-/A-/TN- (β = 1.31, 95%CI, 1.02, 1.62); OSA+/A-/TN- (β = 0.89, 95%CI, 0.42, 1.37); and OSA-/A+/TN subjects, (β = 0.71, 95%CI, 0.38, 1.04); P < .01 for all. OSA+/A-/T- vs. OSA-/A-/T- participants did not show differences in cognitive change over time (β = 0.22, 95%CI, -0.15, 0.39, P =.17). Conclusion Among ATN characterized NL older-adults with OSA, those with evidence of AD pathologic change have the greatest risk of developing AD. Support (if any) AASMBTS#231-BS-20, NIAK23AG068534A, AARG-D- 21-848397, BFFA2022033S