Plasma p-tau217 and neurodegeneration-related biomarkers predict incident cognitive impairment in obstructive sleep apnea: a prospective cohort study.

BACKGROUND

Obstructive sleep apnea (OSA) is associated with cognitive decline, but biomarkers for identifying cognitively unimpaired patients at increased future risk remain limited. We evaluated the prognostic value of plasma biomarkers associated with neuroaxonal injury and Alzheimer's disease-related biology in OSA.

METHODS

In this prospective cohort study, 286 cognitively unimpaired adults with polysomnography-confirmed OSA underwent baseline measurement of plasma NfL, GFAP, p-tau181, p-tau217, Aβ42, and Aβ40 and were followed for incident cognitive impairment. Cox regression, predictive performance analyses, and linear mixed-effects models were used.

RESULTS

During a median follow-up of 4.18 years, 68 participants (23.78%) developed incident cognitive impairment. In fully adjusted Cox models, each 1-SD increase in NfL was associated with a 46% higher risk of incident cognitive impairment (HR = 1.46, 95% CI 1.17-1.83, P = 0.001), and each 1-SD increase in p-tau217 was associated with a 58% higher risk (HR = 1.58, 95% CI 1.25-2.00, P < 0.001). When modeled jointly, both NfL (HR = 1.34, 95% CI 1.06-1.69, P = 0.014) and p-tau217 (HR = 1.47, 95% CI 1.14-1.89, P = 0.003) remained associated with incident cognitive impairment. In longitudinal analyses, higher baseline NfL and p-tau217 were also associated with faster annual declines in MoCA scores when modeled jointly (NfL × time: β = -0.10, 95% CI - 0.18 to - 0.02, P = 0.014; p-tau217 × time: β = -0.16, 95% CI - 0.25 to - 0.07, P = 0.001). Adding both biomarkers to the clinical model increased the C-index from 0.72 to 0.81 and the 4-year time-dependent AUC to 0.81; the optimism-corrected C-index was 0.79.

CONCLUSIONS

Higher plasma NfL and p-tau217 levels were independently associated with incident cognitive impairment and faster longitudinal cognitive decline in cognitively unimpaired patients with OSA.