Apnea‐associated hypoxemia is linked to greater tau deposition in women with Alzheimer’s disease risk

Abstract

AbstractBackgroundObstructive sleep apnea (OSA) is characterized by recurrent pharyngeal airway collapse and drops in blood oxygen levels that lead to intermittent hypoxemia. OSA has been associated with Alzheimer’s disease (AD) pathology, including tau. AD is more prevalent in women, and women tend to have higher levels of tau compared to men. OSA is underdiagnosed, particularly in postmenopausal women where OSA risk is similar to men. We conducted a pilot study examining the relationship between OSA and tau using positron emission tomography (PET) in older women at higher risk for AD who participated in the Women Inflammation and Tau Study (WITS).Method10 older women (aged 71±3.3 years) were recruited to WITS, which required elevated genetic risk of AD and a Montreal Cognitive Assessment score suggestive of mild cognitive impairment (range 13‐20). A home sleep test was completed to derive the apnea‐hypopnea index (AHI), nadir and mean oxygen saturation (Osat), and proportion of time in bed (TIB) with oxygen saturation ≤88% (Osat≤88%). Participants also underwent MK‐6240 PET to determine tau deposition. Standardized uptake value ratio (SUVR) was computed in temporal meta‐region of interest (ROI) Braak Stages I, III‐IV, and V‐VI. Spearman correlation was used to analyze the associations between OSA characteristics and tau PET SUVR in the respective ROIs.ResultIn this initial sample from WITS, 40% had mild OSA (AHI≥5/h and AHI<15/h) and 40% had moderate OSA (AHI≥15/h and AHI<30/h). Greater proportion of TIB with Osat≤88% was associated with higher tau SUVR in temporal meta‐ROI (rho=0.69, p=0.03), Braak III‐IV (rho=0.70, p=0.03), and Braak V‐VI (rho=0.69, p=0.03). No significant relationships were observed between AHI and tau PET SUVR in the respective ROIs (all p>0.40).ConclusionIn this small sample of women with elevated AD risk, OSA was evident in the majority. Additionally, we found positive relationships between proportion of TIB with Osat≤88% and tau deposition in temporal and neocortical regions. These findings suggests that OSA‐related intermittent hypoxemia could potentially contribute to the pathogenesis of tau; however, longitudinal studies are needed. Treatment of OSA may be a possible target to reduce or delay the impact of AD.