0282 WHITE MATTER DAMAGE AND AXONAL DEGENERATION ARE RELATED TO HYPOXIA IN UNTREATED OBSTRUCTIVE SLEEP APNEA

Abstract

Introduction: Mid-life is a critical period for brain health, when vascular risk factors and white matter injury are associated with cognitive impairment, and predict future dementia. Obstructive sleep apnea (OSA) is prevalent in midlife and is characterized by repetitive hypoxic episodes, which may damage brain white matter. Yet few studies have investigated this relationship using objective measures of OSA and white matter health. Therefore we examined white matter lesions and axonal and synaptic degeneration in untreated OSA. Methods: 49 cognitively normal, late middle-aged adults (23 female, age 60.4 +/-5.1 years) were recruited from the Wisconsin Alzheimer's Disease Research Center. Participants had no previous diagnosis or treatment of sleep disordered breathing. Cerebrospinal fluid was collected via lumbar puncture and assayed for markers of axonal degeneration (Neurofilament Light, NFL) and synaptic dysfunction (neurogranin). Volume of white matter hyperintensities (WMH) was quantified by T2 MRI. Sleep architecture and sleep disordered breathing were assessed with polysomnography. Secondary analyses examined CSF biomarkers of Alzheimer's disease pathology (amyloid-beta 42, 40 and tau). Multiple regression was used to test the relationships between CSF markers or WMH and Apnea-Hypopnea Index (AHI) or oxygen saturation (SpO2), controlling for age, time between sleep and CSF or MRI assessments, CSF assay batch and intracranial volume where applicable. CSF markers and white matter hyperintensities were also compared between groups with OSA (AHI>15, n=6) and controls (AHI<5, n=22) with t-tests. Results: Compared to controls, untreated OSA patients had elevated NFL (t=2.2, p=.04) and greater volume of white matter hyperintensities (t=2.2, p=.04). Lower mean SpO2 was associated with greater NFL (b=-7.3, p=.01) and greater WMH (b=-8.5, p=.005). Neither NFL or WMH were significantly associated with AHI. Neurogranin, amyloid and tau did not differ by OSA group, AHI or SpO2. Conclusion: In midlife, untreated OSA and hypoxia are associated with white matter lesions and axonal degeneration. OSA treatment could be a useful strategy to ameliorate cognitive decline mediated by white matter injury.