Sleep stability, emotional memory and risk for neurodegeneration in World Trade Center Responders

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Project Summary World Trade Center (WTC) Responders self-report high levels of poor sleep quality and exhibit a high prevalence of sleep disorders such as obstructive sleep apnea (OSA) and insomnia. Research investigating brain health in this population indicates early-age cognitive impairments and neurodegeneration associated with both physical exposures of particulate neurotoxins at the WTC site and chronic post-traumatic stress disorder (PTSD). There is evidence that poor sleep quality is associated with cognitive impairments, biomarkers of neurodegeneration and dementia in both sleep disorders and the general community. However, it is not known if poor sleep quality contributes to increased risk of neurodegeneration in WTC Responders. Sleep quality is a term that encompasses multiple aspects of sleep initiation, maintenance, quantity, and refreshment upon awakening. It is typically assessed subjectively using questionnaires that evaluate general satisfaction with current sleep-related quality of life, sleep behaviors or symptoms. A potentially useful, and objectively measured, proxy for sleep quality is sleep stability. Metrics of sleep stability can be obtained through the lens of the central nervous system (CNS) with electroencephalography (EEG) or the corresponding autonomic nervous system (ANS) activity using cardiopulmonary coupling (CPC). EEG-measured rapid eye movement (REM) and non-REM (NREM) sleep instability is characteristic of insomnia and OSA. Sleep instability caused by OSA results in impaired sleep-dependent memory and increases in markers of neurodegeneration. Reduced and delayed REM, manifestations of REM instability, are associated with increased risk of dementia in a large community cohort. Quality EEG signals are difficult to obtain at-home but newer, wearable CPC-measuring devices can provide sleep quality and disorder severity measures from the home. CPC measured sleep demonstrates exaggerated night-to-night variability in insomnia. Highly variable sleep schedules predict successful response to treatment with cognitive behavioral therapy for insomnia (CBTi). We plan to enroll 40 WTC Responders who will undergo 2 weeks at-home CPC sleep monitoring followed by an overnight in-lab PSG with pre/post-sleep emotional memory picture task and blood sampling. Aim 1a is to test whether single-night REM sleep instability measured by EEG activity is associated with impaired emotional memory. Exploratory Aim 1b is to test any potential association between impaired overnight memory processing and overnight change in plasma biomarkers Tau and NFL. Aim 2 is to test whether inconsistent sleep quality measured by night-to-night variability in CPC is associated with greater evening plasma Tau and NFL levels.