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Introduction: Sleepiness has been associated with cognitive decline and dementia in the elderly. Older adults with excessive daytime sleepiness appear to be more vulnerable to longitudinal amyloid PET accumulation before the onset of the dementia. However, it remains unclear whether sleepiness is similarly associated with other biomarkers of Alzheimer's disease (AD), axonal integrity, and inflammation, which may also contribute to neurodegeneration and cognitive decline. Methods: In this cross-sectional analysis, we identified 260 cognitively unimpaired adults (>60 years) from the Mayo Clinic Study of Aging, a population-based cohort from Olmsted County (MN), who underwent CSF quantification of AD biomarkers (Aß42, p-tau, p-tau/Aß42) in addition to at least one of the following biomarkers [neurofilament light chain (NfL) interleukin-6 (IL-6), IL-10, and tumor necrosis factor-α (TNF-α)]. We fit linear regression models to assess associations between sleepiness, as measured by the Epworth Sleepiness Scale (ESS), and CSF biomarkers, controlling for age, sex, APOε4 status, body mass index, hypertension, dyslipidemia, and prior diagnosis of obstructive sleep apnea. Results: Higher ESS scores were associated with higher CSF IL-6 and NfL, but not with the other CSF biomarkers. For every ESS score point increase, there was a 0.009 ([95% CI 0.001-0.016], p = 0.033) increase in the log of IL-6 and 0.01 ([95% CI 0.002-0.018], p = 0.016) increase in the log of NfL. A sensitivity analysis showed an association between ESS scores and log of p-tau/Aß42 only in participants with an abnormal ratio (>0.023), highly predictive of amyloid positivity. For every ESS score point increase, there was a 0.006 ([95% CI 0.001-0.012], p = 0.021) increase in the log of CSF p-tau/Aß42. Conclusion: Sleepiness was associated with greater CSF IL-6 and NfL levels, which could contribute to neurodegeneration or alternatively cause sleepiness. Higher NfL levels may result from sleep disruption and/or contribute to sleepiness via disturbed connectivity or damage to wake-promoting centers. Associations between sleepiness and p-tau/Aß42 in participants with abnormal ratio suggest that amyloid positivity contributes to vulnerability to sleep disturbance, which may further amyloid accumulation in a feed-forward loop process. Prospective studies of these markers are needed to determine cause-effect relationships between these associations.
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Postsedation neuroexcitation is sometimes attributed to intravenous injection of the sedative-hypnotic drug propofol. The movements associated with these events have strongly suggested convulsive activity, but they rarely have been comprehensively evaluated. We present video recordings of 3 healthy young patients who underwent elective surgery under conscious sedation and emerged from sedation with transient but repetitive violent motor activity and impaired consciousness. These manifestations required considerable mobilization of multiple health care workers to protect the patient from inflicting harm. All patients received propofol, and all fully recovered without adverse sequelae. We postulate that these movements are propofol related. Importantly, we found no evidence of seizures clinically or electrographically.