Imagine you’re driving a car on a foggy day. As you struggle to see through the thick mist, your reaction time slows down and your focus becomes hazy. Just like the fog impairs your ability to drive, sleepiness in older adults has been found to be associated with inflammation and axonal damage in the brain. In a study of cognitively unimpaired older adults, researchers found that higher levels of sleepiness were linked to increased levels of inflammatory biomarkers (IL-6) and markers of axonal integrity (NfL) in their cerebrospinal fluid. This suggests that inflammation and damage to the brain’s communication pathways may be involved in the development of sleepiness and potentially contribute to cognitive decline and neurodegeneration. These findings highlight the importance of exploring the underlying mechanisms of sleepiness in order to better understand its impact on brain health. If you want to dive deeper into this fascinating research and learn more about the links between sleepiness, inflammation, and axonal integrity, check out the full article!

IntroductionSleepiness 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.MethodsIn 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 (Aβ42, p-tau, p-tau/Aβ42) 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.ResultsHigher 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/Aβ42 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/Aβ42.ConclusionSleepiness 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/Aβ42 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.

Read Full Article (External Site)