Sleep quality in patients with mildly traumatic brain injury (mTBI) is associated with cognitive flexibility, inhibitory control, and plasma levels of neurofilament light (NfL) and tau, according to the study results published in Sleep.
While both TBI and sleep disorders are independently associated with neurodegeneration, previous longitudinal TBI-related dementia studies have not explored the effects of sleep. The study researchers attempted to compare biomarkers for neurodegeneration and cognitive function with sleep quality in patients with mTBI.
This was a retrospective cross-sectional cohort study of participants who signed up for the longitudinal study of the Chronic Effects of Neurotrauma Consortium (CENC) between 2015 and 2016. The CENC, a prospective observational study, included combat-exposed members of the U.S. Military Service and veterans with or without a chronic minor traumatic brain injury (mTBI) from an impact or explosion after September 11, 2001. Study researchers included 182 CENC participants (mTBI- Participant), 138; Control participants, 44) with valid biomarker measurements who had completed baseline registration tests, including blood biomarker measurements of Aβ42, total tau, and NfL assay, and participants’ self-reports of their sleep quality over the past 30 days; using the Pittsburgh Sleep Quality Index (PSQI).
Participants also completed a series of cognitive tests on cognitive flexibility (battery of the Delis-Kaplan Executive Function System) [“stop-go test”]), Inhibition control (flanker inhibition control and attention test), working memory (Digital Span Backwards subtest of the Weschler Adult Intelligence Scale) and delayed verbal learning and memory (California Verbal Learning Test). Investigators also rated them on the risk of obstructive sleep apnea and the severity of postconcussive symptoms.
The study researchers created several linear regression models and compared the results of the control group with the results of the TBI group. They tested the interaction between mTBI and PSQI and used bivariate tests to assess the mTBI relationship to the results.
The results showed that the chronic mTBI population (mean duration since the last mTBI: 8.3 ± 6.4 years) had poorer sleep quality than the non-TBI control population (P = 0.015), but the NfL, Tau -, Aβ42 and cognitive test results did not differ significantly between the groups.
The study researchers isolated the 99 poor sleepers of both groups using the recommended PSQI cutoff of at least 10 for the military, and found that dew was significantly increased in poor sleepers, with a moderate effect size in the mTBI group compared to controls (pg / ml, x = 2.6 and 1.88, respectively; d = 0.57; P = 0.005). The demographics of the subgroups remained similar and showed no general differences between the mTBI subpopulations with regard to the timing or type of mTBI. In addition, the risk of obstructive sleep apnea and neurobehavioral symptoms were higher in the poor sleepers than in the good sleepers in both the mTBI and control groups.
In the mTBI group, there was a significantly higher plasma NfL (d = 0.63) and a trend towards higher plasma tau (d = 0.35) in poor sleepers compared to good sleepers. PSQI was the strongest predictor for NfL (βstd = 0.37; P <0.001) and Tau (βstd = 0.27; P = 0.0028). Poor sleepers in the mTBI group had lower scores for executive function and a significant reduction in stop-go test scores (d = -0.37) after the categorical fluence test (d = -0.65). In the mTBI group, the PSQI (βstd = -0.26; P = 0.009) and the plasma NfL (βstd = -0.25; P = 0.009) correlated negatively with the categorical fluence, but not with other cognitive tests.
The limitations of the study included the inability to assess directivity, the snapshot of sleep quality via PSQI, which only rates the “last 30 days” of sleep quality, the moderate sample size in the mTBI population, and the small sample size in the control subjects .
Ultimately, the study’s researchers concluded that “poor sleep is associated with neurodegeneration and that measures for executive function are selected in mTBI patients” and that their findings “[support] Implementation of validated sleep measures in longitudinal studies to investigate pathobiological mechanisms of TBI-related neurodegeneration that could have therapeutic effects. ”
Werner JK, Shahim P., Pucci JU, et al. Poor sleep correlates with neurodegeneration biomarkers in patients with mild traumatic brain injury: a CENC study. Published online December 6, 2020. Sleep. doi: 10.1093 / sleep / zsaa272