Sleep quality in patients with mild traumatic brain injury (mTBI) is associated with cognitive flexibility, inhibitory control, and plasma levels of neurofilament light (NfL) and tau, according to study results published in Sleep.

While both TBI and sleep disorders are independently linked to neurodegeneration, previous longitudinal TBI-related dementia studies have not investigated the effects of sleep. Study researchers sought to compare biomarkers of neurodegeneration and cognitive function with sleep quality in patients with mTBI,

This was a retrospective cross-sectional cohort study of participants who had enrolled between 2015 and 2016 in the Chronic Effects of Neurotrauma Consortium (CENC) longitudinal study. The CENC, a prospective observational study, included combat-exposed United States military service members and veterans with or without chronic mild traumatic brain injury (mTBI) from an impact or blast after September 11, 2001. Study researchers included 182 CENC participants (mTBI participants, 138; control participants, 44) with valid biomarker measurements who had completed baseline enrollment tests, which included blood biomarker measurements of Aβ42, total tau, and NfL assay, and participants’ self-reports of their sleep quality for the past 30 days, using the Pittsburgh Sleep Quality Index (PSQI).


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The participants also completed a series of cognitive tests on cognitive flexibility (Delis-Kaplan Executive Function System battery [“stop-go test”]), inhibitory control (Flanker Inhibitory 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 assessed them for obstructive sleep apnea risk and postconcussive symptom severity.

The study researchers created multiple linear regression models and compared the results of the control group with the results of the TBI group. They tested for interaction between mTBI and PSQI and used bivariate tests to evaluate mTBI relationship with outcomes.

Results indicated that the chronic mTBI (mean duration since last mTBI: 8.3±6.4 years) population had worse sleep quality than the non-TBI control population (P =.015), but NfL, tau, Aβ42 and cognitive test scores did not differ significantly between the groups.

Isolating the 99 poor sleepers of both groups using the recommended PSQI cutoff of at least 10 for the military, the study researchers found that tau was significantly elevated among poor sleepers, with a moderate effect size in the mTBI group compared with control participants (pg/mL, x̄=2.6, and 1.88 ,respectively; d=0.57; P =.005). The subgroups’ demographics remained similar and demonstrated no overall differences among the mTBI subpopulations regarding timing or type of mTBI. Additionally, obstructive sleep apnea risk and neurobehavioral symptoms were higher in the poor sleepers compared with good sleepers in both the mTBI and control groups.

In the mTBI group, there was significantly higher plasma NfL (d=0.63) and a trend toward higher plasma tau (d=0.35) among poor sleepers compared with good sleepers. PSQI was the strongest predictor of NfL (βstd=0.37; P <.001) and tau (βstd=0.27; P =.0028). Poor sleepers in the mTBI group had lower executive function scores by the categorical fluency test (d=-0.65) and significant reduction in stop-go test scores (d=-0.37). In the mTBI group, the PSQI (βstd=-0.26; P =.009) and plasma NfL (βstd=-0.25; P =.009) negatively correlated with categorical fluency, but not other cognitive tests.

Limitations of the study included the inability to assess directionality, the snapshot of sleep quality via PSQI that assesses only the “last 30 days” of sleep quality, the moderate sample size in the mTBI population, and small sample size in the control participants.

Ultimately, the study researchers concluded that “poor sleep is linked to neurodegeneration and select measures of executive function in mTBI patients” and that their findings “[support] implementation of validated sleep measures in longitudinal studies investigating pathobiological mechanisms of TBI related neurodegeneration, which could have therapeutic implications.”

Reference

Werner JK, Shahim P, Pucci JU, et al. Poor sleep correlates with biomarkers of neurodegeneration in mild traumatic brain injury patients: a CENC Study. Published online December 6, 2020. Sleep. doi:10.1093/sleep/zsaa272