Poor sleep correlates with biomarkers of neurodegeneration in mild traumatic brain injury patients: A CENC study

Study Objectives: Sleep disorders affect over half of mild traumatic brain injury (mTBI) patients. Despite evidence linking sleep and neurodegeneration, longitudinal TBI-related dementia studies have not considered sleep. We hypothesized that poor sleepers with mTBI would have elevated markers of neurodegeneration and lower cognitive function compared to mTBI good sleepers and controls. Our objective was to compare biomarkers of neurodegeneration and cognitive function with sleep quality in warfighters with chronic mTBI. Methods: In an observational warfighters cohort (n = 138 mTBI, 44 controls), the Pittsburgh Sleep Quality Index (PSQI) was compared with plasma biomarkers of neurodegeneration and cognitive scores collected an average of 8 years after injury. Results: In the mTBI cohort, poor sleepers (PSQI ≥ 10, n = 86) had elevated plasma neurofilament light (NfL, x¯ = 11.86 vs 7.91 pg/mL, p = 0.0007, d = 0.63) and lower executive function scores by the categorical fluency (x¯ = 18.0 vs 21.0, p = 0.0005, d = -0.65) and stop-go tests (x¯ = 30.1 vs 31.1, p = 0.024, d = -0.37). These findings were not observed in controls (n = 44). PSQI predicted NfL (beta = 0.22, p = 0.00002) and tau (beta = 0.14, p = 0.007), but not amyloid β42. Poor sleepers showed higher obstructive sleep apnea (OSA) risk by STOP-BANG scores (x¯ = 3.8 vs 2.7, p = 0.0005), raising the possibility that the PSQI might be partly secondary to OSA. Conclusions: Poor sleep is linked to neurodegeneration and select measures of executive function in mTBI patients. This supports implementation of validated sleep measures in longitudinal studies investigating pathobiological mechanisms of TBI related neurodegeneration, which could have therapeutic implications.