Association of probable REM sleep behavior disorder with pathology and years of contact sports play in chronic traumatic
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ORIGINAL PAPER
Association of probable REM sleep behavior disorder with pathology and years of contact sports play in chronic traumatic encephalopathy Jason W. Adams1,2 · Michael L. Alosco1,3 · Jesse Mez1,3 · Victor E. Alvarez1,3,4 · Bertrand R. Huber1,4 · Yorghos Tripodis1,5 · Charles H. Adler6 · Carol Kubilius1 · Kerry A. Cormier1,4,7 · Rebecca Mathais1 · Raymond Nicks1 · Hunter J. Kelley1 · Nicole Saltiel1 · Madeline Uretsky1 · Evan Nair1 · Nurgul Aytan1,3 · Jonathan D. Cherry1,3 · Christopher J. Nowinski1,8 · Neil W. Kowall1,3,4 · Lee E. Goldstein1,9 · Brigid Dwyer3,10 · Douglas I. Katz3,10 · Robert C. Cantu8,11,12,13 · Robert A. Stern1,3,11,12 · Ann C. McKee1,3,4,7,9 · Thor D. Stein1,4,7,9 Received: 19 May 2020 / Revised: 26 July 2020 / Accepted: 1 August 2020 © This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply 2020
Abstract Probable rapid eye movement (REM) sleep behavior disorder (pRBD) is a synucleinopathy-associated parasomnia in which loss of REM sleep muscle atonia results in motor behavior during REM sleep, including dream enactment. Traumatic brain injury is independently associated with increased risk of pRBD and Lewy body disease, and both pRBD and Lewy body disease are often observed in chronic traumatic encephalopathy (CTE). However, the frequency and pathological substrate of pRBD in CTE have not been formally studied and remain unknown. Of the total sample of 247 men, age at death of 63.1 ± 18.8 years (mean ± SD), 80 [32%] were determined by informant report to have symptoms of pRBD. These participants had played more years of contact sports (18.3 ± 11.4) than those without pRBD (15.1 ± 6.5; P = 0.02) and had an increased frequency of Lewy body disease (26/80 [33%] vs 28/167 [17%], P = 0.005). Of the 80 participants with pRBD, 54 [68%] did not have Lewy body disease; these participants were more likely to have neurofibrillary tangles and pretangles in the dorsal and median raphe (41 of 49 [84%] non-LBD participants with pRBD symptoms vs 90 of 136 [66%] non-LBD participants without pRBD symptoms, P = 0.02), brainstem nuclei with sleep regulatory function. Binary logistic regression modeling in the total study sample showed that pRBD in CTE was associated with dorsal and median raphe nuclei neurofibrillary tangles (OR = 3.96, 95% CI [1.43, 10.96], P = 0.008), Lewy body pathology (OR = 2.36, 95% CI [1.18, 4.72], P = 0.02), and years of contact sports participation (OR = 1.04, 95% CI [1.00, 1.08], P = 0.04). Overall, pRBD in CTE is associated with increased years of contact sports participation and may be attributable to Lewy body and brainstem tau pathologies. Keywords Chronic traumatic encephalopathy · REM sleep behavior disorder · Lewy body disease · Repetitive head impacts · Contact sports
Introduction Repetitive head impacts (RHI) and mild traumatic brain injury (TBI) sustained through contact sport participation or exposure to military blast have been associated with the neurodegenerative tauopathy chronic traumatic enceph
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