Jorge, Ricardo E.

Abstract Introduction Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia strongly associated with α-synucleinopathies, most commonly Parkinson’s disease (PD). Among Veterans, posttraumatic stress disorder (PTSD) is common and may influence RBD presentation and outcomes. The extent to which PTSD modifies demographic, medical, and mortality profiles in Veterans with RBD, and how these differ from those with RBD and Parkinson’s disease (PD), remains poorly characterized. Methods We conducted a retrospective cohort study using the Veterans Health Administration Corporate Data Warehouse. Veterans with at least one ICD-9 or ICD-10 diagnostic code for RBD were identified between 1999 - 2020 and categorized into three, mutually-exclusive groups based on the presence or absence of co-occurring ICD codes: RBD-only, RBD+PTSD, or RBD+PD. Demographics, comorbidities (Charlson Comorbidity Index [CCI]), and mortality outcomes were compared using logistic regression models adjusted for age, sex, race/ethnicity, BMI, and CCI. Results The cohort included 11,283 Veterans with RBD only, 17,527 with RBD+PTSD, and 5,675 with RBD+PD. Veterans with RBD+PTSD were younger (mean 58.9 ± 14.9 y) and had higher psychiatric comorbidity (94.2%) compared to RBD only (54.2%) or RBD+PD (46.5%). Those with RBD+PD were older (73.6 ± 8.1 y), predominantly male (98.9%), and had the highest neurological comorbidity (92.6%). Unadjusted mortality was lowest in RBD+PTSD (15.3%) and highest in RBD+PD (53.6%). Adjusted models showed reduced mortality risk for RBD+PTSD (aOR 0.73, 95% CI 0.70–0.80, p < 0.001) and increased risk for RBD+PD (aOR 2.43, 95% CI 2.3–2.6, p < 0.001) vs. RBD alone. Higher age, male sex, and greater comorbidity independently predicted mortality. Conclusion In this large national VA cohort, comorbid PTSD and Parkinson’s disease were associated with distinct demographic and clinical profiles among Veterans with RBD. RBD+PTSD was linked to younger age, greater psychiatric burden, and lower mortality. These findings underscore the heterogeneity of RBD in Veterans and support stratified approaches to surveillance for synucleinopathy and trauma-related sleep disturbances. Support (if any) VA CDA # IK2CX002363-01A1 (MJ); NHLBI K25 #1K25HL152006-01 (JR)

Abstract Introduction Rapid eye movement (REM) sleep behavior disorder (RBD) is the single strongest predictor of Parkinson’s disease (PD) risk. Given neurotrauma and psychiatric morbidity, the aging post-9/11 Veteran cohort is a target population for understanding probable RBD frequency and neuroprotection opportunities. We previously reported over 50% of post-9/11 Veterans screened positive for probable RBD. We aimed to examine frequencies of prodromal PD markers and polysomnography (PSG)-confirmed RBD in post-9/11 Veterans. Methods Veterans with probable RBD based on the single-question RBD screen (n=12) were recruited from the Translational Research Center for Traumatic Brain Injury (TBI) and Stress Disorders (TRACTS) Houston cohort. Participants were assessed for subthreshold parkinsonism (Unified Parkinson’s Disease Rating Scale-III Motor score >3, excluding action tremor), olfactory loss (12-item Sniffin’ Sticks), TBI exposures, autonomic symptoms, orthostasis, excessive daytime sleepiness, post-traumatic stress disorder (PTSD), and psychiatric comorbidities. PSG studies were conducted per American Academy of Sleep Medicine guidelines. A board-certified sleep physician confirmed the presence of REM sleep without atonia. We compared the frequency of prodromal marker positivity between participants with and without subthreshold parkinsonism. Results All 12 participants were male (6 [50%] Black, 3 [25%] Hispanic) with a mean (SD) age of 44.4 ± 6.7 years. PSG data (n=10) revealed REM sleep without atonia in 5 (50%), moderate obstructive sleep apnea (OSA) in 2 (20%), and severe OSA in 2 (20%) participants. Five (41.6%) participants had mild motor dysfunction suggestive of subthreshold parkinsonism on the UPDRS-III (M±SD score of 8.6 ± 5.9), while 7 participants had normal or low UPDRS-III ratings (2.3 ± 1.3; p=0.02). Veterans with subthreshold parkinsonism had lower Sniffin’ Sticks scores than those without (M±SD 9.4 ± 2.07 vs. 11.29 ± 0.76; 95% CI: 0.01–3.76, p=0.049). Conclusion This pilot study suggests that motor and olfactory prodromal PD markers are frequent in post-9/11 Veterans with probable RBD. Larger prospective cohort studies are required to further quantify REM sleep without atonia and assess synuclein-specific biomarkers in this population. Support (if any) Center for Alzheimer’s and Neurodegenerative Diseases at Baylor College of Medicine [MJ]; VA CSR&D (#IK2CX002363-01A1) [MJ]; VA RR&D (B9268-X) [RJ]; NIH/NIA/NINDS (U19-AG071754 & R34-AG056639) [ES]; and AASM [ES].

ABSTRACTBackgroundThe objective of this study was to evaluate citalopram for executive functioning in Huntington's disease (HD).MethodsThe study was randomized, double‐blind, and placebo‐controlled. Thirty‐three adults with HD, cognitive complaints, and no depression (Hamilton Depression [HAM‐D] rating scale ≤12) were administered citalopram 20 mg or placebo (7 visits, 20 weeks), with practice and placebo run‐ins. The primary outcome was change in executive functioning.ResultsThe intent to treat analysis was controlled for practice effects, comparing visits 1 and 2 to visits 5 and 6 for citalopram versus placebo. There were no significant benefits on the executive function composite (treatment‐placebo mean difference −0.167; 95% confidence interval [CI], −0.361 to 0.028; P = .092). Citalopram participants showed improved clinician‐rated depression symptoms on the HAM‐D (t = −2.02; P = 0.05). There were no group differences on motor ratings, self‐reported executive functions, psychiatric symptoms, or functional status.ConclusionsThere was no evidence that short‐term treatment with citalopram improved executive functions in HD. Despite excluding patients with active depression, participants on citalopram showed improved mood, raising the possibility of efficacy for subsyndromal depression in HD. © 2013 International Parkinson and Movement Disorder Society