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Article ; Online: A case of prazosin in treatment of rapid eye movement sleep behavior disorder.

Cho, Yeilim / Iliff, Jeffrey J / Lim, Miranda M / Raskind, Murray / Peskind, Elaine

Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine

2023 Volume 20, Issue 2, Page(s) 319–321

Abstract: Rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by dream-enactment behaviors that emerge during a loss of REM sleep atonia. Untreated RBD carries risks for physical injury from falls or other traumatic events during dream ... ...

Abstract	Rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by dream-enactment behaviors that emerge during a loss of REM sleep atonia. Untreated RBD carries risks for physical injury from falls or other traumatic events during dream enactment as well as risk of injury to the bed partner. Currently, melatonin and clonazepam are the mainstay pharmacological therapies for RBD. However, therapeutic response to these medications is variable. While older adults are most vulnerable to RBD, they are also particularly vulnerable to the adverse effects of benzodiazepines, including increased risk of falls, cognitive impairment, and increased risk of Alzheimer disease. Prazosin is a centrally active alpha-1 adrenergic receptor antagonist often prescribed for trauma nightmares characterized by REM sleep without atonia in patients with posttraumatic stress disorder. We report a case of successful RBD management with prazosin in a patient in whom high-dose melatonin was ineffective. Although there was no observable reduction in dream-enactment behaviors with high-dose melatonin, the possibility of a synergistic effect of prazosin combined with melatonin cannot be ruled out. This case report supports further evaluation of prazosin as a potential therapeutic for RBD. Citation: Cho Y, Iliff JJ, Lim MM, Raskind M, Peskind E. A case of prazosin in treatment of rapid eye movement sleep behavior disorder.
MeSH term(s)	Humans ; Aged ; Melatonin/therapeutic use ; REM Sleep Behavior Disorder/complications ; REM Sleep Behavior Disorder/drug therapy ; Prazosin/therapeutic use ; Clonazepam/therapeutic use ; Stress Disorders, Post-Traumatic/complications
Chemical Substances	Melatonin (JL5DK93RCL) ; Prazosin (XM03YJ541D) ; Clonazepam (5PE9FDE8GB)
Language	English
Publishing date	2023-10-26
Publishing country	United States
Document type	Case Reports
ZDB-ID	2397213-0
ISSN	1550-9397 ; 1550-9389
ISSN (online)	1550-9397
ISSN	1550-9389
DOI	10.5664/jcsm.10888
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Article ; Online: Prazosin for Post-Traumatic Stress Disorder.

Raskind, Murray A / Peskind, Elaine R

The New England journal of medicine

2018 Volume 378, Issue 17, Page(s) 1649–1650

MeSH term(s)	Dreams ; Humans ; Prazosin ; Stress Disorders, Post-Traumatic ; Veterans
Chemical Substances	Prazosin (XM03YJ541D)
Language	English
Publishing date	2018--26
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	207154-x
ISSN	1533-4406 ; 0028-4793
ISSN (online)	1533-4406
ISSN	0028-4793
DOI	10.1056/NEJMc1803171
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Article: Preliminary cross-sectional investigations into the human glymphatic system using multiple novel non-contrast MRI methods.

Levendovszky, Swati Rane / Flores, Jaqueline / Peskind, Elaine R / Václavů, Lena / van Osch, Matthias J P / Iliff, Jeffrey

bioRxiv : the preprint server for biology

2023

Abstract: We discuss two potential non-invasive MRI methods to cross-sectionally study two distinct facets of the glymphatic system and its association with sleep and aging. We apply diffusion-based intravoxel incoherent motion (IVIM) imaging to evaluate ... ...

Abstract	We discuss two potential non-invasive MRI methods to cross-sectionally study two distinct facets of the glymphatic system and its association with sleep and aging. We apply diffusion-based intravoxel incoherent motion (IVIM) imaging to evaluate pseudodiffusion coefficient,
Language	English
Publishing date	2023-08-29
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.08.28.555150
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Article ; Online: Timing matters: Sex differences in inflammatory and behavioral outcomes following repetitive blast mild traumatic brain injury.

Baskin, Britahny M / Logsdon, Aric F / Janet Lee, Suhjung / Foresi, Brian D / Peskind, Elaine / Banks, William A / Cook, David G / Schindler, Abigail G

Brain, behavior, and immunity

2023 Volume 110, Page(s) 222–236

Abstract: Background: Repetitive blast-related mild traumatic brain injury (mTBI) caused by exposure to high explosives is increasingly common among warfighters as well as civilians. While women have been serving in military positions with increased risk of blast ...

Abstract	Background: Repetitive blast-related mild traumatic brain injury (mTBI) caused by exposure to high explosives is increasingly common among warfighters as well as civilians. While women have been serving in military positions with increased risk of blast exposure since 2016, there are few published reports examining sex as a biological variable in models of blast mTBI, greatly limiting diagnosis and treatment capabilities. As such, here we examined outcomes of repetitive blast trauma in female and male mice in relation to potential behavioral, inflammatory, microbiome, and vascular dysfunction at multiple timepoints. Methods: In this study we utilized a well-established blast overpressure model to induce repetitive (3x) blast-mTBI in both female and male mice. Acutely following repetitive exposure, we measured serum and brain cytokine levels, blood-brain barrier (BBB) disruption, fecal microbial abundance, and locomotion and anxiety-like behavior in the open field assay. At the one-month timepoint, in female and male mice we assessed behavioral correlates of mTBI and PTSD-related symptoms commonly reported by Veterans with a history of blast-mTBI using the elevated zero maze, acoustic startle, and conditioned odorant aversion paradigms. Results: Repetitive blast exposure resulted in both similar (e.g., increased IL-6), and disparate (e.g., IL-10 increase only in females) patterns of acute serum and brain cytokine as well as gut microbiome changes in female and male mice. Acute BBB disruption following repetitive blast exposure was apparent in both sexes. While female and male blast mice both exhibited acute locomotor and anxiety-like deficits in the open field assay, only male mice exhibited adverse behavioral outcomes that lasted at least one-month. Discussion: Representing a novel survey of potential sex differences following repetitive blast trauma, our results demonstrate unique similar yet divergent patterns of blast-induced dysfunction in female vs. male mice and highlight novel targets for future diagnosis and therapeutic development.
MeSH term(s)	Female ; Male ; Mice ; Animals ; Humans ; Brain Concussion/complications ; Sex Characteristics ; Stress Disorders, Post-Traumatic/etiology ; Anxiety ; Veterans ; Blast Injuries/complications
Language	English
Publishing date	2023-03-10
Publishing country	Netherlands
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural
ZDB-ID	639219-2
ISSN	1090-2139 ; 0889-1591
ISSN (online)	1090-2139
ISSN	0889-1591
DOI	10.1016/j.bbi.2023.03.003
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Zs.A 2276: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Perivascular Space Burden and Cerebrospinal Fluid Biomarkers in US Veterans With Blast-Related Mild Traumatic Brain Injury.

Yamamoto, Erin A / Koike, Seiji / Luther, Madison / Dennis, Laura / Lim, Miranda M / Raskind, Murray / Pagulayan, Kathleen / Iliff, Jeffrey / Peskind, Elaine / Piantino, Juan A

Journal of neurotrauma

2024

Abstract: Blast-related mild traumatic brain injury (mTBI) is recognized as the "signature injury" of the Iraq and Afghanistan wars. Sleep disruption, mTBI, and neuroinflammation have been individually linked to cerebral perivascular space (PVS) dilatation. ... ...

Abstract	Blast-related mild traumatic brain injury (mTBI) is recognized as the "signature injury" of the Iraq and Afghanistan wars. Sleep disruption, mTBI, and neuroinflammation have been individually linked to cerebral perivascular space (PVS) dilatation. Dilated PVSs are putative markers of impaired cerebrospinal fluid (CSF) and interstitial fluid exchange, which plays an important role in removing cerebral waste. The aim of this cross-sectional, retrospective study was to define associations between biomarkers of inflammation and MRI-visible PVS (MV-PVS) burden in Veterans after blast-related mTBI (blast-mTBI) and controls. The CSF and plasma inflammatory biomarker concentrations were compared between blast-mTBI and control groups and correlated with MV-PVS volume and number per white matter cm
Language	English
Publishing date	2024-01-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	645092-1
ISSN	1557-9042 ; 0897-7151
ISSN (online)	1557-9042
ISSN	0897-7151
DOI	10.1089/neu.2023.0505
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Article ; Online: CSF β-Amyloid and Tau Biomarker Changes in Veterans With Mild Traumatic Brain Injury.

Li, Ge / Iliff, Jeffrey / Shofer, Jane / Mayer, Cynthia L / Meabon, James / Cook, David / Pagulayan, Kathleen F / Raskind, Murray A / Zetterberg, Henrik / Blennow, Kaj / Peskind, Elaine R

Neurology

2024 Volume 102, Issue 7, Page(s) e209197

Abstract: Background and objectives: Moderate-to-severe traumatic brain injuries (TBI) have been reported to increase the risk of Alzheimer disease (AD). Whether mild TBI (mTBI) in veterans confers a similar increased risk of AD is less known. This study ... ...

Abstract	Background and objectives: Moderate-to-severe traumatic brain injuries (TBI) have been reported to increase the risk of Alzheimer disease (AD). Whether mild TBI (mTBI) in veterans confers a similar increased risk of AD is less known. This study investigated early AD changes using CSF biomarkers in veterans with blast mTBI. Methods: This was a cross-sectional case-control study of veterans with mTBI and non-mTBI veterans and civilians from 2 study sources. Blast-mTBI veterans had at least 1 war zone blast or combined blast/impact mTBI meeting Veterans Affairs (VA) and Department of Defense (DoD) criteria for mTBI. Non-mTBI participants had no lifetime history of TBI. All participants underwent standardized clinical and neuropsychological assessments and lumbar puncture for collection of the CSF. CSF biomarkers were measured using MesoScale Discovery assays for Aβ40 and Aβ42 and INNOTEST ELISAs for phosphorylated tau181 (p-tau181) and total tau (t-tau). Results: Our sample comprised 51 participants with mTBI and 85 non-mTBI participants with mean (SD) ages 34.0 (10.1) and 33.5 years (8.9), respectively. All participants but 1 (99%) were male. Differences in CSF AD biomarkers between mTBI and non-mTBI groups were age dependent and most pronounced at older ages (omnibus test Discussion: CSF Aβ levels decreased in middle-aged veterans with blast-related mTBI. These data suggest that chronic neuropathologic processes associated with blast mTBI share properties in common with pathogenic processes known to portend AD onset, thus raising concern that veterans with blast-related mTBI may develop a dementing disorder later in life.
MeSH term(s)	Middle Aged ; Humans ; Male ; Aged ; Female ; Brain Concussion/complications ; Case-Control Studies ; Veterans ; Cross-Sectional Studies ; Amyloid beta-Peptides ; Alzheimer Disease/pathology ; tau Proteins ; Brain Injuries, Traumatic/complications ; Biomarkers ; Memory Disorders/complications
Chemical Substances	Amyloid beta-Peptides ; tau Proteins ; Biomarkers
Language	English
Publishing date	2024-03-13
Publishing country	United States
Document type	Journal Article
ZDB-ID	207147-2
ISSN	1526-632X ; 0028-3878
ISSN (online)	1526-632X
ISSN	0028-3878
DOI	10.1212/WNL.0000000000209197
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Article ; Online: The Relative Effects of Prazosin on Individual PTSD Symptoms: Evidence for Pathophysiologically-Related Clustering.

Hendrickson, Rebecca C / Millard, Steven P / Pagulayan, Kathleen F / Peskind, Elaine R / Raskind, Murray A

Chronic stress (Thousand Oaks, Calif.)

2021 Volume 5, Page(s) 2470547020979780

Abstract: Background: The α: Methods: In a : Results: Prazosin showed the largest effect for distressing dreams, anhedonia, difficulty falling or staying asleep, difficulty concentrating, and hypervigilance. These items were also (a) of higher baseline ... ...

Abstract	Background: The α Methods: In a Results: Prazosin showed the largest effect for distressing dreams, anhedonia, difficulty falling or staying asleep, difficulty concentrating, and hypervigilance. These items were also (a) of higher baseline severity in the underlying population, and (b) more related in how they fluctuated at the level of individual subjects. Covariance analysis did not support a clear cutoff between highly prazosin responsive items and those showing a smaller, not statistically significant response. Conclusions: In this data set, twice daily prazosin substantially reduced not only nightmares and sleep disruption, but the majority of hyperarousal symptoms, with some evidence of efficacy for avoidance symptoms. The relationship of baseline symptom distribution to which symptoms showed significant response to prazosin reinforces the possibility that differences in a clinical trial's participant populations may significantly influence trial outcome. The pattern of symptom endorsement at the level of individual subjects was consistent with prazosin-responsive items sharing a common pathophysiologic mechanism.
Language	English
Publishing date	2021-02-09
Publishing country	United States
Document type	Journal Article
ISSN	2470-5470
ISSN (online)	2470-5470
DOI	10.1177/2470547020979780
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Article ; Online: Associations between Intra-Individual Neurocognitive Variability and Prospective Memory in Veterans with Mild Traumatic Brain Injury History and Posttraumatic Stress Disorder.

Sheppard, David P / Rau, Holly K / Werhane, Madeleine L / Fonseca, Luciana Mascarenhas / Chaytor, Naomi S / Peskind, Elaine R / Pagulayan, Kathleen F

Archives of clinical neuropsychology : the official journal of the National Academy of Neuropsychologists

2022 Volume 37, Issue 6, Page(s) 1221–1227

Abstract: Objective: Mild traumatic brain injury (mTBI) and posttraumatic stress disorder (PTSD) frequently co-occur and are associated with neurocognitive intra-individual variability (IIV) and difficulty with prospective memory (PM). The current study aimed to ... ...

Abstract	Objective: Mild traumatic brain injury (mTBI) and posttraumatic stress disorder (PTSD) frequently co-occur and are associated with neurocognitive intra-individual variability (IIV) and difficulty with prospective memory (PM). The current study aimed to examine associations between IIV and PM in this comorbid group. Method: Fifty veterans with a history of blast mTBI and current comorbid PTSD completed a standardized neurocognitive battery to measure IIV, and the Memory for Intentions Screening Test measuring PM. Results: Adjusting for age, education, and race, higher IIV was associated with poorer time-based PM (p < .001, f2 = .34), but not event-based PM. In a subset of the sample with self-report data, higher IIV was associated with poorer self-reported retrospective memory, but not PM. Conclusions: Cognitive variability on a standardized neuropsychological battery was associated with strategically demanding PM, which is an ecologically relevant ability and highlights the possible connection between subtle cognitive difficulties in-clinic and those experienced in daily life.
MeSH term(s)	Afghan Campaign 2001- ; Brain Concussion/complications ; Brain Concussion/psychology ; Humans ; Iraq War, 2003-2011 ; Memory Disorders/complications ; Memory, Episodic ; Neuropsychological Tests ; Retrospective Studies ; Stress Disorders, Post-Traumatic/complications ; Stress Disorders, Post-Traumatic/psychology ; Veterans/psychology
Language	English
Publishing date	2022-04-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	632972-x
ISSN	1873-5843 ; 0887-6177
ISSN (online)	1873-5843
ISSN	0887-6177
DOI	10.1093/arclin/acac014
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Article ; Online: The dynorphin/kappa opioid receptor mediates adverse immunological and behavioral outcomes induced by repetitive blast trauma.

Lee, Suhjung Janet / Logsdon, Aric F / Yagi, Mayumi / Baskin, Britahny M / Peskind, Elaine R / Raskind, Murray M / Cook, David G / Schindler, Abigail G

Journal of neuroinflammation

2022 Volume 19, Issue 1, Page(s) 288

Abstract: Background: Adverse pathophysiological and behavioral outcomes related to mild traumatic brain injury (mTBI), posttraumatic stress disorder (PTSD), and chronic pain are common following blast exposure and contribute to decreased quality of life, but ... ...

Abstract	Background: Adverse pathophysiological and behavioral outcomes related to mild traumatic brain injury (mTBI), posttraumatic stress disorder (PTSD), and chronic pain are common following blast exposure and contribute to decreased quality of life, but underlying mechanisms and prophylactic/treatment options remain limited. The dynorphin/kappa opioid receptor (KOR) system helps regulate behavioral and inflammatory responses to stress and injury; however, it has yet to be investigated as a potential mechanism in either humans or animals exposed to blast. We hypothesized that blast-induced KOR activation mediates adverse outcomes related to inflammation and affective behavioral response. Methods: C57Bl/6 adult male mice were singly or repeatedly exposed to either sham (anesthesia only) or blast delivered by a pneumatic shock tube. The selective KOR antagonist norBNI or vehicle (saline) was administered 72 h prior to repetitive blast or sham exposure. Serum and brain were collected 10 min or 4 h post-exposure for dynorphin A-like immunoreactivity and cytokine measurements, respectively. At 1-month post-exposure, mice were tested in a series of behavioral assays related to adverse outcomes reported by humans with blast trauma. Results: Repetitive but not single blast exposure resulted in increased brain dynorphin A-like immunoreactivity. norBNI pretreatment blocked or significantly reduced blast-induced increase in serum and brain cytokines, including IL-6, at 4 h post exposure and aversive/anxiety-like behavioral dysfunction at 1-month post-exposure. Conclusions: Our findings demonstrate a previously unreported role for the dynorphin/KOR system as a mediator of biochemical and behavioral dysfunction following repetitive blast exposure and highlight this system as a potential prophylactic/therapeutic treatment target.
MeSH term(s)	Animals ; Male ; Mice ; Blast Injuries/complications ; Blast Injuries/genetics ; Blast Injuries/immunology ; Brain/immunology ; Brain/physiology ; Dynorphins/genetics ; Dynorphins/immunology ; Quality of Life ; Receptors, Opioid, kappa/genetics ; Receptors, Opioid, kappa/immunology
Chemical Substances	Dynorphins (74913-18-1) ; Receptors, Opioid, kappa ; OPRK1 protein, human
Language	English
Publishing date	2022-12-03
Publishing country	England
Document type	Journal Article
ZDB-ID	2156455-3
ISSN	1742-2094 ; 1742-2094
ISSN (online)	1742-2094
ISSN	1742-2094
DOI	10.1186/s12974-022-02643-3
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Article ; Online: Markers of Cerebrovascular Injury, Inflammation, and Plasma Lipids Are Associated with Alzheimer's Disease Cerebrospinal Fluid Biomarkers in Cognitively Normal Persons.

Jansson, Deidre / Wang, Marie / Thomas, Ronald G / Erickson, Michelle A / Peskind, Elaine R / Li, Ge / Iliff, Jeffrey

Journal of Alzheimer's disease : JAD

2022 Volume 86, Issue 2, Page(s) 813–826

Abstract: Background: Alzheimer's disease (AD) is a multifactorial process that takes years to manifest clinically. We propose that brain-derived indicators of cerebrovascular dysfunction and inflammation would inform on AD-related pathological processes early in, ...

Abstract	Background: Alzheimer's disease (AD) is a multifactorial process that takes years to manifest clinically. We propose that brain-derived indicators of cerebrovascular dysfunction and inflammation would inform on AD-related pathological processes early in, and perhaps prior to neurodegenerative disease development. Objective: Define the relationship between cerebrospinal fluid (CSF) markers of cerebrovascular dysfunction and neuroinflammation with AD CSF biomarkers in cognitively normal individuals. Methods: Analytes were measured from CSF and plasma collected at baseline from two randomized control trials. We performed Pearson correlation analysis (adjusting for age, sex, APOE haplotype, and education) between markers of central nervous system (CNS) barrier disruption, cerebrovascular dysfunction, CSF inflammatory cytokines and chemokines, and plasma lipid levels. We then developed a statistical prediction model using machine learning to test the ability of measured CSF analytes and blood lipid profiles to predict CSF AD biomarkers (total tau, phospho-tau (181), Aβ42) in this clinical population. Results: Our analysis revealed a significant association between markers of CNS barrier dysfunction and markers of cerebrovascular dysfunction, acute inflammatory responses, and CSF inflammatory cytokines. There was a significant association of blood lipid profiles with cerebrovascular injury markers, and CSF inflammatory cytokine levels. Using machine learning, we show that combinations of blood lipid profiles, CSF markers of CNS barrier disruption, cerebrovascular dysfunction and CSF inflammatory cytokines predict CSF total tau, p-tau, and, to a lesser extent, Aβ42 in cognitively normal subjects. Conclusion: This suggests that these parallel pathological processes may contribute to the development of AD-related neuropathology in the absence of clinical manifestations.
MeSH term(s)	Alzheimer Disease/pathology ; Amyloid beta-Peptides/cerebrospinal fluid ; Biomarkers/cerebrospinal fluid ; Cerebrovascular Trauma ; Cytokines ; Humans ; Inflammation/cerebrospinal fluid ; Neurodegenerative Diseases ; Peptide Fragments/cerebrospinal fluid ; tau Proteins/cerebrospinal fluid
Chemical Substances	Amyloid beta-Peptides ; Biomarkers ; Cytokines ; Peptide Fragments ; tau Proteins
Language	English
Publishing date	2022-02-04
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1440127-7
ISSN	1875-8908 ; 1387-2877
ISSN (online)	1875-8908
ISSN	1387-2877
DOI	10.3233/JAD-215400
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