bluuebunny/crossref_metadata_2025_split huggingface dataset:
0213 Circadian Entrainment and Cognition in College Students using Antidepressants
Authors: Gilmore Gabriel , Bianchetta Megan , Reinert Oda , Davic Steven , Trimp Gabrielle , Dyche Jeff 
Published: May 2022

Abstract

Introduction
Depression, sleep disturbances, and cognitive deficits often co-occur. Compared to non-medicated controls, people using antidepressant medications (particularly serotonin agonists) often have improved sleep including increased slow wave sleep, quality and continuity. Improvements to cognition after antidepressant treatments are also common including benefits to reaction time, inhibition, and memory. Importantly, circadian deficits, including sleep onset latency, fragmentation, and phase shifts are common in patients with depression, yet the effect of antidepressant medication on circadian indicators is unclear. The current project examined sleep, circadian entrainment, and cognition in college students who were diagnosed with depression and using serotonin agonists and in those without depressive symptoms.

Methods
Participants completed cognitive tasks that assessed reaction time, memory, attention, inhibition, and logical reasoning via the Automated Neuropsychological Assessment Metric between 1100-1700 two times, first at study enrollment and second after a two-week study interval. After initial cognitive assessments, participants wore actigraphs for two weeks from which we extracted their sleep-wake patterns, total sleep time(TST), time in bed(TIB), sleep-onset latency(SOL), sleep efficiency, and wake after sleep onset(WASO). Study 1 included 15 undergraduate students (11F, 7 antidepressant users, Mage=19.53) and Study 2 included 25 graduate students (21F, 13 antidepressant users, Mage=25.37), all recruited from James Madison University.

Results
Study 1 found that undergraduate antidepressant users had longer TIB, TST, and SOL. No cognitive or entrainment differences were found between drug use conditions. Within the antidepressant group, higher dosage predicted shorter TIB(r2=.64, p&lt;.05), poorer spatial processing speed(r2=.73, p&lt;.05) and logical relation performance(r2=.81, p&lt;.05). In study 2, no circadian or cognitive differences were present across drug conditions. Deficits in WASO and sleep efficiency for antidepressant users were present. Within the antidepressant group, years of antidepressant use and dosage predicted poorer reaction time(r2=.84, p&lt;.05), inhibition(r2=.70, p&lt;.05), and spatial processing(r2=.98, p&lt;.05). Self-reported wake episodes also predicted poorer reaction time and inhibition. Years of antidepressant use, dosage, and time of antidepressant use predicted TIB(r2=.73, p&lt;.05), and time of antidepressant use predicted TST(sr2=.79, p&lt;.05).

Conclusion
Future studies should use longitudinal research designs and prospective methods to examine the impact of antidepressant medications on circadian rhythms, sleep and cognition.

Support (If Any)
0221 Pre-Sleep Breath alcohol concentrations (psBrAC) and sleep polysomnography (PSG)
Authors: McCullar Katie , Barker David , McGeary John , Saletin Jared , Gredvig-Ardito Caroline , Carskadon Mary 
Published: May 2022

Abstract

Introduction
Alcohol use before bedtime has been shown to alter sleep including decreasing sleep latency, decreasing sleep efficiency, and fragmenting sleep stage distribution. Few studies manipulate pre-sleep alcohol concentration, instead focusing on a target dose or peak alcohol concentration during the night. Thus, we investigated how presleep breath alcohol concentrations (psBrAC) level (targeting a BrAC of 0.08), are associated with same-night sleep.

Methods
Thirty (15F; ages=22-57, mean=33yr) healthy adults who self-reported moderate drinking were instructed to maintain a consistent sleep schedule (8-9h time in bed) for a least 7-days before entering a cross-over design involving two sets (separated by&gt;3 days) of 3 consecutive nights of in-lab polysomnography. For all nights in each condition, participants drank either mixer alone or mixer+alcohol in 3 portions across 45 minutes ending 1h before lights out. psBrAC was measured within 5 minutes of lights out. PSGs were staged according to Rechtschaffen and Kales (1968). We computed: slow wave sleep (SWS) and REM as percentages of total sleep for the full night (%SWS) & (%REM), %SWS in the first third of the night (%SWST1), %REM in the last third of the night (%REMT3), minutes until sleep onset from lights out (Sleep Latency), and minutes after sleep onset until REM onset. Linear regressions tested if psBrAC on the first mixer+alcohol night predicted changes in sleep using the average of the three nights of sleep in the mixer-only condition as a covariate.

Results
psBrAC values ranged from 0.038 to 0.087 (mean = 0.066) mg/L. We identified minimal influence of BrAC on sleep: % SWS (β = -0.78; p = 0.07), % REM (β = 0.032; p = 0.96), % SWS T1 (β = -0.52; p = 0.522), % REM T3 (β = -1.01; p = 0.125), REM latency (β = 3.95; p = 0.302), and sleep latency (β = -1.23; p = 0.13).

Conclusion
These findings indicate that psBrAC was not associated with any of our sleep variables, when adjusting for sleep on nights without alcohol. Future work will examine peak BrAC as well whether the effects observed change over multiple nights of pre-sleep alcohol consumption.

Support (If Any)
R01AA025593
0264 Sleepiness in cognitively unimpaired older adults is associated with CSF biomarkers of inflammation and axonal integrity
Authors: Carvalho Diego , Louis Erik St , Przybelski Scott , Morgenthaler Timothy , Boeve Bradley , Petersen Ronald , Jack Clifford , Graff-Radford Jonathan , Vemuri Prashanthi , Mielke Michele 
Published: May 2022

Abstract

Introduction
We have previously shown that older adults with excessive daytime sleepiness (EDS) appear to be more vulnerable to longitudinal amyloid PET accumulation before the onset of the dementia. It remains unclear whether this vulnerability is specific to amyloid or extends to other biomarkers of Alzheimer’s disease pathology, or axonal integrity and inflammation, which can also contribute to neurodegeneration and cognitive changes.

Methods
For this cross-sectional analysis, we identified 260 cognitively unimpaired adults (&gt;60 years old) without neurologic disorder who underwent CSF quantification of AD biomarkers (CSF Aβ-42, p-tau181, p-tau217) along with at least one other biomarker of interest (neurofilament light chain [NfL], IL-6, IL-10, and TNF-α) from the Mayo Clinic Study of Aging – a longitudinal population-based cohort in Olmsted County, Minnesota. CSF biomarkers were available in 251-260 individuals, depending on the biomarker. We fit linear regression models to assess whether the CSF biomarkers were associated with sleepiness as measured by the Epworth Sleepiness Scale (ESS), after controlling for age, sex, APOE4 genotype, BMI, hypertension, dyslipidemia, and OSA diagnosis (by chart review).

Results
Higher ESS scores were independently associated with higher CSF IL-6 and NfL, but not with the other biomarkers in the whole sample. For every single-point increase in the ESS score, there was a .008 ([95% CI .001-.016], p=0.033) increase in the log of IL-6 and .01 ([95% CI .002-.018], p=0.016) increase in the log of NfL. A sensitivity analysis showed a correlation between ESS scores and log of p-tau/Aβ-42 ratio only in participants with abnormal ratio (&gt;0.023), after controlling for APOE4 (partial r=.27, p=039).

Conclusion
Our results corroborate previous literature suggesting that higher inflammatory milieu reflected by increased CSF IL-6 is associated with sleepiness. The association between NfL and sleepiness suggests that sleepiness may be related to disturbed connectivity due to axonal damage. Alternatively, NfL may be a surrogate of active axonal injury associated with more disrupted sleep. A correlation between sleepiness and CSF p-tau/ab-42 ratio was only seen in patients with abnormal ratio, suggesting a stronger association between sleepiness and AD pathology as the disease progresses, possibly because AD pathology worsens sleep quality and/or vice-versa.

Support (If Any)
NIH/NIA
0272 Decreased Risk of 2-Year Incidence of Alzheimer’s Disease Among Older Adults Who Report Sleep Symptoms
Authors: Mason Brooke , Wills Chloe , Tubbs Andrew , Seixas Azizi , Turner Arlener , Jean-Louis Girardin , Killgore William , Grandner Michael 
Published: May 2022

Abstract

Introduction
Those with dementia or Alzheimer’s Disease report an elevated amount of sleep difficulties compared to age-matched controls. Sleep-based interventions may be especially useful for this group, such as cognitive behavioral therapy for insomnia or pharmacological interventions. Therefore, it is important to expand the current understanding of the nature of sleep difficulties in those with Alzheimer’s Disease.

Methods
Data from the 2018 Health and Retirement Survey was collected from 17,146 older adults. Poisson regression analyses were used to explore the relationship between Alzheimer’s Disease as diagnosed by a doctor and sleep difficulties. Individuals who reported no Alzheimer’s Disease in the previous wave (N=16,751) were asked if they had since become diagnosed. N=101 individuals reported incident Alzheimer’s Disease in the 2-year gap between assessments. Sleep difficulties were assessed by asking participants if they had difficulties initiating or maintaining sleep, waking up too early, and how rested they felt upon awakening. All 4 of these symptoms were coded as “never,” “sometimes,” or “often.”

Results
Unexpectedly, there was a significant decreased risk of developing Alzheimer’s Disease among those who reported difficulties maintaining sleep (IRR=0.9962; 95%CI[0.9936,0.9988]; p=0.004), and early morning awakenings (IRR=0.9961; 95%CI[0.9938,0.9984]; p=0.001) “sometimes”. When the model was adjusted for sex, race, ethnicity, age, and depression, a similar finding of decreased risk for Alzheimer’s Disease for those who reported difficulties maintaining sleep (IRR=0.9953; 95%CI[0.9927,0.9980]; p&lt;0.001), and early morning awakenings (IRR=0.9954; 95%CI[0.9930,0.9978]; p=0.001), “sometimes” were maintained.

Conclusion
Although previous studies have shown that poor sleep may lead to increased risk of Alzheimer’s and related dementias, the present study, which examined longitudinal data from a large, national sample of older adults, found that there was no association between frequent sleep disturbances and 2-year incidence of Alzheimer’s Disease, and a small association between more mild symptoms and decreased risk. It is possible that the 2-year observation window was insufficient to detect effects. Also, there is a risk of measurement error in collecting self-reported data on sleep and Alzheimer’s diagnoses.

Support (If Any)
The HRS (Health and Retirement Study) is sponsored by the National Institute on Aging (grant number NIA U01AG009740) and is conducted by the University of Michigan.
0273 Sleep Disorders as a Potential Risk Factor for Dementia in Elderly Adults
Authors: Kuhler Cassandra , Wills Chloe , Mason Brooke , Tubbs Andrew , Seixas Azizi , Turner Arlener , Jean-Louis Girardin , Killgore William , Grandner Michael 
Published: May 2022

Abstract

Introduction
Sleep disorders such as insomnia are seen in the early onset of Alzheimer’s disease, the most common form of dementia. Simultaneously, sleep disorders may indicate increased risk for the development of dementia. Due to the rate of comorbidity of these two conditions seen in the elderly population, the relationship between dementia and sleep disorders is a topic of interest for researchers. A bidirectional correlation between the two could have important implications in the clinical field exploring factors that lead to dementia

Methods
Data was assessed from 17,146 older adults from the 2018 Health and Retirement Survey. Participants were surveyed using questionnaires regarding both incident dementia or serious memory impairment in the past 2 years and the presence of a sleep disorder, as diagnosed by a doctor or health professional. Those who reported no dementia in the previous wave (N=16,547) were asked if they had been diagnosed since they were last asked. N=185 individuals reported incident dementia in the 2-years between assessments. Responses were coded to either “Yes” or “No”. A Poisson regression analysis was conducted to explore the relationship between incident dementia and sleep disorders.

Results
In a sample of older adults, unadjusted results indicate that having a sleep disorder was associated with a 0.6% increased risk of new onset dementia (PRR=1.006; 95%CI[1.001,1.012]; p=0.026). These results were sustained when adjusted for sex, age, race, ethnicity, and depression (PRR=1.006; 95%CI[1.001,1.012]; p=0.013).

Conclusion
Chronic sleep disturbances may be a factor used to indicate increased risk for dementia and help with early detection of the disease. These results demonstrate the value of sleep disorders screening among those at risk for dementia. Further research is needed to clarify these findings (e.g., explore specific sleep disorders) and expand the follow-up window (i.e., beyond 2 years).

Support (If Any)
The HRS (Health and Retirement Study) is sponsored by the National Institute on Aging (grant number NIA U01AG009740) and is conducted by the University of Michigan.
0274 Effect of aging on sleep architecture including a novel REM Behavior Disorder phenotype in the PS19 mouse model of tauopathy and effect of a dual orexin receptor antagonist
Authors: Kam Korey , Vetter Kenny , Varga Andrew 
Published: May 2022

Abstract

Introduction
This project examines changes to sleep micro-architecture with aging in the PS19 (MAPT P301S) model of tauopathy and response to a dual orexin receptor antagonist (DORA-12) in aged PS19 mice.

Methods
24-hour video PSG recordings occurred in 28 PS19 mice and 22 littermate controls at 2-3 months (young) and 10-14 months (old).

Results
Spindle density significantly deceased as a function of both advanced age and PS19 genotype without interaction. We observed a significant interaction between age and genotype on slow oscillation (SO) density such that SO density was higher in young PS19 lower in old PS19 mice vs controls without main effects of age or genotype. Phase amplitude coupling of spindles to detected SO events was significantly decreased as a function of age with a trend toward an age/genotype interaction such that the reduction in coupling was greater with aging in PS19 mice vs controls. We observed unexpected dream enactment during REM in 3 of 11 old PS19 but not in young PS19 mice or control mice at any age. Normalized cumulative EMG area during REM sleep, cumulative duration of elevated EMG in REM, and %REM w/o atonia were all significantly increased in mice displaying dream enactment.Old PS19 mice were also video-PSG recorded for 24 hours while receiving 100 mg/kg DORA-12 vs vehicle control orally twice daily. DORA-12 resulted in significant reduction in latency to persistent NREM and REM sleep, and significant increases in spindle density and SO density, without significant difference in spindle-SO coupling. While we did not observe significant differences in dream enactment measures with DORA-12 due to low sample size, all 3 mice with dream enactment displayed decreases in normalized EMG amplitude in REM and %REM with EMG bursts with DORA-12 ranging from 10 to 60%.

Conclusion
Given the importance of spindles, SO’s, and their coupling on cognitive processes, these observations can motivate further evaluation of DORA’s toward such cognitive processes in neurodegenerative models as well as effect of DORA’s on RBD phenotypes.

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0278 Isolated REM sleep behavior disorder is associated with 24-hour rhythm disruption
Authors: Winer Joseph , Lok Renske , Cahuas Ana , Bueno Flavia , Poston Kathleen , Mormino Elizabeth , Zeitzer Jamie , During Emmanuel 
Published: May 2022

Abstract

Introduction
Isolated REM sleep behavior disorder (iRBD), the loss of motor inhibition during REM sleep, is a symptom of prodromal Lewy body disease, with over 80% of iRBD patients eventually phenoconverting to Parkinson’s disease or Dementia with Lewy bodies. Rest-activity rhythm disruption, also an established predictor of Parkinson’s disease, has not been well characterized in patients with iRBD. Here, we tested the hypothesis that accelerometer-based measures of 24-hour rhythms would indicate greater fragmentation and variability in patients with iRBD relative to matched healthy controls.

Methods
N=36 patients with iRBD recruited from the Stanford Sleep Clinic had 24-hour activity continuously monitored for (mean ± SD) 25.3 ± 8.4 days using an Axivity wristworn device. A control dataset of age, sex, and body mass index matched healthy older adults (N=126) was selected from the UK Biobank accelerometer dataset. Raw accelerometer data were processed using the GGIR, nparACT, and ActCR software packages in R, with a focus on nonparametric and 5-parameter cosinor measures of 24-hour rhythms. Functional PCA analyses (fPCA) were applied to detect overall differences in 24-hour rhythms and during sleep.

Results
Patients with iRBD had lower interdaily stability and higher intradaily variability than controls (IS, Cohen’s d=-1.15, Mann-Whitney test p&lt;0.001; IV, d=0.46, p=0.04). Cosine amplitude was lower in iRBD patients (d=-0.22, p=0.001), but mean activity (mesor) did not differ (d=0.03, p=0.31), suggesting differences in rest-activity patterns rather than overall activity levels. A shape naïve approach utilizing fPCA indicated that increased activity during the night may explain overall rhythm differences observed in iRBD.

Conclusion
Multiple metrics of rest-activity rhythms support the hypothesis that 24-hour rhythms are disrupted in iRBD. It remains to be determined whether rhythm fragmentation in iRBD reflects higher activity levels during REM sleep, or if dysfunctional rhythms represent the direct effects of degenerating sleep-wake regulating circuits, indicating the early stages of Lewy body disease.

Support (If Any)
NIA F32AG074625 to JW; NIA P30AG066515 to JW, KP, and EM
0293 The Effect of Sleep Loss on Divergent Thinking using a Remote Associates Task
Authors: Vignali Jonathan , Carlsson Kajsa , Doty Tracy Jill , Thomas Balkin , Burke Tina 
Published: May 2022

Abstract

Introduction
Sleep loss-induced neurobehavioral deficits are a recognized threat to health, safety, and performance. Sleep loss has previously been shown to differentially impact distinct types of cognitive function, although less is known about the higher-order cognitive function, divergent thinking. Understanding the influence of sleep on divergent thinking can assist in developing targeted strategies to mitigate specific cognitive function impairments.

Methods
Eight participants (3M/5F), mean age 27.875y (± 5.5y SD) were studied over the course of 40 days in a crossover design. Participants were randomly assigned to one of two study schedules, with 4 participants in each that alternated the order of sleep restriction and total sleep deprivation. The schedules consisted of a baseline assessment and 6 study phases [sleep extension prior to sleep restriction (10h Time in Bed (TIB)), sleep restriction (6h TIB), recovery following sleep restriction, sleep extension prior to total sleep deprivation (10h TIB), total sleep deprivation (62h), and recovery following sleep restriction. The Remote Associates Task (RAT), a task to assess divergent thinking by presenting a triad of apparently unrelated words with the goal of identifying a unifying 4th word, was administered the evening of the last day of every phase. RAT performance metrics included number of triads attempted, correct responses, repeated trials, and mean correct and incorrect reaction times.

Results
No differences were found in total number of word triads attempted by participants (p=0.18). The number of correct responses during baseline was lower than during sleep restriction, recovery from sleep restriction, and total sleep restriction (p=0.00691), most likely reflecting a steep learning curve. No significant main effect of phase was found for any RAT metric.

Conclusion
These preliminary findings suggest divergent thought as measured by the RAT is conserved across a differential amounts of sleep. More studies are needed to better characterize the impact of sleep loss on divergent thinking as well as possible mediating effects of other higher-order cognitive functions.

Support (If Any)
Department of Defense Military Operational Medicine Research Program (MOMRP)
0298 Kynurenic Acid Synthesis Inhibitor Promotes Enhanced Sleep Recovery Following Acute Sleep Deprivation in Adult Wistar Rats
Authors: Wright Courtney , Milosavljevic Snezana , Pocivavsek Ana 
Published: May 2022

Abstract

Introduction
Sleep disorders and cognitive dysfunction often afflict the general population and are common amongst patients with neuropsychiatric disorders like schizophrenia. Sleep deprivation (SD) disrupts cognitive function, yet little is known about underlying mechanisms. The tryptophan metabolite kynurenic acid (KYNA), an endogenous a7nACh and NMDA receptor antagonist, is synthesized by kynurenine aminotransferase II (KAT II). KYNA is increased in the brain of patients with schizophrenia and our translational studies demonstrate that elevated KYNA disrupts hippocampal learning and sleep architecture in rodents (Pocivavsek et al. 2017 Sleep). We hypothesize a mechanistic link between KYNA, sleep, and cognitive dysfunction.

Methods
In vivo microdialysis in the dorsal hippocampus and simultaneous EEG/EMG telemetry was conducted in adult male Wistar rats (N=3-5 per group). Using a within-subjects experimental design, rats underwent a control and SD day. Animals received either vehicle or KAT II inhibitor PF-04859989 (PF), 30mg/kg s.c., on both days at zeitgeber time (ZT) 0 or ZT6. SD occurred from ZT0-6 by gentle handling. KYNA levels were evaluated in the microdialysate.

Results
SD effectively eliminated REM sleep (100%) and significantly reduced NREM (94%) during ZT0-6. Extracellular KYNA levels in the hippocampus significantly increased with SD (2-way ANOVA, time x SD: **P&lt;0.0001) and PF readily prevented this accumulation. Initial sleep recovery (ZT6-12) did not significantly differ between treatment groups. During the dark phase (ZT12-24), PF treatment of SD animals promoted REM sleep parameters, including total REM duration (2-way ANOVA, SD x treatment ZT: P&lt;0.05). PF treatment enhanced theta spectral power determined by Discrete Fourier transform during REM sleep recovery (ZT12-24). PF alone during the control day enhanced NREM delta power (P&lt;0.05) during the late light phase (ZT6-12).

Conclusion
Importantly, the KAT II inhibitor PF promoted sleep recovery following acute SD, supporting our hypothesis that the accumulation of KYNA may exacerbate sleep disruptions. Changes in sleep parameters elicited by PF, a potential therapeutic avenue, may be indicative of mild somnolence. The present and future complementary experiments with cognitive behavioral tasks in rodents support our understanding of the role of KYNA in modulating sleep and cognition.

Support (If Any)
National Institutes of Health Grant No. NIH R01 NS102209