R. Robert Auger

Idiopathic rapid-eye-movement sleep disorder: associations with antidepressants, psychiatric diagnoses, and other factors, in relation to age of onset.

BACKGROUND A retrospective, case-control chart review was performed to examine the relationship between the age of onset of idiopathic RBD and secondary associations. METHODS Forty-eight idiopathic RBD patients were divided into early-onset and late-onset groups, compared to each other, and to their respective non-RBD controls. RESULTS There were more females in the early-onset group as compared to their older counterparts (45% vs. 11%, p=0.007). Early-onset patients also had significantly more past and present psychiatric diagnoses [85% (both categories) vs. 46% and 36%, respectively, p<0.01 for both comparisons] and antidepressant use (80% vs. 46%, p=0.02) than the late-onset group. In comparison to non-RBD controls, early-onset patients again exhibited more psychiatric diagnoses (odds ratio=17.0 [3.5-83.4], equivalent for past and present diagnoses) and antidepressant use (odds ratio=12.0 [2.7-53.3]). Late-onset patients also had a higher frequency of past (odds ratio=7.2 [1.8-29.6]) and present (odds ratio=4.6 [1.1-19.3]) psychiatric diagnoses as compared to their non-RBD controls, but did not demonstrate a statistically significant difference in antidepressant use. There were otherwise no significant intergroup or intragroup differences with respect to the other assessed variables. CONCLUSIONS Although causality cannot be inferred, numerous implications can be entertained, particularly in the early-onset group, including direct or indirect correlations with medication use and/or psychopathology and the development of RBD. The relatively high number of females in the early-onset group suggests a unique clinical profile for a condition typically characterized as male-predominant.

Clinical practice guideline for the treatment of intrinsic circadian rhythm sleep-wake disorders: Advanced Sleep-Wake Phase Disorder (ASWPD), Delayed Sleep-Wake Phase Disorder (DSWPD), Non-24-Hour Sleep-Wake Rhythm Disorder (N24SWD), and Irregular Sleep-Wake Rhythm Disorder (ISWRD). an update for 2015

A systematic literature review and meta-analyses (where appropriate) were performed and the GRADE approach was used to update the previous American Academy of Sleep Medicine Practice Parameters on the treatment of intrinsic circadian rhythm sleep-wake disorders. Available data allowed for positive endorsement (at a second-tier degree of confidence) of strategically timed melatonin (for the treatment of DSWPD, blind adults with N24SWD, and children/ adolescents with ISWRD and comorbid neurological disorders), and light therapy with or without accompanying behavioral interventions (adults with ASWPD, children/adolescents with DSWPD, and elderly with dementia). Recommendations against the use of melatonin and discrete sleep-promoting medications are provided for demented elderly patients, at a second- and first-tier degree of confidence, respectively. No recommendations were provided for remaining treatments/ populations, due to either insufficient or absent data. Areas where further research is needed are discussed.

Clinical Practice Guideline for the Treatment of Intrinsic Circadian Rhythm Sleep-Wake Disorders: Advanced Sleep-Wake Phase Disorder (ASWPD), Delayed Sleep-Wake Phase Disorder (DSWPD), Non-24-Hour Sleep-Wake Rhythm Disorder (N24SWD), and Irregular Sleep-Wake Rhythm Disorder (ISWRD). An Update for 2015: An American Academy of Sleep Medicine Clinical Practice Guideline.

A systematic literature review and meta-analyses (where appropriate) were performed and the GRADE approach was used to update the previous American Academy of Sleep Medicine Practice Parameters on the treatment of intrinsic circadian rhythm sleep-wake disorders. Available data allowed for positive endorsement (at a second-tier degree of confidence) of strategically timed melatonin (for the treatment of DSWPD, blind adults with N24SWD, and children/ adolescents with ISWRD and comorbid neurological disorders), and light therapy with or without accompanying behavioral interventions (adults with ASWPD, children/adolescents with DSWPD, and elderly with dementia). Recommendations against the use of melatonin and discrete sleep-promoting medications are provided for demented elderly patients, at a second- and first-tier degree of confidence, respectively. No recommendations were provided for remaining treatments/ populations, due to either insufficient or absent data. Areas where further research is needed are discussed.

LIGHT EXPOSURE AMONG ADOLESCENTS WITH DELAYED SLEEP PHASE DISORDER: A PROSPECTIVE COHORT STUDY

The objective of this study was to compare light exposure and sleep parameters between adolescents with delayed sleep phase disorder (DSPD; n = 16, 15.3 ± 1.8 yrs) and unaffected controls (n = 22, 13.7 ± 2.4 yrs) using a prospective cohort design. Participants wore wrist actigraphs with photosensors for 14 days. Mean hourly lux levels from 20:00 to 05:00 h and 05:00 to 14:00 h were examined, in addition to the 9-h intervals prior to sleep onset and after sleep offset. Sleep parameters were compared separately, and were also included as covariates within models that analyzed associations with specified light intervals. Additional covariates included group and school night status. Adolescent delayed sleep phase subjects received more evening (p < .02, 22:00–02:00 h) and less morning (p < .05, 08:00–09:00 h and 10:00–12:00 h) light than controls, but had less pre-sleep exposure with adjustments for the time of sleep onset (p < .03, 5–7 h prior to onset hour). No differences were identified with respect to the sleep offset interval. Increased total sleep time and later sleep offset times were associated with decreased evening (p < .001 and p = .02, respectively) and morning (p = .01 and p < .001, respectively) light exposure, and later sleep onset times were associated with increased evening exposure (p < .001). Increased total sleep time also correlated with increased exposure during the 9 h before sleep onset (p = .01), and a later sleep onset time corresponded with decreased light exposure during the same interval (p < .001). Outcomes persisted regardless of school night status. In conclusion, light exposure interpretation requires adjustments for sleep timing among adolescents with DSPD. Pre- and post-sleep light exposures do not appear to contribute directly to phase delays. Sensitivity to morning light may be reduced among adolescents with DSPD. (Author correspondence: auger.raymond1@mayo.edu)

Jet lag and other sleep disorders relevant to the traveler

Sleep and wakefulness are governed by homeostatic and circadian regulatory processes, and perturbations therein are primarily responsible for the sleep disturbances associated with travel. Misalignment between endogenous rhythms and the light/dark cycle can result in circadian rhythm sleep disorders, including jet lag. This condition will be the primary focus of this review, with an emphasis on predisposing factors, preventative options, and treatment strategies.

The effects of poor sleep quality on cognitive function of patients with cirrhosis

OBJECTIVES This study was conducted to assess the ill-defined relationship between sleep quality and multiple, specific domains of cognitive function in patients with cirrhosis. METHODS A comprehensive battery of neuropsychological tests (divided into six neurocognitive domains) and a standardized, validated measure of sleep quality (Pittsburgh Sleep Quality Index [PSQI]) were administered to patients with cirrhosis and without evidence of overt hepatic encephalopathy, recruited from liver transplant and advanced liver disease clinics (n = 34). An inflammatory bowel disease (IBD) control group (n = 23) was similarly recruited and evaluated to control for the secondary effect of a chronic illness on cognition. PSQI global and component scores were used to predict cognitive function in each neurocognitive domain, using linear regression. RESULTS Global PSQI scores were significantly higher (indicating poorer sleep quality) in the cirrhosis group (median [range] = 10 [1-19]) than in IBD controls = 5 (1-14); p = 0.002). After controlling for age and education, short duration of sleep was associated with impaired memory for patients with cirrhosis; the use of soporific agents was associated with poor visual-perceptual function in patients with IBD. CONCLUSIONS Poor sleep was associated with worsening of the already impaired cognitive function of patients with cirrhosis.

Total sleep time obtained from actigraphy versus sleep logs in an academic sleep center and impact on further sleep testing.

Background While actigraphy has been deemed ideal for the longitudinal assessment of total sleep time (TST) by select groups, endorsement has not been universal and reimbursement is lacking, preventing its widespread use in clinical practice. This study compares longitudinal TST data obtained by actigraphy and logs preceding a clinical evaluation, and secondarily ascertains whether longitudinal TST impacts clinicians’ decisions to proceed with further sleep testing. Methods This was a retrospective, consecutive chart review spanning about 4 months in an academic sleep center. Eighty-four patients wore actigraphs in anticipation of clinical evaluations. Concomitant completion of sleep logs is routinely requested in this setting. Longitudinal TST data available in complete form was reviewed in a blinded fashion among a subset of these patients. A review of text from clinical notes of an expanded cohort with complete actigraphy data (regardless of the degree of completion of logs) enabled determination of the frequency and rationale for cancellation of prescheduled sleep testing. Results Of 84 actigraphy recordings, 90% produced complete data, and 30% produced fully completed logs. Among the subset with both available in complete form, significant mean TST differences were observed on weekends (7.06 ± 2.18 hours versus 8.30 ± 1.93 hours, P = 0.009), but not on weekdays (7.38 ± 1.97 hours versus 7.72 ± 1.62 hours, P = 0.450) for actigraphy and logs, respectively. Further analyses revealed poor agreement between the two measures, with predominantly increased TST estimation with logs. Among those with complete actigraphy data (±logs), testing was cancelled in 11 (15%), eight of whom (73%) presented with hypersomnia and three of whom (27%) presented with insomnia. Determination of insufficient sleep time was cited as the primary reason for cancellation (64%). Conclusion Actigraphy and sleep logs provided discrepant mean TST data on weekends only, and the latter predominantly estimated increased TST. Actigraphy was completed more reliably than logs. Longitudinal TST information influenced clinicians’ decisions to proceed with further testing, particularly among patients presenting with hypersomnia.

Circadian rhythm sleep disorders

Correspondence: Timothy I Morgenthaler Mayo Center for Sleep Medicine, Mayo Clinic College of Medicine, Rochester, MN, USA Email morgenthaler.timothy@mayo.edu Abstract: Misalignment between endogenous circadian rhythms and the light/dark cycle can result in pathological disturbances in the form of erratic sleep timing (irregular sleep–wake rhythm), complete dissociation from the light/dark cycle (circadian rhythm sleep disorder, free-running type), delayed sleep timing (delayed sleep phase disorder), or advanced sleep timing (advanced sleep phase disorder). Whereas these four conditions are thought to involve predominantly intrinsic mechanisms, circadian dysrhythmias can also be induced by exogenous challenges, such as those imposed by extreme work schedules or rapid transmeridian travel, which overwhelm the ability of the master clock to entrain with commensurate rapidity, and in turn impair approximation to a desired sleep schedule, as evidenced by the shift work and jet lag sleep disorders. This review will focus on etiological underpinnings, clinical assessments, and evidence-based treatment options for circadian rhythm sleep disorders. Topics are subcategorized when applicable, and if sufficient data exist. The length of text associated with each disorder reflects the abundance of associated literature, complexity of management, overlap of methods for assessment and treatment, and the expected prevalence of each condition within general medical practice.

Sleep And Neurodegenerative Disorders

The coexistence of neurodegenerative diseases and sleep disorders is increasingly being recognized. While there is considerable evidence suggesting that such conditions are inherent to the neurodegenerative process, most occur as a result of numerous intrinsic and extrinsic factors. Primary sleep disorders such as obstructive sleep apnea increase in prevalence with age and can result in unique clinical scenarios when combined with neurodegenerative diseases. REM sleep behavior disorder seems to exhibit a predilection for specific neurodegenerative entities and may therefore have diagnostic utility and ultimately prove to be a useful marker to identify those disorders best suited for studies investigating preventive therapies. Identification of all factors affecting sleep disturbances is important because sleep complaints significantly influence the rate of institutionalization in elderly individuals. This review highlights various pathophysiologic and clinical investigations concerning sleep findings in neurodegenerative diseases.

Are short (blue) wavelengths necessary for light treatment of seasonal affective disorder

ABSTRACT Despite widely published speculation regarding a potential potency advantage of short-wavelength (blue-appearing) light for Seasonal Affective Disorder (SAD) treatment, there have been few systematic studies. Those comparing short-wavelength to broad-wavelength (white) light under actual clinical conditions suggest equivalent effectiveness. This multicenter, parallel-group design trial was undertaken to compare the effects of light therapy on SAD using blue (~465 nm) versus blue-free (595–612 nm) LED lights. Fifty-six medication-free subjects aged 21–64 years who met DSM-IV-TR criteria for recurrent major depression with winter-type seasonal pattern were enrolled in this blinded study at five participating centers between January and March 2012. Thirty-five subjects met the criteria for randomization to 30 min of either blue (~465 nm) or blue-free (595–612 nm) daily morning light therapy. Twenty-nine subjects completed the study; three subjects withdrew due to treatment-related adverse events, including migraines, and three withdrew for non-study-related reasons. The primary effectiveness variable was depression score (SIGH-ADS) after six weeks of daily light treatment. Secondary effectiveness variables included quality-of-life (QoL) and suicidality ratings. Using an intent-to-treat analysis, mean depression scores were different at baseline for the blue group (29 ± 5 versus 26 ± 5, p = 0.05 blue versus blue-free, respectively), and the initial score was used as a covariate. Baseline scores were not significantly different between treatment groups among those who completed the study, and no significant differences in depression scores were observed after 6 weeks (mean ± SD scores at 6 weeks: 5.6 ± 6.1 versus 4.5 ± 5.3, p = 0.74, blue versus blue-free, respectively). In addition, the proportion of subjects who met remission criteria, defined as a depression score ≤8, was not significantly different between the two groups (p = 0.41); among the 29 subjects who completed the study, 76% of subjects experienced remission by the end of the trial, which coincided with the beginning of spring. The QoL and suicidality ratings were also significantly improved from pre- to post-treatment, with no significant difference between treatments. No subject experienced worsening or non-improved symptoms over the 6-week trial. The main finding of this study is that subjects treated with blue light did not improve more than subjects treated with blue-free light; both showed substantial improvement on multiple measures. Failure to find differences may have resulted from methodological constraints, including a small sample size. Recruitment began mid-winter during an unusually mild season, and the trial was terminated earlier than planned by the study sponsor due to a failure to detect a difference. However, if confirmed in a larger randomized sample, these results suggest that blue wavelengths are not necessary for successful SAD treatment.