Sleep and Depression in Older Adults: A Narrative Review.

PURPOSE OF REVIEW: The sleep-depression association has been recognized for decades. Efforts to clarify this association continue at an increasing pace. This review summarizes recent research on the sleep-depression association in older adults. RECENT FINDINGS: Research over the past 4 years has utilized cross-sectional, longitudinal, cohort, and intervention designs to examine these associations. Short (< 7 h) and long (> 8-9 h) sleep durations and insomnia symptoms are risk factors for depression in older adults. Similarly, short sleep, long sleep, insomnia symptoms, and depression are all risk factors for poorer health in late life, including increased risk of cognitive decline, falls, and poorer quality-of-life. Intervention studies have produced mixed findings, with some studies suggesting that sleep interventions may be potentially effective in improving both insomnia and mood symptoms. Intervention studies incorporating both behavioral and physiological measures of sleep, and larger and diverse samples may enhance the field's understanding of the complex interplay between sleep and mood in older adults.

Race as a Potential Moderator of the Association between Dysfunctional Beliefs about Sleep and Global Sleep Health.

OBJECTIVES: Dysfunctional beliefs about sleep are associated with components of sleep health, but their association with global sleep health is understudied. Beliefs about sleep may systematically vary by race, which may influence the association between dysfunctional beliefs about sleep and global sleep health. This study aimed to investigate whether race influences the association between dysfunctional beliefs about sleep and global sleep health. METHODS: Data were collected as part of an online survey. Participants were Black (n = 181) and White (n = 179) adults who were matched on age, self-reported sex, and level of education. Global sleep health was measured using the RU-SATED and dysfunctional beliefs about sleep were measured using the DBAS-16. Moderation analyses were conducted to investigate whether race moderated the association between DBAS-16 total and subscale scores and RU-SATED total scores. RESULTS: Race moderated the associations between DBAS-16 total score and subscale scores and RU-SATED total score (b = 0.54, p < .001). Higher DBAS-16 scores were significantly associated with lower RU-SATED scores in the white sample, while this association was not significant in the Black sample, except for the Sleep Expectations subscale, where the association was not significant in the White sample, and it was significant in the Black sample. CONCLUSIONS: These findings highlight that the association between dysfunctional beliefs about sleep and global sleep health may systematically vary by race which may have implications for promoting sleep health equity in racial minority populations through clinical and advocacy work. Future studies are needed to investigate what specific factors may be impacting these unique associations.

Characterising the safety of clomiphene citrate in male patients through prostate-specific antigen, haematocrit, and testosterone levels.

OBJECTIVE: To determine the safety profile of clomiphene citrate (CC) in men being treated for hypogonadism or infertility by measuring prostate-specific antigen (PSA), haematocrit (Hct), and testosterone levels. PATIENTS AND METHODS: We identified patients presenting to our institution who were placed on CC, 50 mg every day or every other day, for male infertility and/or symptomatic hypoandrogenism between September 2013 and April 2016. Patients with documented exogenous testosterone, human chorionic gonadotrophin, or anastrozole use within 2 weeks of baseline evaluations were excluded. Our primary outcomes were the effects of CC on PSA, Hct, and total testosterone levels evaluated at the 3, 6, 9, or 12 months of follow-up. Outcomes were averaged within patients across visits and summarised by mean, median, range, standard deviation (SD) and the 95% confidence interval (CI) for the mean. RESULTS: A total of 77 patients had recorded PSA, Hct, and/or testosterone values. The mean (SD, range) age and body mass index was 34 (6, 22-51) years and 31 (6, 22-52) kg/m2 , respectively. The mean (SD) follow-up was 358 (29) days. Within this group, CC concentration was changed in 24 patients (31%) and was discontinued in 24 patients (31%). The median (range) duration of CC therapy before discontinuation was 127 (44-161) days. The use of CC significantly raised both mean total and bioavailable testosterone levels by 200 ng/dL and 126 ng/dL, respectively (P < 0.001). This increase in testosterone had significant clinical effects with improvements in Androgen Deficiency in Aging Male questionnaire scores (P < 0.01) but not Sexual Health Inventory for Men scores. CC had no effect on mean PSA (1 ng/dL, 95% CI 0.8-1.1) or Hct (49%, 95% CI 41-53) levels, which were within normal ranges. CONCLUSIONS: As more men are placed on CC for infertility or hypogonadism, characterising the safety effect profile becomes important. Our study found that CC significantly increased testosterone levels without changing PSA or Hct values. Because the biochemical response to CC can vary, we suggest scheduling laboratory evaluation at regular intervals; however, ordering routine assessment of PSA and Hct may not be necessary.

Acridine orange leukocyte fluorography in mice.

Simultaneous non-invasive visualization of blood vessels and nerves in patients can be obtained in the eye. The retinal vasculature is a target of many retinopathies. Inflammation, readily manifest by leukocyte adhesion to the endothelial lining, is a key pathophysiological mechanism of many retinopathies, making it a valuable and ubiquitous target for disease research. Leukocyte fluorography has been extensively used in the past twenty years; however, fluorescent markers, visualization techniques, and recording methods have differed between studies. The lack of detailed protocol papers regarding leukocyte fluorography, coupled with lack of uniformity between studies, has led to a paucity of standards for leukocyte transit (velocity, adherence, extravasation) in the retina. Here, we give a detailed description of a convenient method using acridine orange (AO) and a commercially available scanning laser ophthalmoscope (SLO, HRA-OCT Spectralis) to view leukocyte behavior in the mouse retina. Normal mice are compared to mice with acute and chronic inflammation. This method can be readily adopted in many research labs.

Move your feet and sleep: A longitudinal dynamic analysis of self-reported exercise, sedentary behavior, and insomnia symptoms.

INTRODUCTION: Insomnia symptoms are associated with poor physical and mental health. Exercise is associated with good sleep while sedentary behavior is associated with poor sleep. This study investigated the longitudinal, dynamic associations among exercise, sedentary behavior, and insomnia symptoms. METHODS: Seven hundred and fifty-six adults (Mage=47.2years, 54.9% female) took part in an online longitudinal study investigating sleep and health across the lifespan. Participants reported duration of moderate-to-strenuous exercise, percentage of day spent sitting, and insomnia symptoms (Insomnia Severity Index [ISI]). The ISI was scored as a total score and two-factor scores: (1) Sleep Disturbance (items 1, 2, 3) and (2) Daytime Dysfunction (items 4, 5, 6, 7). Multilevel modeling was used to examine the typical (i.e., between-persons) and individual (i.e., within-persons) associations among sedentary behavior, exercise, and insomnia symptoms. RESULTS: Sedentary behavior was significantly associated with total ISI scores at both the between-person and within-person levels (ß = 0.036, t = 3.23, p = .001; ß = 0.014, t = 1.99, p = .048). Both between-persons and within-person levels of sedentary behavior were associated with Daytime Dysfunction (ß = 0.028, t = 3.79, p < .001; ß = 0.009, t = 2.08, p = .039). Exercise was associated with total ISI and Daytime Dysfunction scores at the between-persons level but not at the within-persons level (ß = 0.028, t = 2.57, p = .01; ß = -0.002, t = -3.02, p = .003). CONCLUSIONS: Sedentary behavior was a more consistent and robust predictor of insomnia symptoms than exercise. The association between sedentary behavior and insomnia symptoms was dynamic in that when an individual reported being more sedentary than their norm, they also reported more insomnia symptoms. Future analyses should examine potential moderator variables and comorbid conditions.

Multiple sleep disturbances are associated with apathy in individuals with Parkinson's disease.

Background: Parkinson's disease (PD) is associated with both sleep disturbances and apathy, and within PD, apathy has been associated with REM behavior disorder and excessive daytime sleepiness. Whether other forms of sleep disturbance are similarly associated with apathy in PD remains unclear. This study explored associations between a broad array of sleep disturbances and apathy in 50 individuals with idiopathic PD (PD) and 48 matched controls (MC). Methods: Participants were adults aged 53-80 (Mdn = 67), 23 % female, and 96 % white. Sleep disturbances were measured with various questionnaires (ISI, PSQI, PROMIS-SD, ESS, PROMIS-SRI, RBDSQ). Mood was measured with the STAI and BDI-II. Apathy was evaluated using the Apathy Scale (AS). Spearman correlations and regression analyses were performed between measures of sleep disturbance and AS in the total sample and each group. Group correlations were compared using 2-sample Fisher's z test. Results: The AS total score significantly correlated with PROMIS-SRI in the total sample and multiple measures of sleep disturbance in the PD group. The apathy subscales were each significantly correlated with sleep disturbance measures in the total sample, MC, and PD groups. The correlations between several sleep and apathy values were significantly stronger in the PD group than MC. When accounting for anxiety and depression most differences were no longer significant, only the PROMIS-SRI was significantly predictive of the behavioral apathy sub score. Discussion: Evidence supports an association between sleep disturbances and apathy in individuals with PD. Specifically, insomnia severity, poor sleep quality, and daytime sleepiness were uniquely associated with apathy in this group. We did not find these associations in the matched control group. Anxiety and depression are likely involved in the association between sleep and apathy in PD. Experimental studies that manipulate or improve sleep may further elucidate the mechanisms underlying the association between sleep disturbance and apathy in PD.

Challenging beliefs for quality sleep: A systematic review of maladaptive sleep beliefs and treatment outcomes following cognitive behavioral therapy for insomnia.

Cognitive behavioral therapy for insomnia (CBT-I) is an empirically supported intervention for insomnia. Given the strong, consistent support of its efficacy, scholars have become increasingly interested in the behavioral and cognitive mechanisms targeted during CBT-I. The purpose of the systematic review was to synthesize findings from the literature regarding the associations among maladaptive sleep beliefs, a cognitive mechanism implicated in maintaining insomnia, and treatment outcomes following CBT-I. The systematic review was completed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Seventeen studies were included in the final sample of reviewed articles and a study quality assessment was performed for all studies included in the review. The results suggested that reductions in maladaptive sleep beliefs were associated with improved insomnia severity; however, reductions in maladaptive beliefs were not associated with changes in sleep efficiency or other sleep parameters. Moreover, in some cases, improved sleep parameters preceded reductions in maladaptive beliefs. Maladaptive sleep beliefs may be an important target for improving insomnia. Targeting maladaptive sleep beliefs may initiate a trickle-down process that limits the influence of other cognitive and behavioral processes maintaining insomnia. Additional investigation is needed to evaluate the directional relationship between improved insomnia symptoms and reduced maladaptive beliefs.

A First Glimpse at the Latent Structure of Sleep Valuation Using a Sleep Valuation Item Bank.

Introduction: Sleep valuation is the relative worth individuals place on sleep. Our prior study using a Sleep Valuation Item Bank (SVIB) showed that sleep valuation relates to age, gender, and health status. In this study, the psychometric properties of the SVIB and its latent factor structure were explored. We also investigated how sleep valuation factors relate to demographic, psychological, and sleep features. Methods: Participants (N = 854) were recruited through TurkPRIME and completed a survey consisting of demographic, psychological, and sleep-related questions. The distributional properties of the SVIB items were quantified. Cronbach's alpha and correlation analyses were used to assess the internal consistency and test-retest reliability of SVIB items. Iterated principal factoring with a Promax rotation was used on the SVIB to explore its latent factor structure. Multiple regression analyses were used to investigate the variables associated with each factor. Results: The factor analysis identified 29 items with factor loadings ≥0.4 on four major factors, tentatively called (1) sleep wanting, (2) sleep prioritizing, (3) sleep onset preference, and (4) sleep devaluation. While women had higher sleep wanting and lower sleep devaluation scores than men, they had lower sleep prioritizing. Older individuals tended to value sleep less but also devalued it less than younger participants. Finally, although both individuals with insomnia and depression devalued sleep, depressed individuals prioritized it more than those who were less depressed, while individuals with insomnia symptoms wanted sleep and preferred sleep onset more than those with less insomnia symptoms. Discussion: The current SVIB captures broad dimensions of sleep valuation (wanting, prioritizing, preferring) and sleep devaluation. These broad dimensions had distinct patterns across person-level factors. Recognition of individual differences in sleep valuation may help target sleep health advocacy efforts and individualized treatment approaches, including for those with depression or insomnia.

Fidelity of Information Processing on a Psychomotor Vigilance Task Predicts Changes in Self-Reported Sleepiness Ratings.

INTRODUCTION: Daytime sleepiness is a common problem. Although sleepiness is primarily assessed at the self-report unit of analysis, factors that contribute to an individual's experience and report of sleepiness remain poorly understood. While sleepiness is known to impact vigilance performance, the impact of vigilance performance on sleepiness reports is less well understood. We aimed to explore how performance on a psychomotor vigilance task (PVT) relates to changes in self-reported sleepiness in a rested condition. METHODS: Participants were 66 adults (Mdn=23, range 18-49 years old), 47% female, 88% white, with a wide range of insomnia symptoms. Participants rated their sleepiness on a scale from 1 (not sleepy) to 10 (extremely sleepy) at the start (pre) and the end (post) of a 10-minute computerized PVT. Ordinal regression determined whether mean reciprocal reaction time, a measure of overall performance, or the log-transformed signal-to-noise ratio (LSNR), a measure of fidelity of information processing, predicted post-sleepiness, adjusting for pre-sleepiness, insomnia, and potential confounds. RESULTS: Lower LSNR predicted greater change in sleepiness (pre-to-post PVT) and higher post-sleepiness even after adjusting for pre-sleepiness, mean reciprocal reaction time, insomnia, and other potential confounds (p<0.05). DISCUSSION: When adjusting for insomnia symptoms and potential confounds, participants with lower fidelity of information processing reported higher sleepiness than they had reported at the start of the PVT. Possible mechanisms and explanations are discussed in relation to a 3-factor model of sleep-wake states. This line of research may contribute to innovative approaches to assessing and treating sleepiness.

Sleep Valuation Is Associated with Components of Sleep Health and Daytime Functioning in a College Sample: A Survey Study.

Sleep valuation, the worth individuals place on sleep, is an understudied construct in the field of sleep medicine. This study introduced a Sleep Valuation Item Bank and explored how sleep valuation is related to sleep health and daytime functioning within a sample of college students. The participants in this study were 247 (85% white, 83% female) undergraduate students who completed an online survey that included questions from a Sleep Valuation Item Bank and questions about sleep and daytime functioning. Correlation and regression analyses were conducted to determine associations between sleep valuation, aspects of sleep health and daytime functioning. Mediation analyses were conducted to determine whether the sleep health variables explained the associations between sleep valuation and daytime functioning. In correlation analyses, sleep valuation was negatively associated with sleepiness and sleep quality. It was also associated with daytime functioning, including general mental and physical health, depression, and anxiety. In the regression analyses, daytime impairments including poorer physical and mental health, anxiety, and depression were associated with higher sleep valuation. Poorer sleep health, including greater sleepiness and lower sleep quality, explained these associations and were associated with higher sleep valuation. Thus, while daytime impairments, such as anxiety and depression, are related to sleep valuation, this relationship may be due in part to the sleep disturbance that often co-occurs with these impairments.

A Validation Study of PROMIS Sleep Disturbance (PROMIS-SD) and Sleep Related Impairment (PROMIS-SRI) Item Banks in Individuals with Idiopathic Parkinson's Disease and Matched Controls.

BACKGROUND: Parkinson's disease (PD) is associated with sleep disturbance (SD) and sleep-related impairment (SRI). Validation of self-report measures of these problems is needed in PD. The Patient-Reported Outcomes Measurement Information System (PROMIS) includes tools that assess these problems (PROMIS-SD and PROMIS-SRI, respectively). OBJECTIVE: This study aimed to further validate these measures in individuals with PD and matched controls. METHODS: Individuals with early-stage PD (n=50) and matched controls (n=48) completed measures of SD including the PROMIS-SD, Pittsburgh Sleep Quality Index (PSQI), and Insomnia Severity Index (ISI). They also completed measures of daytime impairment including the PROMIS-SRI, Epworth Sleepiness Scale, State-Trait Anxiety Inventory, Beck Depression Inventory 2nd edition, and Parkinson's Disease Questionnaire-39. Internal consistency for the PROMIS measures were assessed using Cronbach's α coefficient and item-total correlations in the total sample. Convergent and divergent validity of the PROMIS item banks were assessed using Spearman correlations. RESULTS: The PROMIS item banks had excellent internal consistency (α>0.94). Supporting convergent validity, the PROMIS-SD had strong correlations with other measures of SD (ρ>0.68, for PSQI and ISI) and the PROMIS-SRI had moderate to strong correlations with all measures of daytime impairment (ρ=0.41-0.72). Supporting divergent validity within the PD group, the PROMIS-SD correlated more strongly with SRI than with the Parkinson's Disease Questionnaire total score, a metric of PD related impairment. CONCLUSION: In middle-aged and older adults, with and without early-stage PD, the PROMIS-SD and PROMIS-SRI are reliable and valid measures of SD and SRI, respectively.

Intravitreal AAV2.COMP-Ang1 Prevents Neurovascular Degeneration in a Murine Model of Diabetic Retinopathy.

Diabetic retinopathy (DR) is the leading cause of blindness in the working-age population in the U.S. The vision-threatening processes of neuroglial and vascular dysfunction in DR occur in concert, driven by hyperglycemia and propelled by a pathway of inflammation, ischemia, vasodegeneration, and breakdown of the blood retinal barrier. Currently, no therapies exist for normalizing the vasculature in DR. Here, we show that a single intravitreal dose of adeno-associated virus serotype 2 encoding a more stable, soluble, and potent form of angiopoietin 1 (AAV2.COMP-Ang1) can ameliorate the structural and functional hallmarks of DR in Ins2Akita mice, with sustained effects observed through six months. In early DR, AAV2.COMP-Ang1 restored leukocyte-endothelial interaction, retinal oxygenation, vascular density, vascular marker expression, vessel permeability, retinal thickness, inner retinal cellularity, and retinal neurophysiological response to levels comparable with nondiabetic controls. In late DR, AAV2.COMP-Ang1 enhanced the therapeutic benefit of intravitreally delivered endothelial colony-forming cells by promoting their integration into the vasculature and thereby stemming further visual decline. AAV2.COMP-Ang1 single-dose gene therapy can prevent neurovascular pathology, support vascular regeneration, and stabilize vision in DR.