Prospective Associations Between Personality Traits and Major Depressive Disorder Symptom Severity: The Mediating Role of Illness Representations.

Major depressive disorder (MDD) patients' personality traits and illness representations are linked to MDD severity. However, the associations between personality and illness representations in MDD and the mediating role of illness representations between personality and MDD severity have not been investigated. This study aimed to prospectively investigate the aforementioned associations and the possible mediating role of illness representations between personality and MDD severity. One hundred twenty-five patients with a MDD diagnosis, aged 48.18 ± 13.92 (84% females), participated in the study. Personality traits were measured with the Traits Personality Questionnaire at baseline. Illness representations were measured with the Illness Perception Questionnaire-Mental Health about five months later (mean = 5.08 ± 1.14 months). MDD severity was measured about 10 months after the baseline assessment (mean = 9.53 ± 2.36 months) with the Beck Depression Inventory. SPSS 29 and AMOS 27 were used to conduct correlational and parallel mediation analyses. According to the results, Neuroticism was positively and Extraversion was negatively linked to MDD severity. Negative MDD impact representations fully mediated these associations. Neuroticism and Extraversion are linked to future MDD severity through patients' representations of MDD's impact. Restructuring maladaptive representations about MDD's impact can be a promising way to reduce symptom severity in patients with high Neuroticism and low Extraversion levels.

Long Objective Sleep Duration is a Marker of Cognitive Impairment in Older Adults: Findings from the Cretan Aging Cohort.

 We examined associations between objective sleep duration and cognitive status in older adults initially categorized as cognitively non-impaired (CNI, n = 57) or diagnosed with mild cognitive impairment (MCI, n = 53). On follow-up, 8 years later, all participants underwent neuropsychiatric/neuropsychological evaluation and 7-day 24-h actigraphy. On re-assessment 62.7% of participants were cognitively declined. Patients who developed dementia had significantly longer night total sleep time (TST) than persons with MCI who, in turn, had longer night TST than CNI participants. Objective long sleep duration is a marker of worse cognitive status in elderly with MCI/dementia and this association is very strong in older adults.

The different roles of homocysteine metabolism in hypertension among normal-weight and obese patients with obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with hypertension. However, the differential mechanisms underlying OSA-related hypertension between normal-weight vs. obese patients is limited. METHODS: We studied 92 patients with OSA and 24 patients with continuous positive airway pressure (CPAP) treatment. Blood pressure (BP) was measured twice during awake and continuously monitored during sleep. Obesity was defined as body mass index ≥28 kg/m2. Serum metabolite levels were assessed by metabolomics. RESULTS: Among 59 normal-weight and 33 obese patients, 651 and 167 metabolites showed differences between hypertension and normotension or were associated with systolic and diastolic BP (SBP, DBP) after controlling confounders. These metabolites involved 16 and 12 Kyoto Encyclopedia of Genes and Genomes enrichment pathways in normal-weight and obese patients respectively, whereas 6 pathways overlapped. Among these 6 overlapping pathways, 4 were related to homocysteine metabolism and 2 were non-specific pathways. In homocysteine metabolism pathway, 13 metabolites were identified. Interestingly, the change trends of 7 metabolites associated with SBP (all interaction-p≤0.083) and 8 metabolites associated with DBP (all interaction-p≤0.033) were opposite between normal-weight and obese patients. Specifically, increased BP was associated with down-regulated folate-dependent remethylation and accelerated transsulfuration in normal-weight patients, whereas associated with enhanced betaine-dependent remethylation and reduced transsulfuration in obese patients. Similar findings were observed in ambulatory BP during sleep. After CPAP treatment, baseline low homocysteine levels predicted greater decrease in DBP among normal-weight but not obese patients. CONCLUSIONS: Mechanisms in OSA-related hypertension differ between normal-weight and obese patients, which are explained by different changes in homocysteine metabolism.

A meta-analysis of the association between insomnia with objective short sleep duration and risk of hypertension.

The aim of this meta-analysis was to examine the association between insomnia with objective short sleep duration (ISSD) with prevalent and incident hypertension in cross-sectional and longitudinal studies, respectively. Data were collected from 6 cross-sectional studies with 5914 participants and 2 longitudinal studies with 1963 participants. Odds ratios (ORs) for prevalent and risk ratios (RRs) for incident hypertension were calculated through meta-analyses of adjusted data from individual studies. Compared to normal sleepers with objective normal sleep duration (NNSD), ISSD was significantly associated with higher pooled OR for prevalent hypertension (pooled OR = 2.67, 95%CI = 1.45-4.90) and pooled RR for incident hypertension (pooled RR = 1.95, 95%CI = 1.19-3.20), respectively. Compared to insomnia with objective normal sleep duration, ISSD was associated with significantly higher pooled OR of prevalent hypertension (pooled OR = 1.94, 95%CI = 1.29-2.92) and pooled RR for incident hypertension (pooled RR = 2.07, 95%CI = 1.47-2.90), respectively. Furthermore, normal sleepers with objective short sleep duration were not associated with either prevalent (pooled OR = 1.21, 95%CI = 0.84-1.75) or incident (pooled RR = 0.97, 95%CI = 0.81-1.17) hypertension compared to NNSD. Our findings suggest that ISSD is a more severe phenotype of the disorder associated with a higher risk of hypertension. Objective short sleep duration might be a valid and clinically useful index of insomnia's impact on cardiovascular health.

Insomnia with objective but not subjective short sleep duration is associated with incident cardiovascular and/or cerebrovascular disease.

STUDY OBJECTIVES: Insomnia with objective short sleep duration (ISSD) has been associated with cardiometabolic outcomes (ie, hypertension or diabetes). We examined whether ISSD, based on objective or subjective sleep measures, is associated with more serious health problems, such as incident cardiovascular and/or cerebrovascular disease (CBVD). METHODS: 1,258 men and women from the Penn State Adult Cohort (56.9% women, aged 48.3 ± 12.95 years) without CBVD at baseline were followed up for 9.21 ± 4.08 years. The presence of CBVD was defined as a history of diagnosis or treatment of heart disease and/or stroke. Insomnia was defined as a complaint of insomnia with a duration ≥ 1 year. Poor sleep was defined as a complaint of difficulty falling asleep, staying asleep, nonrestorative sleep, or early morning awakening. Objective short sleep duration was defined as < 6 hours' sleep based on polysomnography. Subjective short sleep duration was based on the median self-reported percentage of sleep time (ie, < 7 hours). RESULTS: Compared with normal sleepers with normal sleep duration, the highest risk of incident CBVD was in the ISSD group (odds ratio = 2.46, 95% confidence interval = 1.04-5.79), and the second highest was in normal sleepers with short sleep duration (odds ratio = 1.68, 95% confidence interval = 1.11-2.54). The risk of incident CBVD was not significantly increased in poor sleepers or those with insomnia with normal sleep duration. Finally, insomnia with subjective short sleep duration was not associated with increased incident CBVD. CONCLUSIONS: These data add to the cumulative evidence that ISSD, based on objective but not subjective measures, is the more severe biological phenotype of the disorder associated with incident CBVD. CITATION: Pejovic S, Vgontzas AN, Fernandez-Mendoza J, et al. Insomnia with objective but not subjective short sleep duration is associated with incident cardiovascular and/or cerebrovascular disease. J Clin Sleep Med. 2024;20(7):1049-1057.

Short-term stability and night-to-night variability of sleep parameters in nightmares comorbid with chronic insomnia Disorder across multiple nights of polysomnography.

STUDY OBJECTIVES: The purpose of this study was to examine the degree of short-term stability of polysomnographic (PSG) measured sleep parameters and the overall differences between individuals with comorbid nightmares and insomnia compared to those with chronic insomnia disorder alone or good sleeping controls across four nights in the sleep lab. METHODS: A total of 142 good sleeping controls, 126 chronic insomnia alone, and 24 comorbid insomnia/nightmare participants underwent four consecutive nights of 8-hour PSG recordings. Outcomes included sleep continuity, architecture, and REM-related parameters across nights one through four. Intraclass correlation coefficients with mixed-effect variances and repeated-measure analysis of covariance were used, respectively, to determine short-term stability as well as between-participants and time-by-group interaction effects. RESULTS: Wake after sleep onset and stage 1 showed "poor stability" in the comorbid insomnia/nightmare group compared to "moderate stability" in the good sleeping controls and chronic insomnia alone group. Significant between-group effects (all ps < .05) showed that the comorbid insomnia/nightmare group took longer to fall asleep and had a greater first-night-effect in stage 1 compared to good sleeping controls and chronic insomnia alone group; in addition, the comorbid insomnia/nightmare and insomnia alone groups slept shorter, with fewer awakenings and REM periods, compared to the good sleeping controls. CONCLUSIONS: Nightmares are associated with abnormal sleep above and beyond REM disruption, as sleep continuity was the primary aspect in which poor stability and group differences emerged. The greater inability to fall asleep and instability of sleep fragmentation in those with comorbid insomnia/nightmares compared to chronic insomnia alone may be attributed to the impact of presleep anticipatory anxiety and nightmare-related distress itself. CLINICAL TRIAL INFORMATION: The data analyzed in this study does not come from any current or previous clinical trials. Therefore, there is no clinical trial information to report.

Racial/ethnic disparities in the trajectories of insomnia symptoms from childhood to young adulthood.

STUDY OBJECTIVES: To examine differences in the longitudinal prevalence of childhood insomnia symptoms across black/African American, Hispanic/Latinx, and non-Hispanic white groups. METHODS: Participants were 519 children from the Penn State Child Cohort (baseline [V1] from 2000-2005) who were followed up 8 years later as adolescents (V2) and 15 years later as young adults (S3). Mean age at S3 was 24.1 ±â€…2.7 years. Approximately, 76.5% identified as non-Hispanic white, 12.9% as black/African American, 7.1% as Hispanic/Latinx, and 3.5% as "other" race/ethnicity. Insomnia symptoms were defined as parent-reported (childhood) or self-reported (adolescence and young adulthood) moderate-to-severe difficulties initiating/maintaining sleep. Longitudinal trajectories of insomnia symptoms were identified across three-time points and the odds of each trajectory were compared between racial/ethnic groups, adjusting for sex, age, overweight, sleep apnea, periodic limb movements, psychiatric/behavioral disorders, and psychotropic medication use. RESULTS: Black/African Americans compared to non-Hispanic whites were at significantly higher odds of having a childhood-onset persistent trajectory through young adulthood (OR = 2.58, 95% CI [1.29, 5.14]), while Hispanics/Latinx were at nonsignificantly higher odds to have the same trajectory (OR = 1.81, 95% CI [0.77, 4.25]). No significant racial/ethnic differences were observed for remitted and waxing-and-waning trajectories since childhood or incident/new-onset trajectories in young adulthood. CONCLUSIONS: The results indicate that disparities in insomnia symptoms among black/African American and, to a lesser extent, Hispanic/Latinx groups start early in childhood and persist into young adulthood. Identifying and intervening upon upstream determinants of racial/ethnic insomnia disparities are warranted to directly address these disparities and to prevent their adverse health sequelae. CLINICAL TRIAL INFORMATION: N/A; Not a clinical trial.

Impact of long-acting injectable antipsychotics vs. oral medication on relapses of patients with psychosis and bipolar disorder.

Relapse associated with multiple hospital readmissions of patients with chronic and severe mental disorders, such as psychosis and bipolar disorder, is frequently associated with non-adherence to treatment. The primary aim of the study was to compare the effectiveness of long-acting injectable (LAI) treatment, vs. oral medication in reducing readmissions of patients with psychotic or bipolar disorder in a community sample of 164 patients with psychosis and 29 patients with bipolar disorder (n = 193), with poor adherence to oral medication. The mean follow up period was 5.6 years and the number of readmissions were compared for an equal-length period of oral treatment preceding the onset of LAI administration. We observed a significant decrease of 45.2 % in total hospital readmissions after receiving LAIs treatment. The effect was significant both for patients with a pre-LAI treatment history of predominantly voluntary hospitalizations and with predominantly involuntary admissions. In addition, we observed equal effectiveness of first- vs. second-generation LAIs in reducing total hospital readmissions regardless of type of pre-treatment admission history (voluntary vs. involuntary). LAIs appear to be effective in reducing both voluntary and involuntary hospital readmissions in patients with psychosis and bipolar disorder with a history of poor adherence to treatment.

Circadian misalignment impacts the association of visceral adiposity with metabolic syndrome in adolescents.

STUDY OBJECTIVES: Although insufficient sleep is a risk factor for metabolic syndrome (MetS), the circadian timing of sleep (CTS) is also involved in cardiac and metabolic regulation. We examined whether delays and deviations in the sleep midpoint (SM), a measure of CTS, modify the association between visceral adipose tissue (VAT) and MetS in adolescents. METHODS: We evaluated 277 adolescents (median 16 years) who had at least 5 nights of at-home actigraphy (ACT), in-lab polysomnography (PSG), dual-energy X-ray absorptiometry (DXA) scan, and MetS score data. Sleep midpoint (SM), sleep irregularity (SI), and social jetlag (SJL) were examined as effect modifiers of the association between VAT and MetS, including waist circumference, blood pressure, insulin resistance, triglycerides, and cholesterol. Linear regression models adjusted for demographics, ACT-sleep duration, ACT-sleep variability, and PSG-apnea-hypopnea index. RESULTS: The association between VAT and MetS was significantly stronger (p-values for interactions < 0.001) among adolescents with a schooldays SM later than 4:00 (2.66 [0.30] points increase in MetS score), a SI higher than 1 hour (2.49 [0.30]) or a SJL greater than 1.5 hours (2.15 [0.36]), than in those with an earlier SM (<3:00; 1.76 [0.28]), lower SI (<30 minutes; 0.98 [0.70]), or optimal SJL (<30 minutes; 1.08 [0.45]). CONCLUSIONS: A delayed sleep phase, an irregular sleep-wake cycle, and greater social jetlag on schooldays identified adolescents in whom VAT had a stronger association with MetS. Circadian misalignment is a risk factor that enhances the impact of visceral obesity on cardiometabolic morbidity and should be a target of preventative strategies in adolescents.

Age-related differences in the association of mild-to-moderate sleep apnea with incident cardiovascular and cerebrovascular diseases.

BACKGROUND: Mild-to-moderate obstructive sleep apnea (mmOSA) is highly prevalent in the general population. However, studies on its association with incident cardiovascular and/or cerebrovascular disease (CBVD) are limited. We examined the association between mild-to-moderate OSA and incident cardiovascular and/or cerebrovascular (CBVD) in a general population sample, and whether age modifies this association. METHODS: A total of 1173 adults from the Penn State Adult Cohort (20-88 years) without CBVD or severe OSA at baseline were followed-up after 9.2 (±4.1) years. Incident CBVD was defined based on a self-report of a physician diagnosis or treatment for heart disease and/or stroke. Logistic regression examined the association of mild-to-moderate OSA (AHI 5-29.9) with incident CBVD and the combined effect of mmOSA and MetS on incident CBVD after adjusting for multiple confounders. RESULTS: Age significantly modified the association between mmOSA with incident CBVD (p-interaction = 0.04). Mild-to-moderate OSA was significantly associated with incident CBVD in adults aged <60 years (OR = 1.74, 95%CI = 1.06-2.88, p = 0.029), but not in adults aged ≥60 years (OR = 0.71, 95%CI = 0.39-1.27, p = 0.247). Even mild OSA (AHI 5-14.9) carried a significant risk for incident CBDV in adults aged <60 years (OR = 1.86, 95%CI = 1.05-3.28, p = 0.032). An additive effect was found between mmOSA and MetS with incident CBVD in those aged <65 years (OR = 3.84, 95%CI = 1.95-7.56, p<0.001). CONCLUSIONS: The risk of incident CBVD is increased in young and middle-aged but not older adults with mmOSA, which may affect the way we currently diagnose and treat this highly prevalent sleep-related breathing disorder.

Long-term associations between objective sleep quality and quantity and verbal memory performance in normal cognition and mild cognitive impairment.

Introduction: Although the link between sleep and memory function is well established, associations between sleep macrostructure and memory function in normal cognition and Mild Cognitive Impairment remain unclear. We aimed to investigate the longitudinal associations of baseline objectively assessed sleep quality and duration, as well as time in bed, with verbal memory capacity over a 7-9 year period. Participants are a well-characterized subsample of 148 persons (mean age at baseline: 72.8 ± 6.7 years) from the Cretan Aging Cohort. Based on comprehensive neuropsychiatric and neuropsychological evaluation at baseline, participants were diagnosed with Mild Cognitive Impairment (MCI; n = 79) or found to be cognitively unimpaired (CNI; n = 69). Sleep quality/quantity was estimated from a 3-day consecutive actigraphy recording, whereas verbal memory capacity was examined using the Rey Auditory Verbal Learning Test (RAVLT) and the Greek Passage Memory Test at baseline and follow-up. Panel models were applied to the data using AMOS including several sociodemographic and clinical covariates. Results: Sleep efficiency at baseline directly predicted subsequent memory performance in the total group (immediate passage recall: ß = 0.266, p = 0.001; immediate word list recall: ß = 0.172, p = 0.01; delayed passage retrieval: ß = 0.214, p = 0.002) with the effects in Passage Memory reaching significance in both clinical groups. Wake after sleep onset time directly predicted follow-up immediate passage recall in the total sample (ß = -0.211, p = 0.001) and in the MCI group (ß = -0.235, p = 0.02). In the total sample, longer 24-h sleep duration was associated with reduced memory performance indirectly through increased sleep duration at follow-up (immediate passage recall: ß = -0.045, p = 0.01; passage retention index: ß = -0.051, p = 0.01; RAVLT-delayed recall: ß = -0.048, p = 0.009; RAVLT-retention index:ß = -0.066, p = 0.004). Similar indirect effects were found for baseline 24-h time in bed. Indirect effects of sleep duration/time in bed were found predominantly in the MCI group. Discussion: Findings corroborate and expand previous work suggesting that poor sleep quality and long sleep duration predict worse memory function in elderly. Timely interventions to improve sleep could help prevent or delay age-related memory decline among non-demented elderly.

Family Functioning, Illness-Related Self-Regulation Processes, and Clinical Outcomes in Major Depression: A Prospective Study in Greece.

Major depressive disorder (MDD) is a common, seriously impairing, and often recurrent mental disorder. Based on the predictions of the Circumplex Model of Marital and Family Systems and the Common-Sense Self-Regulation Model, the aim of the present prospective study is to examine the predictive value of clinical outcomes of a process model in which associations between perceived family functioning and patient's clinical outcomes (i.e., symptom severity and suicide risk) are mediated by illness representations and coping strategies. A total of 113 patients with a clinical diagnosis of MDD (16.8% males and 83.2% females) aged 47.25 ± 13.98 years and recruited from the outpatient department and the mobile mental health unit of the Psychiatric Clinic of the University Hospital of Heraklion in Crete, Greece, and from a Greek online depression peer-support group participated in the study. Family functioning was assessed in terms of cohesion and flexibility (Family Adaptability and Cohesion Evaluation Scales IV) at baseline. Illness representations (Illness Perception Questionnaire-Mental Health) and coping strategies (Brief Cope Orientation to Problems Experienced) were measured about five months later (5.04 ± 1.16 months). Symptom severity (Beck Depression Inventory) and suicidality (Risk Assessment Suicidality Scale) were measured about 10 months after the baseline assessment (9.56 ± 2.52 months). The results indicated that representations about MDD impact and symptom severity serially mediated the association between family cohesion and suicide risk in MDD. Furthermore, family cohesion was found to be linked with maladaptive coping through MDD impact representations. Family-based psychotherapeutic interventions specifically designed to target unhealthy family functioning, along with negative illness perceptions and dysfunctional coping, could be further developed and explored as adjunctive therapy to standard treatment in MDD.

A Pilot Study on the Effectiveness of Prazosin as a Treatment of Post-Traumatic Stress Disorder-Related Nightmares in Women with Bulimia Nervosa.

Objectives Post-traumatic stress disorder (PTSD) symptoms are reported in over 36% of individuals with bulimia nervosa. To date, none of the clinical trials have examined nightmare reduction in this population. We evaluated the effectiveness of prazosin in bulimic females experiencing PTSD-related nightmares. We hypothesized that prazosin will decrease nightmares, normalize cortisol levels and secretory patterns, and improve sleep. Methods Our seven-week prospective, randomized, double-blind, placebo-controlled crossover pilot trial recruited eight adult women. Each participant received three weeks of prazosin and a placebo, separated by a one-week washout period. The order of treatment was counterbalanced across participants. Self-reports, clinician-administered scales, and salivary cortisol was collected to measure outcomes. Results A significant treatment effect was seen in nightmare intensity on the Clinician-Administered PTSD Scale (CAPS-I) (p=0.026) and a marginally significant effect on nightmare frequency (p=0.069). The only significant main effect of treatment on self-reported sleep parameters was on nightmares. Cortisol secretory patterns did not change, but on average, study participants had significantly higher cortisol levels compared to normative values. ANOVA showed a significant main effect of time for cortisol (F(4, 28) = 6.15, p=.001) but no within or between groups significant effects (ps>.179). Follow-up tests showed the effect of time was linear (F(1, 7) = 10.77, p=.013). Conclusion Prazosin significantly reduced intensity and marginally reduced the frequency of PTSD-related nightmares in bulimia nervosa but did not affect subjective sleep efficiency, quality, cortisol levels, or diurnal cortisol secretory pattern. Larger trials using objective sleep measures are warranted to replicate these findings.

Objective and subjective measures of sleep initiation are differentially associated with DNA methylation in adolescents.

INTRODUCTION: The onset of puberty is associated with a shift in the circadian timing of sleep, leading to delayed sleep initiation [i.e., later sleep onset time (SOT)] due to later bedtimes and/or longer sleep onset latency (SOL). Several genome-wide association studies (GWAS) have identified genes that may be involved in the etiology of sleep phenotypes. However, circadian rhythms are also epigenetically regulated; therefore, epigenetic biomarkers may provide insight into the physiology of the pubertal sleep onset shift and the pathophysiology of prolonged or delayed sleep initiation. RESULTS: The gene-wide analysis indicated differential methylation within or around 1818 unique genes across the sleep initiation measurements using self-report, actigraphy (ACT), and polysomnography (PSG), while GWAS-informed analysis yielded 67 genes. Gene hits were identified for bedtime (PSG), SOL (subjective, ACT and PSG) and SOT (subjective and PSG). DNA methylation within 12 genes was associated with both subjective and PSG-measured SOL, 31 with both ACT- and PSG-measured SOL, 19 with both subjective and ACT-measured SOL, and one gene (SMG1P2) had methylation sites associated with subjective, ACT- and PSG-measured SOL. CONCLUSIONS: Objective and subjective sleep initiation in adolescents is associated with altered DNA methylation in genes previously identified in adult GWAS of sleep and circadian phenotypes. Additionally, our data provide evidence for a potential epigenetic link between habitual (subjective and ACT) SOL and in-lab SOT and DNA methylation in and around genes involved in circadian regulation (i.e., RASD1, RAI1), cardiometabolic disorders (i.e., FADS1, WNK1, SLC5A6), and neuropsychiatric disorders (i.e., PRR7, SDK1, FAM172A). If validated, these sites may provide valuable targets for early detection and prevention of disorders involving prolonged or delayed SOT, such as insomnia, delayed sleep phase, and their comorbidity.

Mild-to-moderate obstructive sleep apnea and mortality risk in a general population sample: The modifying effect of age and cardiovascular/cerebrovascular comorbidity.

About 5.4%-45.7% of the general population has mild-to-moderate obstructive sleep apnea (mmOSA), which is highly comorbid with cardiovascular and/or cerebrovascular diseases (CBVD). We examined the association between mmOSA and all-cause mortality and the modifying effect of age and CBVD. A total of 1681 adults 20-88 years old from the Penn State Adult Cohort (PSAC) (41.9% male) were followed up for 20.1 ± 6.2 years for all-cause mortality. Mild and moderate OSA were defined as an apnea/hypopnea index (AHI) 5-14.9 and 15-29.9 events/hour, respectively. CBVD was defined as a report of a physician diagnosis or treatment for heart disease and/or stroke. Cox proportional hazards regression models were used to estimate all-cause mortality adjusted for confounders. All-cause mortality risk was significantly increased in the mmOSA group in young and middle-aged adults (<60 years) (HR = 1.59, 95%CI 1.08-2.04) but not in older adults (≥60 years) (HR = 1.05, 95%CI 0.80-1.39). A synergistic effect between mmOSA and CBVD was stronger in those <60 years (HR = 3.82, 95%CI 2.25-6.48 in <60 years vs 1.86 95%CI 1.14-3.04 in ≥60 years). There was an additive effect between moderate OSA and hypertension in <60 but not in those ≥60 years. Mild OSA was associated with all-cause mortality only in the presence of CBVD. Mortality risk is increased in young and middle-aged adults with moderate OSA, whereas the mortality risk associated with mild OSA is elevated only, regardless of age, in the presence of comorbid CBVD. AHI cut-offs warranting treatment of mmOSA may need to be adjusted based on age and comorbidities.

Insomnia with objective, but not subjective, short sleep duration is associated with increased risk of incident hypertension: the Sleep Heart Health Study.

STUDY OBJECTIVES: Insomnia with objective short sleep duration has been associated with higher risk of cardiometabolic morbidity. In this study, we examined the association between insomnia with objective short sleep duration, also based on subjective sleep duration, with incident hypertension in the Sleep Heart Health Study. METHODS: We analyzed data from 1,413 participants free of hypertension or sleep apnea at baseline from the Sleep Heart Health Study, with a median follow-up duration of 5.1 years. Insomnia symptoms were defined based on difficulty falling asleep, difficulty returning to sleep, early morning awakening, or sleeping pill use more than half the days in a month. Objective short sleep duration was defined as polysomnography-measured total sleep time < 6 hours. Incident hypertension was defined based on blood pressure measures and/or use of antihypertensive medications at follow-up. RESULTS: Individuals with insomnia who slept objectively < 6 hours had significantly higher odds of incident hypertension compared to normal sleepers who slept ≥ 6 hours (odds ratio = 2.00, 95% confidence interval = 1.09-3.65) or < 6 hours (odds ratio = 2.00, 95% confidence interval = 1.06-3.79) or individuals with insomnia who slept ≥ 6 hours (odds ratio = 2.79, 95% confidence interval = 1.24-6.30). Individuals with insomnia who slept ≥ 6 hours or normal sleepers who slept < 6 hours were not associated with increased risk of incident hypertension compared to normal sleepers who slept ≥ 6 hours. Finally, individuals with insomnia who self-reported sleeping < 6 hours were not associated with significantly increased odds of incident hypertension. CONCLUSIONS: These data further support that the insomnia with objective short sleep duration phenotype based on objective, but not subjective measures, is associated with increased risk of developing hypertension in adults. CITATION: Dai Y, Chen B, Chen L, et al. Insomnia with objective, but not subjective, short sleep duration is associated with increased risk of incident hypertension: the Sleep Heart Health Study. J Clin Sleep Med. 2023;19(8):1421-1428.

IL-6 Enhances the Negative Impact of Cortisol on Cognition among Community-Dwelling Older People without Dementia.

There is growing evidence that high basal cortisol levels and systemic inflammation independently contribute to cognitive decline among older people without dementia. The present cross-sectional study examined (a) the potential synergistic effect of cortisol levels and systemic inflammation on executive function and (b) whether this effect is more prominent among older people with mild cognitive impairment (MCI). A sub-sample of 99 patients with MCI and 84 older people without cognitive impairment (CNI) (aged 73.8 ± 7.0 years) were recruited from a large population-based cohort in Crete, Greece, and underwent comprehensive neuropsychiatric and neuropsychological evaluation and a single morning measurement of cortisol and IL-6 plasma levels. Using moderated regression models, we found that the relation between cortisol and executive function in the total sample was moderated by IL-6 levels (b = -0.994, p = 0.044) and diagnostic group separately (b = -0.632, p < 0.001). Moreover, the interaction between cortisol and IL-6 levels was significant only among persons with MCI (b = -0.562, p < 0.001). The synergistic effect of stress hormones and systemic inflammation on cognitive status appears to be stronger among older people who already display signs of cognitive decline. Targeting hypercortisolemia and inflammation may be a promising strategy toward improving the course of cognitive decline.

Circadian Misalignment Impacts the Association of Visceral Adiposity With Elevated Blood Pressure in Adolescents.

BACKGROUND: Although insufficient sleep has been shown to contribute to obesity-related elevated blood pressure, the circadian timing of sleep has emerged as a novel risk factor. We hypothesized that deviations in sleep midpoint, a measure of circadian timing of sleep, modify the association between visceral adiposity and elevated blood pressure in adolescents. METHODS: We studied 303 subjects from the Penn State Child Cohort (16.2±2.2 years; 47.5% female; 21.5% racial/ethnic minority). Actigraphy-measured sleep duration, midpoint, variability, and regularity were calculated across a 7-night period. Visceral adipose tissue (VAT) was measured with dual-energy X-ray absorptiometry. Systolic blood pressure (SBP) and diastolic blood pressure levels were measured in the seated position. Multivariable linear regression models tested sleep midpoint and its regularity as effect modifiers of VAT on SBP/diastolic blood pressure levels, while adjusting for demographic and sleep covariables. These associations were also examined as a function of being in-school or on-break. RESULTS: Significant interactions were found between VAT and sleep irregularity, but not sleep midpoint, on SBP (P interaction=0.007) and diastolic blood pressure (P interaction=0.022). Additionally, significant interactions were found between VAT and schooldays sleep midpoint on SBP (P interaction=0.026) and diastolic blood pressure (P interaction=0.043), whereas significant interactions were found between VAT and on-break weekdays sleep irregularity on SBP (P interaction=0.034). CONCLUSIONS: A delayed and an irregular sleep midpoint during school and during free-days, respectively, increase the impact of VAT on elevated blood pressure in adolescents. These data suggest that deviations in the circadian timing of sleep contribute to the increased cardiovascular sequelae associated with obesity and that its distinct metrics require measurement under different entrainment conditions in adolescents.

Cretan Aging Cohort-Phase III: Methodology and Descriptive Characteristics of a Long-Term Longitudinal Study on Predictors of Cognitive Decline in Non-Demented Elderly from Crete, Greece.

Identifying modifiable factors that may predict long-term cognitive decline in the elderly with adequate daily functionality is critical. Such factors may include poor sleep quality and quantity, sleep-related breathing disorders, inflammatory cytokines and stress hormones, as well as mental health problems. This work reports the methodology and descriptive characteristics of a long-term, multidisciplinary study on modifiable risk factors for cognitive status progression, focusing on the 7-year follow-up. Participants were recruited from a large community-dwelling cohort residing in Crete, Greece (CAC; Cretan Aging Cohort). Baseline assessments were conducted in 2013-2014 (Phase I and II, circa 6-month time interval) and follow-up in 2020-2022 (Phase III). In total, 151 individuals completed the Phase III evaluation. Of those, 71 were cognitively non-impaired (CNI group) in Phase II and 80 had been diagnosed with mild cognitive impairment (MCI). In addition to sociodemographic, lifestyle, medical, neuropsychological, and neuropsychiatric data, objective sleep was assessed based on actigraphy (Phase II and III) and home polysomnography (Phase III), while inflammation markers and stress hormones were measured in both phases. Despite the homogeneity of the sample in most sociodemographic indices, MCI persons were significantly older (mean age = 75.03 years, SD = 6.34) and genetically predisposed for cognitive deterioration (APOE ε4 allele carriership). Also, at follow-up, we detected a significant increase in self-reported anxiety symptoms along with a substantial rise in psychotropic medication use and incidence of major medical morbidities. The longitudinal design of the CAC study may provide significant data on possible modifiable factors in the course of cognitive progression in the community-dwelling elderly.