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Inflammation, sleep disturbances, and depressed mood among community-dwelling older men.

ABSTRACT: High rates of sleep disturbances occur in depression. Sleep disturbances are linked to heightened inflammation. We sought to determine if sleep disturbances explain a portion of the putative inflammation - depression association among older adults. In late life, age-related immunoregulation changes may modify the inflammation-depression relationship.Cross-sectional associations of a panel of serum inflammatory markers with probable depression (measured with the Geriatric Depression Scale) were assessed among 2560 community-dwelling older men. We tested whether inflammatory marker - probable depression associations were independent of chronic diseases, as well as objective and subjectively measured sleep disturbances. We also tested whether inflammation-probable depression associations were moderated by age.Inflammatory markers were not independently associated with higher odds of probable depression. A significant age by C-reactive protein (CRP) interaction (p=0.01) was detected such that the strength of the CRP-probable depression association decreased with age. When stratifying by the median age of 76, elevated odds of probable depression were found for men with CRP levels above the median only among the younger group (OR=2.08, 95% CI 1.18-3.69). In the final adjusted model, independent effects of chronic diseases and subjective sleep disturbances contributed to a total of 37% attenuation of the original OR (adjusted OR=1.68, 95% CI 0.911-3.10, p=.09).In late-life, associations between inflammatory markers and mood may be explained by both chronic diseases and subjectively reported sleep disturbances. Our findings indicate that the association of CRP with probable depression diminishes in strength with age.

SUBMITTER: Smagula SF

PROVIDER: S-EPMC3997106 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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Inflammation, sleep disturbances, and depressed mood among community-dwelling older men.

Smagula Stephen F SF Ancoli-Israel Sonia S Barrett-Connor Elizabeth E Lane Nancy E NE Redline Susan S Stone Katie L KL Cauley Jane A JA

Journal of psychosomatic research 20140222 5

<h4>Objective</h4>High rates of sleep disturbances occur in depression. Sleep disturbances are linked to heightened inflammation. We sought to determine if sleep disturbances explain a portion of the putative inflammation - depression association among older adults. In late life, age-related immunoregulation changes may modify the inflammation-depression relationship.<h4>Methods</h4>Cross-sectional associations of a panel of serum inflammatory markers with probable depression (measured with the ...[more]

PMID: 24745777

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Project description:To evaluate whether objectively measured sleep characteristics are associated with mortality risk independent of inflammatory burden and comorbidity.The Osteoporotic Fractures in Men Sleep Study (conducted in 2003-2005) included community-dwelling older men (n = 2531; average [standard deviation {SD}] age = 76.3 (5.5) years). Sleep measures from in-home polysomnography and wrist actigraphy and assessments of serum inflammatory markers levels (C-reactive protein, interleukin-6, tumor necrosis factor ?, tumor necrosis factor ? soluble receptor II, and interferon-?) were obtained. Vital status was ascertained over an average (SD) follow-up of 7.4 (1.9 SD) years.Three of the seven main sleep measures examined were independently associated with greater inflammatory burden. Mortality risk associated with prolonged (?10% total sleep time) blood oxygen desaturation and short (<5 hours) sleep duration was attenuated to nonsignificance after adjusting for inflammatory burden or medical burden/lifestyle factors. Severe blood oxygen desaturation (adjusted hazard ratio [aHR] = 1.57, 95% confidence interval [CI] = 1.11-2.22), sleep fragmentation (aHR = 1.32, 95% CI = 1.12-1.57), and a lower percentage of sleep in rapid eye movement (aHR per SD = 0.90, 95% CI = 0.93-0.97) were independently associated with mortality.Short sleep duration and prolonged blood oxygen desaturation were independently associated with inflammatory burden, which attenuated associations between these sleep characteristics and mortality. Medical and life-style factors also substantially attenuated most sleep-mortality associations, suggesting complex relations between sleep, inflammation, and disease. Sleep fragmentation, severe blood oxygen desaturation, and the percentage of sleep time in rapid eye movement were independently related to mortality risk. Future studies with repeated measures of mediators/confounds will be necessary to achieve a mechanistic understanding of sleep-related mortality risk.

Project description:PurposeWe investigated the association between sleep disordered breathing and erectile dysfunction in older men.Materials and methodsWe performed a cross-sectional analysis of community dwelling men age 67 years or older enrolled in the Osteoporotic Fractures in Men Sleep Study. Participants underwent overnight polysomnography (2003 to 2005) and completed sexual health questionnaires (2005 to 2006). We defined sleep disordered breathing using the apnea-hypopnea index or nocturnal hypoxemia. Erectile dysfunction was defined using the MMAS (Massachusetts Male Aging Study) scale and, in sexually active men, the International Index of Erectile Function. We used logistic regression to examine the association between sleep disordered breathing and erectile dysfunction.ResultsMean participant age was 76±5 years. Of the 2,676 men completing the MMAS, 70% had moderate to complete erectile dysfunction. Among 1,099 sexually active men completing the IIEF-5 (5-item International Index of Erectile Function), 26% had moderate to severe erectile dysfunction. A higher apnea-hypopnea index was associated with greater odds of MMAS defined moderate to complete erectile dysfunction after adjusting for age and study site (OR 1.39, 95% CI 1.00-1.92 for severe sleep disordered breathing vs none, p trend=0.008), but not after further adjustment for body mass index, socioeconomic status and comorbidities (OR 1.05, 95% CI 0.75-1.49, p trend=0.452). Greater nocturnal hypoxemia was associated with increased odds of MMAS defined moderate to complete erectile dysfunction (unadjusted OR 1.36, 95% Cl 1.04-1.80 vs none) but this was attenuated after adjustment for age and study site (OR 1.24, 95% CI 0.92-1.66). Sleep disordered breathing was not associated with erectile dysfunction by 5-item International Index of Erectile Function.ConclusionsIn this cross-sectional analysis in older men sleep disordered breathing was associated with higher odds of erectile dysfunction in unadjusted analyses that was largely explained by higher body mass index and increased comorbidity among men with sleep disordered breathing. Prospective studies accounting for obesity and multimorbidity would further clarify the association of sleep disordered breathing and erectile dysfunction.

Project description:To evaluate sleep-wake disturbances in sedentary community-dwelling elderly adults with functional limitations.Cross-sectional.Lifestyle Interventions and Independence in Elder (LIFE) Study.Community-dwelling persons (mean age 78.9) who spent fewer than 20 min/wk in the previous month engaged in regular physical activity and fewer than 125 min/wk of moderate physical activity, and had a Short Physical Performance Battery (SPPB) score of <10 (N = 1,635).Mobility was evaluated according to 400-m walk time (slow gait speed defined as <0.8 m/s) and SPPB score (? 7 defined moderate to severe mobility impairment). Physical inactivity was defined according to sedentary time, as a percentage of accelerometry wear time with activity of <100 counts/min; participants in the top quartile of sedentary time were classified as having a high sedentary time. Sleep-wake disturbances were evaluated using the Insomnia Severity Index (ISI) (range 0-28; ? 8 defined insomnia), Epworth Sleepiness Scale (ESS) (range 0-24; ? 10 defined daytime drowsiness), Pittsburgh Sleep Quality Index (PSQI) (range 0-21; >5 defined poor sleep quality), and Berlin Questionnaire (high risk of sleep apnea).Prevalence rates were 43.5% for slow gait speed and 44.7% for moderate to severe mobility impairment, with 77.0% of accelerometry wear time spent as sedentary time. Prevalence rates were 33.0% for insomnia, 18.1% for daytime drowsiness, 47.8% for poor sleep quality, and 32.9% for high risk of sleep apnea. Participants with insomnia had a mean ISI score of 12.1, those with daytime drowsiness had a mean ESS score of 12.5, and those with poor sleep quality had a mean PSQI score of 9.2. In adjusted models, measures of mobility and physical inactivity were generally not associated with sleep-wake disturbances, using continuous or categorical variables.In a large sample of sedentary community-dwelling elderly adults with functional limitations, sleep-wake disturbances were prevalent but only mildly severe and were generally not associated with mobility impairment or physical inactivity.

Project description:OBJECTIVE:To test the hypothesis that non-frail older men with poorer sleep at baseline are at increased risk of frailty and death at follow-up. METHODS:In this prospective cohort study, subjective (questionnaires) and objective sleep parameters (actigraphy, in-home overnight polysomnography) were measured at baseline in 2505 non-frail men aged ?67years. Repeat frailty status assessment performed an average of 3.4 years later; vital status assessed every four months. Sleep parameters expressed as dichotomized predictors using clinical cut-points. Status at follow-up exam classified as robust, intermediate (pre-frail) stage, frail, or died in interim. RESULTS:None of the sleep disturbances were associated with the odds of being intermediate/frail/dead (vs. robust) at follow-up. Poor subjective sleep quality (multivariable odds ratio [MOR] 1.26, 95% CI 1.01-1.58), greater nighttime wakefulness (MOR 1.31, 95% CI 1.04-1.66), and greater nocturnal hypoxemia (MOR 1.47, 95% CI 1.02-2.10) were associated with a higher odds of frailty/death at follow-up (vs. robust/intermediate). Excessive daytime sleepiness (MOR 1.60, 95% CI 1.03-2.47), greater nighttime wakefulness (MOR 1.57, 95% CI 1.12-2.20), severe sleep apnea (MOR 1.74, 95% CI 1.04-2.89), and nocturnal hypoxemia (MOR 2.28, 95% CI 1.45-3.58) were associated with higher odds of death (vs. robust/intermediate/frail at follow-up). The association between poor sleep efficiency and mortality nearly reached significance (MOR 1.48, 95% CI 0.99-2.22). Short sleep duration and prolonged sleep latency were not associated with frailty/death or death at follow-up. CONCLUSIONS:Among non-frail older men, poor subjective sleep quality, greater nighttime wakefulness, and greater nocturnal hypoxemia were independently associated with higher odds of frailty or death at follow-up, while excessive daytime sleepiness, greater nighttime wakefulness, severe sleep apnea and greater nocturnal hypoxemia were independently associated with an increased risk of mortality.

Project description:BACKGROUND AND OBJECTIVES:Mild hyponatremia is a common finding in older adults; however, the association of lower serum sodium with cognition in older adults is currently unknown. We determined whether lower normal serum sodium is associated with cognitive impairment and risk of cognitive decline in community-dwelling older men. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:Five thousand four hundred thirty-five community-dwelling men aged ?65 years who participated in Osteoporotic Fractures in Men, a cohort study with a median follow-up for cognitive function of 4.6 years, were included in this analysis. Multivariable logistic regression was used to examine the association between baseline fasting serum sodium levels and the odds of prevalent cognitive impairment (cross-sectional analysis; modified Mini-Mental Status [3MS] score <1.5 SD [<84] below or Trail Making Test Part B time >1.5 SD above the mean [>223 seconds]) and cognitive decline (prospective analysis [n=3611]; decrease in follow-up 3MS score or increase in Trails B time >1.5 SD of the mean score/time change [>9 or >67 seconds]). RESULTS:Participants were aged 74±6 years with a fasting mean serum sodium level of 141±3 mmol/L. Fifteen percent (n=274), 12% (n=225), and 13% (n=242) had prevalent cognitive impairment in tertiles 1, 2, and 3, respectively. After adjustment, lower serum sodium was associated with prevalent cognitive impairment (tertile 1 [126-140 mmol/L] versus tertile 2 [141-142 mmol/L], odds ratio [OR], 1.30; 95% confidence interval [95% CI], 1.06 to 1.61). Fourteen percent (n=159), 10% (n=125), and 13% (n=159) had cognitive decline in tertiles 1, 2, and 3, respectively. Lower serum sodium was also associated with cognitive decline (tertile 1 versus tertile 2, OR, 1.37; 95% CI, 1.06 to 1.77). Tertile 3 (143-153 mmol/L) was additionally associated with cognitive decline. Results were similar in sensitivity analyses according to clinical cut-offs and by quartiles. CONCLUSIONS:In community-dwelling older men, serum sodium between 126-140, and 126-140 or 143-153 mmol/L, are independently associated with prevalent cognitive impairment and cognitive decline, respectively.

Project description:Inflammation plays a significant role in the pathophysiology of depression. However, not all individuals exposed to inflammatory challenge develop depression, and identifying those at risk is necessary to develop targeted monitoring, prevention, and treatment strategies. Within a randomized double-blind placebo-controlled study (n = 115), we examined whether leukocyte transcriptome profiles predicted inflammation-induced depressed mood in volunteers who received low-dose intravenous endotoxin (n = 58; aged 18-50). At baseline, transcription factor (TF) activities were assessed using genome-wide transcriptional profiling of peripheral blood mononuclear cells and promoter-based bioinformatic analyses. Then, participants were administered endotoxin. Self-reported depressed mood was assessed using the Profile of Mood States. Based on extant studies linking transcriptional profiles to depressive disorder, we examined whether post-endotoxin depressed mood is predicted by baseline activity of TFs related to immune activation, sympathetic activation, and glucocorticoid insensitivity: respectively, nuclear factor kappa B (NF-kB), cAMP response element-binding protein (CREB), and glucocorticoid receptor (GR). Twenty-one participants (36%) experienced an increase in depressed mood from baseline to 2 h post endotoxin, when depressive response peaks. Bioinformatics analyses controlling for age, sex, ethnicity, body mass index, and physical sickness response revealed that post-endotoxin depressed mood was predicted by increased baseline activity of TFs related to inflammation (NF-kB) and beta-adrenergic signaling (CREB) and by decreased activity of GR-related TFs (P's < 0.001). Inflammation-induced depressed mood is predicted by peripheral transcriptome profiles related to immune activation, sympathetic activation, and glucocorticoid insensitivity. With further replication, these stress-related molecular profiles could be used for a novel genomic approach for identifying individuals at high-risk for the inflammatory subtype of depression.

Dataset Information

Inflammation, sleep disturbances, and depressed mood among community-dwelling older men.

Publications

Inflammation, sleep disturbances, and depressed mood among community-dwelling older men.

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