Abstract
Advanced brain aging is commonly regarded as a risk factor for neurodegenerative diseases, for example, Alzheimer’s dementia, and it was suggested that sleep disorders such as obstructive ...sleep apnea (OSA) are significantly contributing factors to these neurodegenerative processes. To determine the association between OSA and advanced brain aging, we investigated the specific effect of two indices quantifying OSA, namely the apnea–hypopnea index (AHI) and the oxygen desaturation index (ODI), on brain age, a score quantifying age-related brain patterns in 169 brain regions, using magnetic resonance imaging and overnight polysomnography data from 690 participants (48.8% women, mean age 52.5 ± 13.4 years) of the Study of Health in Pomerania. We additionally investigated the mediating effect of subclinical inflammation parameters on these associations via a causal mediation analysis. AHI and ODI were both positively associated with brain age (AHI std. effect 95% CI: 0.07 0.03; 0.12, p-value: 0.002; ODI std. effect 95% CI: 0.09 0.04; 0.13, p-value: < 0.0003). The effects remained stable in the presence of various confounders such as diabetes and were partially mediated by the white blood cell count, indicating a subclinical inflammation process. Our results reveal an association between OSA and brain age, indicating subtle but widespread age-related changes in regional brain structures, in one of the largest general population studies to date, warranting further examination of OSA in the prevention of neurodegenerative diseases.
The objective of this study was to evaluate interrater reliability between manual sleep stage scoring performed in 2 European sleep centers and automatic sleep stage scoring performed by the ...previously validated artificial intelligence-based Stanford-STAGES algorithm.
Full night polysomnographies of 1,066 participants were included. Sleep stages were manually scored in Berlin and Innsbruck sleep centers and automatically scored with the Stanford-STAGES algorithm. For each participant, we compared (1) Innsbruck to Berlin scorings (INN vs BER); (2) Innsbruck to automatic scorings (INN vs AUTO); (3) Berlin to automatic scorings (BER vs AUTO); (4) epochs where scorers from Innsbruck and Berlin had consensus to automatic scoring (CONS vs AUTO); and (5) both Innsbruck and Berlin manual scorings (MAN) to the automatic ones (MAN vs AUTO). Interrater reliability was evaluated with several measures, including overall and sleep stage-specific Cohen's κ.
Overall agreement across participants was substantial for INN vs BER (κ = 0.66 ± 0.13), INN vs AUTO (κ = 0.68 ± 0.14), CONS vs AUTO (κ = 0.73 ± 0.14), and MAN vs AUTO (κ = 0.61 ± 0.14), and moderate for BER vs AUTO (κ = 0.55 ± 0.15). Human scorers had the highest disagreement for N1 sleep (κ
= 0.40 ± 0.16 for INN vs BER). Automatic scoring had lowest agreement with manual scorings for N1 and N3 sleep (κ
= 0.25 ± 0.14 and κ
= 0.42 ± 0.32 for MAN vs AUTO).
Interrater reliability for sleep stage scoring between human scorers was in line with previous findings, and the algorithm achieved an overall substantial agreement with manual scoring. In this cohort, the Stanford-STAGES algorithm showed similar performances to the ones achieved in the original study, suggesting that it is generalizable to new cohorts. Before its integration in clinical practice, future independent studies should further evaluate it in other cohorts.
Abstract
Study Objectives
Periodic limb movements in sleep (PLMS) are frequent motor phenomena; however, population-based data are scarce. We assessed the prevalence of PLMS and factors associated ...with PLMS within two German population-based cohorts, the SHIP-TREND and BiDirect.
Methods
Single-night polysomnography was performed on 1107 subjects recruited from the general population (mean age: 52.9 years, 54.1% men) in the SHIP-TREND and on 247 participants (mean age: 57.6 years, 50.6% men) in the BiDirect. PLMS were evaluated using the standard criteria of the American Academy of Sleep Medicine. Sociodemographic data, behavioral variables, medical history, current medication, and other sleep disorders were assessed.
Results
The prevalence of PLMS index (PLMSI) >15/hour was 32.4% (SHIP-TREND) and 36.4% (BiDirect). In multivariable models, age (odds ratio OR = 1.05 per +1 year), male gender (OR = 2.20), restless legs syndrome (OR = 2.32), physical inactivity (OR = 1.52), current smoking (OR = 1.49), diabetes (OR = 2.13), antidepressant use (OR = 2.27), lower serum magnesium (OR per −0.1 mmol/L = 1.27) showed a positive, and the intake of beta-blockers an inverse association with PLMSI >15/hour in SHIP-TREND. In BiDirect, age (OR = 1.13 per +1 year), body mass index (OR = 1.11 per +1 kg/m2), and restless legs syndrome (OR = 8.77) were significantly associated with PLMSI >15/hour.
Conclusions
A high PLMSI is frequent in the German population. Age, male gender, restless legs syndrome, physical inactivity, current smoking, obesity, diabetes, antidepressant use, and lower magnesium were independently associated with PLMSI >15/hour in at least one of the cohorts.
Background Health-related quality of life (HRQoL) is an important outcome measure in patients with chronic kidney disease. It also has been shown repeatedly to predict mortality in various patient ...populations. In a prospective cohort study, we assessed the association between HRQoL and long-term clinical outcome in kidney transplant recipients. Study Design Prospective prevalent cohort study. Setting & Participants We collected sociodemographic parameters, medical and transplant history, and laboratory data at baseline from 879 prevalent kidney transplant recipients (mean age, 49 ± 13 standard deviation years; 58% men; and 17% with diabetes mellitus). Predictor We assessed HRQoL using the KDQoL-SF (Kidney Disease Quality of Life Short Form) questionnaire and assessed depressive symptoms using the Center for Epidemiologic Studies–Depression Scale. Outcomes All-cause mortality and death-censored transplant loss or death with functioning transplant. Cox regression models and semiparametric competing-risks regression analyses were used to measure associations between HRQoL scores and outcomes. Results Most examined HRQoL domains were associated with clinical outcome in unadjusted models. After adjusting for several important confounders, the 36-Item Short Form Health Survey (SF-36) Physical Composite Score and Physical Functioning and General Health Perception subscale scores remained independently associated with clinical outcomes. Every 10-point increase in SF-36 Physical Composite Score and Physical Functioning and General Health Perception scores was associated with 18% (HR, 0.82; 95% CI, 0.71-0.95), 11% (HR, 0.89; 95% CI, 0.84-0.94), and 7% lower risks of mortality (HR, 0.93; 95% CI, 0.88-1.00), respectively. Limitations Single-center study. Conclusions We showed that the SF-36 Physical Composite Score and Physical Functioning and General Health Perception KDQoL-SF domain scores are associated independently with increased risk of mortality in kidney transplant patients. Regular assessment of HRQoL may be a useful tool to inform health care providers about the prognosis of kidney transplant recipients. Additional studies are needed to assess whether interventions aimed at improving HRQoL would improve clinical outcomes in this patient population.
Previous studies revealed several alterations of the cerebral white matter in patients with major depressive disorder. However, it is unknown if these alterations are associated with vascular changes ...in the brain and other body parts. We compared diffusion tensor imaging derived fractional anisotropy in a well characterized sample of middle-aged patients with major depressive disorder (
= 290) and never-depressed controls (
= 346) by the method of tract-based spatial statistics. Subsequently, the potential role of pulse wave velocity as a mediator of depression- and age-related changes in extracted estimates of fractional anisotropy were analyzed. The results of the tract-based analysis revealed significantly reduced fractional anisotropy in the left posterior thalamic radiation associated with depression. Analyses of extracted data indicated additional reductions of fractional anisotropy bilaterally in the posterior thalamic radiation and in the left sagittal stratum. The analyses of indirect effects did not show any significant mediation of depression-related effects on fractional anisotropy via pulse wave velocity. However, age-related effects on fractional anisotropy were partially mediated by pulse wave velocity. In conclusion, major depressive disorder is associated with detrimental effects on cerebral white matter microstructure properties which are independent of vascular changes, as measured by pulse wave velocity. However, a portion of age-related detrimental effects on white matter is explained by vascular changes. Longitudinal studies are required for investigating changes in white matter and vascular parameters over time and their association with incident depression.
Previous studies on patients with restless legs syndrome (RLS) yielded inconclusive results in the magnetic resonance imaging (MRI)-based analyses of alterations of subcortical structures in the ...brain. The aim of this study was to compare volumes as well as shapes of subcortical structures and the hippocampus between RLS cases and controls. Additionally, the associations between the genetic risks for RLS and subcortical volumes were investigated.
We compared volumetric as well as shape differences assessed by 3 T MRI in the caudate nucleus, hippocampus, globus pallidus, putamen, and thalamus in 39 RLS cases versus 117 controls, nested within a population-based sample. In a subsample, we explored associations between known genetic risk markers for RLS and the volumes of the subcortical structures and the hippocampus.
No significant differences between RLS cases and controls in subcortical and hippocampal shapes and volumes were observed. Furthermore, the genetic risk for RLS was unrelated to any alterations of subcortical and hippocampal gray matter volume.
We conclude that neither RLS nor the genetic risk for the disease give rise to changes in hippocampal and subcortical shapes and gray matter volumes.
Underlying pathomechanisms of brain white matter hyperintensities (WMHs), commonly observed in older individuals and significantly associated with Alzheimer disease and brain aging, have not yet been ...fully elucidated. One potential contributing factor to WMH burden is chronic obstructive sleep apnea (OSA), a disorder highly prevalent in the general population with readily available treatment options.
To investigate potential associations between OSA and WMH burden.
Analyses were conducted in 529 study participants of the Study of Health in Pomerania-Trend baseline (SHIP-Trend-0) study with complete WMH, OSA, and important clinical data available. SHIP-Trend-0 is a general population-based, cross-sectional, observational study to facilitate the investigation of a large spectrum of common risk factors, subclinical disorders, and clinical diseases and their relationships among each other with patient recruitment from Western Pomerania, Germany, starting on September 1, 2008, with data collected until December 31, 2012. Data analysis was performed from February 1, 2019, to January 31, 2021.
The apnea-hypopnea index (AHI) and oxygen desaturation index (ODI) were assessed during a single-night, laboratory-based polysomnography measurement.
The primary outcome was WMH data automatically segmented from 1.5-T magnetic resonance images.
Of 529 study participants (mean SD age, 52.15 13.58 years; 282 female 53%), a total of 209 (40%) or 102 (19%) individuals were diagnosed with OSA according to AHI or ODI criteria (mean SD AHI, 7.98 12.55 events per hour; mean SD ODI, 3.75 8.43 events per hour). Both AHI (β = 0.024; 95% CI, 0.011-0.037; P <.001) and ODI (β = 0.033; 95% CI, 0.014-0.051; P <. 001) were significantly associated with brain WMH volumes. These associations remained even in the presence of additional vascular, metabolic, and lifestyle WMH risk factors. Region-specific WMH analyses found the strongest associations between periventricular frontal WMH volumes and both AHI (β = 0.0275; 95% CI, 0.013-0.042, P < .001) and ODI (β = 0.0381; 95% CI, 0.016-0.060, P < .001) as well as periventricular dorsal WMH volumes and AHI (β = 0.0165; 95% CI, 0.004-0.029, P = .008).
This study found significant associations between OSA and brain WMHs, indicating a novel, potentially treatable WMH pathomechanism.
Our aim was to evaluate the association between the cumulative effect of comorbidity and the risk of restless legs syndrome (RLS) in 2 population-based German cohort studies.
The Dortmund Health ...Study (DHS) (n = 1,312; median follow-up time: 2.1 years) and the Study of Health in Pomerania (SHIP) (n = 4,308; median follow-up time: 5.0 years) were used for the analyses. RLS was assessed at baseline and follow-up according to the RLS minimal criteria. A comorbidity index was calculated as a sum of the following conditions: diabetes, hypertension, myocardial infarction, obesity, stroke, cancer, renal disease, anemia, depression, thyroid disease, and migraine. The relationship between comorbidity and incident RLS was analyzed with multivariate logistic regression models.
An increase in the number of comorbid conditions at baseline predicted prevalent RLS (DHS: trend odds ratio OR = 1.24, 95% confidence interval CI 0.99-1.56; SHIP: trend OR = 1.34, 95% CI 1.18-1.52) and incident RLS (DHS: trend OR = 1.32, 95% CI 1.04-1.68; SHIP: trend OR = 1.59, 95% CI 1.37-1.85) after adjustment for several covariates. The ORs for incident RLS associated with 3 or more comorbid diseases (DHS: OR = 2.51, 95% CI 1.18-5.34; SHIP: OR = 4.30, 95% CI 2.60-7.11) were higher than the ORs for any single disease.
Multimorbidity was a strong risk factor for RLS in these 2 population-based cohort studies. The results support the hypothesis that cumulative disease burden is more important than the presence of a specific single disease in the pathophysiology of RLS.
Introduction
Sleep is increasingly recognized as a major risk factor for neurodegenerative disorders such as Alzheimer's disease (AD).
Methods
Using an magnetic resonance imaging (MRI)–based AD score ...based on clinical data from the Alzheimer's Disease Neuroimaging Initiative 1 (ADNI1) case‐control cohort, we investigated the associations between polysomnography‐based sleep macro‐architecture and AD‐related brain atrophy patterns in 712 pre‐symptomatic, healthy subjects from the population‐based Study of Health in Pomerania.
Results
We identified a robust inverse association between slow‐wave sleep and the AD marker (estimate: −0.019; 95% confidence interval: −0.03 to −0.0076; false discovery rate FDR = 0.0041), as well as with gray matter (GM) thicknesses in typical individual cortical AD‐signature regions. No effects were identified regarding rapid eye movement or non–rapid eye movement (NREM) stage 2 sleep, and NREM stage 1 was positively associated with GM thickness, mainly in the prefrontal cortical regions.
Discussion
There is a cross‐sectional relationship between AD‐related neurodegenerative patterns and the proportion of sleep spent in slow‐wave sleep.
Highlights • Subjective and objective sleep parameters are studied with respect to moon phases. • During full moon, several sleep parameters are impaired, especially among women. • Lunar phases may ...contribute to the complex regulation of sleep.
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