Sleep characteristics and parameters of bone turnover and strength in the adult population: results from the Study of Health in Pomerania-TREND.

Poor sleep quality or sleep deprivation may be related to decreased bone mineral density. We aimed to assess whether associations of sleep characteristics and bone turnover or strength are present in adults from the general population and whether these are independent of common risk factors such as sex, age, and obesity. A total of 1037 participants from the Study of Health in Pomerania-TREND underwent laboratory-based polysomnography and quantitative ultrasound measurements at the heel. Of these participants, 804 completed standardised questionnaires to assess daytime sleepiness, insomnia, and sleep quality. Serum concentrations of two bone turnover markers, intact amino-terminal propeptide of type 1 procollagen (P1NP) and carboxy-terminal telopeptide of type 1 collagen (CTX) were measured. Cross-sectional associations of polysomnography variables (total sleep time, sleep efficiency, time spent wake after sleep onset, oxygen desaturation index, apnea-hypopnea index, and obstructive sleep apnea [OSA]), as well as sleep questionnaire scores with the bone turnover markers and the ultrasound-based stiffness index were assessed in linear regression models. In adjusted models, higher insomnia scores and lower sleep quality scores were related to a higher bone turnover in women but not in men. However, associations between polysomnography variables or questionnaire scores and the stiffness index were absent. Our study provides limited evidence for relationships between sleep characteristics and bone turnover and strength independent of common risk factors for OSA and osteoporosis. Nevertheless, women reporting poor sleep or insomnia in combination with risk factors for osteoporosis might benefit from an evaluation of bone health.

Quality of life in patients with obstructive sleep apnea: Results from the study of health in Pomerania.

Obstructive sleep apnea is known to be an overall public health problem that, among other things, increases morbidity and mortality. Risk factors as well as symptoms of this multidimensional sleep-related breathing disorder negatively affect quality of life. With our study we aimed to expose the association between obstructive sleep apnea and quality of life in the population of Pomerania, Germany. We utilized data from the population-based Study of Health in Pomerania (SHIP). Information on health status and risk factors about 4420 participants (2275 women) were gathered within the cohort SHIP-TREND, of which 1209 (559 women) underwent an overnight polysomnography and completed sleep questionnaires. The quality of life of the participants was measured using the Short-Form 12 questionnaire. For our study, an ordinal regression analysis with age, sex, body mass index and the Short-Form 12 health survey as predictors for apnea-hypopnea index was computed. The potential factors affecting quality of life are different between physical and mental dimensions of quality of life. Significant effects were found regarding age, sex, body mass index and the Short-Form 12 Mental Component Score, but not the Physical Component Score.

Do brachycephaly and nose size predict the severity of obstructive sleep apnea (OSA)? A sample-based geometric morphometric analysis of craniofacial variation in relation to OSA syndrome and the role of confounding factors.

Obstructive sleep apnea is a common disorder that leads to sleep fragmentation and is potentially bidirectionally related to a variety of comorbidities, including an increased risk of heart failure and stroke. It is often considered a consequence of anatomical abnormalities, especially in the head and neck, but its pathophysiology is likely to be multifactorial in origin. With geometric morphometrics, and a large sample of adults from the Study for Health in Pomerania, we explore the association of craniofacial morphology to the apnea-hypopnea index used as an estimate of obstructive sleep apnea severity. We show that craniofacial size and asymmetry, an aspect of morphological variation seldom analysed in obstructive sleep apnea research, are both uncorrelated to apnea-hypopnea index. In contrast, as in previous analyses, we find evidence that brachycephaly and larger nasal proportions might be associated to obstructive sleep apnea severity. However, this correlational signal is weak and completely disappears when age-related shape variation is statistically controlled for. Our findings suggest that previous work might need to be re-evaluated, and urge researchers to take into account the role of confounders to avoid potentially spurious findings in association studies.

Socioeconomic factors do not predict sleep apnea in a population sample from Mecklenburg-Western Pomerania, Germany.

PURPOSE: Socioeconomic factors are known to modulate health. Concerning sleep apnea, influences of income, education, work, and living in a partnership are established. However, results differ between national and ethnic groups. Results also differ between various clinical studies and population-based approaches. The goal of our study was to determine if such factors can be verified in the population of Pomerania, Germany. METHODS: A subgroup from the participants of the population-based Study of Health in Pomerania volunteered for an overnight polysomnography. Their data were subjected to an ordinal regressions analysis with age, sex, body mass index (BMI), income, education, work, and life partner as predictors for the apnea-hypopnea index. RESULTS: Among the subgroup (N = 1209) from the population-based study (N = 4420), significant effects were found for age, sex, and BMI. There were no significant effects for any of the socioeconomic factors. CONCLUSION: Significant effects for well-established factors as age, sex, and BMI show that our study design has sufficient power to verify meaningful associations with sleep apnea. The lack of significant effects for the socioeconomic factors suggests their clinical irrelevance in the tested population.

Value of Cardiopulmonary Exercise Testing in the Prognosis Assessment of Chronic Obstructive Pulmonary Disease Patients: A Retrospective, Multicentre Cohort Study.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is one of the most common chronic diseases associated with high mortality. Previous studies suggested a prognostic role for peak oxygen uptake (VO2peak) assessed during cardiopulmonary exercise testing (CPET) in patients with COPD. However, most of these studies had small sample sizes or short follow-up periods, and despite their relevance, CPET parameters are not included in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) tool for assessment of severity. OBJECTIVES: We therefore aimed to assess the prognostic value of CPET parameters in a large cohort of outpatients with COPD. METHODS: In this retrospective, multicentre cohort study, medical records of patients with COPD who underwent CPET during 2004-2017 were reviewed and demographics, smoking habits, GOLD grade and category, exacerbation frequency, dyspnoea score, lung function measurements, and CPET parameters were documented. Relationships with survival were evaluated using Kaplan-Meier analysis, Cox regression, and receiver operating characteristic (ROC) curves. RESULTS: Of a total of 347 patients, 312 patients were included. Five-year and 10-year survival probability was 75% and 57%, respectively. VO2peak significantly predicted survival (hazard ratio: 0.886 [95% confidence interval: 0.830; 0.946]). The optimal VO2peak threshold for discrimination of 5-year survival was 14.6 mL/kg/min (area under ROC curve: 0.713). Five-year survival in patients with VO2peak <14.6 mL/kg/min versus ≥ 14.6 mL/kg/min was 60% versus 86% in GOLD categories A/B and 64% versus 90% in GOLD categories C/D. CONCLUSIONS: We confirm that VO2peak is a highly significant predictor of survival in COPD patients and recommend the incorporation of VO2peak into the assessment of COPD severity.

[Risk Stratification in Patients with Pulmonary Arterial Hypertension under Treatment - Results of Four German Centers]. / Risikoänderung bei Patienten mit Pulmonaler Arterieller Hypertonie unter medikamentöser Therapie ­ Ergebnisse aus vier deutschen Zentren.

Risk stratification plays an essential role in the management of patients with pulmonary arterial hypertension (PAH). According to the current European guidelines the expected 1-year risk of mortality for PAH patients can be categorized as low, intermediate, or high, based on clinical, non-invasive and hemodynamic data.Data from 131 patients with incident PAH (age 64 ±â€Š14) and frequent comorbidities (in 66.4 %) treated between 2016 and 2018 at 4 German PH centers were analyzed. At baseline, most patients were classified as intermediate risk (76 %), 13.8 % as high risk and only 9.9 % as low risk.During follow-up while on treatment after 12 ±â€Š3 months (range 9-16 months) 64.9 % were still classified as intermediate risk (76 %), 14.4 % as high risk and 20.7 % as low risk.Survival at 12 and 24 months was 96 % and 82 % in the intermediate risk group, while only 89 % and 51 % of the high risk patients were alive at these time points. In contrast, all patients in the low risk category were alive at 24 months.Despite the availability of various treatment options for patients with PAH even in specialized centers only a minority of patients can be stabilized in the low risk group associated with a good outcome.

Monotherapy in patients with pulmonary arterial hypertension at four German PH centres.

BACKGROUND: Although combination therapy is the gold standard for patients with pulmonary arterial hypertension (PAH), some of these patients are still being treated with monotherapy. METHODS: We conducted a retrospective analysis at four German PH centres to describe the prevalence and characteristics of patients receiving monotherapy. RESULTS: We identified 131 incident PAH patients, with a mean age of 64 ± 13.8 years and a varying prevalence of comorbidities, cardiovascular risk factors and targeted therapy. As in other studies, the extent of prescribed PAH therapy varied with age and coexisting diseases, and younger, so-called "typical" PAH patients were more commonly treated early with combination therapy (48% at 4-8 months). In contrast, patients with multiple comorbidities or cardiovascular risk factors were more often treated with monotherapy (69% at 4-8 months). Survival at 12 months was not significantly associated with the number of PAH drugs used (single, dual, triple therapy) and was not different between "atypical" and "typical" PAH patients (89% vs. 85%). CONCLUSION: Although "atypical" PAH patients with comorbidities or a more advanced age are less aggressively treated with respect to combination therapy, the outcome of monotherapy in these patients appears to be comparable to that of dual or triple therapy in "typical" PAH patients.

A Biased Diffusion Approach to Sleep Dynamics Reveals Neuronal Characteristics.

We propose a biased diffusion model of accumulated subthreshold voltage fluctuations in wake-promoting neurons to account for stochasticity in sleep dynamics and to explain the occurrence of brief arousals during sleep. Utilizing this model, we derive four neurophysiological parameters related to neuronal noise level, excitability threshold, deep-sleep threshold, and sleep inertia. We provide the first analytic expressions for these parameters, and we show that there is good agreement between empirical findings from sleep recordings and our model simulation results. Our work suggests that these four parameters can be of clinical importance because we find them to be significantly altered in elderly subjects and in children with autism.

Prevalence and association analysis of obstructive sleep apnea with gender and age differences - Results of SHIP-Trend.

Identification of obstructive sleep apnea and risk factors is important for reduction in symptoms and cardiovascular risk, and for improvement of quality of life. The population-based Study of Health in Pomerania investigated risk factors and clinical diseases in a general population of northeast Germany. Additional polysomnography was applied to measure sleep and respiration with the objective of assessing prevalence and risk factors of obstructive sleep apnea in a German cohort. One-thousand, two-hundred and eight people between 20 and 81 years old (54% men, median age 54 years) underwent overnight polysomnography. The estimated obstructive sleep apnea prevalence was 46% (59% men, 33% women) for an apnea-hypopnea index ≥5%, and 21% (30% men, 13% women) for an apnea-hypopnea index ≥ 15. The estimated obstructive sleep apnea syndrome prevalence (apnea-hypopnea index ≥5; Epworth Sleepiness Scale >10) was 6%. The prevalence of obstructive sleep apnea continuously increased with age for men and women with, however, later onset for women. Gender, age, body mass index, waist-to-hip ratio, snoring, alcohol consumption (for women only) and self-reported cardiovascular diseases were significantly positively associated with obstructive sleep apnea, whereas daytime sleepiness was not. Diabetes, hypertension and metabolic syndrome were positively associated with severe obstructive sleep apnea. The associations became non-significant after adjustment for body mass. Women exhibited stronger associations than men. The prevalence of obstructive sleep apnea was high, with almost half the population presenting some kind of obstructive sleep apnea. The continuous increase of obstructive sleep apnea with age challenges the current theory that mortality due to obstructive sleep apnea and cardiovascular co-morbidities affect obstructive sleep apnea prevalence at an advanced age. Also, gender differences regarding obstructive sleep apnea and associations are significant for recognizing obstructive sleep apnea mechanisms and therapy responsiveness.

Peripheral Artery Disease and Its Clinical Relevance in Patients with Chronic Obstructive Pulmonary Disease in the COPD and Systemic Consequences-Comorbidities Network Study.

RATIONALE: Knowledge about the prevalence of objectively assessed peripheral artery disease (PAD) and its clinical relevance in patients with chronic obstructive pulmonary disease (COPD) is scarce. OBJECTIVES: We aimed to: (1) assess the prevalence of PAD in COPD compared with distinct control groups; and (2) study the association between PAD and functional capacity as well as health status. METHODS: The ankle-brachial index was used to diagnose PAD (ankle-brachial index ≤ 0.9). The 6-minute-walk distance, health status (St. George's Respiratory Questionnaire), COPD Assessment Test, and EuroQol-5-Dimensions were assessed in patients enrolled in the German COPD and Systemic Consequences-Comorbidities Network cohort study. Control groups were derived from the Study of Health in Pomerania. MEASUREMENTS AND MAIN RESULTS: A total of 2,088 patients with COPD (61.1% male; mean [SD] age, 65.3 [8.2] years, GOLD (Global Initiative for Chronic Obstructive Lung Disease) stages I-IV: 9.4, 42.5, 37.5, and 10.5%, respectively) were included, of which 184 patients (8.8%; GOLD stage I-IV: 5.1, 7.4, 11.1, and 9.5%, respectively, vs. 5.9% in patients with GOLD stage 0 in the COPD and Systemic Consequences-Comorbidities Network) had PAD. In the Study of Health in Pomerania, PAD ranged from 1.8 to 4.2%. Patients with COPD with PAD had a significantly shorter 6-minute-walk distance (356 [108] vs. 422 [103] m, P < 0.001) and worse health status (St. George's Respiratory Questionnaire: 49.7 [20.1] vs. 42.7 [20.0] points, P < 0.001; COPD Assessment Test: 19.6 [7.4] vs. 17.9 [7.4] points, P = 0.004; EuroQol-5-Dimensions visual analog scale: 51.2 [19.0] vs. 57.2 [19.6], P < 0.001). Differences remained significant after correction for several confounders. CONCLUSIONS: In a large cohort of patients with COPD, 8.8% were diagnosed with PAD, which is higher than the prevalence in control subjects without COPD. PAD was associated with a clinically relevant reduction in functional capacity and health status.

Cardiopulmonary exercise testing and the 2022 definition of pulmonary hypertension.

Parameters of cardiopulmonary exercise testing significantly discriminate between healthy subjects and patients with pulmonary hypertension (PH), also according to the new 2022 definition of pulmonary hypertension (mean pulmonary arterial pressure mPAP > 20 mmHg). The cut-offs indicating on PH were peakVO2 ≤ 16.7 mL/min/kg (Youden-Index YI = 0.79), petCO2@AT ≤ 34 mmHg (YI = 0.67), and VE/VCO2@AT ≤ 30 (YI = 0.76).

Metabolic cost of unloading pedalling in different groups of patients with pulmonary hypertension and volunteers.

Recently, the parameter internal work (IW) has been introduced as change in oxygen uptake (VO2) between resting and unloading workload in cardiopulmonary exercise testing (CPET). The proportional IW (PIW) was defined as IW divided by VO2 at peak exercise. A second option is to calculate the PIW based on the workload [PIW (Watt)] by considering the aerobic efficiency. The aim of our study was to investigate whether IW and PIW differ between patients with and without pulmonary hypertension and healthy controls. Our study population consisted of 580 patients and 354 healthy controls derived from the Study of Health in Pomerania. The PIW was slightly lower in patients (14.2%) than in healthy controls (14.9%; p = 0.030), but the PIW (Watt) was higher in patients (18.0%) than in the healthy controls (15.9%; p = 0.001). Such a difference was also observed, when considering only the submaximal workload up to the VAT (19.8% in patients and 15.1% in healthy controls; p < 0.001). Since the PIW (Watt) values were higher in patients with pulmonary hypertension, this marker may serve as a useful CPET parameter in clinical practice. In contrast to most of the currently used CPET parameters, the PIW does not require a maximal workload for the patient. Further studies are needed to validate the prognostic significance of the PIW.

Periodontitis is related to lung volumes and airflow limitation: a cross-sectional study.

This study aimed to assess the potential association of periodontal diseases with lung volumes and airflow limitation in a general adult population. Based on a representative population sample of the Study of Health in Pomerania (SHIP), 1463 subjects aged 25-86 years were included. Periodontal status was assessed by clinical attachment loss (CAL), probing depth and number of missing teeth. Lung function was measured using spirometry, body plethysmography and diffusing capacity of the lung for carbon monoxide. Linear regression models using fractional polynomials were used to assess associations between periodontal disease and lung function. Fibrinogen and high-sensitivity C-reactive protein (hs-CRP) were evaluated as potential intermediate factors. After full adjustment for potential confounders mean CAL was significantly associated with variables of mobile dynamic and static lung volumes, airflow limitation and hyperinflation (p<0.05). Including fibrinogen and hs-CRP did not change coefficients of mean CAL; associations remained statistically significant. Mean CAL was not associated with total lung capacity and diffusing capacity of the lung for carbon monoxide. Associations were confirmed for mean probing depth, extent measures of CAL/probing depth and number of missing teeth. Periodontal disease was significantly associated with reduced lung volumes and airflow limitation in this general adult population sample. Systemic inflammation did not provide a mechanism linking both diseases.

Menopause Is Associated with Obstructive Sleep Apnea in a Population-Based Sample from Mecklenburg-Western Pomerania, Germany.

Objective: Menopause is associated with multiple health risks. In several studies, a higher incidence or a higher risk for obstructive sleep apnea (OSA) in post-menopausal than pre-menopausal women is reported. This study was designed to verify such a connection between menopause and OSA in a population-based sample. Methods: For a subsample (N = 1209) of the Study of Health in Pomerania (N = 4420), complete polysomnography data was available. Of these, 559 females completed a structured interview about their menstrual cycle. Splines and ordinal regression analysis were used to analyze the resulting data. Results: In the ordinal regression analysis, a significant association between the apnea-hypopnea index (AHI) and menopause indicated that post-menopausal women had a substantially higher risk of OSA. In accordance with previous studies, risk indicators such as body mass index (BMI), age, and the influence of hysterectomies or total oophorectomies were included in the model. Conclusions: Our results clearly confirmed the assumed connection between menopause and OSA. This is important because OSA is most often associated with male patients, and it warrants further research into the underlying mechanisms.

Acute COPD exacerbation treatment with noninvasive ventilation.

The establishment of a guideline for long-term noninvasive ventilation treatment (LTH-NIV) of acute hypercapnic exacerbations of chronic obstructive pulmonary disease (AECOPD) requiring acute ventilation has proven elusive. Most studies thus far have shown no mortality benefit of long-term noninvasive ventilation treatment. Using retrospective analysis of the data of our patients (n = 143) recruited from 2012 to 2019, we aimed to compare patients discharged with and without long-term noninvasive ventilation. The follow-up results showed no significant difference (p = 0.233) between the groups [LTH-NIV (n = 83); non-NIV (n = 60)] regarding readmission due to clinical worsening. However, the first- and second-year survival rates were 82% and 72%, respectively, in the LTH-NIV group and significantly different (p = 0.023) from 67 and 55% in the non-NIV group. The statistical models showed a significant mortality risk for the non-NIV group, with a hazard ratio (HR) of 2.82 (1.31; 6.03). To the best of our knowledge, this is the first study to demonstrate the mortality benefit of long-term NIV therapy for patients with AECOPD under real-world conditions.

Correlation of Hemodynamic and Respiratory Parameters in Invasive Cardiopulmonary Exercise Testing (iCPET).

Background: Invasive cardiopulmonary exercise testing (iCPET) is an integral part in the advanced diagnostic workup of pulmonary hypertension (PH). Our study evaluated the relation between hemodynamic and respiratory parameters at two different resting conditions and two defined low exercise levels with a close synchronization of measurements in a broad variety of dyspnea patients. Subjects and methods: We included 146 patients (median age 69 years, range 22 to 85 years, n = 72 female) with dyspnea of uncertain origin. Invasive hemodynamic and gas exchange parameters were measured at rest, 45° upright position, unloaded cycling, 25 and 50 W exercise. All measurements were performed in a single RHC procedure. Results: Oxygen uptake (VO2/body mass) correlated significantly with cardiac index (all p ≤ 0.002) at every resting and exercise level and with every method of cardiac output measurement (thermodilution, method of Fick). Mean pulmonary arterial pressure (PAPmean) correlated with all respiratory parameters (respiratory rate, partial end-tidal pressures of oxygen and carbon dioxide [petCO2 and petO2], ventilation/carbon dioxide resp. oxygen ratio [VE/VCO2, VE/VO2], and minute ventilation [VE], all p < 0.05). These correlations improved with increasing exercise levels from rest via unloaded cycling to 25 W. There was no correlation with right atrial or pulmonary arterial wedge pressure. Summary: In dyspnea patients of different etiologies, the cardiac index is closely linked to VO2 at every level of rest and submaximal exercise. PAPmean is the only pressure that correlates with different respiratory parameters, but this correlation is highly significant and stable at rest, unloaded cycling and at 25 W.

Comparison between thermodilution and Fick methods for resting and exercise-induced cardiac output measurement in patients with chronic dyspnea.

Studies comparing thermodilution (TD) and the direct Fick method (dFM) for cardiac output (CO) measurement are rare. We compared CO measurements between TD (2-5 cold water injections), the dFM, and indirect Fick method (iFM) at rest and during exercise, and assessed the effect of averaging different numbers of TD measurements during exercise. This retrospective study included 300 patients (52.3% women, mean age 66 ± 11 years) having pulmonary hypertension (76.0%) or unexplained dyspnea. Invasive hemodynamic and gas exchange parameters were measured at rest (supine; n = 300) and during unloaded cycling (semi-supine; n = 275) and 25-W exercise (semi-supine; n = 240). All three methods showed significant differences in CO measurement (ΔCO) at rest (p ≤ 0.001; ΔCO > 1 L/min: 45.0% [iFM vs. dFM], 42.0% [iFM vs. TD], and 45.7% [TD vs. dFM]). ΔCO (TD vs. dFM) was significant during unloaded cycling (p < 0.001; ΔCO > 1 L/min: 56.6%) but not during 25-W exercise (p = 0.137; ΔCO > 1 L/min: 52.8%). ΔCO (TD vs. dFM) during 25-W exercise was significant when using one or two (p ≤ 0.01) but not three (p = 0.06) TD measurements. Mean ΔCO (TD [≥3 measurements] vs. dFM) was -0.43 ± 1.98 and -0.06 ± 2.29 L/min during unloaded and 25-W exercise, respectively. Thus, TD and dFM CO measurements are comparable during 25-W exercise (averaging ≥3 TD measurements), but not during unloaded cycling or at rest. Individual ΔCOs vary substantially and require critical interpretation to avoid CO misclassification.

Peripheral endothelial dysfunction is associated with gas exchange inefficiency in smokers.

AIMS: To assess the cross-sectional association between exercise capacity, gas exchange efficiency and endothelial function, as measured by flow-mediated dilation (FMD) and nitroglycerin-mediated dilation (NMD) of the brachial artery, in a large-scale population-based survey. METHODS: The study population was comprised of 1416 volunteers 25 to 85 years old. Oxygen uptake at anaerobic threshold (VO2@AT), peak exercise (peakVO2) and ventilatory efficiency (VE vs. VCO2 slope and VE/VCO2@AT) were assessed on a breath-by-breath basis during incremental symptom-limited cardiopulmonary exercise. FMD and NMD measurements at rest were performed using standardised ultrasound techniques. RESULTS: Multivariable logistic regression analyses revealed a significant association between FMD and ventilatory efficiency in current smokers but not in ex-smokers or non-smokers. There was no association between FMD and VO2@AT or peak VO2. In current smokers, for each one millimetre decrement in FMD, VE/VCO2@AT improved by -3.6 (95% CI -6.8, -0.4) in the overall population [VE vs. VCO2 slope -3.9 (-7.1, -0.6)]. These results remained robust after adjusting for all major influencing factors. Neither exercise capacity nor ventilatory efficiency was significantly associated with NMD. CONCLUSION: In current smokers, FMD is significantly associated with ventilatory efficiency. This result may be interpreted as a potential clinical link between smoking and early pulmonary vasculopathy due to smoking.

A 10-year follow-up of key gas exchange exercise parameters in a general population: results of the Study of Health in Pomerania.

BACKGROUND: Cardiopulmonary exercise testing (CPET) is a frequently used method for the evaluation of the cardiorespiratory system. The prognostic relevance of the measured parameters is commonly known. Longitudinal data on cardiorespiratory fitness in a large sample of well-characterised healthy volunteers are rare in the literature. METHODS: CPET data of 615 healthy individuals who voluntarily took part in the Study of Health in Pomerania (SHIP) at three different measurement times were analysed. The median observation time was 10.5 years. The age range was 25-85 years. RESULTS: Over the observed timeframe and with increasing age, a decline in maximum power, peak oxygen uptake (V'O2peak) and oxygen uptake at anaerobic threshold (V'O2 @AT) was detectable. This decline was aggravated with increasing age. For the minute ventilation (V'E)/carbon dioxide production (V'CO2 ) slope, an increase was measured in individuals aged ≥50 years only. CONCLUSION: The present study affirms the decrease in aerobic capacity with increasing age in a selected, well-characterised, healthy study sample, which seems to be less pronounced in females.

Associations between sleep apnea and advanced brain aging in a large-scale population study.

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.