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Abstract Previous studies identified individual-level socioeconomic factors as key determinants of cognitive health. This study investigated the effect of area-based socioeconomic deprivation on cognitive outcomes in midlife to early late-life New Zealanders without cognitive impairment at baseline. Data stemmed from a subsample of the New Zealand Health, Work and Retirement Study, a cohort study on ageing, who completed face-to-face interviews and were reassessed two years later. Cognitive functioning was measured using Addenbrooke’s Cognitive Examination–Revised, adapted for culturally acceptable use in Aotearoa New Zealand. Area-based socioeconomic deprivation was assessed using the New Zealand Deprivation Index (NZDep2006). Linear mixed-effects models analysed the association between area-based socioeconomic deprivation and cognitive outcomes. The analysis included 783 participants without cognitive impairment at baseline (54.7% female, mean age 62.7 years, 25.0% Māori, the Indigenous people of Aotearoa New Zealand). There was an association between higher area-based socioeconomic deprivation and lower cognitive functioning (B = -0.08, 95%CI: -0.15;-0.01; p = .050) and cognitive decline (B = -0.12, 95%CI: -0.20;-0.04, p = .013) over two years, while controlling for covariates. The findings emphasise the importance of considering neighbourhood characteristics and broader socioeconomic factors in strategies aimed at mitigating cognitive health disparities and reducing the impact of dementia in disadvantaged communities.

Abstract Substantial evidence indicates a huge potential for risk reduction of cognitive decline and dementia based on modifiable health and lifestyle factors. To maximize the chances for risk reduction, it is useful to investigate associations of social determinants and lifestyle for brain health. We computed the “LIfestyle for BRAin health” (LIBRA) score for baseline participants of the Leipzig Research Centre for Civilization Diseases (LIFE) Adult Study, a population-based urban cohort in Germany. LIBRA predicts dementia in midlife and early late life populations, comprising 12 modifiable risk factors (heart disease, kidney disease, diabetes, obesity, hypertension, hypercholesterolemia, alcohol consumption, smoking, physical inactivity, diet, depression, cognitive inactivity). Associations of social determinants (living situation, marital status, social isolation, education, net equivalence income, occupational status, socioeconomic status/SES, employment) with LIBRA were inspected using age- and sex-adjusted multivariable linear regression analysis. Z-standardization and sampling weights were applied. Participants (n = 6203) were M = 57.4 (SD = 10.6, range 40–79) years old and without dementia, 53.0% were women. Except for marital status, all considered social determinants were significantly associated with LIBRA. Beta coefficients for the association with higher LIBRA scores were most pronounced for low SES (β = 0.80, 95% CI [0.72–0.88]; p

While many structural and biochemical changes in the brain have previously been associated with older age, findings concerning functional properties of neuronal networks, as reflected in their electrophysiological signatures, remain rather controversial. These discrepancies might arise due to several reasons, including diverse factors determining general spectral slowing in the alpha frequency range as well as amplitude mixing between the rhythmic and non-rhythmic parameters. We used a large dataset (N = 1703, mean age 70) to comprehensively investigate age-related alterations in multiple EEG biomarkers taking into account rhythmic and non-rhythmic activity and their individual contributions to cognitive performance. While we found strong evidence for an individual alpha peak frequency (IAF) decline in older age, we did not observe a significant relationship between theta power and age while controlling for IAF. Not only did IAF decline with age, but it was also positively associated with interference resolution in a working memory task primarily in the right and left temporal lobes suggesting its functional role in information sampling. Critically, we did not detect a significant relationship between alpha power and age when controlling for the 1/f spectral slope, while the latter one showed age-related alterations. These findings thus suggest that the entanglement of IAF slowing and power in the theta frequency range, as well as 1/f slope and alpha power measures, might explain inconsistencies reported previously in the literature. Finally, despite the absence of age-related alterations, alpha power was negatively associated with the speed of processing in the right frontal lobe while 1/f slope showed no consistent relationship to cognitive performance. Our results thus demonstrate that multiple electrophysiological features, as well as their interplay, should be considered for the comprehensive assessment of association between age, neuronal activity, and cognitive performance.

Abstract Objectives Growing evidence suggests a protective effect of high mental demands at work on cognitive function in later life. However, evidence on corresponding associations in older adults at increased risk for dementia is currently lacking. This study investigates the association between mental demands at work and cognitive functioning in the population of the AgeWell.de-trial. Methods Cross-sectional investigation of the association between global cognitive functioning (Montreal Cognitive Assessment) and mental demands at work in older individuals at increased risk for dementia (Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE)score ≥ 9; n = 941, age: 60–77 years). Occupational information was matched to Occupational Information Network (O*NET)-descriptors. Associations between cognitive function and O*NET-indices executive, verbal and novelty were investigated using generalized linear models. Results Higher values of index verbal (b = .69, p = .002) were associated with better cognitive function when adjusting for covariates. No association was observed for indices executive (b = .37, p = .062) and novelty (b = .45, p = .119). Higher education, younger age, and employment were linked to better cognitive function, while preexisting medical conditions did not change the associations. Higher levels of depressive symptomatology were associated with worse cognitive function. Conclusions Higher levels of verbal demands at work were associated with better cognitive function for older adults with increased dementia risk. This suggests an advantage for older persons in jobs with high mental demands even after retirement and despite prevalent risk factors. Longitudinal studies are warranted to confirm these results and evaluate the potential of workplaces to prevent cognitive decline through increased mental demands.

PurposeSocial isolation is considered a risk factor for dementia. However, less is known about social isolation and dementia with respect to competing risk of death, particularly in the oldest-old, who are at highest risk for social isolation, dementia and mortality. Therefore, we aimed to examine these associations in a sample of oldest-old individuals.MethodsAnalyses were based on follow-up (FU) 5–9 of the longitudinal German study AgeCoDe/AgeQualiDe. Social isolation was assessed using the short form of the Lubben Social Network Scale (LSNS-6), with a score ≤ 12 indicating social isolation. Structured interviews were used to identify dementia cases. Competing risk analysis based on the Fine-Gray model was conducted to test the association between social isolation and incident dementia.ResultsExcluding participants with prevalent dementia, n = 1,161 individuals were included. Their mean age was 86.6 (SD = 3.1) years and 67.0% were female. The prevalence of social isolation was 34.7% at FU 5, 9.7% developed dementia and 36.0% died during a mean FU time of 4.3 (SD = 0.4) years. Adjusting for covariates and cumulative mortality risk, social isolation was not significantly associated with incident dementia; neither in the total sample (sHR: 1.07, 95%CI 0.65-1.76, p = 0.80), nor if stratified by sex (men: sHR: 0.71, 95%CI 0.28-1.83, p = 0.48; women: sHR: 1.39, 95%CI 0.77-2.51, p = 0.27).ConclusionIn contrast to the findings of previous studies, we did not find an association between social isolation and incident dementia in the oldest-old. However, our analysis took into account the competing risk of death and the FU period was rather short. Future studies, especially with longer FU periods and more comprehensive assessment of qualitative social network characteristics (e.g., loneliness and satisfaction with social relationships) may be useful for clarification.

Abstract Background Subjective cognitive decline (SCD) is recognized as a risk stage for Alzheimer’s disease (AD) and other dementias, but its prevalence is not well known. We aimed to use uniform criteria to better estimate SCD prevalence across international cohorts. Methods We combined individual participant data for 16 cohorts from 15 countries (members of the COSMIC consortium) and used qualitative and quantitative (Item Response Theory/IRT) harmonization techniques to estimate SCD prevalence. Results The sample comprised 39,387 cognitively unimpaired individuals above age 60. The prevalence of SCD across studies was around one quarter with both qualitative harmonization/QH (23.8%, 95%CI = 23.3–24.4%) and IRT (25.6%, 95%CI = 25.1–26.1%); however, prevalence estimates varied largely between studies (QH 6.1%, 95%CI = 5.1–7.0%, to 52.7%, 95%CI = 47.4–58.0%; IRT: 7.8%, 95%CI = 6.8–8.9%, to 52.7%, 95%CI = 47.4–58.0%). Across studies, SCD prevalence was higher in men than women, in lower levels of education, in Asian and Black African people compared to White people, in lower- and middle-income countries compared to high-income countries, and in studies conducted in later decades. Conclusions SCD is frequent in old age. Having a quarter of older individuals with SCD warrants further investigation of its significance, as a risk stage for AD and other dementias, and of ways to help individuals with SCD who seek medical advice. Moreover, a standardized instrument to measure SCD is needed to overcome the measurement variability currently dominant in the field.

Background: The high prevalence of mental disorders related to posttraumatic stress among Syrian refugees is often in contrast with their low utilization of mental health care in the host countries. Mental health self-stigma, i.e., internalized stigma of having a mental disorder, could prevent individuals from seeking mental health care. Therefore, we aimed to provide evidence on different aspects of mental health self-stigmatization among adult Syrian refugees with posttraumatic stress symptoms residing in Germany. Moreover, we investigated associations with sociodemographic and psychopathological variables in order to identify those at higher risk of self-stigmatization.Material and Methods: Overall, 133 participants with mild to moderate posttraumatic stress symptoms were recruited in the metropolitan areas of Leipzig, Dresden and Halle, Germany, using a multimodal approach. Mental health self-stigma was assessed using the Self-Stigma of Mental Illness Scale – Short Form (SSMIS-SF), consisting of four subscales (Stereotype awareness, Stereotype agreement, Application to self , Harm to self-esteem), each scoring from 5 (low) to 45 (high) points. Linear regression analysis was used to test associations of sociodemographic and psychopathological variables with self-stigma subscales.Results: On average, self-stigma ratings ranged from 16.5 (SD = 6.6) points on Application to self to 28.3 (SD = 7.5) points on Stereotype awareness. Results showed higher scores on Application to self for individuals who were younger (t = 2.65, p = 0.009) and single (F = 5.70, p = 0.004). Regression analyses yielded statistically significant associations between having multiple comorbidities and a higher Application to self stigma (β = 0.18, p = 0.044), controlling for sociodemographic covariates.Discussion: Mental health self-stigma was increased among Syrian refugees in Germany. Correlates of increased self-stigma could inform efforts to improve access to mental health care among Syrian refugees with mental ill-health. Longitudinal studies following an intersectional approach by concurrently examining multiple forms of public and internalized stigma could provide helpful insights for developing tailored stigma reduction efforts in this context.

Abstract Background In the absence of treatment options, the WHO emphasizes the identification of effective prevention strategies as a key element to counteract the dementia epidemic. Regarding the complex nature of dementia, trials simultaneously targeting multiple risk factors should be particularly effective for prevention. So far, however, only few such multi-component trials have been launched, but yielding promising results. In Germany, comparable initiatives are lacking, and translation of these complex interventions into routine care was not yet done. Therefore, AgeWell.de will be conducted as the first multi-component prevention trial in Germany which is closely linked to the primary care setting. Methods AgeWell.de will be designed as a multi-centric, cluster-randomized controlled multi-component prevention trial. Participants will be older community-dwelling general practitioner (GP) patients (60–77 years; n = 1,152) with increased dementia risk according to CAIDE (Cardiovascular Risk Factors, Aging, and Incidence of Dementia) Dementia Risk Score. Recruitment will take place at 5 study sites across Germany. GP practices will be randomized to either intervention A (advanced) or B (basic). GPs will be blinded to their respective group assignment, as will be the statistician conducting the randomization. The multi-component intervention (A) includes nutritional counseling, physical activity, cognitive training, optimization of medication, management of vascular risk factors, social activity, and, if necessary, further specific interventions targeting grief and depression. Intervention B includes general health advice on the intervention components and GP treatment as usual. We hypothesize that over the 2-year follow-up period the intervention group A will benefit significantly from the intervention program in terms of preserved cognitive function/delayed cognitive decline (primary outcome), and other relevant (secondary) outcomes (e.g. quality of life, social activities, depressive symptomatology, cost-effectiveness). Discussion AgeWell.de will be the first multi-component trial targeting risk of cognitive decline in older adults in Germany. Compared to previous trials, AgeWell.de covers an even broader set of interventions suggested to be beneficial for the intended outcomes. The findings will add substantial knowledge on modifiable lifestyle factors to prevent or delay cognitive decline. Trial registration German Clinical Trials Register (reference number: DRKS00013555).

Background: Increasingly more very old people are active drivers. Sensory, motor and cognitive limitations, and medication can increase safety risks. Timely attention to driving safety in the patient–doctor relationship can promote patient-centred solutions. Aim: To explore the following questions: do GPs know which patients drive a car? Is fitness to drive addressed with patients? Design & setting: Cross-sectional data from patient interviews and GP survey in the ninth follow-up phase of a prospective primary care cohort (the German Study on Ageing, Cognition and Dementia in Primary Care Patients (AgeCoDe) and the Study on Needs, Health Service Use, Costs and Health-Related Quality of Life in a large sample of ‘oldest-old’ primary care patients (≥85 years; AgeQualiDe)) . Method: The sample consisted of patients in the age group ≥85 years and their GPs. Independent reports were gathered on driving activity from the GP and the patient, and information was gained from GPs on whether driving ability was discussed with the patient. Statistical analyses included validity parameters and bivariate characterisation of subgroups (non-parametric significance tests, effect size). Results: Self-reports of 553 patients were available (69.5% female; mean age 90.5 years; 15.9% drive a car). For 427 patients, GP data were also available: GPs recognised 67.1% correctly as drivers and 94.9% as non-drivers. GPs said that they had discussed fitness to drive with 32.1% of potentially driving patients. Among drivers who were not recognised and with whom driving had not been discussed, there were more patients with a low educational level. Conclusion: The GP’s assessment of driving activity among very old patients showed moderate sensitivity and good specificity. Driving ability was seldom discussed. Asking an appropriate question during assessment could increase GPs’ awareness of older patients’ automobility.

Syria has been the main country of citizenship of refugees in Germany since 2013. Syrians face numerous human rights violations in their country that can be accompanied by the experience of potentially traumatic events, loss and displacement. Along the migration process, refugees are exposed to various factors that can have an impact on mental health. The aim of this study is to investigate sociodemographic, war- and flight-related as well as post-migration factors as predictors of posttraumatic stress, depression, somatization and anxiety in Syrian refugees with posttraumatic stress symptoms based in Germany. Data were based on the baseline sample of the “Sanadak” randomized-controlled trial. A total of 133 adult Syrian refugees participated in the study. A questionnaire covered sociodemographic and flight-related questions as well as standardized instruments for symptoms of PTSD (PDS-5), depression (PHQ-9), somatization (PHQ-15), anxiety (GAD-7), generalized self-efficacy (GSE), religiousness (Z-Scale), social support (ESSI) and mental health stigma (SSMIS-SF). Linear regression models were executed to predict mental health outcomes. Sociodemographic predictors (i.e., female sex, higher education) and flight-related predicting factors (i.e., variability of traumatic events) have a negative impact on mental health in Syrian refugees with posttraumatic stress symptoms in Germany. Mental health stigma predicts worse mental health outcomes. Post-migration factors have a major impact on mental health, such as low income, lack of social support, low life satisfaction or a strongly felt connection to Syria. Somatization is an important manifestation of mental distress in Syrian refugees with posttraumatic stress symptoms. Our study showed a range of factors predicting the mental health of Syrian refugees with posttraumatic stress symptoms. Measures to foster mental health could be securing financial security, promoting gender equality and tailored psychosocial programs addressing mental health stigma, loss and social support networks.

Abstract Introduction The coronavirus disease‐19 (COVID‐19) pandemic presents challenges to the conduct of randomized clinical trials of lifestyle interventions. Methods World‐Wide FINGERS is an international network of clinical trials to assess the impact of multidomain lifestyle intervention on cognitive decline in at‐risk adults. Individual trials are tailoring successful approaches from the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) to local cultures and environments. The network convened a forum for researchers to discuss statistical design and analysis issues they faced during the pandemic. We report on experiences of three trials that, at various stages of conduct, altered designs and analysis plans to navigate these issues. We provide recommendations for future trials to consider as they develop and launch behavioral intervention trials. Results The pandemic led researchers to change recruitment plans, interrupt timelines for assessments and intervention delivery, and move to remote intervention and assessment protocols. The necessity of these changes add emphasis to the importance, in study design and analysis, of intention to treat approaches, flexibility, within‐site stratification, interim power projections, and sensitivity analyses. Discussion Robust approaches to study design and analysis are critical to negotiate issues related to the intervention. The world‐wide network of similarly oriented clinical trials will allow us to evaluate the effectiveness of responses to the pandemic across cultures, local environments, and phases of the pandemic.

Objective: To investigate which factors are associated with the willingness to pay (WTP) for health insurance.Methods: The analysis (n = 1,248 individuals) is based on data of a large population-based study—the Health Study of the Leipzig Research Centre for Civilization Diseases (LIFE-Adult-Study). With regard to WTP for health insurance, a contingent valuation method with a payment card was used. Several explanatory variables were included. For example, personality factors (in terms of agreeableness, conscientiousness, extraversion, neuroticism, and openness to experience) were assessed using the NEO-16 Adjective Measure.Results: Average WTP for health insurance per month equaled about €240 which corresponds to ~14% of household net equivalent income. Multiple regressions showed that an increased WTP was associated with lower age (β = −1.7, p < 0.001), higher (log) household net equivalent income (β = 153.6, p < 0.001), higher social support (β = 2.0, p < 0.05), and private health insurance (β = 131.1, p < 0.001). Furthermore, an increased WTP for health insurance was associated with higher openness to experience (β = 10.1, p < 0.05), whereas it was not associated with agreeableness, conscientiousness, extraversion, and neuroticism.Conclusion: The quite large amount of average WTP for health insurance may suggest that individuals accept current contributions to health insurances and would probably accept higher contributions. While previous studies mainly focused on individuals in late life, we identified a link between socioeconomic, health-related factors, and personality factors (in terms of openness to experience) and WTP in the general adult population.

ObjectivesSocial isolation is increasing in aging societies and several studies have shown a relation with worse cognition in old age. However, less is known about the association in the oldest-old (85+); the group that is at highest risk for both social isolation and dementia.MethodsAnalyses were based on follow-up 5 to 9 of the longitudinal German study on aging, cognition, and dementia in primary care patients (AgeCoDe) and the study on needs, health service use, costs, and health-related quality of life in a large sample of oldest-old primary care patients (AgeQualiDe), a multi-center population-based prospective cohort study. Measurements included the Lubben Social Network Scale (LSNS-6), with a score below 12 indicating social isolation, as well as the Mini-Mental Status Examination (MMSE) as an indicator of cognitive function.ResultsDementia-free study participants (n = 942) were M = 86.4 (SD = 3.0) years old at observation onset, 68.2% were women. One third (32.3%) of them were socially isolated. Adjusted linear hybrid mixed effects models revealed significantly lower cognitive function in individuals with smaller social networks (β = 0.5, 95% CI = 0.3–0.7, p < .001). Moreover, changes in an individual’s social network size were significantly associated with cognitive changes over time (β = 0.2, 95% CI = 0.1–0.4, p = .003), indicating worse cognitive function with shrinking social networks.ConclusionSocial isolation is highly prevalent among oldest-old individuals, being a risk factor for decreases in cognitive function. Consequently, it is important to maintain a socially active lifestyle into very old age. Likewise, this calls for effective ways to prevent social isolation.

Abstract Background The prevalence of pain is very common in the oldest age group. Managing pain successfully is a key topic in primary care, especially within the ageing population. Different care settings might have an impact on the prevalence of pain and everyday life. Methods Participants from the German longitudinal cohort study on Needs, Health Service Use, Costs and Health-related Quality of Life in a large Sample of Oldest-old Primary Care Patients (85+) (AgeQualiDe) were asked to rate their severity of pain as well as the impairment with daily activities. Besides gender, age, education, BMI and use of analgesics we focused on the current housing situation and on cognitive state. Associations of the dependent measures were tested using four ordinal logistic regression models. Model 1 and 4 consisted of the overall sample, model 2 and 3 were divided according to no cognitive impairment (NCI) and mild cognitive impairment (MCI). Results Results show a decline in pain at very old age but nonetheless a high prevalence among the 85+ year olds. Sixty-three per cent of the participants report mild to severe pain and 69% of the participants mild to extreme impairment due to pain with daily activities. Use of analgesics, depression and living at home with care support are significantly associated with higher and male gender with lower pain ratings. Conclusions Sufficient pain management among the oldest age group is inevitable. Outpatient care settings are at risk of overlooking pain. Therefore focus should be set on pain management in these settings.

Obesity is a risk factor for cognitive decline and gray matter volume loss in aging. Studies have shown that different metabolic factors, e.g., dysregulated glucose metabolism and systemic inflammation, might mediate this association. Yet, even though these risk factors tend to co-occur, they have mostly been investigated separately, making it difficult to establish their joint contribution to gray matter volume structure in aging. Here, we therefore aimed to determine a metabolic profile of obesity that takes into account different anthropometric and metabolic measures to explain differences in gray matter volume in aging. We included 748 elderly, cognitively healthy participants (age range: 60 – 79 years, BMI range: 17 – 42 kg/m2) of the LIFE-Adult Study. All participants had complete information on body mass index, waist-to-hip ratio, glycated hemoglobin, total blood cholesterol, high-density lipoprotein, interleukin-6, C-reactive protein, adiponectin and leptin. Voxelwise gray matter volume was extracted from T1-weighted images acquired on a 3T Siemens MRI scanner. We used partial least squares correlation to extract latent variables with maximal covariance between anthropometric, metabolic and gray matter volume and applied permutation/bootstrapping and cross-validation to test significance and reliability of the result. We further explored the association of the latent variables with cognitive performance. Permutation tests and cross-validation indicated that the first pair of latent variables was significant and reliable. The metabolic profile was driven by negative contributions from body mass index, waist-to-hip ratio, glycated hemoglobin, C-reactive protein and leptin and a positive contribution from adiponectin. It positively covaried with gray matter volume in temporal, frontal and occipital lobe as well as subcortical regions and cerebellum. This result shows that a metabolic profile characterized by high body fat, visceral adiposity and systemic inflammation is associated with reduced gray matter volume and potentially reduced executive function in older adults. We observed the highest contributions for body weight and fat mass, which indicates that factors underlying sustained energy imbalance, like sedentary lifestyle or intake of energy-dense food, might be important determinants of gray matter structure in aging.

Background: Anxiety in adults is a common mental health problem. However, studies on anxiety in the oldest-old are lacking. We sought to identify the age- and gender-specific prevalence of anxiety symptoms in a large sample of general practice patients. Furthermore, we investigated relevant associations of anxiety specifically with respect to recent experience of loss.Methods: Based on the German Study on Ageing, Cognition and Dementia in general practice patients, a sample of 897 patients aged 82 years and older was assessed. Anxiety was assessed using the short form of the Geriatric Anxiety Inventory (GAI-SF). For the assessment of loss, patients were asked whether there were cases of death in their closer social environment since the last assessment. Descriptive and logistic regression analyses were run.Results: Of the oldest-old individuals (aged 82+ years, mean age: 86.8), 14.5% (95% CI 12.4–16.8) suffered from anxiety symptoms. Highest prevalence rates were found for 82- to 85-year-old women (17.2%, 95% CI 12.6–22.1) and for 86- to 90-year-old patients (both sexes) in general (15.9%, 95% CI 12.6–19.2). Older individuals who experienced cases of death in their close social environment within the last 18 months had almost twice the odds [odds ratio (OR) 1.91, 95% confidence interval (CI) 1.15–3.17] of reporting anxiety compared to those without a recent loss. As expected, depression and impaired cognitive status were associated with the presence of anxiety symptoms. No relation was found between social network, gender, age, frailty, or physical illness and anxiety in regression analysis.Conclusions: This study provides for the first time age- and gender-specific prevalence rates of anxiety symptoms and associated risk factors among a large population-based sample of oldest-old primary care attenders. Anxiety is highly prevalent in individuals aged 82 years and older. Depression, impaired cognitive status, and recent experience of loss are associated with late-life anxiety. Our findings support the idea that recent experience of loss should be taken seriously in the context of clinical practice with respect to diagnosing and treating anxiety in old age.

In rats decreased bioavailability of nitric oxide induces oxidative stress and right heart failure. Oxidative stress can activate matrix metalloproteinase-2 (MMP2). We addressed the question whether increasing oxidative defense by administration of the SOD mimetic Tempol or direct inhibition of MMP2 activity by SB-3CT mitigates right heart failure. Rats received l-NAME for four weeks and during week three and four treatment groups received either Tempol or SB-3CT in addition. After four weeks heart function was analyzed by echocardiography, organ weights and expression of NPPB and COL1A1 were analyzed, oxidative stress was monitored by DHE-staining and MMP2 activity was quantified by proteolytic auto-activation, zymography, and troponin I degradation. l-NAME induced oxidative stress and MMP2 activity stronger in the right ventricle than in the left ventricle. Troponin I, a MMP2 substrate, was degraded in right ventricles. Tempol reduced oxidative stress and preferentially affected the expression of fibrotic genes (i.e. COL1A1) and fibrosis. Tempol and SB-3CT mitigated right but not left ventricular hypertrophy. Neither SB-3CT nor Tempol alone strongly improved right ventricular function. In conclusion, both MMP2 activity and oxidative stress contribute to right ventricular failure but neither is MMP2 activation linked to oxidative stress nor does oxidative stress and MMP2 activity have common targets.

Abstract Aims The conditions of hypoxia are suggested to induce permanent atrial fibrillation (AF). The regulation of COX4I2 and COX4I1 depends on oxygen availability in tissues. A role of COX4I2 in the myocardium of AF patients is supposed for pathogenesis of AF and subsequent alterations in the electron transfer chain (ETC) under hypoxia. Methods and results In vitro, influence of hypoxia on HeLa 53 cells was studied and elevated parts of COX 4I2 were confirmed. Myocardial biopsies were taken ex vivo from the patients' Right Atria with SR (n = 31) and AF (n = 11), respectively. RT‐ PCR for mRNA expresson, mitochondrial respiration by polarography and the protein content of cytochrome c oxidase (CytOx) subunit 4I1 and CytOx subunit 4I2 by ELISA were studied. Clinical data were correlated to the findings of gene expressions in parallel. Patients with permanent AF had a change in isoform 4I2/4I1 expression along with a decrease of isoform COX 4I1 expression. The 4I2/4I1 ratio of mRNA expression was increased from 0.630 to 1.058 in comparison. However, the protein content of CytOx subunit 4 was much lower in the AF group, whereas the respiration/units enzyme activity in both groups remained the same. Conclusions This study describes a possible molecular correlate for the development of AF. Due to the known functional significance of COX 4I2, mitochondrial dysfunction can be assumed as a part of the pathogenesis of AF.