Sarkopenie: Untersuchungen zu Prävalenz, Assoziation mit metabolischen und funktionellen Parametern sowie potentiellen therapeutischen Ansätzen im Rahmen der Berliner Altersstudie II (BASE-II)

Die Sarkopenie, das zentrale Thema dieser Arbeit, bezeichnet einen fortschreitenden und generalisierten Prozess eines zunehmenden Verlustes an Muskelmasse, Muskelkraft und muskulärer Funktion, welcher ab einem bestimmten Ausmaß auch zu negativen Folgen wie erhöhter Sturzhäufigkeit und funktionellen Einbußen führen kann. Die Sarkopenie gilt als wesentlich mit dem Alterungsprozess und den damit einhergehenden Veränderungen in der Muskulatur assoziiert. Der Schwerpunkt dieser Arbeit lag auf der Bestimmung der Prävalenz der Sarkopenie gemäß den zum Zeitpunkt der Untersuchungen empfohlenen diagnostischen Kriterien und der Analyse von Zusammenhängen zwischen Sarkopenie einerseits und möglichen Ursachen sowie auch Folgen der Sarkopenie andererseits. Ergänzt wurde dieser Schwerpunkt durch methodische Fragestellungen in Hinblick auf die diagnostischen Kriterien und Überlegungen hinsichtlich möglicher therapeutischer Optionen. In den vorgestellten Originalarbeiten konnte gezeigt werden, dass auch bei noch vergleichsweise gesunden älteren Menschen eine als relevant hoch einzuschätzende Prävalenz der Sarkopenie vorliegen kann. Es zeigte sich dabei auch, dass methodische Aspekte wie die Verwendung unterschiedlicher Parameter der Muskelmasse die Erhebung der Sarkopenieprävalenz stark beeinflussen können. Ferner waren signifikante Unterschiede zwischen zwei dieser untersuchten Parameter zu beobachten was deren Assoziation zu Pre-Frailty/Frailty und zu selbstberichteten Limitationen der physischen Performance und damit potentiellen Folgen der Sarkopenie angeht. In weiteren Analysen konnte gezeigt werden, dass ein Diabetes mellitus Typ 2 mit Sarkopenie assoziiert ist und eine niedrige Muskelmasse mit einer ausgeprägteren Insulinresistenz einherzugehen scheint, wobei hier die Kausalität aufgrund der Limitation querschnittlicher Analysen vorerst unklar bleibt. In weiteren Analysen ergaben sich zudem Hinweise, dass Störungen der thyreoidalen Funktion eine Sarkopenie begünstigen könnten. Dieser mögliche Effekt scheint sich jedoch insbesondere in Hinblick auf eine hypothyreote Stoffwechsellage in höherem Alter abzuschwächen. Ein positiver Zusammenhang zwischen der Einnahme von Angiotensin Converting Enzyme (ACE) – Hemmern und mehreren Parametern der Sarkopenie, hypothetisch möglich aufgrund potentieller protektiver Effekte von ACE-Hemmern auf die Skelettmuskulatur, fand sich nicht

Clinical outcome of a patient with lysosomal acid lipase deficiency and first results after initiation of treatment with Sebelipase alfa: A case report

We report on a case of very rare autosomal recessive cholesteryl ester storage disease due to lysosomal acid lipase deficiency (LALD). LALD is caused by mutations in the lysosomal acid lipase A (LIPA) gene resulting in cholesteryl ester accumulation in liver, spleen, and macrophages. It can lead to liver failure, accelerated atherosclerosis and premature death. Until recently, treatment options were limited to lipid-lowering medications to control dyslipidemia. Presently, a long-term enzyme replacement therapy with Sebelipase alfa, a recombinant human lysosomal acid lipase, is available for patients with LALD. Our patient's condition became conspicuous at the age of two due to a xanthogranuloma of the chin together with increased lipid levels, elevated liver enzymes and hepatomegaly. It took another five years until our patient was diagnosed with LALD after genetic testing. A bi-weekly therapy with intravenous Sebelipase alfa was started at the age of 26 years. It led to normalization of lipid levels, reduction of liver enzymes and beginning regression of hepatomegaly in the absence of adverse drug reactions after 46 infusions. Since LALD can take a fatal course even in patients with a long-term stable condition, it is essential to identify affected patients early and to treat them appropriately by enzyme replacement therapy. LALD should be suspected in patients with low high-density lipoprotein cholesterol (HDL-C) and high low-density lipoprotein cholesterol (LDL-C) in conjunction with elevated liver enzymes or hepatomegaly. A registry for LALD patients shall help to advance our understanding of the disease as well as improve patient care (NCT01633489)

Long-term gait measurements in daily life: Results from the Berlin Aging Study II (BASE-II)

BACKGROUND: Walking ability is an important prerequisite for activity, social participation and independent living. While in most healthy adults, this ability can be assumed as given, limitations in walking ability occur with increasing age. Furthermore, slow walking speed is linked to several chronic conditions and overall morbidity. Measurements of gait parameters can be used as a proxy to detect functional decline and onset of chronic conditions. Up to now, gait characteristics used for this purpose are measured in standardized laboratory settings. There is some evidence, however, that long-term measurements of gait parameters in the living environment have some advantages over short-term laboratory measurements. METHODS: We evaluated cross-sectional data from an accelerometric sensor worn in a subgroup of 554 participants of the Berlin Aging Study II (BASE-II). Data from the two BASE-II age groups (age between 22-36 years and 60-79 years) were used for the current analysis of accelerometric data for a minimum of two days and a maximum of ten days were available. Real world walking speed, number of steps, maximum coherent distance and total distance were derived as average data per day. Linear regression analyses were performed on the different gait parameters in order to identify significant determinants. Additionally, Mann-Whitney-U-tests were performed to detect sex-specific differences. RESULTS: Age showed to be significantly associated with real world walking speed and with the total distance covered per day, while BMI contributed negatively to the number of walking steps, maximum coherent distance and total distance walked. Additionally, sex was associated with walking steps. However, R2-values for all models were low. Overall, women had significantly more walking steps and a larger coherent distance per day when compared to men. When separated by age group, this difference was significant only in the older participants. Additionally, walking speed was significantly higher in women compared to men in the subgroup of older people. CONCLUSIONS: Age- and sex-specific differences have to be considered when objective gait parameters are measured, e.g. in the context of clinical risk assessment. For this purpose normative data, differentiating for age and sex would have to be established to allow reliable classification of long-term measurements of gait

Low muscle strength and increased arterial stiffness go hand in hand

Low handgrip strength and increased arterial stiffness are both associated with poor health outcomes, but evidence on the relationship between handgrip strength and arterial stiffness is limited. In this cross-sectional analysis of combined baseline datasets from the LipidCardio and Berlin Aging Study II cohorts we aimed to examine whether handgrip strength (HGS) is associated with arterial stiffness. 1511 participants with a median age of 68.56 (IQR 63.13-73.08) years were included. Arterial stiffness was assessed by aortal pulse wave velocity (PWV) with the Mobil-O-Graph device. Handgrip strength was assessed with a handheld dynamometer.The mean HGS was 39.05 +/- 9.07 kg in men and 26.20 +/- 7.47 kg in women. According to multivariable linear regression analysis per 5 kg decrease in handgrip strength there was a mean increase in PWV of 0.08 m/s after adjustment for the confounders age, sex, coronary artery disease, systolic blood pressure, body mass index, cohort, and smoking. Thus, there was evidence that low handgrip strength and increased arterial stiffness go hand in hand. Arterial stiffness can possibly create the missing link between low handgrip strength and increased cardiovascular morbidity and mortality. Causality and direction of causality remain to be determined

Vitamin D insufficiency is associated with metabolic syndrome independent of insulin resistance and obesity in young adults ‐ The Berlin Aging Study II

Purpose: Age-related changes affect vitamin D absorption and metabolism. Low 25-hydroxyvitamin D concentrations have been reported as risk factor for the development of metabolic syndrome (MetS). However, recent evaluations suggest this association might be explained by obesity or insulin resistance (IR) in subjects with MetS. Our aim was to analyze associations between vitamin D insufficiency and MetS in a young cohort without diabetes and two senior cohorts with and without diabetes. Methods: Four hundred sixteen young and 1357 older BASE-II participants were analyzed. Type 2 diabetes (T2D) was defined according to European Society of Cardiology (ESC) guidelines, MetS as suggested by International Diabetes Federation/American Heart Association/National Heart, Lung and Blood Institute (IDF/AHA/NHLBI 2009). Vitamin D insufficiency was defined as 25-hydroxyvitamin D concentrations <50 nmol/L. Among other confounders, BMI and IR were taken into account. Results: MetS was prevalent in 7.7% of the young and in 35.6% of the older BASE-II participants and T2D occurred in 12.7% of the older participants. In young subjects without diabetes, vitamin D insufficiency was associated with an independent 3.2-fold increased odds of having MetS (OR: 3.2 CI: 1.0-8.7; p = 0.042). However, in the older participants, this association was lost once BMI was taken into account among those with diabetes, and once IR was taken into account among those without diabetes. Conclusion: Independent associations between vitamin D insufficiency and MetS were only found among young subjects without diabetes. In the older adults, BMI annihilated these associations among subjects without diabetes as did HOMA-IR among subjects with diabetes

Vitamin D supplementation is associated with slower epigenetic aging

Adverse effects of low vitamin D level on mortality and morbidity are controversially discussed. Especially older people are at risk for vitamin D deficiency and therefore exposed to its potentially harmful consequences. A way of measuring differences in the biological age is through DNA methylation age (DNAm age) and its deviation from chronological age, DNAm age acceleration (DNAmAA). We previously reported on an association between vitamin D deficiency and higher 7-CpG DNAmAA in participants of the Berlin Aging Study II (BASE-II). In this study, we employ a quasi-interventional study design to assess the relationship between DNAmAA of five epigenetic clocks and vitamin D supplementation. Longitudinal data were available for 1,036 participants of BASE-II that were reexamined on average 7.4 years later in the GendAge study (mean age at follow-up: 75.6 years, SD = 3.8 years, age range: 64.9-94.1 years, 51.9% female). DNAmAA was estimated with the 7-CpG clock, Horvath's clock, Hannum's clock, PhenoAge, and GrimAge. Methylation data were obtained through methylation-sensitive single nucleotide primer extension (MS-SNuPE) or Illumina's Infinium "MethylationEPIC" array. Vitamin D-deficient participants who chose to start vitamin D supplementation after baseline examination showed a 2.6-year lower 7-CpG DNAmAA (p = 0.011) and 1.3-year lower Horvath DNAmAA (p = 0.042) compared to untreated and vitamin D-deficient participants. DNAmAA did not statistically differ between participants with successfully treated vitamin D deficiency and healthy controls (p > 0.16). Therefore, we conclude that intake of vitamin D supplement is associated with lower DNAmAA in participants with vitamin D deficiency

Hyperlipidemias in elderly patients: results from the Berlin Aging Study II (BASEII), a cross-sectional study

Background: Hyperlipidemias are common and the last decades have seen substantially growing evidence of their causative role in the development of atherosclerosis and subsequent cardiovascular diseases. Since hyperlipidemias usually do not cause direct clinical symptoms, they often remain undiagnosed until a serious cardiovascular event occurs. Especially for LDL-hypercholesteremia, there are well-established treatment options available to prevent the occurrence of atherosclerosis. However, there is a lack of knowledge regarding the proper treatment of elderly patients. The goal of this study was to assess the prevalence of hyperlipidemia in a group of young and a group of elderly community-dwelling participants and to determine to what extent treatment of hyperlipidemia should be initiated or required. Methods: Crossectional data from a total of 2151 subjects (1657 in the elderly group, mean age 69, and 494 in the young group (control group), mean age 29) of the Berlin Aging Study II (BASE-II) were available. Medical history was assessed and recorded by trained physicians and prevalence of lipid disorders was determined with laboratory tests, including a lipid-profile. Results: A large proportion of subjects (39%) were unaware of an existing lipid disorder. The prevalence of hyperlipidemia was more frequent in the elderly group (76%) compared to the young group (41%). Hypercholesterolemia was the most common diagnosed disorder (64%), followed by hyperlipoproteinemia(a) (18%), hypertriglyceridemia (7%) and combined hyperlipoproteinaemia (5%). Only a minority of this cohort was treated with lipid-lowering medication (17%) and of those treatment targets according to ESC guidelines were reached only in 16.5 %. Conclusions: Hyperlipidemias appear underdiagnosed and undertreated. As the prevalence of these disorders increases with age and with regard to their role as a major modifiable risk factor for cardiovascular disease it seems to be advisable to aim for more consistent and sustainable screening and treatment of these common disorders. Trial registration: BASE-II registered with the clinical trial registry Deutsches Register Klinischer Studien (DRKS00009277)

Correction: Long-term gait measurements in daily life: Results from the Berlin Aging Study II (BASE-II)

[This corrects the article DOI: 10.1371/journal.pone.0225026.]

Relationship between Lipoprotein (a) and cognitive function – Results from the Berlin Aging Study II

It has been suggested that an age-related loss of cognitive function might be driven by atherosclerotic effects associated with altered lipid patterns. However, the relationship between Lipoprotein (a) [Lp(a)] and healthy cognitive aging has not yet been sufficiently investigated. For the current analysis we used the cross-sectional data of 1,380 Berlin Aging Study II (BASE-II) participants aged 60 years and older (52.2% women, mean age 68 ± 4 years). We employed the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD)-Plus test battery to establish latent factors representing continuous measures of domain specific cognitive functions. Regression models adjusted for APOE genotypes, lipid parameters and other risk factors for cognitive impairment were applied to assess the association between Lp(a) and performance in specific cognitive domains. Men within the lowest Lp(a)-quintile showed better cognitive performance in the cognitive domain executive functions and processing speed (p = 0.027). No significant results were observed in women. The results of the current analysis of predominantly healthy BASE-II participants point towards an association between low Lp(a) concentrations and better cognitive performance. However, evidence for this relationship resulting from the current analysis and the employment of a differentiated cognitive assessment is rather weak

Social Class

Discussion of class structure in fifth-century Athens, historical constitution of theater audiences, and the changes in the comic representation of class antagonism from Aristophanes to Menander