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Endres K.,Institute for Clinical Chemistry | Fahrenholz F.,Institute for Clinical Chemistry | Lotz J.,Johannes Gutenberg University Mainz | Hiemke C.,Institute for Clinical Chemistry | And 5 more authors.
Neurology | Year: 2014

Objective: We investigated induction of a-secretase A disintegrin and metalloprotease 10 (ADAM10) by the synthetic retinoid acitretin (Neotigason; Actavis, München-Riem, Germany) in patients with mild to moderate Alzheimer disease (AD) via measurement of CSF content of a-secretase-derived amyloid precursor protein (APPs-a). Methods: Twenty-one patients clinically diagnosed with mild to moderate AD received acitretin (30 mg per day) or placebo in a 4-week double-blind study. Primary endpoint was the difference of CSF APPs-a ratios calculated from the APPs-a levels after treatment and at baseline. We monitored safety and tolerability of the treatment. In addition, we assessed biomarkers such as b-amyloid 42 (Ab42) under treatment conditions. Results: The acitretin group showed a significant increase in CSF APPs-a levels compared with the placebo group (difference 0.38, 95% confidence interval 0.03-0.72, p 5 0.035) within this rather short treatment period. The synthetic retinoid acitretin was overall safe and well tolerated. Conclusions: Our pilot study highlights that acitretin is able to enhance the nonamyloidogenic APP processing in human patients. Clinical consequences of this regulation should be investigated in larger and longer trials in patients with AD to evaluate acitretin's potential to serve as a novel therapeutic drug. Classification of evidence: This study provides Class III evidence that in patients with AD, oral acitretin increases CSF APPs-a levels. © 2014 American Academy of Neurology.

Drey M.,Friedrich - Alexander - University, Erlangen - Nuremberg | Zech A.,University of Hamburg | Freiberger E.,Friedrich - Alexander - University, Erlangen - Nuremberg | Bertsch T.,Institute for Clinical Chemistry | And 4 more authors.
Gerontology | Year: 2012

Background: It has been unclear which training mode is most effective and feasible for improving physical performance in the risk group of prefrail community-dwelling older adults. Objective: The purpose of the present study was to compare the effects of strength training (ST) versus power training (PT) on functional performance in prefrail older adults. This study was registered at clinicaltrials.gov as NCT00783159. Methods: 69 community-dwelling older adults (>65 years) who were prefrail according to the definition of Fried were included in a 12-week exercise program. The participants were randomized into an ST group, a PT group and a control group. All participants were supplemented with vitamin D 3 orally before entering the intervention period. The primary outcome was the global score on the Short Physical Performance Battery (SPPB). Secondary outcomes were muscle power, appendicular lean mass (aLM) measured by dual energy X-ray absorptiometry and self-reported functional deficits (Short Form of the Late-Life Function and Disability Instrument, SF-LLFDI). Results: Regarding changes in the SPPB score during the intervention, significant heterogeneity between the groups was observed (p = 0.023). In pair-wise comparisons, participants in both training groups significantly (PT: p = 0.012, ST: 0.009) increased their SPPB score (PT: Δ mean = 0.8, ST: Δ mean = 1.0) compared to the control group, with no statistical difference among training groups (p = 0.301). No statistical differences were found in changes in aLM (p = 0.769), muscle power (p = 0.308) and SF-LLFDI (p = 0.623) between the groups. Muscle power significantly increased (p = 0.017) under vitamin D 3 intake. Conclusions: In prefrail community-dwelling adults, PT is not superior to ST, although both training modes resulted in significant improvements in physical performance. With regard to dropout rates, ST appears to be advantageous compared to PT. The high prevalence of vitamin D 3 deficiency and the slight improvement of physical performance under vitamin D 3 supplementation among study participants underline the relevance of this approach in physical exercise interventions. © 2011 S. Karger AG, Basel.

Bahrmann P.,Friedrich - Alexander - University, Erlangen - Nuremberg | Heppner H.-J.,Friedrich - Alexander - University, Erlangen - Nuremberg | Christ M.,Nuremberg Hospital | Bertsch T.,Institute for Clinical Chemistry | Sieber C.,Friedrich - Alexander - University, Erlangen - Nuremberg
Aging Clinical and Experimental Research | Year: 2012

Background and aims: The new high sensitivity cardiac Troponin T (cTnThs) assay has recently been introduced in our clinic and ensures higher sensitivity than the fourth-generation cardiac troponin T (cTnT) assay from the same manufacturer (Roche Diagnostics). We determined the diagnostic performance of the cTnThs compared with the cTnT assay in geriatric patients, especially those with non-ST elevation myocardial infarction (NSTEMI). Methods: We retrospectively analysed 253 patients (age 82±8 years; 82 men, 172 women) with diagnoses of suspected NSTEMI admitted to our Department of Geriatric Medicine. Patients were divided into one group of 113 patients using cTnThs, and another of 140 patients using cTnT for diagnosis. Each group included patients at the same months but different years, in either cTnThs or cTnT assays. NSTEMI was diagnosed according to current guidelines. Results: Baseline characteristics were similar in both groups. The proportions of patients with elevated cardiac troponin (cTn) levels significantly increased from 35% in the cTnT group to 76% in the cTnThs group (p<0.001), although no coronary cause for the elevated cTn levels was shown in about two-thirds of these patients. In patients with NSTEMI, 58% in the cTnThs group vs 42% in the cTnT group were diagnosed within 4 hours of the onset of symptoms, whereas 42% in the cTnThs group vs 58% in the cTnT group were diagnosed more than 4 hours later (p=0.018). Conclusions: The prevalence of elevated cTn has more than doubled with the use of cTnThs. However, no coronary cause was found in two-thirds of our geriatric patients, although more NSTEMI patients were diagnosed earlier by cTnThs. ©2012, Editrice Kurtis.

Drey M.,Friedrich - Alexander - University, Erlangen - Nuremberg | Krieger B.,Friedrich - Alexander - University, Erlangen - Nuremberg | Sieber C.C.,Friedrich - Alexander - University, Erlangen - Nuremberg | Bauer J.M.,Friedrich - Alexander - University, Erlangen - Nuremberg | And 3 more authors.
Journal of the American Medical Directors Association | Year: 2014

Objectives: Sarcopenia, age-related muscle wasting, is associated with increased morbidity and mortality in the affected individuals. The pathogenesis of sarcopenia is not yet fully understood. A multifactorial concept is currently favored. The reduced number of motor units as a potential mechanism of muscle mass loss is explored in the present study. Design: This is a cross-sectional study. Setting: The participants were community-dwelling older adults. Participants: The participants were sarcopenic (75) and nonsarcopenic (74) according to the criteria of the European Working Group on Sarcopenia in Older People aged 65 to 94 years. Measurements: The motor unit number index (MUNIX) of the hypothenar muscle was used to assess the number and size [motor unit size index (MUSIX)] of motor units. Results: The participants with pathologic MUNIX and MUSIX (n= 23) are significantly more frequently sarcopenic (n= 17, P= .029) than nonsarcopenic (n= 6). The participants with pathologic MUNIX and MUSIX (n= 23) had significantly less muscle mass than the nonsarcopenic controls (P < .001). After adjusting for age and sex, only gait speed has shown no difference between the 2 groups. Pearson's correlation coefficient between MUSIX and the reciprocal value of MUNIX is 0.87 (P < .001). Conclusions: Sarcopenia induced by a small number of motoneurons can be identified by applying the MUNIX method to the hypothenar muscle. An enlargement of motor units because of motoneuron loss seems to preserve physical performance. © 2014 American Medical Directors Association, Inc.

Drey M.,Friedrich - Alexander - University, Erlangen - Nuremberg | Sieber C.C.,Friedrich - Alexander - University, Erlangen - Nuremberg | Bauer J.M.,Friedrich - Alexander - University, Erlangen - Nuremberg | Bauer J.M.,Geriatric Center Oldenburg | And 9 more authors.
Experimental Gerontology | Year: 2013

Introduction: Sarcopenia is considered to be an enormous burden for both the individuals affected and for society at large. A multifactorial aetiology of this geriatric syndrome has been discussed. Amongst other pathomechanisms, the degeneration of the neuromuscular junction (NMJ) may be of major relevance. The intact balance between the pro-synaptic agent agrin and the anti-synaptic agent neurotrypsin ensures a structurally and functionally intact NMJ. Excessive cleavage of the native motoneuron-derived agrin by neurotrypsin into a C-terminal Agrin Fragment (CAF) leads to functional disintegration at the NMJ and may consecutively cause sarcopenia. The present study evaluates the hypothesis that CAF serum concentration is a potential marker for the loss of appendicular lean mass in older adults. It also explores how CAF concentration is influenced by vitamin D supplementation and physical exercise. Method: Serum was taken from 69 (47 female) prefrail community-dwelling older adults participating in a training intervention study to measure the CAF concentration using the Western blot technique. All participants were supplemented orally with vitamin D3 before the training intervention period commenced. Appendicular lean mass (aLM) was evaluated by dual energy X-ray absorptiometry. Multiple linear regression models were used to identify factors significantly associated with CAF concentration. Results: Appendicular lean mass, age and sex were identified as significant explanatory factors for CAF concentration. Gait speed and hand grip strength were not associated with CAF concentration. Male participants showed a strong correlation (r = - 0.524) between CAF serum concentration and aLM, whereas this was not the case (r = - 0.219) in females. Vitamin D supplementation and physical exercise were significantly associated with a reduction in CAF concentration, especially in participants with initially high CAF concentrations. Conclusions: C-terminal Agrin Fragment could be a potential marker for identifying sarcopenia in a subgroup of affected individuals in the future. The decline of muscle mass seems to be a CAF-associated process in males, whereas the situation in females may be more complex and multifactorial. CAF concentration is reduced by vitamin D supplementation and physical exercise and therefore suggests a potentially positive effect on NMJs. Further prospective studies of sarcopenic patients in addition to muscle biopsy and electromyographical investigations are planned to verify the external validity of the CAF concept. © 2012 Elsevier Inc.

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