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142 Publications visible to you, out of a total of 142
First evidence for glial pathology in late life minor depression: S100B is increased in males with minor depression.
LIFE Adult

Abstract (Expand)

Minor depression is diagnosed when a patient suffers from 2 to 4 depressive symptoms for at least 2 weeks. Though minor depression is a widespread phenomenon, its pathophysiology has hardly been studied. … To get a first insight into the pathophysiological mechanisms underlying this disorder we assessed serum levels of biomarkers for plasticity, glial and neuronal function: brain-derived neurotrophic factor (BDNF), S100B and neuron specific enolase (NSE). 27 subjects with minor depressive episode and 82 healthy subjects over 60 years of age were selected from the database of the Leipzig population-based study of civilization diseases (LIFE). Serum levels of BDNF, S100B and NSE were compared between groups, and correlated with age, body-mass index (BMI), and degree of white matter hyperintensities (score on Fazekas scale). S100B was significantly increased in males with minor depression in comparison to healthy males, whereas other biomarkers did not differ between groups (p = 0.10-0.66). NSE correlated with Fazekas score in patients with minor depression (rs = 0.436, p = 0.048) and in the whole sample (rs = 0.252, p = 0.019). S100B correlated with BMI (rs = 0.246, p = 0.031) and with age in healthy subjects (rs = 0.345, p = 0.002). Increased S100B in males with minor depression, without alterations in BDNF and NSE, supports the glial hypothesis of depression. Correlation between white matter hyperintensities and NSE underscores the vascular hypothesis of late life depression.

Authors: M. Polyakova, C. Sander, K. Arelin, L. Lampe, T. Luck, M. Luppa, J. Kratzsch, K. T. Hoffmann, S. Riedel-Heller, A. Villringer, P. Schoenknecht, M. L. Schroeter

Date Published: 27th Oct 2015

Publication Type: Not specified

Human Diseases: mental depression

Alzheimer's Disease FDG PET Imaging Pattern in an Amyloid-Negative Mild Cognitive Impairment Subject.
LIFE Adult

Abstract (Expand)

The revised NIA-AA diagnostic criteria for Alzheimer's disease (AD) and mild cognitive impairment (MCI) due to AD make use of amyloid pathology and neurodegeneration biomarkers which increase the … diagnostic confidence in the majority of patients. However, in daily praxis, cases with conflicting biomarker constellations occur. A MCI subject underwent neuropsychological testing supplemented by FDG and amyloid PET/MRI as well as CSF sampling. In this subject, the biomarkers of Abeta deposition were negative. [18F]FDG PET, however, showed an AD-typical hypometabolism. Further studies are required to determine frequency and relevance of cases with neurodegeneration-first biomarker constellations to improve our understanding on pathogenesis and diagnosis of AD.

Authors: S. Tiepolt, M. Patt, K. T. Hoffmann, M. L. Schroeter, O. Sabri, H. Barthel

Date Published: 25th Sep 2015

Publication Type: Not specified

Human Diseases: cognitive disorder, Alzheimer's disease

Mortality in Individuals with Subjective Cognitive Decline: Results of the Leipzig Longitudinal Study of the Aged (LEILA75+).
LIFE Adult

Abstract (Expand)

BACKGROUND: Studies have shown that dementia and cognitive impairment can increase mortality, but less is known about the association between subjectively perceived cognitive deficits (subjective … cognitive decline, SCD) and mortality risk. OBJECTIVE: In this study, we analyzed mortality in non-demented individuals with SCD in a general population sample aged 75+ years. METHOD: Data were derived from the Leipzig Longitudinal Study of the Aged (LEILA75+). We used the Kaplan-Meier survival method to estimate survival times of individuals with and without SCD and multivariable Cox proportional hazards regression to assess the association between SCD and mortality risk, controlled for covariates. RESULTS: Out of 953 non-demented individuals at baseline, 117 (12.3% ) expressed SCD. Participants with SCD showed a significantly higher case-fatality rate per 1,000 person-years (114.8, 95% CI = 90.5-145.7 versus 71.7, 95% CI = 64.6-79.5) and a significantly shorter mean survival time than those without (5.4 versus 6.9 years, p < 0.001). The association between SCD and mortality remained significant in the Cox analysis; SCD increased mortality risk by about 50% (adjusted Hazard Ratio = 1.51) during the study period. Besides SCD, older age, male gender, diabetes mellitus, stroke, and lower global cognitive functioning were also significantly associated with increased mortality. CONCLUSION: Our findings suggest an increased mortality risk in non-demented older individuals with SCD. Even though further studies are required to analyze potential underlying mechanisms, subjective reports on cognitive deficits may be taken seriously in clinical practice not only for an increased risk of developing dementia and AD but also for a broader range of possible adverse health outcomes.

Authors: T. Luck, S. Roehr, F. Jessen, A. Villringer, M. C. Angermeyer, S. G. Riedel-Heller

Date Published: 24th Sep 2015

Publication Type: Not specified

Human Diseases: dementia

Subjective Cognitive Decline in Older Adults: An Overview of Self-Report Measures Used Across 19 International Research Studies.
LIFE Adult

Abstract (Expand)

Research increasingly suggests that subjective cognitive decline (SCD) in older adults, in the absence of objective cognitive dysfunction or depression, may be a harbinger of non-normative cognitive … decline and eventual progression to dementia. Little is known, however, about the key features of self-report measures currently used to assess SCD. The Subjective Cognitive Decline Initiative (SCD-I) Working Group is an international consortium established to develop a conceptual framework and research criteria for SCD (Jessen et al., 2014, Alzheimers Dement 10, 844-852). In the current study we systematically compared cognitive self-report items used by 19 SCD-I Working Group studies, representing 8 countries and 5 languages. We identified 34 self-report measures comprising 640 cognitive self-report items. There was little overlap among measures- approximately 75% of measures were used by only one study. Wide variation existed in response options and item content. Items pertaining to the memory domain predominated, accounting for about 60% of items surveyed, followed by executive function and attention, with 16% and 11% of the items, respectively. Items relating to memory for the names of people and the placement of common objects were represented on the greatest percentage of measures (56% each). Working group members reported that instrument selection decisions were often based on practical considerations beyond the study of SCD specifically, such as availability and brevity of measures. Results document the heterogeneity of approaches across studies to the emerging construct of SCD. We offer preliminary recommendations for instrument selection and future research directions including identifying items and measure formats associated with important clinical outcomes.

Authors: L. A. Rabin, C. M. Smart, P. K. Crane, R. E. Amariglio, L. M. Berman, M. Boada, R. F. Buckley, G. Chetelat, B. Dubois, K. A. Ellis, K. A. Gifford, A. L. Jefferson, F. Jessen, M. J. Katz, R. B. Lipton, T. Luck, P. Maruff, M. M. Mielke, J. L. Molinuevo, F. Naeem, A. Perrotin, R. C. Petersen, L. Rami, B. Reisberg, D. M. Rentz, S. G. Riedel-Heller, S. L. Risacher, O. Rodriguez, P. S. Sachdev, A. J. Saykin, M. J. Slavin, B. E. Snitz, R. A. Sperling, C. Tandetnik, W. M. van der Flier, M. Wagner, S. Wolfsgruber, S. A. Sikkes

Date Published: 24th Sep 2015

Publication Type: Not specified

Human Diseases: cognitive disorder, dementia

Nicotinamide: a vitamin able to shift macrophage differentiation toward macrophages with restricted inflammatory features.
LIFE - Leipzig Research Center for Civilization Diseases

Abstract (Expand)

The differentiation of human monocytes into macrophages is influenced by environmental signals. Here we asked in how far nicotinamide (NAM), a vitamin B3 derivative known to play a major role in … nicotinamide adenine dinucleotide (NAD)-mediated signaling events, is able to modulate monocyte differentiation into macrophages developed in the presence of granulocyte macrophage colony-stimulating factor (GM-MO) or macrophage colony-stimulating factor (M-MO). We found that GM-MO undergo biochemical, morphological and functional modifications in response to NAM, whereas M-MO were hardly affected. GM-MO exposed to NAM acquired an M-MO-like structure while the LPS-induced production of pro-inflammatory cytokines and COX-derived eicosanoids were down-regulated. In contrast, NAM had no effect on the production of IL-10 or the cytochrome P450-derived eicosanoids. Administration of NAM enhanced intracellular NAD concentrations; however, it did not prevent the LPS-mediated drain on NAD pools. In search of intracellular molecular targets of NAM known to be involved in LPS-induced cytokine and eicosanoid synthesis, we found NF-kappaB activity to be diminished. In conclusion, our data show that vitamin B3, when present during the differentiation of monocytes into GM-MO, interferes with biochemical pathways resulting in strongly reduced pro-inflammatory features.

Authors: R. Weiss, E. Schilling, A. Grahnert, V. Kolling, J. Dorow, U. Ceglarek, U. Sack, S. Hauschildt

Date Published: 20th Sep 2015

Publication Type: Not specified

Towards a comprehensive picture of alloacceptor tRNA remolding in metazoan mitochondrial genomes.
LIFE - Leipzig Research Center for Civilization Diseases

Abstract (Expand)

Remolding of tRNAs is a well-documented process in mitochondrial genomes that changes the identity of a tRNA. It involves a duplication of a tRNA gene, a mutation that changes the anticodon and the … loss of the ancestral tRNA gene. The net effect is a functional tRNA that is more closely related to tRNAs of a different alloacceptor family than to tRNAs with the same anticodon in related species. Beyond being of interest for understanding mitochondrial tRNA function and evolution, tRNA remolding events can lead to artifacts in the annotation of mitogenomes and thus in studies of mitogenomic evolution. Therefore, it is important to identify and catalog these events. Here we describe novel methods to detect tRNA remolding in large-scale data sets and apply them to survey tRNA remolding throughout animal evolution. We identify several novel remolding events in addition to the ones previously mentioned in the literature. A detailed analysis of these remoldings showed that many of them are derived from ancestral events.

Authors: A. H. Sahyoun, M. Holzer, F. Juhling, C. Honer zu Siederdissen, M. Al-Arab, K. Tout, M. Marz, M. Middendorf, P. F. Stadler, M. Bernt

Date Published: 18th Sep 2015

Publication Type: Not specified

The value of noncoronary atherosclerosis for identifying coronary artery disease: results of the Leipzig LIFE Heart Study.
Genetical Statistics and Systems Biology, LIFE Heart

Abstract (Expand)

BACKGROUND: Despite the widespread use of noninvasive testing prior to invasive coronary diagnostic the diagnostic yield of elective coronary angiography has been reported low in subjects with suspected … obstructive CAD. OBJECTIVE: To determine the predictive value of noncoronary atherosclerosis (NCA) in subjects with suspected stable coronary artery disease (CAD) intended to invasive coronary angiography. METHODS: Ultrasound-based assessment of carotid artery plaque (CAP), carotid intima-media thickness (CIMT) and ankle-brachial index (ABI) was performed in 2216 subjects with suspected CAD prior to coronary angiography. Logistic regression and c-statistics were used to analyze the diagnostic value of NCA for the presence of obstructive CAD and the intention to revascularization. RESULTS: Percentage of positive results of elective coronary angiography was low but comparable to other studies (41% obstructive CAD). We identified 1323 subjects (60%) with NCA, most of them were characterized by CAP (93%). CAP independently predicted obstructive CAD in addition to traditional risk factors and clinical factors while CIMT and ABI failed to improve the prediction. The presence of NCA and typical angina were the strongest predictors for obstructive CAD (OR 4.0 and 2.4, respectively). A large subgroup of patients (n = 703, 32%) with atypical clinical presentation and lack of NCA revealed a low indication for revascularization <15% indicating a large proportion of subjects with non-obstructive CAD in this subgroup. CONCLUSION: The evaluation of noncoronary atherosclerosis has the potential to impact clinical decision making and to direct subsequent diagnostic procedures in subjects with suspected coronary artery disease. CLINICAL TRIAL REGISTRATION: NCT00497887.

Authors: A. Weissgerber, M. Scholz, A. Teren, M. Sandri, D. Teupser, S. Gielen, J. Thiery, G. Schuler, F. Beutner

Date Published: 13th Sep 2015

Publication Type: Not specified

Human Diseases: coronary artery disease, atherosclerosis

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