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142 Publications visible to you, out of a total of 142
Incident subjective memory complaints and the risk of subsequent dementia.
LIFE Adult

Abstract (Expand)

OBJECTIVE: In this study, we aimed to analyze the association between new-incident-subjective memory complaints (SMC) and risk of subsequent dementia in a general population sample aged 75+ years. … METHOD: Data were derived from follow-up (FUP) waves I-V of the population-based Leipzig Longitudinal Study of the Aged (LEILA75+). We used the Kaplan-Meier survival method to estimate dementia-free survival times of individuals with and without incident SMC and multivariable Cox proportional hazards regression to assess the association between incident SMC and risk of subsequent dementia, controlled for covariates. RESULTS: Of 443 non-demented individuals, 58 (13.1%) developed dementia during a subsequent 5.4-year follow-up period. Participants with incident SMC showed a significantly higher progression to dementia (18.5% vs. 10.0%; P=0.010) and a significantly shorter mean dementia-free survival time than those without (6.2 vs. 6.8 years; P=0.008). The association between incident SMC and risk of subsequent dementia remained significant in the multivariable Cox analysis (adjusted hazard ratio=1.8; P=0.028). CONCLUSION: Our findings suggest higher progression to dementia and shorter dementia-free survival in older individuals with incident SMC. These findings support the notion that such subjective complaints should be taken seriously in clinical practice as possible early indicators of incipient dementia.

Authors: T. Luck, M. Luppa, H. Matschinger, F. Jessen, M. C. Angermeyer, S. G. Riedel-Heller

Date Published: 10th Sep 2014

Publication Type: Not specified

Human Diseases: dementia

Genomic and epigenomic co-evolution in follicular lymphomas.
LIFE Adult

Abstract (Expand)

Follicular lymphoma (FL) with a t(14;18) is a B-cell neoplasm clinically characterized by multiple recurrencies. In order to investigate the clonal evolution of this lymphoma, we studied paired primary … and relapse tumor samples from 33 patients with recurrent non-transformed t(14;18)-positive FL. We reconstructed phylogenetic trees of the evolution by taking advantage of the activation-induced cytidine deaminase (AID)-mediated somatic hypermutation (SHM) active in the germinal center reaction using sequences of the clonal VHDHJH rearrangements of the immunoglobulin heavy chain (IGH) locus. Mutational analysis of the IGH locus showed evidence for ongoing somatic mutation and for counter-selection of mutations affecting the BCR conformation during tumor evolution. We further followed evolutionary divergence by targeted sequencing of gene loci affected by aberrant SHM as well as of known driver genes of lymphomagenesis, and by array-based genome-wide chromosomal imbalance and DNA methylation analysis. We observed a wide spectrum of evolutionary patterns ranging from almost no evolution to divergent evolution within recurrent non-transformed t(14;18) FL. Remarkably, we observed a correlation of the magnitude of evolutionary divergence across all genetic and epigenetic levels suggesting co-evolution. The distribution of coding mutations in driver genes and the correlation with SHM suggest CREBBP and AID to be potential modifiers of genetic and epigenetic co-evolution in FL.

Authors: M. Loeffler, M. Kreuz, A. Haake, D. Hasenclever, H. Trautmann, C. Arnold, K. Winter, K. Koch, W. Klapper, R. Scholtysik, M. Rosolowski, S. Hoffmann, O. Ammerpohl, M. Szczepanowski, D. Herrmann, R. Kuppers, C. Pott, R. Siebert

Date Published: 17th Jul 2014

Publication Type: Not specified

Human Diseases: follicular lymphoma

Association between mental demands at work and cognitive functioning in the general population - results of the health study of the Leipzig research center for civilization diseases (LIFE).
LIFE Adult

Abstract (Expand)

BACKGROUND: The level of mental demands in the workplace is rising. The present study investigated whether and how mental demands at work are associated with cognitive functioning in the general … population. METHODS: The analysis is based on data of the Health Study of the Leipzig Research Centre for Civilization Disease (LIFE). 2,725 participants aged 40-80 years underwent cognitive testing (Trail-Making Test, Verbal Fluency Test) and provided information on their occupational situation. Participants over the age of 65 years additionally completed the Mini-Mental State Examination. Mental demands at work were rated by a standardized classification system (O*NET). The association between mental demands and cognitive functioning was analyzed using Generalized Linear Modeling (GENLIN) adjusted for age, gender, self-regulation, working hour status, education, and health-related factors. RESULTS: Univariate as well as multivariate analyses demonstrated significant and highly consistent effects of higher mental demands on better performance in cognitive testing. The results also indicated that the effects are independent of education and intelligence. Moreover, analyses of retired individuals implied a significant association between high mental demands at work of the job they once held and a better cognitive functioning in old age. CONCLUSIONS: In sum, our findings suggest a significant association between high mental demands at work and better cognitive functioning. In this sense, higher levels of mental demands - as brought about by technological changes in the working environment - may also have beneficial effects for the society as they could increase cognitive capacity levels and might even delay cognitive decline in old age.

Authors: F. S. Then, T. Luck, M. Luppa, K. Arelin, M. L. Schroeter, C. Engel, M. Loffler, J. Thiery, A. Villringer, S. G. Riedel-Heller

Date Published: 11th Jun 2014

Publication Type: Not specified

Validation of a brief step-test protocol for estimation of peak oxygen uptake.
LIFE Heart

Abstract (Expand)

BACKGROUND: Physical exercise capacity has been shown to predict cardiovascular disease incidence and is increasingly measured in epidemiological studies. However, direct measurement of peak oxygen … uptake is too time consuming in large-scale studies. We therefore investigated whether a brief 3-minute step-test protocol can be used to estimate peak oxygen uptake in these settings. DESIGN AND METHODS: A group of 97 subjects performed the YMCA step test and a maximal treadmill test with continuous measurement of oxygen uptake. Correlation and linear regression analyses were used to identify VO2peak predictors obtained from the step test and to develop models for VO2peak estimation. RESULTS: The YMCA model, including the 1-minute heart beat count, predicted VO2peak with R = 0.83. A novel simplified model based on the heart rate at 45 s of recovery performed comparable (R = 0.83). However, models based on heart rate measures were only valid in subjects who completed the test according to protocol, but not in subjects who terminated prematurely. For the applicability in subjects with low exercise capacity, a new model including gas exchange analysis enabled prediction of VO2peak (R = 0.89). All models were validated in an independent sample (r = 0.86-0.91). Exercise time of the step test was less than one-hird of standard ergospirometry (treadmill test: 654 +/- 151 s, step test: 180 s, p < 0.001). CONCLUSION: In large-scale epidemiological studies with limited time slots for exercise testing and significant proportions of subjects with low exercise capacity a modified version of the YMCA step test may be used to predict VO2peak.

Authors: F. Beutner, R. Ubrich, S. Zachariae, C. Engel, M. Sandri, A. Teren, S. Gielen

Date Published: 1st May 2014

Publication Type: Not specified

Functional connectivity in major depression: increased phase synchronization between frontal cortical EEG-source estimates.
LIFE Adult

Abstract (Expand)

Structural and metabolic alterations in prefrontal brain areas, including the subgenual (SGPFC), medial (MPFC) and dorsolateral prefrontal cortex (DLPFC), have been shown in major depressive disorder … (MDD). Still it remains largely unknown how brain connectivity within these regions is altered at the level of neuronal oscillations. Therefore, the goal was to analyze prefrontal electroencephalographic phase synchronization in MDD and its changes after antidepressant treatment. In 60 unmedicated patients and 60 healthy controls (HC), a 15-min resting electroencephalogram (EEG) was recorded in subjects at baseline and in a subgroup of patients after 2 weeks of antidepressant medication. EEG functional connectivity between the SGPFC and the MPFC/DLPFC was assessed with eLORETA (low resolution brain electromagnetic tomography) by means of lagged phase synchronization. At baseline, patients revealed increased prefrontal connectivity at the alpha frequency between the SGPFC and the left DLPFC/MPFC. After treatment, an increased connectivity between the SGPFC and the right DLPFC/MPFC at the beta frequency was found for MDD. A positive correlation was found for baseline beta connectivity and reduction in scores on the Hamilton depression rating scale. MDD is characterized by increased EEG functional connectivity within frontal brain areas. These EEG markers of disturbed neuronal communication might have potential value as biomarkers.

Authors: S. Olbrich, A. Trankner, T. Chittka, U. Hegerl, P. Schonknecht

Date Published: 30th Apr 2014

Publication Type: Not specified

Human Diseases: major depressive disorder

Conceptualizing neuropsychiatric diseases with multimodal data-driven meta-analyses - the case of behavioral variant frontotemporal dementia.
LIFE Adult

Abstract (Expand)

INTRODUCTION: Uniform coordinate systems in neuroimaging research have enabled comprehensive systematic and quantitative meta-analyses. Such approaches are particularly relevant for neuropsychiatric … diseases, the understanding of their symptoms, prediction and treatment. Behavioral variant frontotemporal dementia (bvFTD), a common neurodegenerative syndrome, is characterized by deep alterations in behavior and personality. Investigating this 'nexopathy' elucidates the healthy social and emotional brain. METHODS: Here, we combine three multimodal meta-analyses approaches - anatomical and activation likelihood estimates and behavioral domain profiles - to identify neural correlates of bvFTD in 417 patients and 406 control subjects and to extract mental functions associated with this disease by meta-analyzing functional activation studies in the comprehensive probabilistic functional brain atlas of the BrainMap database. RESULTS: The analyses identify the frontomedian cortex, basal ganglia, anterior insulae and thalamus as most relevant hubs, with a regional dissociation between atrophy and hypometabolism. Neural networks affected by bvFTD were associated with emotion and reward processing, empathy and executive functions (mainly inhibition), suggesting these functions as core domains affected by the disease and finally leading to its clinical symptoms. In contrast, changes in theory of mind or mentalizing abilities seem to be secondary phenomena of executive dysfunctions. CONCLUSIONS: The study creates a novel conceptual framework to understand neuropsychiatric diseases by powerful data-driven meta-analytic approaches that shall be extended to the whole neuropsychiatric spectrum in the future.

Authors: M. L. Schroeter, A. R. Laird, C. Chwiesko, C. Deuschl, E. Schneider, D. Bzdok, S. B. Eickhoff, J. Neumann

Date Published: 26th Apr 2014

Publication Type: Not specified

Human Diseases: frontotemporal dementia

Structural and functional MRI study of the brain, cognition and mood in long-term adequately treated Hashimoto's thyroiditis.
LIFE Adult

Abstract (Expand)

The current study investigated neuropsychological and underlying structural and functional brain alterations in long-term adequately treated patients with Hashimoto's thyroiditis in order to examine … much discussed residual complaints in patients in relation to possible long-term neural alterations with a specific interest in the underlying autoimmune process. Eighteen patients with treated hypothyroidism due to Hashimoto's thyroiditis (mean age 32, range 18-54 years; two males; mean treatment duration 4.4 years) and 18 healthy matched control subjects underwent 3-Tesla magnetic resonance imaging (MRI). Voxel-based morphometry was used to investigate grey matter density, resting-state functional MRI to analyse the brain connectivity of areas known to be altered in hypothyroidism and event-related functional MRI to examine brain activity during associative memory encoding. Neuropsychological assessment included memory, working memory, psychomotor speed and attention. We previously reported subclinically reduced mood in this study population and investigated its neural correlates here. Thyroid stimulating hormone, free triiodthyronine, free thyroxine and thyroid peroxidase antibodies were measured in serum. We did not find cognitive deficits or alterations in grey matter density, functional connectivity or associative memory-related brain activity in comparison to the control group and cognition was unrelated to thyroid serum measures in the patient group. Thyroid peroxidase antibodies in the patient group correlated with increased grey matter density in right amygdala and enhanced connectivity between subcallosal and parahippocampal areas. Treatment duration was associated with brain structure in frontal and occipital cortex and connectivity between left amygdala and frontal cortex. Mood correlated with brain areas associated with distinct functional networks, but not with those most prominently affected in depression. In conclusion, no cognitive or neural alterations were detected in this young and otherwise healthy cohort of patients in comparison to a healthy control group and current mood status could not be related to depression-related networks. However, autoimmune activity and treatment duration showed a relationship with depression and hypothyroidism-related brain structure and function. They are thus promising factors to further investigate residual complaints despite biochemically adequate treatment in patients with Hashimoto's thyroiditis. Given the small sample size, all findings require replication.

Authors: E. M. Quinque, S. Karger, K. Arelin, M. L. Schroeter, J. Kratzsch, A. Villringer

Date Published: 19th Mar 2014

Publication Type: Not specified

Human Diseases: autoimmune thyroiditis, hypothyroidism

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