Publications

43 Publications visible to you, out of a total of 43

Abstract (Expand)

Background: Hippocampal volume, assessed via high-resolution MRI, is associated with memory and visuospatial performance in humans (Squire, 2004) and specifically prone to develop atrophy with age (Apostolova,2015). This process has been linked to neurodegenerative diseases, such as Alzheimer’s disease (Apostolova,2015) and a decline of cognitive functions (Bruno,2016). However, due to differences in study-design and characteristics certain heterogeneity in results remains, in particular considering subfieldspecific effects (deFlores,2015). Therefore, we aim to determine the association of volumes of the whole hippocampus and its subfields on cognition in a large population-based cohort. Methods: Subjects: 1956 healthy participants from the Leipzig Research-Center-for-Civilization-Disease, aged 19-82years with MRI and neuropsychological tests (mean-age=57.61,±15.08SD). Exclusion: stroke, major-brain-pathologies, central-nervous-medication. Independent Variables: Volume of hippocampus and its subfields (CornuAmmonis1, 2-3, 4-DentateGyrus,(Pre-)subiculum). Dependent Variables: Verbal word-list learning, verbal-fluency, TrailMakingTask-(TMT)-A&B. Covariates: sex, age, years-of-education, total grey-mattervolume Image Analysis on high-resolution T1-images assessed at 3T. Hippocampal volumes were estimated using automatic segmentation analysis implemented in FreeSurfer (www.freesurfer.net). Statistical Analysis: Independent and dependent variables were first entered into Pearson Correlations. Variables with a correlation coefficient of r>0.1 were entered into multiple linear-regressions and adjusted for potential confounding(forward inclusion-model). Results: According to bivariate correlations, better performance in verbal-learning, verbal-fluency and TMT-A&B correlated moderately with larger whole-hippocampal volume and the volumes of all subfields(all |r|>0.102, all p0.046, all p0.5). Conclusions: Using a large cross-sectional cohort of healthy adults we found that volumes of the whole-hippocampus and subfields covering the CA4/dentate-gyrus region were weakly, yet specifically associated with verbal-learning and spatial processing-speed. Our preliminary results are in line with previous studies presuming a differential involvement of the hippocampus in tasks of verbal-learning and spatial processing (Oosterman,2010). Upcoming analyses implementing parcellation along the anteriorposterior- axis and random-effect-models might help to further disentangle these effects.

Authors: S. Huhn, R. Zhang, Frauke Beyer, L. Lampe, T. Luck, S. G. Riedel-Heller, M. L. Schroeter, Markus Löffler, M. Stumvoll, A. Villringer, A. V. Witte

Date Published: 1st Jul 2017

Publication Type: Not specified

Human Diseases: cognitive disorder, dementia

Abstract (Expand)

BACKGROUND: Completion of advance directives (ADs) and power of attorney (POA) documents may protect a person's autonomy in future health care situations when the individual lacks decisional capacity. As such situations become naturally much more common in old age, we specifically aimed at providing information on (i) the frequency of ADs/POA in oldest-old individuals and (ii) factors associated with having completed ADs/POA. METHODS: We analyzed data of oldest-old primary care patients (85+ years; including community-dwelling and institutionalized individuals) within the German AgeQualiDe study. Patients were initially recruited via their general practitioners (GPs). We calculated frequencies of ADs and POA for health care with 95% confidence intervals (CI) and used multivariable logistic regression analysis to evaluate the association between having ADs and POA and participants' socio-demographic, cognitive, functional, and health-related characteristics. RESULTS: Among 868 GP patients participating in AgeQualiDe (response = 90.9%), n = 161 had dementia and n = 3 were too exhausted/ill to answer the questions. Out of the remaining 704 (81.1%) dementia-free patients (mean age = 88.7 years; SD = 3.0), 69.0% (95%-CI = 65.6-72.4) stated to having ADs and 64.6% (95%-CI = 61.1-68.2) to having a POA for health care. Individual characteristics did not explain much of the variability of the presence/absence of ADs and POA (regression models: Nagelkerke's R(2) = 0.034/0.051). The most frequently stated reasons for not having ADs were that the older adults trust their relatives or physicians to make the right decisions for them when necessary (stated by 59.4% and 44.8% of those without ADs). Among the older adults with ADs, the majority had received assistance in its preparation (79.0%), most frequently from their children/grandchildren (38.3%). Children/grandchildren were also the most frequently stated group of designated persons (76.7%) for those with a POA for health care. CONCLUSIONS: Our findings suggest a high dissemination of ADs and POA for health care in the oldest-old in Germany. Some adults without ADs/POA perhaps would have completed advance care documents, if they had had received more information and support. When planning programs to offer advanced care planning to the oldest old, it might be helpful to respond to these specific needs, and also to be sensitive to attitudinal differences in this target group.

Authors: T. Luck, F. S. Rodriguez, B. Wiese, C. van der Leeden, K. Heser, H. Bickel, J. In der Schmitten, H. H. Koenig, S. Weyerer, S. Mamone, T. Mallon, M. Wagner, D. Weeg, A. Fuchs, C. Brettschneider, J. Werle, M. Scherer, W. Maier, S. G. Riedel-Heller

Date Published: 13th Apr 2017

Publication Type: Journal article

Abstract (Expand)

Obesity is a complex neurobehavioral disorder that has been linked to changes in brain structure and function. However, the impact of obesity on functional connectivity and cognition in aging humans is largely unknown. Therefore, the association of body mass index (BMI), resting-state network connectivity, and cognitive performance in 712 healthy, well-characterized older adults of the Leipzig Research Center for Civilization Diseases (LIFE) cohort (60-80 years old, mean BMI 27.6 kg/m(2) +/- 4.2 SD, main sample: n = 521, replication sample: n = 191) was determined. Statistical analyses included a multivariate model selection approach followed by univariate analyses to adjust for possible confounders. Results showed that a higher BMI was significantly associated with lower default mode functional connectivity in the posterior cingulate cortex and precuneus. The effect remained stable after controlling for age, sex, head motion, registration quality, cardiovascular, and genetic factors as well as in replication analyses. Lower functional connectivity in BMI-associated areas correlated with worse executive function. In addition, higher BMI correlated with stronger head motion. Using 3T neuroimaging in a large cohort of healthy older adults, independent negative associations of obesity and functional connectivity in the posterior default mode network were observed. In addition, a subtle link between lower resting-state connectivity in BMI-associated regions and cognitive function was found. The findings might indicate that obesity is associated with patterns of decreased default mode connectivity similar to those seen in populations at risk for Alzheimer's disease. Hum Brain Mapp 38:3502-3515, 2017. (c) 2017 Wiley Periodicals, Inc.

Authors: F. Beyer, S. Kharabian Masouleh, J. M. Huntenburg, L. Lampe, T. Luck, S. G. Riedel-Heller, M. Loeffler, M. L. Schroeter, M. Stumvoll, A. Villringer, A. V. Witte

Date Published: 12th Apr 2017

Publication Type: Journal article

Human Diseases: obesity

Abstract (Expand)

INTRODUCTION: A global dementia epidemic is projected for the year 2050 with an ever-rising number of individuals living with the syndrome worldwide. However, increasingly, studies are emerging from high-income countries (HIC) that show a positive trend towards a possible decrease in dementia occurrence. Therefore, we aim to systematically summarise evidence regarding secular trends in the incidence of dementia in HIC. METHODS AND ANALYSIS: We will conduct a systematic review of the literature on secular trends in dementia incidence in HIC according to the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) and the Meta-analysis of Observational Studies in Epidemiology (MOOSE) statements. To do so, we will search the databases MEDLINE (PubMed interface), EMBASE (Ovid interface) and Web of Science (Web of Science interface), as well as the grey literature on unpublished studies. To be eligible, studies must have been published in English or German since 1990 and provide sufficient information on prespecified eligibility criteria regarding outcome measurement and methodological approach. Study selection, data extraction and risk of bias assessment will be performed independently by 2 reviewers. Disagreement will be resolved by discussion and/or the involvement of a third researcher. Data abstraction will include study and participant characteristics, outcomes and methodological aspects. Results will be described and discussed regarding methodology. Depending on the number of studies found and the heterogeneity between the studies, we plan to combine outcome data through meta-analysis in order to get pooled incidence measures. ETHICS AND DISSEMINATION: No primary data will be collected; thus, ethical approval is not required. The results will be disseminated through a peer-reviewed publication and conference presentations. PROSPERO REGISTRATION NUMBER: CRD42016043232.

Authors: S. Roehr, A. Pabst, T. Luck, S. G. Riedel-Heller

Date Published: 7th Apr 2017

Publication Type: Journal article

Human Diseases: dementia, Alzheimer's disease

Abstract (Expand)

BACKGROUND: The Generalized Anxiety Disorder Scales GAD-7 and GAD-2 are instruments for the assessment of anxiety. The aims of this study are to test psychometric properties of these questionnaires, to provide normative values, and to investigate associations with sociodemographic factors, quality of life, psychological variables, and behavioral factors. METHODS: A German community sample (n=9721) with an age range of 18-80 years was surveyed using the GAD-7 and several other questionnaires. RESULTS: Confirmatory factor analyses confirmed the unidimensionality and measurement invariance of the GAD-7 across age and gender. Females were more anxious than males (mean scores: M=4.07 vs. M=3.01; effect size: d=0.33). There was no linear age trend. A total of 5.9% fulfilled the cut-off criterion of 10 and above. Anxiety was correlated with low quality of life, fatigue, low habitual optimism, physical complaints, sleep problems, low life satisfaction, low social support, low education, unemployment, and low income. Cigarette smoking and alcohol consumption were also associated with heightened anxiety, especially in women. When comparing the GAD-7 (7 items) with the ultra-short GAD-2 (2 items), the GAD-7 instrument was superior to the GAD-2 regarding several psychometric criteria. LIMITATIONS: The response rate (33%) was low. Because of the cross-sectional character of the study, causal conclusions cannot be drawn. A further limitation is the lack of a gold standard for diagnosing anxiety. CONCLUSIONS: The GAD-7 can be recommended for use in clinical research and routine.

Authors: A. Hinz, A. M. Klein, E. Brahler, H. Glaesmer, T. Luck, S. G. Riedel-Heller, K. Wirkner, A. Hilbert

Date Published: 1st Mar 2017

Publication Type: Not specified

Human Diseases: generalized anxiety disorder

Abstract (Expand)

The disparity between the chronological age of an individual and their brain-age measured based on biological information has the potential to offer clinically relevant biomarkers of neurological syndromes that emerge late in the lifespan. While prior brain-age prediction studies have relied exclusively on either structural or functional brain data, here we investigate how multimodal brain-imaging data improves age prediction. Using cortical anatomy and whole-brain functional connectivity on a large adult lifespan sample (N=2354, age 19-82), we found that multimodal data improves brain-based age prediction, resulting in a mean absolute prediction error of 4.29 years. Furthermore, we found that the discrepancy between predicted age and chronological age captures cognitive impairment. Importantly, the brain-age measure was robust to confounding effects: head motion did not drive brain-based age prediction and our models generalized reasonably to an independent dataset acquired at a different site (N=475). Generalization performance was increased by training models on a larger and more heterogeneous dataset. The robustness of multimodal brain-age prediction to confounds, generalizability across sites, and sensitivity to clinically-relevant impairments, suggests promising future application to the early prediction of neurocognitive disorders.

Authors: F. Liem, G. Varoquaux, J. Kynast, F. Beyer, S. Kharabian Masouleh, J. M. Huntenburg, L. Lampe, M. Rahim, A. Abraham, R. C. Craddock, S. Riedel-Heller, T. Luck, M. Loeffler, M. L. Schroeter, A. V. Witte, A. Villringer, D. S. Margulies

Date Published: 1st Mar 2017

Publication Type: Journal article

Abstract (Expand)

Background and objectives: Obesity has been associated with increased risk of dementia. Grey and white matter (WM) of the brain are commonly used as biomarkers for early detection of dementia. However, considering WM, available neuroimaging studies had mainly small sample size and yielded less conclusive results (Kullmann et al., 2015). Recently, a positive correlation between obesity and fractional anisotropy (FA) in a middle age group was reported (Birdsill et al. 2017). Furthermore, obesity is related to many medical problems such as diabetes and hypertension. Diabetes and hypertension were found to be correlated with brain structures independently (de Leeuw et al., 2002; Weinstein et al., 2015). Yet, studies rarely investigated non-lesion WM microstructure and its association with diabetes and blood pressure. Therefore we aim to investigate the relation between abdominal obesity, diabetes, blood pressure and WM microstructural variability in a large cohort of community-dwelling healthy adults. Methods: The sample included dementia-free participants (mean age 55 ± 16 years; 50.7% women) of the LIFE cohort with brain MRI scans (n = 1255). WM microstructure was measured with diffusion tensor imaging (DTI). Mean FA was derived from the individual WM skeleton processed by tract-based-spatial-statistic method. Linear regression models were used to assess the relationships between diabetes, blood pressure, waist to hip ratio (WHR) and DTI parameters. Adjustments were made for age, sex, education and Apoe4. Results: The preliminary result indicated diabetes, systolic blood pressure and WHR were independently associated with lower FA, and diabetes explained the most variance besides age. Subgroup analysis revealed both systolic blood pressure and WHR were negatively associated with mean FA in the non-diabetes group (n=1101). Conclusions: The preliminary result of our study indicates that diabetes accelerated brain aging on directional diffusion of WM. Abdominal fat and blood pressure were associated with WM variabilities independently from age, sex and diabetes. With subsequent analysis of additional DTI measures, blood parameters, WM hyperintensity maps and voxel-based microstructural WM “integrity”, we aim to further characterize the associations between obesity, diabetes, blood pressure and WM microstructure. This will contribute to the existing literature and help to disentangle the underlying mechanism.

Authors: Rui Zhang, Frauke Beyer, L. Lampe, T. Luck, S. G. Riedel-Heller, M. Stumvoll, Markus Löffler, M. L. Schroeter, A. Villringer, A. V. Witte

Date Published: 2017

Publication Type: Not specified

Human Diseases: diabetes mellitus, obesity, hypertension

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