dementia

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A cognitive disorder resulting from a loss of brain function affecting memory, thinking, language, judgement and behavior.


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LIFE Adult

This population-based study examined 10,000 participants randomly selected from the Leipzig population (2011 to 2014). A follow-up is to be carried out from 2017 - 2020. The study mainly included people aged between 40 and 79. All participants underwent a 6-hour study program and people over 60 years of age were invited two more times to in-depth study of cognition and depression and the brain (MRI, EEG). Extensive measurements of genome, metabolome and transcriptome are available. The LIFE-ADULT ...

Programme: LIFE Management Cluster

Public web page: http://life.uni-leipzig.de/en/adults/life_adult.html

Start date: 1st Jan 2009

ASSOCIATION OF HIPPOCAMPAL VOLUMES WITH COGNITIVE TASKS IN A LARGE POPULATION-BASED COHORT
LIFE - Leipzig Research Center for Civilization Diseases

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

Secular trends in the incidence of dementia in high-income countries: a protocol of a systematic review and a planned meta-analysis.
LIFE Adult

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

Predicting behavioral variant frontotemporal dementia with pattern classification in multi-center structural MRI data.
LIFE Adult

Abstract (Expand)

PURPOSE: Frontotemporal lobar degeneration (FTLD) is a common cause of early onset dementia. Behavioral variant frontotemporal dementia (bvFTD), its most common subtype, is characterized by deep … alterations in behavior and personality. In 2011, new diagnostic criteria were suggested that incorporate imaging criteria into diagnostic algorithms. The study aimed at validating the potential of imaging criteria to individually predict diagnosis with machine learning algorithms. MATERIALS & METHODS: Brain atrophy was measured with structural magnetic resonance imaging (MRI) at 3 Tesla in a multi-centric cohort of 52 bvFTD patients and 52 healthy control subjects from the German FTLD Consortium's Study. Beside group comparisons, diagnosis bvFTD vs. controls was individually predicted in each subject with support vector machine classification in MRI data across the whole brain or in frontotemporal, insular regions, and basal ganglia known to be mainly affected based on recent meta-analyses. Multi-center effects were controlled for with a new method, "leave one center out" conjunction analyses, i.e. repeatedly excluding subjects from each center from the analysis. RESULTS: Group comparisons revealed atrophy in, most consistently, the frontal lobe in bvFTD beside alterations in the insula, basal ganglia and temporal lobe. Most remarkably, support vector machine classification enabled predicting diagnosis in single patients with a high accuracy of up to 84.6%, where accuracy was highest in a region-of-interest approach focusing on frontotemporal, insular regions, and basal ganglia in comparison with the whole brain approach. CONCLUSION: Our study demonstrates that MRI, a widespread imaging technology, can individually identify bvFTD with high accuracy in multi-center imaging data, paving the road to personalized diagnostic approaches in the future.

Authors: S. Meyer, K. Mueller, K. Stuke, S. Bisenius, J. Diehl-Schmid, F. Jessen, J. Kassubek, J. Kornhuber, A. C. Ludolph, J. Prudlo, A. Schneider, K. Schuemberg, I. Yakushev, M. Otto, M. L. Schroeter

Date Published: 29th Mar 2017

Publication Type: Journal article

Human Diseases: frontotemporal dementia

Outcomes of stable and unstable patterns of subjective cognitive decline - results from the Leipzig Longitudinal Study of the Aged (LEILA75+).
LIFE Adult

Abstract (Expand)

BACKGROUND: Subjective cognitive decline (SCD), i.e., the self-perceived feeling of worsening cognitive function, may be the first notable syndrome of preclinical Alzheimer's disease and other … dementias. However, not all individuals with SCD progress. Stability of SCD, i.e., repeated reports of SCD, could contribute to identify individuals at risk, as stable SCD may more likely reflect the continuous neurodegenerative process of Alzheimer's and other dementias. METHODS: Cox regression analyses were used to assess the association between stability of SCD and progression to MCI and dementia in data derived from the population-based Leipzig Longitudinal Study of the Aged (LEILA75+). RESULTS: Of 453 cognitively unimpaired individuals with a mean age of 80.5 years (SD = 4.2), 139 (30.7 %) reported SCD at baseline. Over the study period (M = 4.8 years, SD = 2.2), 84 (18.5 %) individuals had stable SCD, 195 (43.1 %) unstable SCD and 174 (38.4 %) never reported SCD. Stable SCD was associated with increased risk of progression to MCI and dementia (unadjusted HR = 1.8, 95 % CI = 1.2-2.6; p < .01), whereas unstable SCD yielded a decreased progression risk (unadjusted HR = 0.5, 95 % CI = 0.4-0.7; p < .001) compared to no SCD. When adjusted for baseline cognitive functioning, progression risk in individuals with stable SCD was significantly increased in comparison to individuals with unstable SCD, but not compared to individuals without SCD. CONCLUSIONS: Our results, though preliminary, suggest that stable SCD, i.e., repeated reports of SCD, may yield an increased risk of progression to MCI and dementia compared to unstable SCD. Baseline cognitive scores, though within a normal range, seem to be a driver of progression in stable SCD. Future research is warranted to investigate whether stability could hold as a SCD research feature.

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

Date Published: 4th Nov 2016

Publication Type: Journal article

Human Diseases: dementia, Alzheimer's disease

Which types of mental work demands may be associated with reduced risk of dementia?
LIFE Adult

Abstract (Expand)

INTRODUCTION: Previous studies have demonstrated that an overall high level of mental work demands decreased dementia risk. In our study, we investigated whether this effect is driven by specific mental … work demands and whether it is exposure dependent. METHODS: Patients aged 75+ years were recruited from general practitioners and participated in up to seven assessment waves (every 1.5 years) of the longitudinal AgeCoDe study. Analyses of the impact of specific mental work demands on dementia risk were carried out via multivariate regression modeling (n = 2315). RESULTS: We observed a significantly lower dementia risk in individuals with a higher level of "information processing" (HR, 0.888), "pattern detection" (HR, 0.878), "mathematics" (HR, 0.878), and "creativity" (HR, 0.878). Yet, exposure-dependent effects were only significant for "information processing" and "pattern detection." DISCUSSION: Our longitudinal observations suggest that dementia risk may be reduced by some but not all types of mental work demands.

Authors: F. S. Then, T. Luck, K. Heser, A. Ernst, T. Posselt, B. Wiese, S. Mamone, C. Brettschneider, H. H. Konig, S. Weyerer, J. Werle, E. Mosch, H. Bickel, A. Fuchs, M. Pentzek, W. Maier, M. Scherer, M. Wagner, S. G. Riedel-Heller

Date Published: 30th Oct 2016

Publication Type: Journal article

Human Diseases: dementia

Differential Risk of Incident Alzheimer's Disease Dementia in Stable Versus Unstable Patterns of Subjective Cognitive Decline.
LIFE Adult

Abstract (Expand)

BACKGROUND: It is unknown whether longitudinal stability versus instability in subjective cognitive decline (SCD) is a modifying factor of the association between SCD and risk of incident Alzheimer's … disease (AD) dementia. OBJECTIVE: We tested the modifying role of temporal stability of the SCD report on AD dementia risk in cognitively normal elderly individuals. METHODS: We analyzed data of 1,990 cognitively normal participants from the longitudinal AgeCoDe Study. We assessed SCD with/without associated worries both at baseline and first follow-up 18 months later. Participants were then classified either as (a) Controls (CO, with no SCD at both baseline and follow-up 1, n = 613), (b) inconsistent SCD (with SCD reported only at baseline or at follow-up 1, n = 637), (c) consistent SCD but without/or with inconsistent worries (n = 610) or (d) consistent SCD with worries (n = 130). We estimated incident AD dementia risk over up to 6 years for each group with Cox-Proportional Hazard Regression analyses adjusted for age, gender, education, ApoE4 status, and depression. RESULTS: Compared to CO, inconsistent SCD was not associated with increased risk of incident AD dementia. In contrast, risk was doubled in the group of consistent SCD without/ with inconsistent worries, and almost 4-fold in the group of consistent SCD with worries. These results could be replicated when using follow-up 1 to follow-up 2 response patterns for group definition. CONCLUSION: These findings suggest that longitudinal stability versus instability is an important modifying factor of the association between SCD and AD dementia risk. Worrisome SCD that is also consistently reported over time is associated with greatly increased risk of AD dementia.

Authors: S. Wolfsgruber, L. Kleineidam, M. Wagner, E. Mosch, H. Bickel, D. Lupsilonhmann, A. Ernst, B. Wiese, S. Steinmann, H. H. Konig, C. Brettschneider, T. Luck, J. Stein, S. Weyerer, J. Werle, M. Pentzek, A. Fuchs, W. Maier, M. Scherer, S. G. Riedel-Heller, F. Jessen

Date Published: 4th Oct 2016

Publication Type: Journal article

Human Diseases: dementia, Alzheimer's disease

Response to the letter on 'Validating new diagnostic imaging criteria for primary progressive aphasia via anatomical likelihood estimation meta-analyses'.
LIFE Adult

Abstract

Not specified

Authors: S. Bisenius, J. Neumann, M. L. Schroeter

Date Published: 20th Jul 2016

Publication Type: Not specified

Human Diseases: dementia, aphasia

Education as protector against dementia, but what exactly do we mean by education?
LIFE Adult

Abstract (Expand)

OBJECTIVES: even though a great number of research studies have shown that high education has protective effects against dementia, some studies did not observe such a significant effect. In that respect, … the aim of our study was to investigate and compare various operationalisation approaches of education and how they impact dementia risk within one sample. METHODS: data were derived from the Leipzig longitudinal study of the aged (LEILA75+). Individuals aged 75 and older underwent six cognitive assessments at an interval of 1.5 years and a final follow-up 15 years after the baseline assessment. We operationalised education according to different approaches used in previous studies and analysed the impact on dementia incidence via multivariate cox regression modelling. RESULTS: the results showed that whether education is identified as significant protector against dementia strongly depends on the operationalisation of education. Whereas the pure number of years of education showed statistically significant protective effects on dementia risk, other more complex categorical classification approaches did not. Moreover, completing >10 years of education or a tertiary level seems to be an important threshold to significantly reduce dementia risk. CONCLUSION: findings suggest a protective effect of more years of education on a lower dementia risk with a particular critical threshold of completing >10 years of education. Further, the findings highlight that, when examining risks and protective factors of dementia, a careful consideration of the underlying definitions and operationalisation approaches is required.

Authors: F. S. Then, T. Luck, M. C. Angermeyer, S. G. Riedel-Heller

Date Published: 9th Apr 2016

Publication Type: Journal article

Human Diseases: dementia

Compression of dementia morbidity by higher education
LIFE - Leipzig Research Center for Civilization Diseases

Abstract (Expand)

Objectives: The concept of compression of morbidity suggests that compressing cognitive morbidity into a shorter lifetime period would result in a better cumulative lifetime cognitive functioning. Some … lifestyle factors, like higher education, that are known to protect cognitive functioning in old age and lower dementia risk, could compress cognitive morbidity. Therefore the aim of our study was to investigate whether higher education leads to a better cumulative lifetime cognitive functioning and, hence, the compression of cognitive morbidity. Methods: Data were derived from the population-based Leipzig longitudinal study of the aged (LEILA75+). From 1998-2005, individuals aged 75 years and older underwent up to seven assessments at a 1.5-year interval and a long-term follow-up assessment after 15 years (2013). Analyses on the impact of higher education on compression of cognitive morbidity were carried out via multilevel logistic mixed-models and tobit analyses using the participants’ age as time scale (n=742). Results: The results revealed that more years of education were significantly associated with a better cognitive functioning but not with the age at dementia onset or the age at death. Computation of cumulative lifetime cognitive functioning was weighted for survival probability and indicated a gain of 21 MMSE points during the lifetime period 75 through 100 years of age by having more than 12 years of education compared to having less than 9 years of education. Conclusion: Overall, the findings suggest a compression of cognitive morbidity by higher education prior to dementia onset. More years of education could therefore contribute to a better cognitive functioning even under consideration of survival probability. Hence, efforts to ensure access to higher education for as many people in a population as possible might compress disease burden due to cognitive morbidity.

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

Date Published: 1st Mar 2016

Publication Type: Not specified

Human Diseases: dementia

Incident Subjective Cognitive Decline Does Not Predict Mortality in the Elderly--Results from the Longitudinal German Study on Ageing, Cognition, and Dementia (AgeCoDe).
LIFE Adult

Abstract (Expand)

OBJECTIVE: Subjective cognitive decline (SCD) might represent the first symptomatic representation of Alzheimer's disease (AD), which is associated with increased mortality. Only few studies, … however, have analyzed the association of SCD and mortality, and if so, based on prevalent cases. Thus, we investigated incident SCD in memory and mortality. METHODS: Data were derived from the German AgeCoDe study, a prospective longitudinal study on the epidemiology of mild cognitive impairment (MCI) and dementia in primary care patients over 75 years covering an observation period of 7.5 years. We used univariate and multivariate Cox regression analyses to examine the relationship of SCD and mortality. Further, we estimated survival times by the Kaplan Meier method and case-fatality rates with regard to SCD. RESULTS: Among 971 individuals without objective cognitive impairment, 233 (24.0%) incidentally expressed SCD at follow-up I. Incident SCD was not significantly associated with increased mortality in the univariate (HR = 1.0, 95% confidence interval = 0.8-1.3, p = .90) as well as in the multivariate analysis (HR = 0.9, 95% confidence interval = 0.7-1.2, p = .40). The same applied for SCD in relation to concerns. Mean survival time with SCD was 8.0 years (SD = 0.1) after onset. CONCLUSION: Incident SCD in memory in individuals with unimpaired cognitive performance does not predict mortality. The main reason might be that SCD does not ultimately lead into future cognitive decline in any case. However, as prevalence studies suggest, subjectively perceived decline in non-memory cognitive domains might be associated with increased mortality. Future studies may address mortality in such other cognitive domains of SCD in incident cases.

Authors: S. Roehr, T. Luck, K. Heser, A. Fuchs, A. Ernst, B. Wiese, J. Werle, H. Bickel, C. Brettschneider, A. Koppara, M. Pentzek, C. Lange, J. Prokein, S. Weyerer, E. Mosch, H. H. Konig, W. Maier, M. Scherer, F. Jessen, S. G. Riedel-Heller

Date Published: 15th Jan 2016

Publication Type: Not specified

Human Diseases: dementia

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