Johannes Hertel

Bio: Johannes Hertel is an academic researcher from National University of Ireland, Galway. The author has contributed to research in topics: Dementia & Population. The author has an hindex of 21, co-authored 72 publications receiving 1237 citations. Previous affiliations of Johannes Hertel include University of Luxembourg & University of Greifswald.

Circulating metabolites and general cognitive ability and dementia : Evidence from 11 cohort studies

Abstract: Introduction Identifying circulating metabolites that are associated with cognition and dementia may improve our understanding of the pathogenesis of dementia and provide crucial readouts for preventive and therapeutic interventions. Methods We studied 299 metabolites in relation to cognition (general cognitive ability) in two discovery cohorts (N total = 5658). Metabolites significantly associated with cognition after adjusting for multiple testing were replicated in four independent cohorts (N total = 6652), and the associations with dementia and Alzheimer's disease (N = 25,872) and lifestyle factors (N = 5168) were examined. Results We discovered and replicated 15 metabolites associated with cognition including subfractions of high-density lipoprotein, docosahexaenoic acid, ornithine, glutamine, and glycoprotein acetyls. These associations were independent of classical risk factors including high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, glucose, and apolipoprotein E (APOE) genotypes. Six of the cognition-associated metabolites were related to the risk of dementia and lifestyle factors. Discussion Circulating metabolites were consistently associated with cognition, dementia, and lifestyle factors, opening new avenues for prevention of cognitive decline and dementia.

Parkinson's disease-associated alterations of the gut microbiome predict disease-relevant changes in metabolic functions.

Abstract: Parkinson’s disease (PD) is a systemic disease clinically defined by the degeneration of dopaminergic neurons in the brain. While alterations in the gut microbiome composition have been reported in PD, their functional consequences remain unclear. Herein, we addressed this question by an analysis of stool samples from the Luxembourg Parkinson’s Study (n = 147 typical PD cases, n = 162 controls). All individuals underwent detailed clinical assessment, including neurological examinations and neuropsychological tests followed by self-reporting questionnaires. Stool samples from these individuals were first analysed by 16S rRNA gene sequencing. Second, we predicted the potential secretion for 129 microbial metabolites through personalised metabolic modelling using the microbiome data and genome-scale metabolic reconstructions of human gut microbes. Our key results include the following. Eight genera and seven species changed significantly in their relative abundances between PD patients and healthy controls. PD-associated microbial patterns statistically depended on sex, age, BMI, and constipation. Particularly, the relative abundances of Bilophila and Paraprevotella were significantly associated with the Hoehn and Yahr staging after controlling for the disease duration. Furthermore, personalised metabolic modelling of the gut microbiomes revealed PD-associated metabolic patterns in the predicted secretion potential of nine microbial metabolites in PD, including increased methionine and cysteinylglycine. The predicted microbial pantothenic acid production potential was linked to the presence of specific non-motor symptoms. Our results suggest that PD-associated alterations of the gut microbiome can translate into substantial functional differences affecting host metabolism and disease phenotype.

Personalized whole-body models integrate metabolism, physiology, and the gut microbiome.

Abstract: Comprehensive molecular-level models of human metabolism have been generated on a cellular level. However, models of whole-body metabolism have not been established as they require new methodological approaches to integrate molecular and physiological data. We developed a new metabolic network reconstruction approach that used organ-specific information from literature and omics data to generate two sex-specific whole-body metabolic (WBM) reconstructions. These reconstructions capture the metabolism of 26 organs and six blood cell types. Each WBM reconstruction represents whole-body organ-resolved metabolism with over 80,000 biochemical reactions in an anatomically and physiologically consistent manner. We parameterized the WBM reconstructions with physiological, dietary, and metabolomic data. The resulting WBM models could recapitulate known inter-organ metabolic cycles and energy use. We also illustrate that the WBM models can predict known biomarkers of inherited metabolic diseases in different biofluids. Predictions of basal metabolic rates, by WBM models personalized with physiological data, outperformed current phenomenological models. Finally, integrating microbiome data allowed the exploration of host-microbiome co-metabolism. Overall, the WBM reconstructions, and their derived computational models, represent an important step toward virtual physiological humans.

Effectiveness and Safety of Dementia Care Management in Primary Care: A Randomized Clinical Trial.

Abstract: Importance Dementia care management (DCM) can increase the quality of care for people with dementia. Methodologically rigorous clinical trials on DCM are lacking. Objective To test the effectiveness and safety of DCM in the treatment and care of people with dementia living at home and caregiver burden (when available). Design, Setting, and Participants This pragmatic, general practitioner–based, cluster-randomized intervention trial compared the intervention with care as usual at baseline and at 12-month follow-up. Simple 1:1 randomization of general practices in Germany was used. Analyses were intent to treat and per protocol. In total, 6838 patients were screened for dementia (eligibility: 70 years and older and living at home) from January 1, 2012, to March 31, 2016. Overall, 1167 (17.1%) were diagnosed as having dementia, and 634 (9.3%) provided written informed consent to participate. Interventions Dementia care management was provided for 6 months at the homes of patients with dementia. Dementia care management is a model of collaborative care, defined as a complex intervention aiming to provide optimal treatment and care for patients with dementia and support caregivers using a computer-assisted assessment determining a personalized array of intervention modules and subsequent success monitoring. Dementia care management was targeted at the individual patient level and was conducted by 6 study nurses with dementia care–specific qualifications. Main Outcomes and Measures Quality of life, caregiver burden, behavioral and psychological symptoms of dementia, pharmacotherapy with antidementia drugs, and use of potentially inappropriate medication. Results The mean age of 634 patients was 80 years. A total of 407 patients received the intended treatment and were available for primary outcome measurement. Of these patients, 248 (60.9%) were women, and 204 (50.1%) lived alone. Dementia care management significantly decreased behavioral and psychological symptoms of dementia (b = −7.45; 95% CI, −11.08 to −3.81; P P = .045) compared with care as usual. Patients with dementia receiving DCM had an increased chance of receiving antidementia drug treatment (DCM, 114 of 291 [39.2%] vs care as usual, 31 of 116 [26.7%]) after 12 months (odds ratio, 1.97; 95% CI, 0.99 to 3.94; P = .03). Dementia care management significantly increased quality of life (b = 0.08; 95% CI, 0 to 0.17; P = .03) for patients not living alone but did not increase quality of life overall. There was no effect on potentially inappropriate medication (odds ratio, 1.86; 95% CI, 0.62 to 3.62; P = .97). Conclusions and Relevance Dementia care management provided by specifically trained nurses is an effective collaborative care model that improves relevant patient- and caregiver-related outcomes in dementia. Implementing DCM in different health care systems should become an active area of research. Trial Registration clinicaltrials.gov Identifier:NCT01401582

Validity and reliability.

Abstract: For the statistical consultant working with social science researchers the estimation of reliability and validity is a task frequently encountered. Measurement issues differ in the social sciences in that they are related to the quantification of abstract, intangible and unobservable constructs. In many instances, then, the meaning of quantities is only inferred. Let us begin by a general description of the paradigm that we are dealing with. Most concepts in the behavioral sciences have meaning within the context of the theory that they are a part of. Each concept, thus, has an operational definition which is governed by the overarching theory. If a concept is involved in the testing of hypothesis to support the theory it has to be measured. So the first decision that the research is faced with is \" how shall the concept be measured? \" That is the type of measure. At a very broad level the type of measure can be observational, self-report, interview, etc. These types ultimately take shape of a more specific form like observation of ongoing activity, observing video-taped events, self-report measures like questionnaires that can be open-ended or close-ended, Likert-type scales, interviews that are structured, semi-structured or unstructured and open-ended or close-ended. Needless to say, each type of measure has specific types of issues that need to be addressed to make the measurement meaningful, accurate, and efficient. Another important feature is the population for which the measure is intended. This decision is not entirely dependent on the theoretical paradigm but more to the immediate research question at hand. 6/14/2016 2 A third point that needs mentioning is the purpose of the scale or measure. What is it that the researcher wants to do with the measure? Is it developed for a specific study or is it developed with the anticipation of extensive use with similar populations? Once some of these decisions are made and a measure is developed, which is a careful and tedious process, the relevant questions to raise are \" how do we know that we are indeed measuring what we want to measure? \" since the construct that we are measuring is abstract, and \" can we be sure that if we repeated the measurement we will get the same result? \". The first question is related to validity and second to reliability. Validity and reliability are two important characteristics of behavioral measure and are referred to as …

ADHD Prevalence Estimates Across Three Decades: An Updated Systematic Review and Meta-Regression Analysis

Abstract: BACKGROUND Previous studies have identified significant variability in attention-deficit / hyperactivity disorder (ADHD) prevalence estimates worldwide, largely explained by methodological procedures. However, increasing rates of ADHD diagnosis and treatment throughout the past few decades have fuelled concerns about whether the true prevalence of the disorder has increased over time. METHODS We updated the two most comprehensive systematic reviews on ADHD prevalence available in the literature. Meta-regression analyses were conducted to test the effect of year of study in the context of both methodological variables that determined variability in ADHD prevalence (diagnostic criteria, impairment criterion and source of information), and the geographical location of studies. RESULTS We identified 154 original studies and included 135 in the multivariate analysis. Methodological procedures investigated were significantly associated with heterogeneity of studies. Geographical location and year of study were not associated with variability in ADHD prevalence estimates. CONCLUSIONS Confirming previous findings, variability in ADHD prevalence estimates is mostly explained by methodological characteristics of the studies. In the past three decades, there has been no evidence to suggest an increase in the number of children in the community who meet criteria for ADHD when standardized diagnostic procedures are followed.

Dementia: a public health priority

Abstract: Zakljucno, potrebno je i nadalje svakodnevno raditi na prevenciji demencije, osiguravati resurse i osmisljavati strategije borbe protiv demencije, jer ce broj osoba s demencijom i u Hrvatskoj u buducnosti biti veci. No, s obzirom da se u svijetu ulažu znatna sredstva u podrucju istraživanja demencije, za ocekivati je pozitivnih pomaka, kako na podrucju terapije, rane dijagnostike, tako i na podrucju rehabilitacije osoba s demencijom. Stoga - vrijeme je na nasoj strani!

Facing up to the global challenges of ageing.

Abstract: Longer human lives have led to a global burden of late-life disease However, some older people experience little ill health, a trait that should be extended to the general population Interventions into lifestyle, including increased exercise and reduction in food intake and obesity, can help to maintain healthspan Altered gut microbiota, removal of senescent cells, blood factors obtained from young individuals and drugs can all improve late-life health in animals Application to humans will require better biomarkers of disease risk and responses to interventions, closer alignment of work in animals and humans, and increased use of electronic health records, biobank resources and cohort studies