Gerontology (GERONTOLOGY)

Publisher: Karger

Journal description

As the ratio of people over sixty-five continues to rise, understanding the basic mechanisms of aging and age-related diseases has become a matter of urgent necessity. ëGerontologyí responds to this need by drawing experimental contributions from diverse medical, biological and behavioral disciplines to provide a primary source of high-quality papers covering all aspects of aging in man and animals. Recent research on the clinical problems of aging and the practical applications of laboratory results is also included to support the fundamental goals of extending active life and enhancing its quality. Informative reviews and an open debate section for stimulating, speculative articles carry strong reader approval.

Current impact factor: 2.68

Impact Factor Rankings

2015 Impact Factor Available summer 2015
2013 / 2014 Impact Factor 2.681
2012 Impact Factor 2.676
2011 Impact Factor 2.777
2010 Impact Factor 2.203
2009 Impact Factor 1.661
2008 Impact Factor 1.69
2007 Impact Factor 1.358
2006 Impact Factor 1.439
2005 Impact Factor 1.636
2004 Impact Factor 1.31
2003 Impact Factor 1.6
2002 Impact Factor 1.48
2001 Impact Factor 1.418
2000 Impact Factor 1.424
1999 Impact Factor 1.711
1998 Impact Factor 1.5
1996 Impact Factor 0.969
1995 Impact Factor 0.778
1994 Impact Factor 1.101
1993 Impact Factor 1.17
1992 Impact Factor 1.074

Impact factor over time

Impact factor
Year

Additional details

5-year impact 2.76
Cited half-life 8.10
Immediacy index 0.44
Eigenfactor 0.01
Article influence 0.87
Website Gerontology website
Other titles Gerontology (Online)
ISSN 0304-324X
OCLC 44723306
Material type Document, Periodical, Internet resource
Document type Internet Resource, Computer File, Journal / Magazine / Newspaper

Publisher details

Karger

  • Pre-print
    • Author can archive a pre-print version
  • Post-print
    • Author can archive a post-print version
  • Conditions
    • On author's server or institutional server
    • Server must be non-commercial
    • Publisher's version/PDF cannot be used
    • Publisher copyright and source must be acknowledged
    • Must link to publisher version
  • Classification
    ​ green

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Frailty is a geriatric syndrome resulting from age-related cumulative decline across multiple physiologic systems, impaired homeostatic reserve, and reduced capacity to resist stress. Based on recent estimates, 10% of community-dwelling older individuals are frail and another 41.6% are prefrail. Frail elders account for the highest health care costs in industrialized nations. Impaired physical function is a major indicator of frailty, and functional performance tests are useful for the identification of frailty. Objective instrumented assessments of physical functioning that are feasible for home frailty screening have not been adequately developed. Objective: To examine the ability of wearable sensor-based in-home assessment of gait, balance, and physical activity (PA) to discriminate between frailty levels (nonfrail, prefrail, and frail). Methods: In an observational cross-sectional study, in-home visits were completed in 125 older adults (nonfrail: n = 44, prefrail: n = 60, frail: n = 21) living in Tucson, Ariz., USA, between September 2012 and November 2013. Temporal-spatial gait parameters (speed, stride length, stride time, double support, and variability of stride velocity), postural balance (sway of hip, ankle, and center of mass), and PA (percentage of walking, standing, sitting, and lying; mean duration and variability of single walking, standing, sitting, and lying bouts) were measured in the participant's home using validated wearable sensor technology. Logistic regression was used to assess the most sensitive gait, balance, and PA variables for identifying prefrail participants (vs. nonfrail). Multinomial logistic regression was used to identify variables sensitive to discriminate between three frailty levels. Results: Gait speed (area under the curve, AUC = 0.802), hip sway (AUC = 0.734), and steps/day (AUC = 0.736) were the most sensitive parameters for the identification of prefrailty. Multinomial regression revealed that stride length (AUC = 0.857) and double support (AUC = 0.841) were the most sensitive gait parameters for discriminating between three frailty levels. Interestingly, walking bout duration variability was the most sensitive PA parameter for discriminating between three frailty levels (AUC = 0.818). No balance parameter discriminated between three frailty levels. Conclusion: Our results indicate that unique parameters derived from objective assessment of gait, balance, and PA are sensitive for the identification of prefrailty and the classification of a subject's frailty level. The present findings highlight the potential of wearable sensor technology for in-home assessment of frailty status. © 2014 S. Karger AG, Basel.
    Gerontology 12/2014; DOI:10.1159/000369095
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    ABSTRACT: It has been shown that pathogen-specific secretory IgA (SIgA) antibody (Ab) is the major player at mucosal surfaces for host defense. However, alterations in the mucosal immune system occur in advanced aging, which results in a failure of induction of SIgA Abs for the protection from infectious diseases. Signs of mucosal senescence first appear in the gut immune system. Further, changes in the intestinal microbiota most likely influence mucosal immunity. To overcome the immunological aging decline in mucosal immunity, several adjuvant systems including mucosal dendritic cell targeting have been shown to be attractive and effective immunological strategies. Similarly, microfold (M) cells involved in the antigen (Ag) uptake are ideal targets for facilitating Ag-specific mucosal immune responses. However, the numbers of M cells are reduced in aged mice. In this regard, Spi-B, an essential transcription factor for the functional and structural differentiation of M cells, could be a potent strategy for the induction of effective mucosal immunity in aging. © 2014 S. Karger AG, Basel.
    Gerontology 12/2014; DOI:10.1159/000368897
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    ABSTRACT: Atherosclerosis is a complex disease which can be described as an excessive fibrofatty, proliferative, inflammatory response to damage to the artery wall involving several cell types such as smooth muscle cells, monocyte-derived macrophages, lymphocytes, dendritic cells and platelets. On the other hand, atherosclerosis is a typical age-related degenerative pathology, which is characterized by signs of cell senescence in the arterial wall including reduced cell proliferation, irreversible growth arrest and apoptosis, increased DNA damage, the presence of epigenetic modifications, shortening of telomere length and mitochondrial dysfunction. The most prominent characteristics of mitochondrial aging are their structural alterations and mitochondrial DNA damage. The mechanisms of mitochondrial genome damage in the development of chronic age-related diseases such as atherosclerosis are not yet well understood. This review focuses on the latest findings from studies of those mutations of the mitochondrial genome which may play an important role in the development of atherosclerosis and which are, at the same time, also markers of mitochondrial aging and cell senescence. © 2014 S. Karger AG, Basel.
    Gerontology 12/2014; DOI:10.1159/000368923
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    ABSTRACT: Background: Zebrafish have become a valuable model for the study of developmental biology and human disease, such as cardiovascular disease. It is difficult to discriminate between disease-related and age-related alterations. Objective: This study was aimed to investigate the effects and potential mechanisms of age-related cardiac modifications in an older zebrafish population. Methods: In this study, we calculated the survival rate and measured the spinal curvature through the aging process. A swimming challenge test was performed and showed that swimming capacity and endurance dramatically dropped in older fish groups. Results: To find out the effect of stress on zebrafish during the aging process, we recorded electrocardiograms on zebrafish and showed that during stress, aging not only led to a significant reduction in heart rate, but also caused other age-related impairments, such as arrhythmias and ST-T depression. Echocardiography showed a marked increase in end-diastolic ventricular dimensions and in isovolumic relaxation time and a notably slower mean and peak velocity of the bulboventricular valve in older zebrafish, but stroke volume and cardiac output were not different in young and old zebrafish. Both nppa and nppb (cardiac fetal genes for natriuretic factor) expression detected by real-time polymerase chain reaction analysis increased in older fish compared to the younger group. Histological staining revealed fibrosis within cardiomyocytes and an increase in ventricular myocardial density and a decrease in epicardial vessel dimensions in older fish hearts that may correlate with a deterioration of cardiac function and exercise capacity. Conclusion: These data suggest that cardiac functional modifications in zebrafish are comparable to those in humans and may partly be due to changes in the cardiovascular system including cardiac fetal gene reprogramming, myocardial density, and epicardial vessel dimensions. © 2014 S. Karger AG, Basel.
    Gerontology 12/2014; DOI:10.1159/000369094
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    ABSTRACT: Biodemography is a promising scientific approach based on using demographic data and methods for getting insights into biological mechanisms of observed processes. Recently, new important developments have happened in biodemographic studies of aging and longevity that call into question conventional aging theories and open up novel research directions. Recent studies found that the exponential increase of the mortality risk with age (the famous Gompertz law) continues even at extreme old ages in humans, rats, and mice, thus challenging traditional views about old-age mortality deceleration, mortality leveling-off, and late-life mortality plateaus. This new finding represents a challenge to many aging theories, including the evolutionary theory that explains senescence by a declining force of natural selection with age. Innovative ideas are needed to explain why exactly the same exponential pattern of mortality growth is observed not only at reproductive ages, but also at very-old postreproductive ages (up to 106 years), long after the force of natural selection becomes negligible (when there is no room for its further decline). Another important recent development is the discovery of long-term 'memory' for early-life experiences in longevity determination. Siblings born to young mothers have significantly higher chances to live up to 100 years, and this new finding, confirmed by two independent research groups, calls for its explanation. As recent studies found, even the place and season of birth matter for human longevity. Beneficial longevity effects of young maternal age are observed only when children of the same parents are compared, while the maternal age effect often could not be detected in across-families studies, presumably being masked by between-family variation. It was also found that male gender of centenarian has a significant positive effect on the survival of adult male biological relatives (brothers and fathers) but not of female relatives. Finally, large gender differences are found in longevity determinants for males and females, suggesting a higher importance of occupation history for male centenarians as well as a higher importance of home environment history for female centenarians. © 2014 S. Karger AG, Basel.
    Gerontology 12/2014; DOI:10.1159/000369011
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    ABSTRACT: Background: Future time perspective has been associated with subjective well-being, though depending on the line of research considered either an open-ended future time perspective or a limited future time perspective has been associated with high well-being. Most of this research however has conceptualized future time perspective as a one-dimensional construct, whereas recent evidence has demonstrated that there are likely at least two different underlying dimensions, a focus on opportunities and a focus on limitations. This project first seeks to replicate the two-dimensional structure of the Future Time Perspective Scale, and then examines the associations these dimensions may have with different measures of subjective well-being and a biological index of chronic stress. Objective: To test if the two dimensions of the Future Time Perspective Scale, a focus on opportunities and a focus on limitations, differentially associate with two measures of subjective well-being and a biological indicator of chronic stress, namely hair cortisol. Method: Sixty-six community-dwelling participants with a mean age of 72 years (SD = 5.83) completed the Future Time Perspective Scale, Center for Epidemiologic Studies Depression Scale, and Philadelphia Geriatric Center Morale Scale. Participants also provided a 3-cm-long hair strand to index cortisol accumulation over the past 3 months. Following the results of a factor analysis, a mediation model was created for each dimension of the Future Time Perspective Scale, and significance testing was done through a bootstrapping approach to harness maximal statistical power. Results: Factor analysis results replicated the two-dimensional structure of the Future Time Perspective Scale. Both dimensions were then found to have unique associations with well-being. Specifically, a high focus on opportunities was associated with fewer depressive symptoms and higher morale, whereas a low focus on limitations was associated with reduced hair cortisol, though this association was mediated by subjective well-being. Conclusion: Results replicate and extend previous research by pointing to the multi-dimensional nature of the Future Time Perspective Scale. While an open future time perspective was overall beneficial for well-being, the exact association each dimension had with well-being differed depending on whether subjective measures of well-being or biological indices of chronic stress were considered. © 2014 S. Karger AG, Basel.
    Gerontology 12/2014; DOI:10.1159/000368716
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    ABSTRACT: Technologies that provide immersive experiences continue to become more ubiquitous across all age groups. This paper presents a review of the literature to provide a snapshot of the current state of research involving the use of immersive technologies and the elderly. A narrative literature review was conducted using the ScienceDirect, EBSCOhost, Springerlink and ERIC databases to summarize primary studies from which conclusions were drawn into a holistic interpretation. The majority of the studies examined the effect of immersive technologies on elder peoples' age-related declines, including sensory and motor changes (vision, hearing, motor skills), cognitive changes and social changes. Various immersive technologies have been described and tested to address these age-related changes, and have been categorized as 'games and simulations', 'robotics' and 'social technologies'. In most cases, promising results were found for immersive technologies to challenge age-related declines, especially through the increase of morale. © 2014 S. Karger AG, Basel.
    Gerontology 12/2014; DOI:10.1159/000365754
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    ABSTRACT: Sarcopenia is age-associated deterioration of muscle mass and function caused by a wide scope of physiological and pathological changes ranging from hormonal disorders to loss of subcellular homeostasis. Recent research indicates that mitochondrial dysregulation with advanced age plays a central role in the development of sarcopenia due to the multifactorial functions of this organelle in energy supply, redox regulation, crosstalk with nuclear gene expression and apoptosis. In order to fulfill these roles, it is crucial that mitochondria maintain their own structural and functional integrity through biogenesis, antioxidant defense, fusion/fission dynamics and autophagy (mitophagy). Unfortunately, mitochondria undergo age-associated changes that compromise the above-mentioned properties that eventually contribute to the development of sarcopenia. The peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) is involved in the transcriptional regulation of numerous nuclear and mitochondrial gene products participating in the cellular events that control muscle mass and function. Thus, it is not surprising that maintaining an optimal intracellular PGC-1α level and signaling activity is crucial in protecting the muscle from many degradative and destructive processes, such as proteolysis, oxidative damage, inflammation, uncontrolled autophagy and apoptosis. Physical exercise is a powerful stimulus to PGC-1α expression and signaling. Recent research indicates that PGC-1α-controlled mitochondrial biogenesis is not limited by old age per se and that elderly individuals can still benefit from increased muscular activity in terms of skeletal muscle health that ultimately contributes to quality of life in old age. © 2014 S. Karger AG, Basel.
    Gerontology 12/2014; DOI:10.1159/000365947
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    ABSTRACT: The aim of this mini-review is to describe the potential application of surface electromyography (sEMG) techniques in aging studies. Aging is characterized by multiple changes of the musculoskeletal system physiology and function. This paper will examine some of the innovative methods used to monitor age-related alterations of the neuromuscular system from sEMG signals. A description of critical assumptions which underlie some of these approaches is emphasized. The first part focuses on the evolution of the recording techniques and describes some methodological issues. The second part focuses on how to use the following techniques to characterize aging: amplitude and spectral sEMG signal analysis, muscle fiber conduction velocity estimation, and myoelectric fatigue assessment. The last part describes a number of advanced sEMG approaches which seem promising in the geriatric population to estimate motor unit number, size, recruitment thresholds, and firing rates. © 2014 S. Karger AG, Basel.
    Gerontology 12/2014; DOI:10.1159/000368655
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    ABSTRACT: Background: Little information is available on the potential association between polypharmacy and risk of mortality. Objective: To determine in a population-based study whether polypharmacy is associated with increased risk of mortality in elderly persons. Methods: In this population-based, prospective study of 5,052 people aged 65 years and older (Neurological Disorders in Central Spain), current medications were recorded. Cox proportional hazards models, adjusted for sociodemographics and comorbidity factors, were used to assess the risk of death up to 13.3 years later, comparing the polypharmacy group (≥6 drugs) to those who were taking 1-5 drugs and those in a nonmedicated group (0 drugs). Results: Out of 5,052 participants, 2,550 (50.5%) died over a median follow-up of 6.5 years, including 361 (28.8%) deaths among 931 nonmedicated participants, 1,946 (51.4%) deaths among 3,787 participants taking 1-5 drugs daily, and 243 (72.8%) among 334 participants on polypharmacy. In an unadjusted Cox model, risk of mortality was increased in participants on polypharmacy [hazard ratio (HR) = 2.78, 95% confidence interval [CI]: 2.36-3.27, p < 0.001) and in those taking between 1 and 5 drugs (HR = 1.47, 95% CI: 1.31-1.64, p < 0.001) versus those who were nonmedicated (reference group). In a Cox model that adjusted for a variety of demographic factors and comorbidities, HR remained increased in participants on polypharmacy (HR = 1.83, 95% CI: 1.51-2.21, p < 0.001). Conclusion: This study provides evidence that polypharmacy is associated with increased risk of mortality in elderly people. The extent to which polypharmacy is the proximate cause rather than a marker of this increase risk remains to be determined. © 2014 S. Karger AG, Basel.
    Gerontology 12/2014; DOI:10.1159/000365328
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    ABSTRACT: Ageing is a prominent risk factor for atherosclerosis and cardiovascular disease. Vascular smooth muscle cells (VSMCs) are an integral part of atherosclerotic plaque formation, progression and subsequent rupture. Emerging evidence suggests that VSMC behaviour is modified by age, which in turn may affect disease outcome in the elderly. In this review, we discuss the effect of age on VSMC behaviour, proliferation, migration, apoptosis, inflammation, extracellular matrix synthesis and calcification. In addition, we discuss the multiple signalling factors underlying these behavioural changes including angiotensin-II, matrix metalloproteinases, monocyte chemotactic protein-1, and transforming growth factor-β1. Understanding the molecular processes underpinning altered VSMC behaviour with age, may lead to the identification of novel therapeutic targets for suppressing atherosclerosis in the elderly population. © 2014 S. Karger AG, Basel.
    Gerontology 12/2014; DOI:10.1159/000368576
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    ABSTRACT: New neurons are continuously generated and added to neural circuits in the adult brain. However, increasing age imposes changes in neural progenitor cells and their microenvironment that lead to a reduction of neurogenesis. Age-related decreased production of new neurons in the neurogenic dentate gyrus has been associated with memory impairments. Several mechanisms are known that might counteract this decline in cognitive functions. Here, we give an overview of ageing-related changes in neurogenesis in the brain of humans and rodents. We discuss possible causes for reduced neurogenesis with age, its consequences on cognition, and how neurogenesis might be restored in old age. © 2014 S. Karger AG, Basel.
    Gerontology 11/2014; DOI:10.1159/000368575
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    ABSTRACT: Background: Elder abuse and metabolic syndromes are both important public health issues and are associated with increased morbidity and mortality. This study aimed to examine the associations between elder abuse and risk for metabolic syndromes. Methods: The Chicago Health and Aging Project (CHAP) cohort is a population-based study (n = 4,586). We identified 676 participants with some form of elder abuse reported to a social services agency. The primary independent variable was elder abuse reported to a social services agency. Outcomes were metabolic syndrome as categorized by World Health Organization (WHO), American Heart Association (AHA) and International Diabetes Federation (IDF) criteria. Bivariate and logistic regression analyses were used to assess the association between elder abuse and different definitions of metabolic syndromes. Results: In the bivariate analyses, elder abuse victims were more likely than those without elder abuse to have metabolic syndromes [22.4 vs. 10.7% (WHO), 50.7 vs. 40.0% (AHA) and 47.7 vs. 33.5% (IDF)]. After adjusting for potential confounding factors, elder abuse was associated with an increased risk for metabolic syndromes according to WHO [OR, 3.95 (2.86-5.47)], AHA [OR, 2.03 (1.56-2.64)] and IDF [OR, 2.55 (1.97-3.29)] criteria. Interaction term analyses indicate that the association between elder abuse and metabolic syndromes may be moderated by sociodemographic characteristics but not by health-related or psychosocial factors. Conclusion: Elder abuse is associated with an increased risk for metabolic syndromes. Research is needed to examine the association between elder abuse and cardiovascular disease. © 2014 S. Karger AG, Basel.
    Gerontology 11/2014; DOI:10.1159/000368577
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    ABSTRACT: The most common form of sensory disability is age-related hearing loss (ARHL), also referred to as presbycusis. ARHL is a complex disorder with a mixture of genetic and environmental components, a combination that leads to a progressive decline in hearing function with increased age. In the last 15 years, there has been a vast increase in our knowledge of the genes that underlie congenital deafness and the critical components of hearing. In contrast, knowledge of the pathological processes involved in ARHL remains very limited. The mouse has proved an essential tool in the identification of early-onset deafness genes and in revealing the basic mechanisms of hearing. As focus is now turning toward elucidating the most common form of hearing loss, ARHL, the mouse will again play a fundamental role in this research. Here, we review the need for an animal model and discuss the suitability of the mouse as an ARHL model. Finally, we outline the ways in which hearing researchers are utilising the mouse in the investigation of ARHL and provide perspectives on the need for these data to be integrated with the results of human genetic studies. © 2014 S. Karger AG, Basel.
    Gerontology 11/2014; DOI:10.1159/000368399
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    ABSTRACT: Significant advances in health and social wellbeing have led to linear gains in life expectancy and an accompanying increase in the burden imposed by age-related morbidities. Complex alterations in hormonal networks which regulate homeostasis and survival may underlie this poor adaptation to later life, as exemplified by an increased fracture risk amongst post-menopausal women. Beyond overt under- or overactivity of hormonal axes, changes in the concentrations of regulatory hormones may also impact on health and disease. Subclinical hyperthyroidism, a disorder characterised by normal thyroxine levels in the presence of decreased thyroid-stimulating hormone, is, for instance, independently associated with an increased risk of atrial fibrillation amongst elderly populations. Both the menopause and subclinical thyroid disease demonstrate the difficulty in reversing endocrine changes in later life, with minimal impact from thyroxine therapy in subclinical hypothyroidism and multiple reports of harm resulting from hormone replacement therapy in peri- and post-menopausal women. Given these findings, strategies to locally regulate hormone bioavailability by altering pre-receptor metabolism may offer greater therapeutic potential in the fight against age-related disease. This review aims to provide an overview of the ageing endocrine system and its potential impact on health and disease in the elderly. It will postulate that strategies to coordinate pre-receptor hormone metabolism and a greater understanding of putative hormonal longevity pathways may offer key new drug targets in the fight against ageing, and will argue against applying the conventional endocrine maxim of 'block and replace' to hormonal changes seen during ageing. © 2014 S. Karger AG, Basel.
    Gerontology 11/2014; DOI:10.1159/000367692
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    ABSTRACT: Background: Polypharmacy and hyperpolypharmacy are proxy indicators for inappropriate medicine use. Inappropriate medicine use in older people leads to adverse clinical outcomes. Objective: The objectives of this study were to investigate the prevalence and trends of polypharmacy and hyperpolypharmacy in older people in New Zealand from 2005 to 2013, analyzing the pharmaceutical collections maintained by the Ministry of Health. Methods: A repeated cross-sectional analysis of population-level dispensing data was conducted from January 1, 2005 to December 31, 2013. Polypharmacy and hyperpolypharmacy in individuals were defined as the use of 5-9 medicines and ≥10 medicines, respectively, dispensed concurrently for a period of ≥90 days. Differences in polypharmacy and hyperpolypharmacy between 2005 and 2013 were examined. A multinomial regression model was used to predict sociodemographic characteristics associated with polypharmacy and hyperpolypharmacy. Results: Polypharmacy and hyperpolypharmacy were found to be higher in 2013 compared to 2005 (polypharmacy: 29.5 vs. 23.4%, p < 0.001; hyperpolypharmacy: 2.1 vs. 1.3%, p < 0.001). The risk of polypharmacy and hyperpolypharmacy was higher in females, in those aged 80-84 years, in the Māori population (for polypharmacy) and the Middle Eastern, Latin American, or African population (for hyperpolypharmacy), in people living in the Southern-district health board, and in individuals with increasing deprivation. Conclusion: The population of New Zealand is aging and the number of older people with multiple chronic conditions is increasing. The proportion of older people exposed to polypharmacy and hyperpolypharmacy has increased in 2013 compared to 2005. Our study provides important information to alert health policy makers, researchers, and clinicians about the dire need to reduce the medication burden in older New Zealanders. © 2014 S. Karger AG, Basel.
    Gerontology 11/2014; DOI:10.1159/000368191
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    ABSTRACT: Environmentally embedded (nonwearable) sensor technology is in continuous use in elder housing to monitor a new set of 'vital signs' that continuously measure the functional status of older adults, detect potential changes in health or functional status, and alert healthcare providers for early recognition and treatment of those changes. Older adult participants' respiration, pulse, and restlessness are monitored as they sleep. Gait speed, stride length, and stride time are calculated daily, and automatically assess for increasing fall risk. Activity levels are summarized and graphically displayed for easy interpretation. Falls are detected when they occur and alerts are sent immediately to healthcare providers, so time to rescue may be reduced. Automated health alerts are sent to healthcare staff, based on continuously running algorithms applied to the sensor data, days and weeks before typical signs or symptoms are detected by the person, family members, or healthcare providers. Discovering these new functional status 'vital signs', developing automated methods for interpreting them, and alerting others when changes occur have the potential to transform chronic illness management and facilitate aging in place through the end of life. Key findings of research in progress at the University of Missouri are discussed in this viewpoint article, as well as obstacles to widespread adoption. © 2014 S. Karger AG, Basel.
    Gerontology 11/2014; DOI:10.1159/000366518