Research topic areas
The numerous disciplines linked to scientific output on very old populations confirm Mussi et al.’s [17] conclusions on the multidisciplinary nature of this research area. Indeed, the literature focusing on this collective is widely dispersed among specialized journals in different areas. Geriatrics and gerontology represent horizontal disciplines, treating elderly people who often have different, generalized problems associated with aging or geriatric syndromes. At the same time, old people also have diseases linked to other organs and organ systems that must be addressed by specialists from other disciplines, and this relationship is reflected in the corresponding research streams.
Dementia occupies a preeminent position in the research performed, as this is the main cause of dependence and disability among very old people [36]. In fact, in the UK the associated costs of this group of diseases exceed the combined costs incurred by heart diseases and cancer [37]. Since the turn of the 21st century, then, dementia has emerged as a priority for health systems in high-income countries [38]. Theander and Gustafson [11] identified documents on dementia published from 1974 to 2009, noting a much larger increase in this area of research than in the total body of medical literature indexed in MEDLINE. This finding reflects the growing interest and investments in the area as a response to the increasing life expectancy and population aging.
Alzheimer’s disease is positioned as the main entity studied in research on age-associated dementias (n = 575), confirming the results reported by Serrano-Pozo et al. [24]. These authors analyzed the literature on Alzheimer’s disease published from 1975 to 2014, observing a steady growth of research output over the study period, especially in publications focused on the 80 + age group starting in the 1990s. This trend contrasts with findings for other age groups, in whom Alzheimer’s research actually decreased; the authors attributed these results to the demographic changes associated with increasing life expectancy in developed countries. Furthermore, starting around the year 2000, investigators noted an increase in certain document types, such as clinical trials, systematic reviews, and meta-analyses, reflecting the general advances in knowledge in relation to this topic. Alzheimer’s disease is the most common type of dementia, accounting for up to 70% of all cases [11, 14, 39], and its prevalence and associated mortality has seen the most pronounced growth over the past several decades in the very old population [4]. Nevertheless, the relative dearth of research into other kinds of dementia (“Dementia, Vascular” n = 44; “Lewy Body Disease” n = 44; and negligible research in other pathologies) shows the need to promote research focusing on dementias other than Alzheimer’s in very old people. The scant research identified on “Frontotemporal dementia,” which is the second cause of dementia, is probably due to its earlier onset compared to Alzheimer’s [40].
Frailty constitutes another popular research topic associated with aging, as this is a very prevalent geriatric syndrome (≈ 30%) in people aged 80 years or older. Clinical manifestations include muscle weakness, fatigue, and slow motor performance, among others, and these are often accompanied by social vulnerability and dependence [14] along with a higher risk of falls, depression, disability, and mortality [41]. The ongoing COVID-19 pandemic stands out as the clearest example of how frailty can contribute decisively to situations of vulnerability in very old people and to a more severe clinical presentation of other diseases [42, 43].
The mingled impacts of different clinical and social factors underline why clinical research in very old people must necessarily take into account other social and technological considerations in order to reduce disease incidence and associated harms, both in patients and in their family members and caregivers [23]. In our study, this link is reflected in the co-occurrence of different descriptors related to dementias, such as “caregivers,” “terminal care,” “palliative care,” and “social support.” Our findings on the relevance of caregiving, specialized care, ethics, and social and care support for patients and their family members corroborate those reported by Baldwin et al. [8]. Their analysis identified “treatment,” “professional care,” and “end-of-life issues”—as well as “decision making”—as key themes of the literature on ethics and dementia. The authors also called for making greater efforts to identify potential abuse in people with dementia, both by family members and professional caregivers, given their dependent and vulnerable state. Certain gaps in research were also identified, including on how family members perceive ethical aspects, and how these are defined and established among physicians, family members and caregivers.
More recently, Shi et al. [9] studied research on family caregivers of people with dementia, highlighting that the increased prevalence of dementia in very old people and their lengthening life expectancy can increase the risk of diverse health problems in family members, including depression, stress, anxiety, and other physical or psychological disorders. Caregivers have even been called “silent patients” or “secondary patients” whose needs should be addressed through specific strategies to protect and provide them with the required support; such strategies show unequal development across different countries [23].
For their part, Asghar et al. [44] studied assistive technology for people with dementia, signaling the relevance of telecare devices, activity monitoring, warning and reminder systems, fall detection, ease of mobility and communication, among other related aspects. This research is tied to descriptors like “independent living,” “health services for the aged,” and “activities of daily living.”
The development of research in the area of fracture surgery is also notable, showing substantial growth over the past several years. Hip fractures are the most relevant surgical pathology in people of advanced age, due both to the high incidence and the potential for negative effects on quality of life, autonomy, and level of frailty in this collective. These impacts have driven important advances in areas like minimally invasive surgery and complex fracture management [26].
The descriptors referring to nutrition underscore the relevance of diet in relation with preventive and therapeutic treatments in very old people, as well as for addressing the deterioration of nutrition associated with factors like difficulty swallowing, loss of appetite, and reduced access to healthy diet [25]. Conversely, none of the clusters contain descriptors related with exercise or physical activity (e.g. “exercise” n = 121 or “exercise therapy” n = 57). Efforts to promote the integration of investigators from these areas into research on the pathologies identified could be warranted. Physical activity in relation to aging constitutes an area of active research, as Müller et al. [16] have pointed out. These authors report that the most highly cited literature in this area studies the association between physical activity and health-related outcomes, which may be a relevant factor for preventing dementia. Moreover, once the benefits of physical activity have been established, this study calls for continued research into designing effective and economically feasible interventions for physical activity. For their part, Gu et al. [14] draw attention to different factors in addition to physical activity, like emerging trends of research associated with healthy aging, such as diet, working memory, and active aging, pointing to the relevance that anti-aging medicine may have as a novel research field that considers all the above-mentioned aspects as well as genetic factors associated with aging and anti-aging pharmacological research.
Two prominent research clusters, focused on pathologies that are not specifically associated with very old populations, are devoted to cardiovascular diseases and neoplasms. Coronary artery disease and stroke, in particular, are the main causes of death worldwide and in all regions except Africa, explaining the importance of these areas in research [32]. More specifically, heart valve diseases attract special interest, especially degenerative aortic stenosis, the most frequent heart valve disease in patients of advanced age. The scientific output on this topic reflects the importance of the field in terms of both epidemiological aspects and treatment via transcatheter aortic valve replacement or surgery.
Other cardiovascular diseases studied in very old patients are aneurysms and myocardial infarction, which follow stroke as the top cardiovascular diseases studied in this population. The rising prevalence of these diseases [45], along with major advances in research, are behind this trend, as described in different bibliometric studies. For example, Shi et al. [46] examined studies related to risk factors and prevention for stroke as well as pathophysiology and atrial fibrillation ablation, while Hwang and Jun [47] reviewed documents related to complications and procedures associated with endovascular aneurysm repair, and Feng et al. [48] investigated stroke interventions (drugs, devices and behavioral interventions). The prevention and management of these pathologies also receive considerable attention [49], for instance the control of risk factors like hypertension [50] and the application of artificial intelligence as a decision-making tool for the clinical management of stroke and heart disease [51].
Likewise, a substantial body of research revolves around rehabilitation and patients’ adaptation to their new health state and living conditions following a cardiovascular event. Chow et al. [32] points out the importance of this research in driving improvements in patient outcomes. Indeed, the increase in scientific output on stroke contributed to reducing its associated mortality, and in turn, these positive trends have led researchers to direct more attention to aspects like pain management and rehabilitation.
The presence of lung and colorectal cancer in the cluster on neoplasms responds to the fact that these are among the cancers causing the highest mortality in very old people [3, 4]. On the other hand, the importance of skin neoplasms in our results is probably due to different factors, for example, the aggressiveness of melanomas among elderly people or the challenges for oncological practice derived from treatment complexity in people with multiple comorbidities [52]. Other important issues have to do with the fragility of aging skin and environmental factors like solar radiation, making skin care in very old people a priority for dermatological research [53].
The cluster on neoplasms also includes an important line of research on anti-vascular endothelial growth factor A (anti-VEGF) treatments, both for different cancers and for age-related macular degeneration. Although the latter is not a neoplasm, it is the primary cause of vision loss in old people and is mediated by VEGF. In any case, there are still many unanswered questions along this research stream, for example related to the best anti-VEGF medications or the identification of biomarkers that would enable better assessment of treatment efficacy [54].
Finally, the cluster around bacterial infections and anti-bacterial agents shows the importance of clinical entities like urinary tract infections and infections associated with the implantation of prostheses, especially those caused by staphylococci and Klebsiella spp., in very old people [55]. Urinary tract infections—often aggravated by bacterial resistance [56]—are the most common infections in this population due to the degenerative nature of the urinary tract [57], and they are also responsible for worsening patients’ functional status. Research addressing this problem has seen notable growth in the past several years around questions like multidrug resistance and the most appropriate treatments for different types of infections [33].