Open research questions in Frailty in Older Adults

What the literature leaves open

• 1 Strengths and limitations This study has several strengths, including its focus on older adults from lower-SES backgrounds, a population underrepresented in CF research.

  Prevalence and associated factors of cognitive frailty among community dwelling older adults of lower socioeconomic status stratified by sex · 2026 · DOI

• Background The relationship between frailty and healthcare resource utilization in older patients with colorectal cancer (CRC) remains insufficiently quantified.

  The mediating pathways of frailty on healthcare costs and length of stay in older patients with colorectal cancer: a multicenter retrospective study · 2026 · DOI

• Comprehensive geriatric assessment (CGA) was rarely reported, patients with moderate to severe dementia were frequently excluded, and no study described the entire GR care process in a holistic manner.

  Current evidence on the core components of the geriatric rehabilitation process: a systematic review · 2026 · DOI

• Abstract Background Geriatric rehabilitation (GR) is a key component of integrated care for older persons with multimorbidity, yet its fundamental care process and core components that enable effective GR remain poorly defined and highly variable.

  Current evidence on the core components of the geriatric rehabilitation process: a systematic review · 2026 · DOI

• Frailty is a phenotypic risk factor for AD, but its causal role remains unclear - partly due to reliance on composite scores that may obscure distinct mechanisms.

  Domains of Frailty as Early Risk Factors for Alzheimer's Disease -- Genetic and Causal Evidence · 2026 · DOI

• 6 Conclusion This work has several limitations. This study is based on a secondary analysis of programmatic data, meaning participants were not randomly selected and received tailored interventions within the program. Therefore, while we observed improvements in frailty status and associated outcomes, these findings may not be solely attributable to the intervention. However, the correlation between frailty reduction and fewer adverse events is consistent with broader literature, suggesting that lowering frailty—regardless of the mechanism - remains a critical objective in community-based elder care. Another important limitation regards the empirical process for detecting negative events such as death, hospitalisation and institutionalisation: information is collected from participants or their relatives. In some cases, it was not possible to receive information on people who suddenly disappeared, which may have led us to underestimate the frequency of negative events. However, this was possible for both groups (improved/stable and worsened) so as not to influence the analysis. The second limitation is that the presented data are the result of a secondary analysis of the information collected during the day-to-day running of the program, which means that important elements may have been missed. In fact, the frequency of telephone monitoring varies by level of frailty, from one call every 3 months for the “Robust” to one every week or even more for the “Very Frail”; again, this should not affect the analysis because the comparison was made within the same level of frailty among individuals who were offered the same protocols. An additional methodological consideration concerns the temporal relationship between frailty trajectory classification and outcome occurrence. Frailty trajectories were defined using the first and last available SFGE assessments, while mortality outcomes were recorded throughout follow-up. This may introduce a potential survivor or immortal time bias, as participants needed to survive long enough to undergo repeated assessments. However, within the LLE program, participants were routinely monitored through scheduled contacts approximately every 6 months, and mortality information was continuously updated during follow-up. Furthermore, comparisons were performed within baseline frailty strata, partially limiting heterogeneity in follow-up intensity and risk profile. A further limitation of this study is the lack of clinical data that, of course, affect the trends we described. Furthermore, the classification of frailty change into three categories (improved, stable, worsened) does not capture the magnitude of transitions: a change from Robust to Pre-frail and from Robust to Very frail is both classified as “worsened.” This approach, while more reliable given the category-level validation of the SFGE, necessarily reduces the granularity of the information on individual trajectories. The program-based nature of the sample represents an additional source of potential selection bias: participants were not randomly selected from the general population but were identified through municipal registries and voluntarily enrolled.

  Impact of biopsychosocial frailty trends on survival and quality of life of older adults: a secondary analysis of data from a community-based active monitoring program · 2026 · DOI

• Future studies could address the measurement and classification limitations noted above by employing latent class analysis with categorical variable specification, by using continuous indicators with greater distributional overlap across classes, and by applying recently developed methods for integrating multiple imputation with mixture models. 7%) were excluded rather than imputed, as combining multiple imputation with latent profile analysis requires special- ised procedures that are not well established in the survey-weighted context.

  Multisystem frailty phenotypes and associated factors among older adults in Türkiye: A nationally representative study · 2026 · DOI

• Abstract Background While intrinsic capacity (IC) and frailty are established predictors of adverse health outcomes, their dynamic trajectories and synergistic impact on dementia risk remain underexplored.

  Dual trajectories of intrinsic capacity and frailty: a joint predictor framework for dementia risk in middle-aged and older adults · 2026 · DOI

• The ICOPE scale developed by the WHO has been found to be sensitive and pragmatic for assessing decline in intrinsic capacity (IC) among older adults (29). However, although a formal risk of bias assessment is not always requisite for scoping reviews, it is essential to acknowledge the variability in study quality among the included studies and has potential impact on the interpretation of findings. Important limitations in the validation studies still exist and must be addressed urgently. First, the specificity of the scale tends to vary, producing noticeable irregularities in sensory (such as vision) and cognitive areas. For example, Giudici et al. (30) reported a specificity of 2.7% for vision screening and 55.6% for cognitive factors. This indicates that the scale may produce a large number of false-positive results, which can cause overuse of full evaluations and misappropriation of healthcare resources. On the other hand, vitality only has a sensitivity of 51.3% (31), failing to address issues such as malnutrition. Furthermore, the scale emphasizes constraints in adapting to different cultures or physiologies. Second, the samples used in the validation studies are often unrepresentative. At present, the research on older adults has been conducted primarily among community-dwelling older adults, which is on a particular urban site (e.g., Beijing, Hong Kong, and Shanghai), with average age of 84 years. This focus excludes younger older adults and those living in rural areas, limiting the generalizability of the validation results to broader, more diverse populations. Further, majority of the studies are cross-sectional in nature (25), resulting in a lack of longitudinal data needed to assess the predictive validity of the scale, more specifically, its long-term capacity to serve as an early indicator of falls (32) or cognitive decline (33). Moreover, a significant lack of standardization, and challenges in adaptability to culturally specific issues are evident. The ICOPE scale items (e.g., “date of the week”) may be subject to environmental factors, including language and education (22), and the criteria for “vitality” or “mental state” assessment (e.g., MNA–SF and GDS scales) vary between regions (34). This variability makes direct comparison of the findings with other studies and restricts the global applicability of the scale (35). In conclusion, the comorbid conditions were not assessed for their multidimensional interactions.

  Current status and progress of validation studies on the ICOPE scale: a scoping review · 2026 · DOI

• This study has several strengths, including its multicenter design, focus on a high-risk elderly population, and applica- tion of advanced statistical methods (competing risk anal- ysis, non-linear modeling). However, several limitations should be acknowledged. First, the retrospective design introduces potential selec- tion bias. Second, frailty was assessed using a single screen- ing instrument (G8) rather than a full multidimensional geriatric assessment. Although G8 is widely validated in oncogeriatric populations, the categorical thresholds (mild, moderate, severe) were exploratory and cohort-specific, limiting comparability with other frailty frameworks. Third, unmeasured variables such as functional status, sarcopenia, and social support may influence outcomes. Fourth, the cohort represented a highly selected elderly surgical popu- lation (79.9% ASA ≥ 3), limiting generalizability to younger or healthier patients. Fifth, surgeon experience, learning curve status, and center volume were not captured—estab- lished determinants of RARP outcomes [13]. The observed 30-day mortality (2.0%) and conversion-to-open rate (4.9%) substantially exceed benchmarks for high-volume centers 1 3Journal of Robotic Surgery (2026) 20:529 (mortality < 0.2%, conversion 1–2%). This discrepancy reflects: (a) the high-risk frail population; (b) inter-center heterogeneity; and (c) possible inclusion of early learning curve cases. In a post-hoc sensitivity analysis comparing high-volume (≥ 50 RARP/year, n = 312) vs. lower-volume centers (n = 275), major complications (11.5% vs. 18.5%, p = 0.02) and 30-day mortality (1.0% vs. 3.3%, p = 0.048) differed significantly, confirming center-level heterogeneity. Thus, our findings should not be generalized to high-volume experienced centers without independent validation. Sixth, detailed adjudication of mortality causes was not uniformly available, limiting interpretation of procedure-related versus competing medical mortality. Seventh, the predictive model requires external validation before clinical implementation. Eighth, the low number of cancer-specific events limits sta- tistical power for cancer-specific survival analysis; longer follow-up is needed. Ninth, postoperative renal outcomes (AKI/AKD) were not assessed; a recent series identified preoperative eGFR as the primary predictor of renal com- plications after RARP, and frailty may interact with baseline renal function [32]. Future studies should incorporate renal outcomes. Despite these limitations, our study provides a nuanced understanding of frailty in elderly patients undergoing RARP and highlights the importance of competing risk methodology in this population.

  Impact of frailty on perioperative and oncologic outcomes after robotic radical prostatectomy: a multicenter study with competing risk analysis · 2026 · DOI

• Finally, given the substantial influence of non- comorbidity- related factors on LOS, further research is required to explore integration of the FRIC with psychosocial, environmental and system- level variables to more comprehensively explain the vari- ation in hospital outcomes including LOS in older inpatients.

  The Frailty Related Index of Comorbidities is More Strongly Associated With Length of Stay Than Other Established Measures of Frailty and Function in an Australian Subacute Inpatient Cohort · 2026 · DOI

• should incorporate multi-domain neuropsychological batteries, alongside imaging and biomarker approaches, to provide a more granular characterization of cognitive function. Despite these limitations, the present study offers preliminary evidence that may inform future sex-specific, precision-oriented interventions. In conclusion, there exist gender differences in the relationship between physical frailty and cognitive function in rural China, with women showing a stronger association. The results indicate that women's cognitive function is more vulnerable to the effects of frailty; however, future prospective studies are needed to confirm this conclusion. Y.H., J.T., and J.Y. conceived the study and analyzed the data. J.T. and H.Q. conducted the experiments and performed sample collection. Y.H. and W.L. wrote the manuscript. J.Y. and W.L. designed the project and acquired funding. All authors reviewed and approved the manuscript. All authors ensure the accuracy and integrity of all aspects of the work.

  Gender differences in the association between physical frailty and cognitive function among older adults: A cross-sectional study in rural Guizhou, China · 2026 · DOI

• Some limitations should be acknowledged. First, our sample included exclusively hypertensive out- patients ≥ 75 years, limiting generalizability to com- munity-dwelling individuals from other clinical set- tings, where frailty and motor impairment may be less prevalent. Accordingly, the specific geriatric set- ting may have contributed to the high rates of both frailty and falls. On the other hand, the specific study setting may limit the applicability of our results to older individuals with more severe motor and func- tional impairment, who are less likely to access out- patient services. Although follow-up data collection included a review of electronic clinical records, we cannot exclude the possibility of misclassification of outcome events—potentially related to unblinded adjudication—as well as underreporting or inaccura- cies in event timing due to recall bias from patients or caregivers. Moreover, mortality may have led to early censoring, preventing the occurrence of falls or syncope events and thereby potentially underestimat- ing the true risk in the most vulnerable individuals. Finally, detailed information on the characteristics and aetiology of syncopal episodes was not available, nor was it possible to determine whether patients had undergone diagnostic evaluations for syncope or falls. Author contribution Study concept and design: Giulia Rivasi, Marco Capacci, Alessandro Mengozzi, Andrea Ungar. Acquisition of data: all authors. Analysis and interpretation of data: Giulia Rivasi, Marco Capacci, Alessandro Mengozzi, Enrico Mossello, Agostino Virdis, Andrea Ungar. Drafting of the manuscript: Giulia Rivasi, Marco Capacci, Alessandro Mengozzi, Andrea Ungar. Critical revision of the manuscript for important intellectual content: all authors. Final approval of version to be published: all authors. Agreement to be account- able for all aspects of the work: all authors. Funding Open access funding provided by Università degli Studi di Firenze within the CRUI-CARE Agreement. The study was supported by Fondazione Cassa di Risparmio di Firenze. We acknowledge co-funding from the European Union - Next Generation EU, in the context of the National Recovery and Resilience Plan, Investment PE8—Project Age-It: “Ageing Well in an Ageing Society”. This resource was co-financed by the Next Generation EU [DM 1557 11.10.2022]. Views and opinions expressed are however those of the authors only and do not necessarily reflect those of the European Union or the European Commission. Neither the European Union nor the European Commission can be held responsible for them. The sponsors did not influence the study design, conduct or reporting. Data availability The data that support the findings of this study are available from the corresponding author upon reason- able request.

  Risk of falls and syncope across frailty levels in hypertensive older adults: a longitudinal study · 2026 · DOI

• This study has several limitations. First, as the data were derived from a cross-sectional survey, causal relationships between potential risk factors and oral frailty cannot be established. Second, the sample was limited to elderly patients undergoing elective surgery at a single tertiary hospital in Shijiazhuang, Hebei Province, over a specific period, which may restrict the generalizability of the findings. Third, data were primarily self-reported, without objective validation, potentially introducing recall and social desirability biases, which could affect accuracy and reliability.

  Prevalence and associated factors of oral frailty in elderly patients undergoing elective surgery: a secondary analysis of a cross-sectional study · 2026 · DOI

• Additional research adopting longitudinal designs and larger, more diverse samples will help clarify the utility of ICOPE Step 1 for frailty identification and prevention across different populations and healthcare systems.

  The World Health Organization Integrated Care for Older People (ICOPE) Framework and the Association with Frailty in Older Adults · 2026 · DOI

• The ICOPE domains used are screening instruments rather than gold-standard diagnostic measures; for example, three-item cognitive screening is less comprehensive than full neuropsychological testing, and two-question psychological screening is not equivalent to clinical depression diagnosis.

  The World Health Organization Integrated Care for Older People (ICOPE) Framework and the Association with Frailty in Older Adults · 2026 · DOI

• Some questions were derived from self-report measures, particularly for sensory function and psychological symptoms, which may introduce recall bias and social desirability bias.

  The World Health Organization Integrated Care for Older People (ICOPE) Framework and the Association with Frailty in Older Adults · 2026 · DOI

• The cross-sectional design limits the ability to make causal inferences and determine whether IC decline precedes frailty development or occurs concurrently.

  The World Health Organization Integrated Care for Older People (ICOPE) Framework and the Association with Frailty in Older Adults · 2026 · DOI

• This review has some limitations that affect the interpreta- tion of our findings. First, the methodological quality of the included studies was uniformly low (NOS scores 0-4 points; no study achieved “good quality” ≥ 7 points), with weaknesses in representative sampling, documentation of syndrome differen- tiation, and control for confounding factors. These limitations reduce the robustness and generalizability of pooled preva- lence estimates, although our systematic assessment provides benchmarks for future research. Second, the evidence base was exclusively derived from TCM studies. Despite comprehensive database searches, no studies from KM or Kampo studies met the inclusion criteria. Therefore, the findings represent TCM- specific evidence that cannot be generalized to other East Asian medicine traditions, which may conceptualize frailty patterns differently, using distinct diagnostic terminology and theoreti- cal frameworks. This finding underscores the need for targeted research in underrepresented traditions. Third, substantial heterogeneity (I2 > 80% for most patterns) reflects variations in diagnostic criteria, practitioner qualifications, patient popula- tions, and the absence of standardized protocols. Meta-analysis was conducted despite these limitations to provide exploratory prevalence estimates for hypothesis generation, enable system- atic comparisons, and quantify heterogeneity to highlight areas 17 Prevalence of TEAM Patterns among Elderly with Frailtywww.journal-jop.org requiring standardization. This approach balanced quantitative synthesis with extensive narrative synthesis while acknowledg- ing the exploratory nature of the findings. Fourth, the limited number of studies (fewer than 10 per syndrome pattern) pre- cluded formal sensitivity analyses and the assessment of publi- cation bias, thereby limiting the evaluation of result robustness.

  Prevalence of Traditional East Asian Medicine Patterns among Older Adults with Frailty: a systematic review of observational studies · 2026 · DOI

• This study demonstrates several methodological strengths. The survey was methodically designed following a system- atic, evidence-based approach, aligning with the European Consensus Statement. Prior to dissemination, content valid- ity and clarity were assured through the process of pretest- ing, which was conducted by experts in the field. Cross- national collaboration facilitated a structured comparison of varying health systems. The integration of descriptive and qualitative analysis in accordance with SRQR stand- ards resulted in enhanced transparency and depth of interpretation. However, it is important to acknowledge the inherent limitations of this approach. The exclusive involvement of a select and small group of experts along with the limited regional distribution may compromise the representativeness of the study. The data coverage was revealed to be inconsist- ent, as the Austrian experts could only describe phase 1 GR. Consequently, the later rehabilitation phases (3 and 4) could not be fully recorded in all three countries. Furthermore, the utilization of self-reported data from designated experts may introduce subjective biases. Despite the differences in termi- nology and care structures being clarified, it is possible that these factors may have influenced the interpretation between countries. Despite these limitations, the study provides valu- able comparative insights and highlights structural gaps and development needs in GR in the DACH region.

  Geriatric rehabilitation in Germany, Austria, and Switzerland (DACH region): a current state analysis · 2026 · DOI

• OBJECTIVE: The emergency department length of stay (EDLOS) is one of the essential parameters of emergency healthcare management efficacy, and prominent factors that contribute to EDLOS are critical in enhancing emergency department (ED) patient care effectiveness, particularly for older patients, which is rarely investigated.

  Evaluation of factors affecting the length of stay of geriatric patients in the emergency department · 2023 · DOI

• However, it has not been tested in US community settings, likely yields large numbers of false positives (particularly in community settings), and its predictive validity of favorable outcomes after nutritional interventions is unknown.

  Screening Community-Living Older Adults for Protein Energy Malnutrition and Frailty: Update and Next Steps · 2019 · DOI

• Objective: frailty is a central concept in geriatric medicine, yet its utility in the Emergency Department (ED) is not well understood nor well utilised.

  Identification of older adults with frailty in the Emergency Department using a frailty index: results from a multinational study · 2017 · DOI

• The Short Physical Performance Battery (SPPB) is one of the most validated tools to assess this, but its capacity to predict long-term mortality in very old population attending primary care has not been studied.

  Lower limb function and 10-year survival in population aged 75 years and older · 2015 · DOI

• PURPOSE OF THE STUDY: Numerous studies have discovered negative health consequences associated with spousal caregiving at the end of life; however, little is known about how care-recipient cognitive status impacts caregiver health outcomes, specifically in the area of frailty, and whether health consequences remain over time.

  Does Dementia Caregiving Accelerate Frailty? Findings From the Health and Retirement Study · 2014 · DOI

Most-cited papers in Frailty in Older Adults

• Geriatric Syndromes: Clinical, Research, and Policy Implications of a Core Geriatric Concept · Journal of the American Geriatrics Society · 2007 · 1,509 citations
• Effect of Structured Physical Activity on Prevention of Major Mobility Disability in Older Adults · JAMA · 2014 · 1,251 citations
• Prevalence of frailty in 62 countries across the world: a systematic review and meta-analysis of population-level studies · Age and Ageing · 2020 · 951 citations
• Transitions Between Frailty States Among Community-Living Older Persons · Archives of Internal Medicine · 2006 · 934 citations
• Designing Randomized, Controlled Trials Aimed at Preventing or Delaying Functional Decline and Disability in Frail, Older Persons: A Consensus Report · Journal of the American Geriatrics Society · 2004 · 737 citations
• What is Comprehensive Geriatric Assessment (CGA)? An umbrella review · Age and Ageing · 2017 · 493 citations
• Weight Change in Old Age and its Association with Mortality · Journal of the American Geriatrics Society · 2001 · 458 citations
• Screening the Elderly · Journal of the American Geriatrics Society · 1985 · 392 citations
• Changes in frailty and incident cardiovascular disease in three prospective cohorts · European Heart Journal · 2024 · 328 citations
• Reliability of the Barthel Index when used with older people · Age and Ageing · 2005 · 319 citations

Most recent work

• Impact of the family cohesion-centered frailty intervention on older gastric cancer patients: a non-randomized controlled trial · BMC Medicine · 2026
• Frailty and the biology of accelerated ageing · European Heart Journal · 2026
• Changes in frailty and incident risk of degenerative bone and joint diseases and their multimorbidity: a prospective cohort study · Frontiers in Public Health · 2026
• Self-Management of Geriatric Syndromes–longitudinal data on medical and psychosocial factors in older patients · Scientific Data · 2026
• Early outpatient follow‐up, hospital‐free survival, and health‐related quality of life in older adults after hospitalization for acute myocardial infarction · Journal of Hospital Medicine · 2026
• Geriatric rehabilitation in Germany, Austria, and Switzerland (DACH region): a current state analysis · European Geriatric Medicine · 2026
• Prevalence of Traditional East Asian Medicine Patterns among Older Adults with Frailty: a systematic review of observational studies · Journal of Pharmacopuncture · 2026
• The World Health Organization Integrated Care for Older People (ICOPE) Framework and the Association with Frailty in Older Adults · Annals of Geriatric Medicine and Research · 2026
• Hospital Frailty Risk Score Predicts Long-Term Hospital Readmissions in Very Old Patients with Heart Failure · Journal of Clinical Medicine · 2026
• An explainable online frailty prediction model for community-dwelling older adults based on machine learning algorithms: a cross-sectional study based on retrospective health data · Annals of Medicine · 2026

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