Introduction
Estimates from the 2022 census of the US reveal that about 17.3% of the total population was older than 65 years of age. 1 Previous surveys have revealed that chronic conditions were relatively more common in older US adults. 2 Infectious diseases are responsible for about one-third of the deaths in older people according to a 2001 study. 3 The most common infections include urinary tract infections and pneumonia. 4 Another comorbid condition includes cancer. Estimates from 2019 revealed that 1,944,280 adults ages 85 and older were alive with a history of cancer, representing one-third of all men and one-fourth of all women in the age group in the United States. 5 Similar estimates have been noted for cardiovascular disease and dementia. Dramatic changes are anticipated in the US population. Anticipated estimations reveal that individuals ≥85 years of age will account for 4.3% of the population in 2050, representing a more than two-fold increase from 2010. 6 These future projections will lead to a significant burden in terms of morbidity, mortality, and costs related to diseases in the frail population. In estimating mortality and morbidity, one of the scoring systems that has been extensively studied is frailty index. 7 Frailty phenotype is defined as a distinct clinical syndrome meeting three or more of five phenotypic criteria: weakness, slowness, low level of physical activity, self-reported exhaustion, and unintentional weight loss. The presence of three or more phenotypic criteria is termed as frailty. 8 The Frailty Index (FI) was created by Rockwood and colleagues through an extensive evaluation of older adults, encompassing various deficits such as diseases, physical limitations, cognitive impairments, psychosocial risks, and common geriatric issues, excluding frailty itself. 7 To qualify as a deficit, a variable must be acquired with age, linked to adverse outcomes, and not peak too early. 7 Frailty index is deemed as a more sensitive indicator of outcomes because it overcomes age-associated factors and therefore, the importance of chronological age is decreased. The final criterion of the frailty index ensures that deficits included in the calculation are informative by avoiding those prevalent in nearly all older adults, as they lose their discriminatory value. 8 For instance, while nocturia disrupts sleep and is age-associated, it is too widespread (seen in over 90% of men aged 75 or older) to contribute to the index. Typically, the index incorporates between 30 and 70 deficits out of a potential total of 80, maintaining a balance between comprehensiveness and practicality. 8 It is important to note that different frailty indices have different parameters and therefore, their utilization and interpretation might vary. For example, the Clinical Frailty Scale (CFS) is a 9-point assessment tool that provides an overview of an older adult’s overall fitness or frailty level. A CFS score of 5 or higher is generally considered frail. 9 The Frail Index of Cumulative Deficits (FI-CD) involves tallying 30 or more health-related issues such as comorbidities, symptoms, disabilities, or any health deficiencies, with the premise that a greater number of health deficits indicates higher frailty; frailty was defined as a ratio of more than 0.25, indicating over 8 out of 32 deficits. 9 The Short Physical Performance Battery (SPPB) calculates a score based on three timed tasks and each task is scored from 0 (poor performance) to 4 (excellent performance), with a total score ranging from 0 to 12. A score of 6 or lower indicates frailty. 9
Infections
The most common types of infections in the frail population include pneumonia, urinary tract infection and abdominal infections. In a study conducted in Korea using a deficit-accumulation frailty index (FI), patients with FI > 0.25, defined as moderately to severely frail, were more likely to meet CURB-65 criteria. The same cohort was likely to have a prolonged hospitalization with discharge disposition being a long-term care facility. 10 Another study utilizing the same scale revealed that more post-care acute interventions were needed in patients with higher frailty scores. 11 Further indexing systems, for example the FI-LAB, was useful in determining rate of complications and mortality in frail patients with community acquired pneumonia. 12
Urinary tract infections have also been studied using the modified Frailty Index (mFI) and patients with higher scores were more likely to have post-operative urinary retention as compared to patients with lower scores. 13 Older patients with inflammatory bowel disease were also evaluated for serious infections using frailty indices, however, frailty was not associated with an increased risk of serious infection. 14 However, the utility of such indices was relatively limited in patients with orthopaedic infections. 15
Viral infections and their outcomes in older patients were also evaluated. In a study with older patients and herpesvirus infections, frailty indices were not associated with adverse or favourable outcomes. 16 In fact, paradoxical results were seen in a patient cohort with cytomegalovirus infection as a positive serology was inversely related to frailty. 17
HIV disease has also been extensively studied, particularly in quantifying vulnerability in older patients with HIV. 18 Certain markers suggestive of a weakened immune system in HIV patients have been correlated with frailty. Frailty was associated with elevated expression of glucose-transporter 1, expression of total monocytes, increased levels of immune activation markers suggesting that increased immune activation was not only present in frail patients but suggestive of abnormal lipid profile in frail patients with HIV. 18 Long-term outcomes, specifically, worsening of cognitive function was related to higher levels of frailty. 19
Table 1 illustrates the aforementioned frailty indices.
Cancer
Identification of patients at risk of frailty is perhaps the first step towards optimizing and predicting outcomes in such a cohort. Carolina Frailty Index (CFI) based on geriatric assessment was also studied. The tool emerged as a significantly valid aid in not only identifying frailty but predicting all-cause mortality in older adults with cancer. 20
Frailty indices have been widely studied in older patients with cancer. Gastric cancer in octogenarians was studied using a modified frailty index based on albumin <3.4 g/dl, hematocrit <35% and creatinine levels >2 mg/dL. 21 Patients with higher modified frailty indices had increased risk of post-operative complications and decreased cancer-free survival. 21
Kim et al. also evaluated another validated index, Laboratory Frailty Index, based on hemodynamic and clinical parameters. 22 Increased scores had less associations with preoperative optimization but were associated with prolonged length of stay, higher rates of re-admission and increased mortality. 22
The Memorial Sloan Kettering-Frailty Index (MSK-FI) was also evaluated for older surgical patients with cancer. 23 However, this tool was found to be useful for both perioperative and postoperative outcomes in surgical oncology based on older patients. 23 Similar results were also observed in oncological older patients with COVID-19. 24
Long-termoutcomes after oncological interventions have also been assessed using frailty indices. A deficit accumulation frailty index (DAFI) was used to evaluate breast cancer survivors who were diagnosed at 60 years of age and about 5–15 years free of disease. More patients scored poorly on language and memory. 25 Additionally, frailty syndrome was more commonly observed in the same cohort. 25 Cognitive decline was linearly proportional to increased DAFI scores. 25 Patients with gynecological cancer were also evaluated using the Frailty Index (FI). 26 The results of the study revealed that FI was one of the strongest predictors of 1-year mortality. 26
In one of the large-scale studies, the International Myeloma Working Group (IMWG) frailty index was utilized to investigate outcomes in older patients with multiple myeloma. 27 Frail patients had a complicated progression-free interval. 27 Interestingly, prognostic assessment could be performed by using both frailty index and the staging system. 27
Older patients with lymphomas with incurable tumors were assessed for frailty using a Deficit Accumulation Index (DAI). 28 Frail patients have an increased risk of depression and distress. 28
Hospital Frailty Risk Score (HFRS) was evaluated in older patients with head and neck cancer. Higher rates of readmissions at 30-days, increased cost of resource utilization, and longer length of stay were associated with higher scores.
Evaluation of patients with pancreatic cancer reveal slightly different results. The modified frailty index (mFI) was used to assess response to therapy and long-term outcomes. 29 Patients with lower scores were more likely to receive 5-fluorouracil, irinotecan and oxaliplatin. 29 However, toxicity, readmission rates and complications were not related to the index at all. 29 Interestingly, the same mFI was associated with higher rate of 30-day adverse outcomes in neurosurgical patients who were frail. 30 The mFI was also studied in older patients receiving PD-1 inhibitors for lung cancer. 31 There was no significant difference in the occurrence of adverse events in frail patients. 31 However, the cohort was at higher odds of multiple adverse events and chemotherapy-induced pneumonitis. 31
Table 2 presents a summary of these indices.
Frailty and cardiovascular disease
4.1. Frailty and ACS
Different results have been observed with frailty in elderly patients with acute coronary syndrome. In one study, a frailty index based on 5 components of the Fried score and albumin concentration, as malnutrition index, was assessed with respect to postdischarge all-cause mortality. 32 The results concluded that the index could be used as a marker for long-term prognosis. However, in another study, frailty was termed as an indicator for short-term outcomes and prognosis. 33
4.2. Frailty and myocardial infarction
Frailty has been explored intensively in patients with cardiovascular disease. The rate of 30-day readmissions increased with frailty in patients with frailty ( p < 0.001). 34 Percutaneous coronary intervention was needed in 86.40% of low-risk, 66.03% of intermediate-risk, and 58.90% of high-risk patients ( p < 0.001). 34 Intermediate and high-risk frailty had longer length of stay, higher total cost, and were more likely to be discharged to a skilled facility ( p < 0.001). 34 Further studies discussed the similar indices with respect to increased Charlson comorbidity index. 35
Intensive cardiac care is less common in patients with frailty and with increased all-cause mortality postdischarge. 36 However, mortality rates were not cardiac specific. 36 Apart from frailty index, MELD-XI score has also been evaluated for prognosis with higher MELD-XI scores correlating with a poor prognosis. 37
4.3. Frailty and valvular heart disease
Valvular heart disease (VHD) poses a significant health challenge, particularly among the aging population. Frailty, characterized by diminished physiological reserves and increased vulnerability to stressors, has garnered attention due to its association with adverse outcomes in various medical conditions, including cardiovascular disease. 38 – 40
Assessing frailty in VHD patients becomes paramount for risk evaluation and tailored care. Studies have shown that frail individuals undergoing cardiac interventions, such as aortic valve replacement, face increased adverse outcomes. 41 , 42 The utilization of tools like the FRAIL Scale has been deemed useful in evaluating the frailty status of heart valve disease patients. 43 These assessments aid in identifying patients who might benefit from targeted interventions to improve their overall resilience.
The potential benefits of exercise training in mitigating frailty and enhancing recovery among elderly VHD patients have gained attention. 44 The postoperative period following cardiac surgery or interventions presents a critical juncture for implementing exercise programs. 44 Tailored exercise regimens can help improve cardiovascular fitness, muscle strength, and overall functional capacity, thereby contributing to better postoperative outcomes. 44 Integrating exercise training into the care continuum for elderly VHD patients can potentially enhance their quality of life and reduce the impact of frailty-related challenges.
Frailty has been observed to influence disease-specific health status among cardiovascular disease patients. 45 The integration of frailty assessment into the evaluation of VHD patients can provide insights into their overall well-being and prognosis, enabling healthcare providers to design personalized interventions that address both the cardiac condition and frailty-related issues.
Table 3 discusses the frailty indices mentioned.
Dementia
Frailty has been a cause of major complications in patients with dementia. It has been proposed that patients with physical frailty are at higher risk of cognitive decline resulting in higher rates of mortality. 46 This is partly related to neuropsychology as assessed by a study focusing on frailty scales; the higher the rate of neuropsychological decline, higher the rate of frailty and associated mortality. 46 , 47 Additionally, the syndrome has been associated with depression and reduced activities of daily living. 48 Further studies have discussed that prefrailty is associated with a decreased disability free interval in older adults. 49 Interestingly, genetics has been described to play a limited role in this regard. In a study examining the Rockwood frailty index (FI) based on 44 health deficits, a 10% increase in FI was associated with an increased risk of dementia (hazard ratio [HR] 1.17 (95% confidence interval [CI] 1.07, 1.18)). 49 However, higher hazard ratios were not observed when APOE ɛ4 carrier status was considered. 50 Furthermore, some frailty indices also have a relationship with increased caregiver burden in patients with dementia. 51
A Dutch study constructed a frailty index to measure comorbidity burden in patients with dementia. 52 It was concluded in the study that short-term predictive value of frailty is higher in patients with dementia as these characteristics are likely to change over time. 52 The type of scale used has been debated widely given the many scales that have been used globally, for example, the FI scale or CFI scale. 50 , 53 – 55
Frailty and COVID-19 pandemic
Frailty was also associated with negative outcomes in COVID-19 patients. In a study based in Sweden, frailty was assessed using a 48-item electronic Frailty Index (eFI), the Clinical Frailty Scale, and the Hospital Frailty Risk Score, while comorbidity was measured with the Charlson Comorbidity Index. 56 The eFI was significantly associated with higher risks of in-hospital mortality, 30-day mortality, 6-month mortality, and longer hospital stays, independent of age and sex. 56 In another study based in the UK, frailty was assessed by specialist COVID-19 teams using the Clinical Frailty Scale (CFS), categorizing patients based on their scores: fit (CFS 1–2), vulnerable (CFS 3–4), showing initial signs of frailty (CFS 5–6), and severe or very severe frailty (CFS 7–9). 57 Compared to those with a CFS score of 1–2, patients with higher CFS scores had increased hazard ratios for time from hospital admission to death and increased odds ratios for day-7 mortality, indicating a stronger association with frailty severity. 57
Future interventions
It is important to determine the utility of these indices in both short and long-term using similar measures. While frailty indices are widely used and applicable in concomitant syndromes of dementia and infections, the role of such indices in cardiovascular disease and cancer has not been extensively studied. Specific measures for each of these conditions should be assessed taking into account confounding factors in order to better assess poor prognostic outcomes including mortality, readmission rates and complications. As discussed above, these frailty indices can also be used to screen population into a high and low-risk cohort so that targeted approaches can be used. Frailty indices have been used on multiple levels. However, the common use is in tertiary care centers and university-associated healthcare institutions suggesting that most of the resource allocation for frail patients is primarily in these centers and a more homogeneous resource allocation is warranted.
Conclusions
In conclusion, this comprehensive review underscores the pivotal role of frailty indices in predicting outcomes across a spectrum of health conditions, including infections, cancer, cardiovascular disease, and dementia. The evidence presented highlights the versatility of frailty assessments in anticipating complications, mortality, and long-term consequences in various patient populations. As the aging population grows and healthcare systems face increasing challenges, understanding and leveraging frailty indices become crucial for tailored interventions and optimized care. However, the review also emphasizes the need for future research to delve deeper into the specific nuances of frailty in cardiovascular diseases and cancer, ensuring a better understanding of its impact and applicability. Overall, this research about frailty indices contributes valuable insights for healthcare professionals, guiding them in enhancing patient care and outcomes across diverse health conditions.
Disclaimers: The authors have no disclaimers to declare.
Source of support: The authors have no sources of support to declare.
Conflicts of interest: The authors have no conflicts of interest to declare.
References
1 United States Census Bureau Quick facts United States https://www.census.gov/quickfacts/fact/table/US/AGE775222#AGE775222 2022 Accessed November 30, 2023
2 Boersma P Black LI Ward BW Prevalence of multiple chronic conditions among US adults, 2018 Prev Chronic Dis 2020 Sep 17 E106 10.5888/pcd17.200130 32945769 PMC7553211
3 Mouton CP Bazaldua OV Pierce B Espino DV Common infections in older adults Am Fam Physician 2001 63 2 257 268 11201692
4 Mouton CP Bazaldua OV Pierce B Espino DV Common infections in older adults Health Care Food Nutr Focus 2001 18 3 1 7 11688342
5 National Cancer Institute Age and cancer risk https://www.cancer.gov/about-cancer/causes-prevention/risk/age#:~:text=Age%20and%20Cancer%20Risk,-Advancing%20age%20is&text=The%20incidence%20rates%20for%20cancer,groups%2060%20years%20and%20older March 5 2021 Accessed November 30, 2023
6 Yazdanyar A Newman AB The burden of cardiovascular disease in the elderly: morbidity, mortality, and costs Clin Geriatr Med 2009 Nov 25 4 563 vii 10.1016/j.cger.2009.07.007 19944261 PMC2797320
7 Chen X Mao G Leng SX Frailty syndrome: an overview Clin Interv Aging 2014 Mar 9 433 441 https://doi/10.2147/CIA.S45300 24672230 10.2147/CIA.S45300 PMC3964027
8 Cesari M Gambassi G van Kan GA Vellas B The frailty phenotype and the frailty index: different instruments for different purposes Age Ageing 2014 Jan 43 1 10 12 https://doi/10.1093/ageing/aft160 24132852 10.1093/ageing/aft160
9 Zhang D Tang W Dou LY Luo J Sun Y Four different frailty models predict health outcomes in older patients with stable chronic obstructive pulmonary disease BMC Geriatr 2022 22 1 57 10.1186/s12877-022-02750-z 35034605 PMC8761265
10 Park CM Kim W Rhim HC Frailty and hospitalization-associated disability after pneumonia: a prospective cohort study BMC Geriatr 2021 Feb 21 1 111 10.1186/s12877-021-02049-5 33546614 PMC7864132
11 Park CM Kim W Lee ES Comparison of frailty index to pneumonia severity measures in older patients with pneumonia J Am Med Dir Assoc 2022 Jan 23 1 165 169 10.1016/j.jamda.2021.08.044 34624243
12 Huang S Wang Y Chen L Chen X Use of a frailty index based upon routine laboratory data to predict complication and mortality in older community-acquired pneumonia patients Arch Gerontol Geriatr 2022 Jul–Aug; 101 104692 10.1016/j.archger.2022.104692 35349877
13 Tuddenham SA Gearhart SL Wright EJ Iii Handa VL Frailty and postoperative urinary tract infection BMC Geriatr 2022 Oct 22 1 828 10.1186/s12877-022-03461-1 36307754 PMC9617308
14 Singh S Heien HC Sangaralingham L Frailty and risk of serious infections in biologic-treated patients with inflammatory bowel diseases Inflamm Bowel Dis 2021 Oct 27 10 1626 1633 10.1093/ibd/izaa327 33325507 PMC8522787
15 Erne F Wallmeier V Ihle C The modified 5-item frailty index determines the length of hospital stay and accompanies with mortality rate in patients with bone and implant-associated infections after trauma and orthopedic surgery Injury 2023 Apr 54 4 1125 1131 10.1016/j.injury.2023.01.042 36754703
16 Wang GC Han C Detrick B Herpesvirus infections and risk of frailty and mortality in older women: women’s health and aging studies J Am Geriatr Soc 2016 May 64 5 998 1005 10.1111/jgs.14090 27131018 PMC4882224
17 Matheï C Vaes B Wallemacq P Degryse J Associations between cytomegalovirus infection and functional impairment and frailty in the BELFRAIL Cohort J Am Geriatr Soc 2011 Dec 59 12 2201 2208 10.1111/j.1532-5415.2011.03719.x 22092044
18 Guaraldi G Brothers TD Zona S A frailty index predicts survival and incident multimorbidity independent of markers of HIV disease severity AIDS 2015 Aug 29 13 1633 1641 10.1097/QAD.0000000000000753 26372273
19 Paul RH Cooley SA Garcia-Egan PM Ances BM Cognitive performance and frailty in older HIV-positive adults J Acquir Immune Defic Syndr 2018 Nov 79 3 375 380 10.1097/QAI.0000000000001790 29957675 PMC10733865
20 Guerard EJ Deal AM Chang Y Frailty index developed from a cancer-specific geriatric assessment and the association with mortality among older adults with cancer J Natl Compr Cancer Netw 2017 Jul 15 7 894 902 10.6004/jnccn.2017.0122 28687577
21 Lu J Zheng HL Li P High preoperative modified frailty index has a negative impact on short- and long-term outcomes of octogenarians with gastric cancer after laparoscopic gastrectomy Surg Endosc 2018 May 32 5 2193 2200 10.1007/s00464-018-6085-4 29423551
22 Kim Y Song K Kang CM Lee H Impact of preoperative laboratory frailty index on mortality and clinical outcomes in older surgical patients with cancer Sci Rep 2022 Jun 12 1 9200 10.1038/s41598-022-13426-4 35654943 PMC9163125
23 Shahrokni A Tin A Alexander K Development and evaluation of a new frailty index for older surgical patients with cancer JAMA Netw Open 2019 May 2 5 e193545 10.1001/jamanetworkopen.2019.3545 31074814 PMC6512296
24 Kim SJ Fessele KL Tin AL The association between Memorial Sloan Kettering Frailty Index with 30-day survival among patients aged ≥75 with cancer and COVID-19 J Geriatr Oncol 2022 May 13 4 416 419 10.1016/j.jgo.2021.12.014 34955444 PMC8687748
25 Ahles TA Schofield E Li Y Relationship between cognitive functioning and frailty in older breast cancer survivors J Geriatr Oncol 2022 Jan 13 1 27 32 10.1016/j.jgo.2021.07.011 34366276 PMC9262141
26 Orlandini L Nestola T Colloca GF Ferrini A Cesari M The Frailty Index in older women with gynecological cancer Aging Clin Exp Res 2020 Aug 32 8 1561 1565 10.1007/s40520-020-01473-8 31981102
27 Facon T Dimopoulos MA Meuleman N A simplified frailty scale predicts outcomes in transplant-ineligible patients with newly diagnosed multiple myeloma treated in the FIRST (MM-020) trial Leukemia 2020 Jan 34 1 224 233 10.1038/s41375-019-0539-0 31427722 PMC7214253
28 Gilmore N Kehoe L Bauer J The relationship between frailty and emotional health in older patients with advanced cancer Oncologist 2021 26 12 e2181 e2191 10.1002/onco.13975 34510642 PMC8649062
29 Rittberg R Zhang H Lambert P Kudlovich R Kim CA Dawe DE Utility of the modified frailty index in predicting toxicity and cancer outcomes for older adults with advanced pancreatic cancer receiving first-line palliative chemotherapy J Geriatr Oncol 2021 Jan 12 1 112 117 10.1016/j.jgo.2020.07.004 32798212
30 Youngerman BE Neugut AI Yang J Hershman DL Wright JD Bruce JN The modified frailty index and 30-day adverse events in oncologic neurosurgery J Neuro Oncol 2018 Jan 136 1 197 206 10.1007/s11060-017-2644-0 29139096
31 Li J Zhang X Zhou S Zhou Y Liu X Association between PD-1 inhibitor-related adverse events and frailty assessed by frailty index in lung cancer patients Cancer Med 2023 Apr 12 8 9272 9281 10.1002/cam4.5669 36727563 PMC10166957
32 Sanchis J Ruiz V Sastre C Frailty tools for assessment of long-term prognosis after acute coronary syndrome Mayo Clin Proc Innov Qual Outcomes 2020 Dec 4 6 642 648 10.1016/j.mayocpiqo.2020.06.011 33367209 PMC7749270
33 Alonso Salinas GL Sanmartín Fernández M Pascual Izco M Frailty is a short-term prognostic marker in acute coronary syndrome of elderly patients Eur Heart J Acute Cardiovasc Care 2016 Sep 5 5 434 440 10.1177/2048872616644909 27091834
34 Heaton J Singh S Nanavaty D Okoh AK Kesanakurthy S Tayal R Impact of frailty on outcomes in acute ST-elevated myocardial infarctions undergoing percutaneous coronary intervention Cathet Cardiovasc Interv 2023 Mar 101 4 773 786 10.1002/ccd.30595 PMC10082419 36806859
35 Ekerstad N Pettersson S Alexander K Frailty as an instrument for evaluation of elderly patients with non-ST-segment elevation myocardial infarction: a follow-up after more than 5 years Eur J Prev Cardiol 2018 Nov 25 17 1813 1821 10.1177/2047487318799438 30247067
36 Patel A Goodman SG Yan AT Frailty and outcomes after myocardial infarction: insights from the CONCORDANCE registry J Am Heart Assoc 2018 Sep 7 18 e009859 10.1161/JAHA.118.009859 30371219 PMC6222944
37 Çõnar T Şaylõk F Selçuk M Akbulut T Orhan AL The predictive value of the MELD-XI score for short- and long-term mortality in elderly patients with non-ST elevation myocardial infarction Aging Clin Exp Res 2022 Apr 34 4 887 895 10.1007/s40520-021-02004-9 34648172
38 Afilalo J Frailty in patients with cardiovascular disease: why, when, and how to measure Curr Cardiovasc Risk Rep 2011 Oct 5 5 467 472 10.1007/s12170-011-0186-0 21949560 PMC3165117
39 Afilalo J Alexander KP Mack MJ Frailty assessment in the cardiovascular care of older adults J Am Coll Cardiol 2014 Mar 63 8 747 762 10.1016/j.jacc.2013.09.070 24291279 PMC4571179
40 Finn M Green P The influence of frailty on outcomes in cardiovascular disease Rev Esp Cardiol 2015 Aug 68 8 653 656 10.1016/j.rec.2015.04.005 26129717 PMC4879674
41 Sohn B Choi JW Hwang HY Jang MJ Kim KH Kim KB Frailty index is associated with adverse outcomes after aortic valve replacement in elderly patients J Kor Med Sci 2019 Aug 34 31 e205 10.3346/jkms.2019.34.e205 PMC6689491 31392853
42 Borregaard B Dahl JS Lauck SB Association between frailty and self-reported health following heart valve surgery Int J Cardiol Heart Vasc 2020 Nov 31 100671 10.1016/j.ijcha.2020.100671 33235899 PMC7670239
43 Duchnowski P Szymański P Kuśmierczyk M Hryniewiecki T Usefulness of FRAIL scale in heart valve diseases Clin Interv Aging 2020 Mar 15 1071 1075 10.2147/CIA.S239054 32753858 PMC7358089
44 Tamuleviciute-Prasciene E Drulyte K Jurenaite G Kubilius R Bjarnason-Wehrens B Frailty and exercise training: how to provide best care after cardiac surgery or intervention for elder patients with valvular heart disease BioMed Res Int 2018 Sep 2018 9849475 10.1155/2018/9849475 30302342 PMC6158962
45 Nguyen DD Arnold SV Impact of frailty on disease-specific health status in cardiovascular disease Heart 2023 Jun 109 13 977 983 10.1136/heartjnl-2022-321631 36604164 PMC10272004
46 Wallace LMK Theou O Darvesh S Neuropathologic burden and the degree of frailty in relation to global cognition and dementia Neurology 2020 Dec 95 24 e3269 e3279 10.1212/WNL.0000000000010944 32989103 PMC7836651
47 Wallace L Hunter S Theou O Fleming J Rockwood K Brayne C Frailty and neuropathology in relation to dementia status: the Cambridge City over-75s Cohort study Int Psychogeriatr 2021 Oct 33 10 1035 1043 10.1017/S1041610220003932 33586645
48 Panza F Solfrizzi V Frisardi V Different models of frailty in predementia and dementia syndromes J Nutr Health Aging 2011 Aug 15 8 711 719 10.1007/s12603-011-0126-1 21968870
49 Ekram ARMS Ryan J Espinoza SE The association between frailty and dementia-free and physical disability-free survival in community-dwelling older adults Gerontology 2023 69 5 549 560 10.1159/000528984 36617406 PMC10238577
50 Bai G Wang Y Kuja-Halkola R Frailty and the risk of dementia: is the association explained by shared environmental and genetic factors? BMC Med 2021 Oct 19 1 248 10.1186/s12916-021-02104-3 34657626 PMC8522144
51 Sugimoto T Ono R Kimura A Physical frailty correlates with behavioral and psychological symptoms of dementia and caregiver burden in Alzheimer’s disease J Clin Psychiatry 2018 Nov 79 6 17m11991 10.4088/JCP.17m11991 30474939
52 Haaksma ML Rizzuto D Ramakers IHGB The impact of frailty and comorbidity on institutionalization and mortality in persons with dementia: a prospective cohort study J Am Med Dir Assoc 2019 Feb 20 2 165 170e2 10.1016/j.jamda.2018.06.020 30145169
53 Kelaiditi E Canevelli M Andrieu S Frailty index and cognitive decline in Alzheimer’s disease: data from the impact of cholinergic treatment use study J Am Geriatr Soc 2016 Jun 64 6 1165 1170 10.1111/jgs.13956 27321595
54 Wightman H Quinn TJ Mair FS Lewsey J McAllister DA Hanlon P Frailty in randomised controlled trials for dementia or mild cognitive impairment measured via the frailty index: prevalence and prediction of serious adverse events and attrition Alzheimer’s Res Ther 2023 Jun 15 1 110 10.1186/s13195-023-01260-3 37312157 PMC10262528
55 Park CM Sison SDM McCarthy EP Claims-based frailty index as a measure of dementia severity in medicare claims data J Gerontol A Biol Sci Med Sci 2023 78 11 2145 2151 10.1093/gerona/glad166 37428879 PMC10613007
56 Mak JKL Eriksdotter M Annetorp M Two years with COVID-19: the electronic frailty index identifies high-risk patients in the Stockholm GeroCovid study Gerontology 2023 69 4 396 405 10.1159/000527206 36450240 PMC9747746
57 Hewitt J Carter B Vilches-Moraga A The effect of frailty on survival in patients with COVID-19 (COPE): a multicentre, European, observational cohort study Lancet Public Health 2020 Aug 5 8 e444 e451 10.1016/S2468-2667(20)30146-8 32619408 PMC7326416