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Figure 1.
PRISMA Diagram of the Study Selection Process
PRISMA Diagram of the Study Selection Process

AMED indicates Allied and Complementary Medicine Database; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-analyses.

Figure 2.
Forest Plot of the Incidence Rates (per 1000 Person-Years) of Frailty Among Community-Dwelling Older Adults
Forest Plot of the Incidence Rates (per 1000 Person-Years) of Frailty Among Community-Dwelling Older Adults

Weights are from random-effects analysis. Forty-five studies were included.

Figure 3.
Forest Plot of the Incidence Rates (per 1000 Person-Years) of Prefrailty Among Community-Dwelling Older Adults
Forest Plot of the Incidence Rates (per 1000 Person-Years) of Prefrailty Among Community-Dwelling Older Adults

Weights are from random-effects analysis. Twenty-one studies were included.

Table 1.  
Descriptive Characteristics of 46 Studies Included in the Systematic Review
Descriptive Characteristics of 46 Studies Included in the Systematic Review
Table 2.  
Results of Univariable and Multivariable Random-Effects Meta-regression of the Sources of Between-Study Heterogeneity
Results of Univariable and Multivariable Random-Effects Meta-regression of the Sources of Between-Study Heterogeneity
1.
Sander  M, Oxlund  B, Jespersen  A,  et al.  The challenges of human population ageing.  Age Ageing. 2015;44(2):185-187. doi:10.1093/ageing/afu189PubMedGoogle ScholarCrossref
2.
United Nations Department of Economic and Social Affairs (DESA)/Population Division. World Population Prospects 2019. https://population.un.org/wpp/Download/Standard/Population/. Accessed January 26, 2019.
3.
Collard  RM, Boter  H, Schoevers  RA, Oude Voshaar  RC.  Prevalence of frailty in community-dwelling older persons: a systematic review.  J Am Geriatr Soc. 2012;60(8):1487-1492. doi:10.1111/j.1532-5415.2012.04054.xPubMedGoogle ScholarCrossref
4.
Clegg  A, Young  J, Iliffe  S, Rikkert  MO, Rockwood  K.  Frailty in elderly people.  Lancet. 2013;381(9868):752-762. doi:10.1016/S0140-6736(12)62167-9PubMedGoogle ScholarCrossref
5.
Cheng  MH, Chang  SF.  Frailty as a risk factor for falls among community dwelling people: evidence from a meta-analysis.  J Nurs Scholarsh. 2017;49(5):529-536. doi:10.1111/jnu.12322PubMedGoogle ScholarCrossref
6.
Persico  I, Cesari  M, Morandi  A,  et al.  Frailty and delirium in older adults: a systematic review and meta-analysis of the literature.  J Am Geriatr Soc. 2018;66(10):2022-2030. doi:10.1111/jgs.15503PubMedGoogle ScholarCrossref
7.
Kojima  G.  Frailty as a predictor of nursing home placement among community-dwelling older adults: a systematic review and meta-analysis.  J Geriatr Phys Ther. 2018;41(1):42-48. doi:10.1519/JPT.0000000000000097PubMedGoogle ScholarCrossref
8.
Kojima  G.  Frailty as a predictor of disabilities among community-dwelling older people: a systematic review and meta-analysis.  Disabil Rehabil. 2017;39(19):1897-1908. doi:10.1080/09638288.2016.1212282PubMedGoogle ScholarCrossref
9.
Kojima  G, Iliffe  S, Walters  K.  Frailty Index as a predictor of mortality: a systematic review and meta-analysis.  Age Ageing. 2018;47(2):193-200. doi:10.1093/ageing/afx162PubMedGoogle ScholarCrossref
10.
Lin  HS, Watts  JN, Peel  NM, Hubbard  RE.  Frailty and post-operative outcomes in older surgical patients: a systematic review.  BMC Geriatr. 2016;16(1):157. doi:10.1186/s12877-016-0329-8PubMedGoogle ScholarCrossref
11.
Kojima  G.  Frailty as a predictor of emergency department utilization among community-dwelling older people: a systematic review and meta-analysis.  J Am Med Dir Assoc. 2019;20(1):103-105. doi:10.1016/j.jamda.2018.10.004PubMedGoogle ScholarCrossref
12.
Bock  JO, König  HH, Brenner  H,  et al.  Associations of frailty with health care costs: results of the ESTHER cohort study.  BMC Health Serv Res. 2016;16:128. doi:10.1186/s12913-016-1360-3PubMedGoogle ScholarCrossref
13.
Gwyther  H, Shaw  R, Jaime Dauden  EA,  et al.  Understanding frailty: a qualitative study of European healthcare policy-makers’ approaches to frailty screening and management.  BMJ Open. 2018;8(1):e018653. doi:10.1136/bmjopen-2017-018653PubMedGoogle ScholarCrossref
14.
Morley  JE.  Frailty: diagnosis and management.  J Nutr Health Aging. 2011;15(8):667-670. doi:10.1007/s12603-011-0338-4PubMedGoogle ScholarCrossref
15.
Buckinx  F, Rolland  Y, Reginster  JY, Ricour  C, Petermans  J, Bruyère  O.  Burden of frailty in the elderly population: perspectives for a public health challenge.  Arch Public Health. 2015;73(1):19. doi:10.1186/s13690-015-0068-xPubMedGoogle ScholarCrossref
16.
Ambagtsheer  RC, Beilby  JJ, Visvanathan  R, Dent  E, Yu  S, Braunack-Mayer  AJ.  Should we screen for frailty in primary care settings? a fresh perspective on the frailty evidence base: a narrative review.  Prev Med. 2019;119:63-69. doi:10.1016/j.ypmed.2018.12.020PubMedGoogle ScholarCrossref
17.
Fried  LP, Tangen  CM, Walston  J,  et al; Cardiovascular Health Study Collaborative Research Group.  Frailty in older adults: evidence for a phenotype.  J Gerontol A Biol Sci Med Sci. 2001;56(3):M146-M156. doi:10.1093/gerona/56.3.M146PubMedGoogle ScholarCrossref
18.
Rockwood  K, Stadnyk  K, MacKnight  C, McDowell  I, Hébert  R, Hogan  DB.  A brief clinical instrument to classify frailty in elderly people.  Lancet. 1999;353(9148):205-206. doi:10.1016/S0140-6736(98)04402-XPubMedGoogle ScholarCrossref
19.
Dent  E, Kowal  P, Hoogendijk  EO.  Frailty measurement in research and clinical practice: a review.  Eur J Intern Med. 2016;31:3-10. doi:10.1016/j.ejim.2016.03.007PubMedGoogle ScholarCrossref
20.
Lang  PO, Michel  JP, Zekry  D.  Frailty syndrome: a transitional state in a dynamic process.  Gerontology. 2009;55(5):539-549. doi:10.1159/000211949PubMedGoogle ScholarCrossref
21.
Galluzzo  L, O’Caoimh  R, Rodríguez-Laso  Á,  et al; Work Package 5 of the Joint Action ADVANTAGE.  Incidence of frailty: a systematic review of scientific literature from a public health perspective.  Ann Ist Super Sanita. 2018;54(3):239-245.PubMedGoogle Scholar
22.
Kaeberlein  M, Rabinovitch  PS, Martin  GM.  Healthy aging: the ultimate preventative medicine.  Science. 2015;350(6265):1191-1193. doi:10.1126/science.aad3267PubMedGoogle ScholarCrossref
23.
Moher  D, Liberati  A, Tetzlaff  J, Altman  DG; PRISMA Group.  Preferred Reporting Items for Systematic Reviews and Meta-analyses: the PRISMA statement.  BMJ. 2009;339:b2535. doi:10.1136/bmj.b2535PubMedGoogle ScholarCrossref
24.
Stroup  DF, Berlin  JA, Morton  SC,  et al; Meta-analysis of Observational Studies in Epidemiology (MOOSE) Group.  Meta-analysis of Observational Studies in Epidemiology: a proposal for reporting.  JAMA. 2000;283(15):2008-2012. doi:10.1001/jama.283.15.2008PubMedGoogle ScholarCrossref
25.
PROSPERO. Incidence of Frailty Among Community-Dwelling Older Adults. CRD42019121302. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=121302. Accessed January 26, 2019.
26.
Xue  QL.  The frailty syndrome: definition and natural history.  Clin Geriatr Med. 2011;27(1):1-15. doi:10.1016/j.cger.2010.08.009PubMedGoogle ScholarCrossref
27.
Ofori-Asenso  R, Lee Chin  K, Mazidi  M,  et al.  Natural regression of frailty among community-dwelling older adults: a systematic review and meta-analysis.  Gerontologist. 2019;gnz064. doi:10.1093/geront/gnz064PubMedGoogle Scholar
28.
Aguayo  GA, Donneau  AF, Vaillant  MT,  et al.  Agreement between 35 published frailty scores in the general population.  Am J Epidemiol. 2017;186(4):420-434. doi:10.1093/aje/kwx061PubMedGoogle ScholarCrossref
29.
Kojima  G.  Prevalence of frailty in nursing homes: a systematic review and meta-analysis.  J Am Med Dir Assoc. 2015;16(11):940-945. doi:10.1016/j.jamda.2015.06.025PubMedGoogle ScholarCrossref
30.
Munn  Z, Moola  S, Lisy  K, Riitano  D, Tufanaru  C.  Methodological guidance for systematic reviews of observational epidemiological studies reporting prevalence and cumulative incidence data.  Int J Evid Based Healthc. 2015;13(3):147-153. doi:10.1097/XEB.0000000000000054PubMedGoogle ScholarCrossref
31.
Sikkema  M, de Jonge  PJ, Steyerberg  EW, Kuipers  EJ.  Risk of esophageal adenocarcinoma and mortality in patients with Barrett’s esophagus: a systematic review and meta-analysis.  Clin Gastroenterol Hepatol. 2010;8(3):235-244. doi:10.1016/j.cgh.2009.10.010PubMedGoogle ScholarCrossref
32.
Tansel  A, Katz  LH, El-Serag  HB,  et al.  Incidence and determinants of hepatocellular carcinoma in autoimmune hepatitis: a systematic review and meta-analysis.  Clin Gastroenterol Hepatol. 2017;15(8):1207-1217.e4. doi:10.1016/j.cgh.2017.02.006PubMedGoogle ScholarCrossref
33.
Yousef  F, Cardwell  C, Cantwell  MM, Galway  K, Johnston  BT, Murray  L.  The incidence of esophageal cancer and high-grade dysplasia in Barrett’s esophagus: a systematic review and meta-analysis.  Am J Epidemiol. 2008;168(3):237-249. doi:10.1093/aje/kwn121PubMedGoogle ScholarCrossref
34.
Sutton  A, Abrams  K, Jones  D, Sheldon  T, Song  F.  Methods for Meta-analysis in Medical Research. London, United Kingdom: Wiley; 2000.
35.
Delgado-Rodríguez  M, Llorca  J.  Bias.  J Epidemiol Community Health. 2004;58(8):635-641. doi:10.1136/jech.2003.008466PubMedGoogle ScholarCrossref
36.
Kojima  G, Taniguchi  Y, Iliffe  S, Jivraj  S, Walters  K.  Transitions between frailty states among community-dwelling older people: a systematic review and meta-analysis.  Ageing Res Rev. 2019;50:81-88. doi:10.1016/j.arr.2019.01.010PubMedGoogle ScholarCrossref
37.
Higgins  JP, Thompson  SG, Deeks  JJ, Altman  DG.  Measuring inconsistency in meta-analyses.  BMJ. 2003;327(7414):557-560. doi:10.1136/bmj.327.7414.557PubMedGoogle ScholarCrossref
38.
World Bank. World Bank country and lending groups. https://datahelpdesk.worldbank.org/knowledgebase/articles/906519-world-bank-country-and-lending-groups. Published 2019. Accessed January 29, 2019.
39.
Egger  M, Davey Smith  G, Schneider  M, Minder  C.  Bias in meta-analysis detected by a simple, graphical test.  BMJ. 1997;315(7109):629-634. doi:10.1136/bmj.315.7109.629PubMedGoogle ScholarCrossref
40.
Barendregt  JJ, Doi  SA, Lee  YY, Norman  RE, Vos  T.  Meta-analysis of prevalence.  J Epidemiol Community Health. 2013;67(11):974-978. doi:10.1136/jech-2013-203104PubMedGoogle ScholarCrossref
41.
Ahmad  NS, Hairi  NN, Said  MA,  et al.  Prevalence, transitions and factors predicting transition between frailty states among rural community-dwelling older adults in Malaysia.  PLoS One. 2018;13(11):e0206445. doi:10.1371/journal.pone.0206445PubMedGoogle ScholarCrossref
42.
Alencar  MA, Dias  JMD, Figueiredo  LC, Dias  RC.  Transitions in frailty status in community-dwelling older adults.  Top Geriatr Rehabil. 2015;31(2):105-112. doi:10.1097/TGR.0000000000000055Google ScholarCrossref
43.
Ayers  E, Shapiro  M, Holtzer  R, Barzilai  N, Milman  S, Verghese  J.  Symptoms of apathy independently predict incident frailty and disability in community-dwelling older adults.  J Clin Psychiatry. 2017;78(5):e529-e536. doi:10.4088/JCP.15m10113PubMedGoogle ScholarCrossref
44.
Baulderstone  L, Yaxley  A, Luszcz  M, Miller  M.  Diet liberalisation in older Australians decreases frailty without increasing the risk of developing chronic disease.  J Frailty Aging. 2012;1(4):174-182.PubMedGoogle Scholar
45.
Bentur  N, Sternberg  SA, Shuldiner  J.  Frailty transitions in community dwelling older people.  Isr Med Assoc J. 2016;18(8):449-453.PubMedGoogle Scholar
46.
Borrat-Besson  C, Ryser  V, Wernli  B. Transitions between frailty states: a European comparison. In: Börsch-Supan  A, Brandt  M, Litwin  H, Weber  G, eds.  Active Ageing and Solidarity Between Generations in Europe: First Results From SHARE After the Economic Crisis. Gottingen, Germany: Hubert & Co; 2013:175-185. doi:10.1515/9783110295467.175
47.
Castrejón-Pérez  RC, Jiménez-Corona  A, Bernabé  E,  et al.  Oral disease and 3-year incidence of frailty in Mexican older adults.  J Gerontol A Biol Sci Med Sci. 2017;72(7):951-957.PubMedGoogle Scholar
48.
Chhetri  JK, Zheng  Z, Xu  X, Ma  C, Chan  P.  The prevalence and incidence of frailty in pre-diabetic and diabetic community-dwelling older population: results from Beijing Longitudinal Study of Aging II (BLSA-II).  BMC Geriatr. 2017;17(1):47. doi:10.1186/s12877-017-0439-yPubMedGoogle ScholarCrossref
49.
Dalrymple  LS, Katz  R, Rifkin  DE,  et al.  Kidney function and prevalent and incident frailty.  Clin J Am Soc Nephrol. 2013;8(12):2091-2099. doi:10.2215/CJN.02870313PubMedGoogle ScholarCrossref
50.
Doba  N, Tokuda  Y, Goldstein  NE, Kushiro  T, Hinohara  S.  A pilot trial to predict frailty syndrome: the Japanese Health Research Volunteer Study.  Exp Gerontol. 2012;47(8):638-643. doi:10.1016/j.exger.2012.05.016PubMedGoogle ScholarCrossref
51.
Doi  T, Makizako  H, Tsutsumimoto  K,  et al.  Transitional status and modifiable risk of frailty in Japanese older adults: a prospective cohort study.  Geriatr Gerontol Int. 2018;18(11):1562-1566. doi:10.1111/ggi.13525PubMedGoogle ScholarCrossref
52.
Ensrud  KE, Ewing  SK, Fredman  L,  et al; Study of Osteoporotic Fractures Research Group.  Circulating 25-hydroxyvitamin D levels and frailty status in older women.  J Clin Endocrinol Metab. 2010;95(12):5266-5273. doi:10.1210/jc.2010-2317PubMedGoogle ScholarCrossref
53.
Espinoza  SE, Jung  I, Hazuda  H.  Frailty transitions in the San Antonio Longitudinal Study of Aging.  J Am Geriatr Soc. 2012;60(4):652-660. doi:10.1111/j.1532-5415.2011.03882.xPubMedGoogle ScholarCrossref
54.
Gale  CR, Baylis  D, Cooper  C, Sayer  AA.  Inflammatory markers and incident frailty in men and women: the English Longitudinal Study of Ageing.  Age (Dordr). 2013;35(6):2493-2501. doi:10.1007/s11357-013-9528-9PubMedGoogle ScholarCrossref
55.
García-Esquinas  E, José García-García  F, León-Muñoz  LM,  et al.  Obesity, fat distribution, and risk of frailty in two population-based cohorts of older adults in Spain.  Obesity (Silver Spring). 2015;23(4):847-855. doi:10.1002/oby.21013PubMedGoogle ScholarCrossref
56.
García-Esquinas  E, Rahi  B, Peres  K,  et al.  Consumption of fruit and vegetables and risk of frailty: a dose-response analysis of 3 prospective cohorts of community-dwelling older adults.  Am J Clin Nutr. 2016;104(1):132-142. doi:10.3945/ajcn.115.125781PubMedGoogle ScholarCrossref
57.
Gill  TM, Gahbauer  EA, Allore  HG, Han  L.  Transitions between frailty states among community-living older persons.  Arch Intern Med. 2006;166(4):418-423. doi:10.1001/archinte.166.4.418PubMedGoogle ScholarCrossref
58.
Gnjidic  D, Hilmer  SN, Blyth  FM,  et al.  High-risk prescribing and incidence of frailty among older community-dwelling men.  Clin Pharmacol Ther. 2012;91(3):521-528. doi:10.1038/clpt.2011.258PubMedGoogle ScholarCrossref
59.
Gomes  CDS, Guerra  RO, Wu  YY,  et al.  Social and economic predictors of worse frailty status occurrence across selected countries in North and South America and Europe.  Innov Aging. 2018;2(3):igy037. doi:10.1093/geroni/igy037PubMedGoogle ScholarCrossref
60.
Gruenewald  TL, Seeman  TE, Karlamangla  AS, Sarkisian  CA.  Allostatic load and frailty in older adults.  J Am Geriatr Soc. 2009;57(9):1525-1531. doi:10.1111/j.1532-5415.2009.02389.xPubMedGoogle ScholarCrossref
61.
Hyde  Z, Flicker  L, Smith  K,  et al.  Prevalence and incidence of frailty in Aboriginal Australians, and associations with mortality and disability.  Maturitas. 2016;87:89-94. doi:10.1016/j.maturitas.2016.02.013PubMedGoogle ScholarCrossref
62.
Iwasaki  M, Yoshihara  A, Sato  M,  et al.  Dentition status and frailty in community-dwelling older adults: a 5-year prospective cohort study.  Geriatr Gerontol Int. 2018;18(2):256-262. doi:10.1111/ggi.13170PubMedGoogle ScholarCrossref
63.
Kalyani  RR, Tian  J, Xue  QL,  et al.  Hyperglycemia and incidence of frailty and lower extremity mobility limitations in older women.  J Am Geriatr Soc. 2012;60(9):1701-1707. doi:10.1111/j.1532-5415.2012.04099.xPubMedGoogle ScholarCrossref
64.
Kim  M, Suzuki  T, Kojima  N,  et al.  Association between serum β2-microglobulin levels and prevalent and incident physical frailty in community-dwelling older women.  J Am Geriatr Soc. 2017;65(4):e83-e88. doi:10.1111/jgs.14733PubMedGoogle ScholarCrossref
65.
Lanziotti Azevedo da Silva  S, Campos Cavalcanti Maciel  Á, de Sousa Máximo Pereira  L, Domingues Dias  JM, Guimarães de Assis  M, Corrêa Dias  R.  Transition patterns of frailty syndrome in community-dwelling elderly individuals: a longitudinal study.  J Frailty Aging. 2015;4(2):50-55.PubMedGoogle Scholar
66.
Lee  JSW, Auyeung  TW, Leung  J, Kwok  T, Woo  J.  Transitions in frailty states among community-living older adults and their associated factors.  J Am Med Dir Assoc. 2014;15(4):281-286. doi:10.1016/j.jamda.2013.12.002PubMedGoogle ScholarCrossref
67.
Liu  ZY, Wei  YZ, Wei  LQ,  et al.  Frailty transitions and types of death in Chinese older adults: a population-based cohort study.  Clin Interv Aging. 2018;13:947-956. doi:10.2147/CIA.S157089PubMedGoogle ScholarCrossref
68.
Lorenzo-López  L, López-López  R, Maseda  A, Buján  A, Rodríguez-Villamil  JL, Millán-Calenti  JC.  Changes in frailty status in a community-dwelling cohort of older adults: the VERISAÚDE study.  Maturitas. 2019;119:54-60. doi:10.1016/j.maturitas.2018.11.006PubMedGoogle ScholarCrossref
69.
Ottenbacher  KJ, Graham  JE, Al Snih  S,  et al.  Mexican Americans and frailty: findings from the Hispanic established populations epidemiologic studies of the elderly.  Am J Public Health. 2009;99(4):673-679. doi:10.2105/AJPH.2008.143958PubMedGoogle ScholarCrossref
70.
Pilleron  S, Ajana  S, Jutand  MA,  et al.  Dietary patterns and 12-year risk of frailty: results from the Three-City Bordeaux Study.  J Am Med Dir Assoc. 2017;18(2):169-175. doi:10.1016/j.jamda.2016.09.014PubMedGoogle ScholarCrossref
71.
Pollack  LR, Litwack-Harrison  S, Cawthon  PM,  et al.  Patterns and predictors of frailty transitions in older men: the Osteoporotic Fractures in Men Study.  J Am Geriatr Soc. 2017;65(11):2473-2479. doi:10.1111/jgs.15003PubMedGoogle ScholarCrossref
72.
Potier  F, Degryse  JM, Bihin  B,  et al.  Health and frailty among older spousal caregivers: an observational cohort study in Belgium.  BMC Geriatr. 2018;18(1):291. doi:10.1186/s12877-018-0980-3PubMedGoogle ScholarCrossref
73.
Ramsay  SE, Papachristou  E, Watt  RG,  et al.  Influence of poor oral health on physical frailty: a population‐based cohort study of older British men.  J Am Geriatr Soc. 2018;66(3):473-479. doi:10.1111/jgs.15175PubMedGoogle ScholarCrossref
74.
Sandoval-Insausti  H, Pérez-Tasigchana  RF, López-García  E, García-Esquinas  E, Rodríguez-Artalejo  F, Guallar-Castillón  P.  Macronutrients intake and incident frailty in older adults: a prospective cohort study.  J Gerontol A Biol Sci Med Sci. 2016;71(10):1329-1334. doi:10.1093/gerona/glw033PubMedGoogle ScholarCrossref
75.
Saum  KU, Schöttker  B, Meid  AD,  et al.  Is polypharmacy associated with frailty in older people? results from the ESTHER cohort study.  J Am Geriatr Soc. 2017;65(2):e27-e32. doi:10.1111/jgs.14718PubMedGoogle ScholarCrossref
76.
Semba  RD, Bartali  B, Zhou  J, Blaum  C, Ko  CW, Fried  LP.  Low serum micronutrient concentrations predict frailty among older women living in the community.  J Gerontol A Biol Sci Med Sci. 2006;61(6):594-599. doi:10.1093/gerona/61.6.594PubMedGoogle ScholarCrossref
77.
Serra-Prat  M, Papiol  M, Vico  J, Palomera  E, Arús  M, Cabré  M.  Incidence and risk factors for frailty in the community-dwelling elderly population: a two-year follow-up cohort study.  J Gerontol Geriatr Res. 2017;6(6):452. doi:10.4172/2167-7182.1000452Google Scholar
78.
Shah  M, Paulson  D, Nguyen  V.  Alcohol use and frailty risk among older adults over 12 years: the Health and Retirement Study.  Clin Gerontol. 2018;41(4):315-325. doi:10.1080/07317115.2017.1364681PubMedGoogle ScholarCrossref
79.
Stephan  AJ, Strobl  R, Holle  R,  et al.  Male sex and poverty predict abrupt health decline: deficit accumulation patterns and trajectories in the KORA-Age cohort study.  Prev Med. 2017;102:31-38. doi:10.1016/j.ypmed.2017.06.032PubMedGoogle ScholarCrossref
80.
Swiecicka  A, Eendebak  RJAH, Lunt  M,  et al; European Male Ageing Study Group.  Reproductive hormone levels predict changes in frailty status in community-dwelling older men: European Male Ageing Study prospective data.  J Clin Endocrinol Metab. 2018;103(2):701-709. doi:10.1210/jc.2017-01172PubMedGoogle ScholarCrossref
81.
Thompson  MQ, Theou  O, Adams  RJ, Tucker  GR, Visvanathan  R.  Frailty state transitions and associated factors in South Australian older adults.  Geriatr Gerontol Int. 2018;18(11):1549-1555. doi:10.1111/ggi.13522PubMedGoogle ScholarCrossref
82.
Tom  S, Wyman  A, Woods  N,  et al.  Regional differences in incident prefrailty and frailty.  J Womens Health (Larchmt). 2017;26(9):992-998. doi:10.1089/jwh.2016.6041Google ScholarCrossref
83.
Trevisan  C, Veronese  N, Maggi  S,  et al.  Marital status and frailty in older people: gender differences in the Progetto Veneto Anziani longitudinal study.  J Womens Health (Larchmt). 2016;25(6):630-637. doi:10.1089/jwh.2015.5592PubMedGoogle ScholarCrossref
84.
Wang  MC, Li  TC, Li  CI,  et al.  Frailty, transition in frailty status and all-cause mortality in older adults of a Taichung community-based population.  BMC Geriatr. 2019;19(1):26. doi:10.1186/s12877-019-1039-9PubMedGoogle ScholarCrossref
85.
Woods  NF, LaCroix  AZ, Gray  SL,  et al; Women’s Health Initiative.  Frailty: emergence and consequences in women aged 65 and older in the Women’s Health Initiative Observational Study [published correction appears in J Am Geriatr Soc. 2017;65(7):1631-1632].  J Am Geriatr Soc. 2005;53(8):1321-1330. PubMedGoogle ScholarCrossref
86.
Zaslavsky  O, Walker  RL, Crane  PK, Gray  SL, Larson  EB.  Glucose levels and risk of frailty.  J Gerontol A Biol Sci Med Sci. 2016;71(9):1223-1229. doi:10.1093/gerona/glw024PubMedGoogle ScholarCrossref
87.
Doi  T, Makizako  H, Tsutsumimoto  K,  et al.  Transitional status and modifiable risk of frailty in Japanese older adults: a prospective cohort study.  Geriatr Gerontol Int. 2018;18(11):1562-1566. doi:10.1111/ggi.13525PubMedGoogle ScholarCrossref
88.
Hanlon  P, Nicholl  BI, Jani  BD, Lee  D, McQueenie  R, Mair  FS.  Frailty and pre-frailty in middle-aged and older adults and its association with multimorbidity and mortality: a prospective analysis of 493 737 UK Biobank participants.  Lancet Public Health. 2018;3(7):e323-e332. doi:10.1016/S2468-2667(18)30091-4PubMedGoogle ScholarCrossref
89.
Vetrano  DL, Palmer  K, Marengoni  A,  et al; Joint Action ADVANTAGE WP4 Group.  Frailty and multimorbidity: a systematic review and meta-analysis.  J Gerontol A Biol Sci Med Sci. 2018.PubMedGoogle Scholar
90.
Ofori-Asenso  R, Chin  KL, Curtis  AJ, Zomer  E, Zoungas  S, Liew  D.  Recent patterns of multimorbidity among older adults in high-income countries.  Popul Health Manag. 2019;22(2):127-137. doi:10.1089/pop.2018.0069PubMedGoogle ScholarCrossref
91.
Peralta  M, Ramos  M, Lipert  A, Martins  J, Marques  A.  Prevalence and trends of overweight and obesity in older adults from 10 European countries from 2005 to 2013.  Scand J Public Health. 2018;46(5):522-529. doi:10.1177/1403494818764810PubMedGoogle ScholarCrossref
92.
Samper-Ternent  R, Al Snih  S.  Obesity in older adults: epidemiology and implications for disability and disease.  Rev Clin Gerontol. 2012;22(1):10-34. doi:10.1017/S0959259811000190PubMedGoogle ScholarCrossref
93.
García-Esquinas  E, José García-García  F, León-Muñoz  LM,  et al.  Obesity, fat distribution, and risk of frailty in two population-based cohorts of older adults in Spain.  Obesity (Silver Spring). 2015;23(4):847-855. doi:10.1002/oby.21013PubMedGoogle ScholarCrossref
94.
Stenholm  S, Strandberg  TE, Pitkälä  K, Sainio  P, Heliövaara  M, Koskinen  S.  Midlife obesity and risk of frailty in old age during a 22-year follow-up in men and women: the Mini-Finland follow-up survey.  J Gerontol A Biol Sci Med Sci. 2014;69(1):73-78. doi:10.1093/gerona/glt052PubMedGoogle ScholarCrossref
95.
Feng  Z, Lugtenberg  M, Franse  C,  et al.  Risk factors and protective factors associated with incident or increase of frailty among community-dwelling older adults: a systematic review of longitudinal studies.  PLoS One. 2017;12(6):e0178383. doi:10.1371/journal.pone.0178383PubMedGoogle ScholarCrossref
96.
Ng  TP, Feng  L, Nyunt  MS, Larbi  A, Yap  KB.  Frailty in older persons: multisystem risk factors and the Frailty Risk Index (FRI).  J Am Med Dir Assoc. 2014;15(9):635-642. doi:10.1016/j.jamda.2014.03.008PubMedGoogle ScholarCrossref
97.
Espinoza  SE, Fried  LP.  Risk factors for frailty in the older adult.  Clin Geriatr. 2007;15(6):37-44.Google Scholar
98.
Kojima  G, Iliffe  S, Walters  K.  Smoking as a predictor of frailty: a systematic review.  BMC Geriatr. 2015;15:131. doi:10.1186/s12877-015-0134-9PubMedGoogle ScholarCrossref
99.
Siriwardhana  DD, Hardoon  S, Rait  G, Weerasinghe  MC, Walters  KR.  Prevalence of frailty and prefrailty among community-dwelling older adults in low-income and middle-income countries: a systematic review and meta-analysis.  BMJ Open. 2018;8(3):e018195. doi:10.1136/bmjopen-2017-018195PubMedGoogle ScholarCrossref
100.
Franse  CB, van Grieken  A, Qin  L, Melis  RJF, Rietjens  JAC, Raat  H.  Socioeconomic inequalities in frailty and frailty components among community-dwelling older citizens.  PLoS One. 2017;12(11):e0187946. doi:10.1371/journal.pone.0187946PubMedGoogle ScholarCrossref
101.
Epping-Jordan  JE, Pruitt  SD, Bengoa  R, Wagner  EH.  Improving the quality of health care for chronic conditions.  Qual Saf Health Care. 2004;13(4):299-305. doi:10.1136/qshc.2004.010744PubMedGoogle ScholarCrossref
102.
Gordon  EH, Peel  NM, Samanta  M, Theou  O, Howlett  SE, Hubbard  RE.  Sex differences in frailty: a systematic review and meta-analysis.  Exp Gerontol. 2017;89:30-40. doi:10.1016/j.exger.2016.12.021PubMedGoogle ScholarCrossref
103.
Puts  MTE, Toubasi  S, Andrew  MK,  et al.  Interventions to prevent or reduce the level of frailty in community-dwelling older adults: a scoping review of the literature and international policies.  Age Ageing. 2017;46(3):383-392.PubMedGoogle Scholar
104.
Apóstolo  J, Cooke  R, Bobrowicz-Campos  E,  et al.  Effectiveness of interventions to prevent pre-frailty and frailty progression in older adults: a systematic review.  JBI Database System Rev Implement Rep. 2018;16(1):140-232. doi:10.11124/JBISRIR-2017-003382PubMedGoogle ScholarCrossref
105.
Chin A Paw  MJ, van Uffelen  JG, Riphagen  I, van Mechelen  W.  The functional effects of physical exercise training in frail older people: a systematic review.  Sports Med. 2008;38(9):781-793. doi:10.2165/00007256-200838090-00006PubMedGoogle ScholarCrossref
106.
de Labra  C, Guimaraes-Pinheiro  C, Maseda  A, Lorenzo  T, Millán-Calenti  JC.  Effects of physical exercise interventions in frail older adults: a systematic review of randomized controlled trials.  BMC Geriatr. 2015;15:154. doi:10.1186/s12877-015-0155-4PubMedGoogle ScholarCrossref
107.
Giné-Garriga  M, Roqué-Fíguls  M, Coll-Planas  L, Sitjà-Rabert  M, Salvà  A.  Physical exercise interventions for improving performance-based measures of physical function in community-dwelling, frail older adults: a systematic review and meta-analysis.  Arch Phys Med Rehabil. 2014;95(4):753-769.e3. doi:10.1016/j.apmr.2013.11.007PubMedGoogle ScholarCrossref
108.
Travers  J, Romero-Ortuno  R, Bailey  J, Cooney  MT.  Delaying and reversing frailty: a systematic review of primary care interventions.  Br J Gen Pract. 2019;69(678):e61-e69. doi:10.3399/bjgp18X700241PubMedGoogle ScholarCrossref
109.
Noubiap  JJ, Balti  EV, Bigna  JJ, Echouffo-Tcheugui  JB, Kengne  AP.  Dyslipidaemia in Africa: comment on a recent systematic review: authors’ reply.  Lancet Glob Health. 2019;7(3):e308-e309. doi:10.1016/S2214-109X(18)30517-5PubMedGoogle ScholarCrossref
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    What is the status of Frail Older Adults in Low Income Regions?
    Jagadish Chhetri, M.D | Department of Neurobiology, Neurology and Geriatrics, Xuanwu Hospital of Capital Medical University, Beijing Institute of Geriatrics, Beijing, China; NSGG, Kathmandu, Nepal
    In this meta-analysis on the global incidence of frailty and prefrailty, the authors have shown that there is a very high risk of being frail or prefrail in old age. Moreover, it is quite worrying to see that older people in Low and middle income countries (LMICs) had higher risk (almost double) of developing frailty or prefrailty compared to the high income countries (HICs).

    In the last decade, the concept of frailty has profoundly captured the attention of researchers and clinicians worldwide. “Frailty” originally considered as a mere research entity is now acknowledged as a modern geriatric giant
    as it could lead to many adverse outcomes in old age including repeated hospitalizations, high healthcare cost, disability and death. Hence, many HICs have long been working on reducing the burden of frailty by conducting researches extensively to identify modifiable risk factors of frailty, and even by establishing frailty clinics for screening and providing possible intervention techniques. While on the other hand there is very limited evidence of frailty in LMICs, particularly in the low income countries (LICs) (both in literature and clinical practice), although there has been indication of almost half of the older population in these regions to be frail, which is alarming.

    In this context, perhaps it is about time to consider frailty as a public health priority, even in the lowest income regions, so as to lower the unseen burden of frailty. Training of the clinicians to identify frail older patients in the community, and conduct studies to investigate country specific risk-factors could be the first step to address the negative consequences of frailty. Implementation of public health strategies based on these findings could further lower the risk of developing frailty or prefrailty in the LICs.
    CONFLICT OF INTEREST: None Reported
    READ MORE
    Original Investigation
    Geriatrics
    August 2, 2019

    社区老年人中虚弱和衰弱的全球发病率: 系统评价和荟萃分析

    Author Affiliations
    • 1School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia
    • 2Melbourne Medical School, University of Melbourne, Parkville, Victoria, Australia
    • 3Division of Food and Nutrition Science, Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden
    • 4Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Melbourne, Victoria, Australia
    • 5Department of Health Services, Policy, and Practice, Brown University School of Public Health, Providence, Rhode Island
    • 6Center of Innovation in Long Term Services and Supports, Providence Veterans Affairs Medical Center, Providence, Rhode Island
    • 7Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, United Kingdom
    • 8Institute of Biomedicine, University of Turku, Turku, Finland
    • 9Department of Aged Care, Royal Melbourne Hospital and University of Melbourne, Melbourne, Victoria, Australia
    • 10Centre for Research Excellence in Frailty and Healthy Ageing, University of Adelaide, Adelaide, South Australia, Australia
    JAMA Netw Open. 2019;2(8):e198398. doi:10.1001/jamanetworkopen.2019.8398
    关键点 español English

    问题  60 岁或以上的社区成年人的虚弱和衰弱的发病率是多少?

    结果  在这次涉及来自 28 个国家的 120,000 多名老年人数据的系统评价和荟萃分析中,估计虚弱和衰弱的发病率情况为每 1,000 人每年分别有 43.4 例和 150.6 例新发病例。虚弱和衰弱的发病率因性别、诊断标准和国家收入水平而异。

    意义  这项研究结果表明,社区生活的老年人患虚弱和衰弱的风险很高;因此,需要适当的干预措施。

    Abstract

    Importance  Frailty is a common geriatric syndrome of significant public health importance, yet there is limited understanding of the risk of frailty development at a population level.

    Objective  To estimate the global incidence of frailty and prefrailty among community-dwelling adults 60 years or older.

    Data Sources  MEDLINE, Embase, PsycINFO, Web of Science, CINAHL Plus, and AMED (Allied and Complementary Medicine Database) were searched from inception to January 2019 without language restrictions using combinations of the keywords frailty, older adults, and incidence. The reference lists of eligible studies were hand searched.

    Study Selection  In the systematic review, 2 authors undertook the search, article screening, and study selection. Cohort studies that reported or had sufficient data to compute incidence of frailty or prefrailty among community-dwelling adults 60 years or older at baseline were eligible.

    Data Extraction and Synthesis  The methodological quality of included studies was assessed using The Joanna Briggs Institute’s Critical Appraisal Checklist for Prevalence and Incidence Studies. Meta-analysis was conducted using a random-effects (DerSimonian and Laird) model.

    Main Outcomes and Measures  Incidence of frailty (defined as new cases of frailty among robust or prefrail individuals) and incidence of prefrailty (defined as new cases of prefrailty among robust individuals), both over a specified duration.

    Results  Of 15 176 retrieved references, 46 observational studies involving 120 805 nonfrail (robust or prefrail) participants from 28 countries were included in this systematic review. Among the nonfrail individuals who survived a median follow-up of 3.0 (range, 1.0-11.7) years, 13.6% (13 678 of 100 313) became frail, with the pooled incidence rate being 43.4 (95% CI, 37.3-50.4; I2 = 98.5%) cases per 1000 person-years. The incidence of frailty was significantly higher in prefrail individuals than robust individuals (pooled incidence rates, 62.7 [95% CI, 49.2-79.8; I2 = 97.8%] vs 12.0 [95% CI, 8.2-17.5; I2 = 94.9%] cases per 1000 person-years, respectively; P for difference < .001). Among robust individuals in 21 studies who survived a median follow-up of 2.5 (range, 1.0-10.0) years, 30.9% (9974 of 32 268) became prefrail, with the pooled incidence rate being 150.6 (95% CI, 123.3-184.1; I2 = 98.9%) cases per 1000 person-years. The frailty and prefrailty incidence rates were significantly higher in women than men (frailty: 44.8 [95% CI, 36.7-61.3; I2 = 97.9%] vs 24.3 [95% CI, 19.6-30.1; I2 = 8.94%] cases per 1000 person-years; prefrailty: 173.2 [95% CI, 87.9-341.2; I2 = 99.1%] vs 129.0 [95% CI, 73.8-225.0; I2 = 98.5%] cases per 1000 person-years). The incidence rates varied by diagnostic criteria and country income level. The frailty and prefrailty incidence rates were significantly reduced when accounting for the risk of death.

    Conclusions and Relevance  Results of this study suggest that community-dwelling older adults are prone to developing frailty. Increased awareness of the factors that confer high risk of frailty in this population subgroup is vital to inform the design of interventions to prevent frailty and to minimize its consequences.

    Introduction

    The increasing average life expectancy has contributed to aging of the world’s population.1 By 2050, approximately 21.3% of the global population will be 60 years or older,2 up from 9.2% in 1990. Frailty, a clinical syndrome characterized by marked vulnerability due to decline in reserve and function across multiple physiologic systems, is common among older people.3,4 Frailty manifests as the inability to tolerate stressful events and has been associated with adverse outcomes, such as falls,5 delirium,6 institutionalization,7 incident disability,8 and mortality.9 Frailty is also an independent risk factor for poor outcomes after surgery (eg, prolonged hospitalizations, increased susceptibility to deconditioning, and faster functional decline)10 and is associated with higher health care use11 and corresponding costs.12 There is a growing interest among stakeholders in aged care to better understand the patterns and determinants of frailty.13

    Frailty is difficult to diagnose, particularly within primary care settings, due to its coexistence with other age-related conditions and as a result of the lack of a universally accepted clinical definition.14,15 There is also debate about frailty screening, especially in relation to screening eligibility, as well as where and when it should be done.16

    Frailty phenotype and deficit accumulation are 2 main approaches to frailty assessment.4 Using the phenotype approach, Fried et al17 defined frailty as a predominantly physical condition requiring the presence of 3 or more of the following 5 components: weight loss, exhaustion, weakness, slowness, and low physical activity. However, Rockwood et al18 characterized frailty as an accumulation of deficits (symptoms, signs, functional impairment, and laboratory abnormalities) and stipulated that more deficits confer greater risk. These 2 frailty conceptualizations have been extensively validated and are widely used. Beyond these conceptualizations of frailty, several other definitions are present in the literature.19 Many definitions consider frailty to be a dynamic process with an identifiable intermediate stage, usually referred to as prefrailty.20

    Since 2000, frailty-related research has increased exponentially.15 Nonetheless, the epidemiological evidence on frailty is dominated by a focus on prevalence. Incidence remains poorly understood. Although Galluzzo et al21 previously performed a systematic review on frailty incidence, their analysis focused on European ADVANTAGE Joint Action countries and included 6 studies, with no meta-analysis performed. With a growing worldwide interest in healthy aging,22 improved understanding of the incidence of frailty may help deepen the discourse around the maintenance of functional ability in old age. Therefore, we conducted a systematic review and meta-analysis to summarize the available global epidemiological data on the incidence of frailty and prefrailty among community-dwelling adults 60 years or older.

    Methods

    This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses23 (PRISMA) and Meta-analysis of Observational Studies in Epidemiology24 (MOOSE) reporting guidelines. The study protocol is registered at PROSPERO (CRD42019121302).25

    Study Eligibility Criteria

    Two of us (R.O-A. and K.L.C) independently determined study eligibility, and any disagreements were resolved via consensus involving a third reviewer (D. Liew). The inclusion criteria were cohort studies that reported or had sufficient data to compute incidence of frailty or prefrailty among community-dwelling adults 60 years or older at baseline. Frailty status was considered categorically as robust, prefrail, or frail.26 Frailty could have been diagnosed by any method, but studies needed to specify their definition. For the Fried phenotype, individuals are often classified as robust, prefrail, or frail if 0, 1 to 2, or 3 or more of the criteria (ie, weight loss, exhaustion, weakness, slowness, and low physical activity) are met, respectively.17 For the deficit accumulation approach, the definitions of robust, prefrail, and frail were as specified by study authors, as has been done previously.27,28 Incidence of frailty was defined as new cases of frailty among robust or prefrail individuals, and incidence of prefrailty was defined as new cases of prefrailty among robust individuals, both over a specified duration. When multiple studies used the same cohort, the study with the most complete data on the largest number of participants was selected.

    Exclusion criteria included studies focusing on institutionalized or hospitalized adults, residents of nursing homes (because these populations are often predominantly frail),29 or populations selected on the basis of an index disease. Studies reporting the mean frailty scores but without data on incidence were excluded, as were randomized clinical trials. Studies of individuals across the life span were excluded unless data were specifically available for those 60 years or older at baseline.

    Search and Selection of Studies

    In the systematic review, 2 of us (R.O-A. and K.L.C.) undertook the search, article screening, and study selection. MEDLINE, Embase, PsycINFO, Web of Science, CINAHL Plus, and AMED (Allied and Complementary Medicine Database) were searched from inception to January 2019 without language restrictions using combinations of the keywords frailty, older adults, and incidence. eTable 1 in the Supplement lists the search terms and strategy for MEDLINE (via Ovid), which were adapted for other databases. The reference lists of eligible studies were hand searched. Conference abstracts, editorials, and meeting reports were excluded.

    Study Quality Assessment and Data Extraction

    Two of us (R.O-A. and K.L.C.) evaluated each included study for methodological quality using The Joanna Briggs Institute’s Critical Appraisal Checklist for Prevalence and Incidence Studies.30 This checklist consists of 9 criteria, and studies were ineligible if fewer than 5 of the criteria were achieved.

    The following information was collected from individual articles: study details (authors, year of publication, country, and study name), participant characteristics (sample size and percentage of women), frailty measurement method, duration of follow-up, and incidence data. Sex-stratified or age-stratified incidence data were collected, where available. Authors were contacted for additional data or clarification, when required.

    Statistical Analysis

    For each study, we recorded or calculated incidence rates of frailty or prefrailty per 1000 person-years based on the event rates and the mean duration of follow-up.27,31-33 Exact methods according to the Poisson distribution were adopted to calculate 95% CIs for incidence rates.34 There were 2 kinds of studies, including (1) those that used a 100% survivor cohort (ie, assessed frailty status at 2 time points, excluding persons who died in-between) and (2) those that accounted for people in the cohort who died without developing frailty. Therefore, to improve the comparability of these 2 types of studies, as well as to minimize the consequences of survivorship bias,35 we recalculated the incidence rate in the latter studies (ie, studies that reported transition to deaths) by restricting the sample to the surviving cohort with frailty data.27,36

    A random-effects (DerSimonian and Laird) meta-analysis was conducted using the log-transformed incidence rates and corresponding 95% CIs. The random-effects model was selected a priori due to the anticipated heterogeneity of the included studies. Statistical evidence of between-study heterogeneity was examined using the Cochran Q test and the I2 statistic.37I2 values of 25%, 50%, and 75% were considered to be low, moderate, and high degrees of heterogeneity, respectively.37 The robustness of pooled estimates were assessed via leave-1-out sensitivity analyses. A study was considered to be influential if the pooled estimate without it was not within the 95% CIs of the overall pooled estimate. Sex-specific incidence data were pooled, as were the incidence rates by assessment method. To examine the extent to which the pooled incidence rates were explained by these factors, we also performed random-effects meta-regression using the following variables: measurement method (physical phenotype vs other), country income level (lower-income and middle-income country [LMIC] vs high-income country [HIC]), study region (North America, Europe, Asia, or other), person-years of follow-up (per unit increase), whether the study enrolled only elderly people 70 years or older (no vs yes), study population (mix, female only, or male only), and publication years (2009 or earlier, 2010 to 2014, or 2015 to 2019). The HICs were defined as any country with a gross national income per capita in 2017 of US $12 056 or more.38 Differences between subgroups were compared via a χ2 test. Publication bias was assessed via visual inspection of funnel plots, and statistical assessment was evaluated using the Egger test.39

    To provide context of the burden of frailty, data on the proportion of older adults who were nonfrail were pooled using the respective study baseline data, if reported. The meta-analysis was performed using the Freeman-Tukey double arcsine transformed proportions to stabilize the variance.40

    All analyses were performed using statistical software (Stata, version 15.0/IC; StataCorp LP). Two-tailed P < .05 was considered statistically significant.

    Results
    Selection Process

    Of 15 176 retrieved citations, 142 articles were selected for full-text assessment (Figure 1). After full-text evaluation, 42 studies met the eligibility criteria. Four additional studies were retrieved by reference screening, resulting in a total of 46 studies (involving 48 cohorts) included in the systematic review. No study was excluded on the basis of The Joanna Briggs Institute methodological review.30

    Study Characteristics

    The characteristics of the 46 included studies are summarized in Table 1. The studies involved 120 805 nonfrail (robust or prefrail) older adults from 28 countries. Nine studies were from Asia, 14 from North America, 2 from South America, 15 from Europe, and 4 from Australia, and 2 were cross-regional studies. eFigure 1 in the Supplement shows the geographical spread of the countries where data were collected. The median sample size across studies was 1054 (range, 44-28 181), and the median follow-up was 3.0 (range, 1.0-11.7) years. In 30 studies involving 101 259 participants, 73.3% were women. Frailty was assessed using the original or modified versions of the Fried criteria in 39 studies, 4 studies used the Frailty Index, and 1 study used both the Frailty Index and the Fried criteria, whereas 2 studies used other criteria. Among the studies using the deficit accumulation approach, the number of deficits used ranged from 20 to 44.

    In 31 studies, data on baseline proportion of older adults without frailty were available. In these studies, involving 118 411 individuals at baseline, the pooled proportion without frailty was 82.8% (95% CI, 75.8%-88.8%; I2 = 99.8%). The pooled proportion that was nonfrail was 86.5% (95% CI, 78.9%-92.7%; I2 = 99.8%) across studies that used the Fried criteria and 58.9% (95% CI, 44.2%-72.8%; I2 = 99.6%) across studies that used other criteria (P for difference < .001).

    Incidence of Frailty

    To estimate the global incidence of frailty, data were included from 46 studies.41-81,83-86 Among people without frailty at baseline who survived a median follow-up of 3.0 (range, 1.0-11.7) years, 13.6% (13 678 of 100 313) became frail. The pooled incidence rate of frailty was 43.4 (95% CI, 37.3-50.4; I2 = 98.5%) cases per 1000 person-years (Figure 2). There was no evidence of publication bias as determined by funnel plot visualization (eFigure 2 in the Supplement) or via the Egger test (P = .48). A leave-1-out sensitivity analysis did not show a dominance of any single study (eTable 2 in the Supplement).

    The pooled frailty incidence rate was 40.0 (95% CI, 34.5-48.5; I2 = 98.2%) cases per 1000 person-years when using the Fried phenotype. The pooled frailty incidence rate was 71.3 (95% CI, 56.9-89.3; I2 = 94.0%) cases per 1000 person-years when using other criteria (P for difference = .003).

    Among 20 studies that reported transitions to death, the proportion of nonfrail people who died over a median follow-up of 4.5 years was 12.9% (5989 of 46 358). When factoring in the risk of death, the pooled incidence rate of frailty was 35.9 (95% CI, 28.0-46.1; I2 = 98.7%) cases per 1000 person-years (eFigure 3 in the Supplement). Restricting the analyses to those who survived in these 19 studies resulted in a pooled frailty incidence rate of 44.1 (95% CI, 34.0-57.2; I2 = 98.8%) cases per 1000 person-years (eFigure 4 in the Supplement).

    Twenty studies reported the incidence of frailty among 19 613 people who were prefrail and 17 523 people who were robust at baseline and who survived over a median follow-up of 3.0 years. During the follow-up, 4.6% (807 of 17 523) of individuals who were robust and 18.5% (3628 of 19 613) of individuals who were prefrail developed frailty. The pooled frailty incidence rates among the robust and prefrail individuals were 12.0 (95% CI, 8.2-17.5; I2 = 94.9%) and 62.7 (95% CI, 49.2-79.8; I2 = 97.8%) cases per 1000 person-years, respectively, with the difference being statistically significant (P value for difference < .001).

    Ten studies directly compared frailty incidence between 11 959 men and 13 870 women who survived a median follow-up of 4.0 years. Among the men and women, 9.2% (1099 of 11 959) and 15.6% (2164 of 13 870), respectively, developed frailty. The pooled incidence rates of frailty in men and women in these studies were 24.3 (95% CI, 19.6-30.1; I2 = 89.4%) and 44.8 (95% CI, 36.7-61.3; I2 = 97.9%) cases per 1000 person-years, respectively, with the difference being statistically significant (P value for difference = .01).

    Only 2 studies48,75 reported age-stratified frailty incidence rate, with inconsistent age groups being used. Therefore, data were not pooled, although both studies reported consistent increases in frailty incidence with increasing age.

    Incidence of Prefrailty

    Twenty-one studies41,42,46,51,53,57,59,60,65-69,71,72,77,79-83 reported data on the global incidence of prefrailty among 32 268 community-dwelling older adults who were robust at baseline and survived a median follow-up of 2.5 (range, 1.0-10.0) years. During the follow-up, 30.9% (9974 of 32 268) became prefrail. The pooled incidence rate of prefrailty was 150.6 (95% CI, 123.3-184.1; I2 = 98.9%) cases per 1000 person-years (Figure 3). There was no evidence of publication bias as determined by visual inspection of funnel plots (eFigure 5 in the Supplement) or by means of the Egger test. A leave-1-out sensitivity analysis did not alter the results (eTable 3 in the Supplement).

    The pooled incidence rate of prefrailty was 150.9 (95% CI, 120.2-182.6; I2 = 98.8%) cases per 1000 person-years when using the Fried phenotype. The pooled incidence rate of prefrailty was 140.4 (95% CI, 97.2-202.9; I2 = 93.4%) cases per 1000 person-years when using other criteria (P for difference = .52).

    Among 13 studies that reported transitions to death, the proportion of robust people who died over a median follow-up of 4.0 years was 7.8% (1253 of 16 134). When factoring in the risk of death, the pooled incidence rate of prefrailty was 110.6 (95% CI, 84.8-144.2; I2 = 98.9%) cases per 1000 person-years (eFigure 6 in the Supplement). Restricting the analyses to those who survived in these 13 studies resulted in a pooled prefrailty incidence rate of 122.7 (95% CI, 95.7-157.5; I2 = 98.7%) cases per 1000 person-years (eFigure 7 in the Supplement).

    Four studies directly compared incidence of prefrailty among 4003 men and 3655 women who survived a median follow-up of 4.2 years. In all, 32.6% (1305 of 4003) of the men and 40.1% (1465 of 3655) of the women became prefrail, at a pooled incidence rate of 129.0 (95% CI, 73.8-225.0; I2 = 98.5%) and 173.2 (95% CI, 87.9-341.2; I2 = 99.1%) cases per 1000 person-years, respectively (P for difference = .12). No study reported age-stratified prefrailty incidence data.

    Meta-regression

    In the multivariable random-effects meta-regression, measuring frailty as a physical phenotype was associated with higher incidence than using other methods (adjusted odds ratio [aOR], 1.48; 95% CI, 1.02-2.15), although no statistically significant difference was observed for prefrailty incidence (Table 2). Study region was not significantly associated with frailty and prefrailty incidence, but HICs were associated with a lower incidence of frailty (aOR, 0.63; 95% CI, 0.42-0.95) and prefrailty (aOR, 0.30; 95% CI, 0.21-0.84) compared with LMICs. Studies published after 2009 were associated with lower frailty incidence. The variables included in the multivariable models collectively explained about 63.9% and 38.1% of the between-study variance for frailty and prefrailty incidence, respectively.

    Discussion

    We performed a systematic review and meta-analysis to estimate the incidence of frailty and prefrailty among community-dwelling older adults. Our results indicate the following: (1) frailty and prefrailty incidence rates were approximately 43 and 151 new cases per 1000 person-years, respectively; (2) the incidence of frailty and prefrailty was higher in women than men; and (3) the incidence of frailty and prefrailty varied by frailty measurement method used and by country income level.

    Although not necessarily synonymous with aging, frailty is highly prevalent among older people.3,4 Our pooled baseline data suggested that approximately 1 in 6 community-dwelling older people may have frailty. Frailty has been associated with adverse health outcomes, such as falls, disability, and death, as well as increased use of health care resources.8,9,12 Therefore, efforts to reduce the burden of frailty could have substantial public health consequences.

    Prevention of frailty requires a sound understanding of the risk factors. For example, it has been demonstrated that individual chronic diseases (eg, cancers, type 2 diabetes,63,66,71 and depression,77,85,87 or their co-occurrence [ie, multimorbidity]) have been shown to increase the risk of frailty.88,89 With an estimated 66% of older people having at least 2 chronic medical conditions,90 effective preventive strategies are paramount to reduce overall disease burden. The rising prevalence of obesity among older adults91,92 needs greater attention because this condition, particularly abdominal obesity, may increase the risk of frailty through the association with proinflammatory processes, insulin resistance, fat infiltration of skeletal muscles, and hormonal alterations.93,94 Many other sociodemographic, physical, biological, lifestyle (eg, smoking), and psychological factors may equally contribute to the development of frailty and thus require tailored solutions in different settings.95-98

    We found a higher incidence of frailty and prefrailty in LMICs than HICs in our study, which is consistent with prior observations of significantly higher prevalence of frailty and prefrailty in LMICs compared with HICs.99 Some studies59,87,100 found that high income and educational levels and greater access to and quality of health care confer lower frailty risk, which may partly explain the disparity in frailty incidence between LMICs and HICs, presenting opportunity to prevent or delay the onset of chronic pathologies associated with increased risk of frailty.88,101

    Our meta-analysis suggests higher incidence of frailty and prefrailty in women than men. Previous studies have shown consistently higher prevalence rates3,99 and frailty scores102 among women than men across all age groups. The sex differences may be attributable to both biological and socioeconomic factors. Nonetheless, women have been found to better tolerate frailty, as evidenced by lower mortality rates at any frailty level or age, suggesting the existence of a male-female health-survival paradox.102

    To date, several interventions incorporating exercise, nutrition, cognitive training, geriatric assessment, hormone therapy, and management and prehabilitation have been evaluated for their effectiveness at delaying or reversing frailty.103-107 Most of these interventions have demonstrated feasibility, with adherence rates of about 70%.103 However, a recent systematic review reported that, among the available primary care interventions to delay or reverse frailty, strength training and protein supplementation ranked highest in terms of relative effectiveness and ease of implementation.108 Conversely, mild-intensity mixed exercises, as well as educational or health promotion activities, typically were in the midzone for both relative effectiveness and ease of implementation, whereas comprehensive geriatric assessments and home visits were ranked mid to low for both relative effectiveness and ease of implementation. In general, interventions targeting behavioral change ranked low in relative effectiveness and at the midzone for ease of implementation.108 However, it needs emphasizing that most interventions have been tested in people who were frail or prefrail.103,108 Our meta-analysis showed that, among people who were robust, there were approximately 12 and 151 new cases of frailty and prefrailty per 1000 person-years, respectively, suggesting that interventions aimed at preventing frailty and prefrailty in robust populations could be important.

    The lower pooled incidence when frailty was defined as a physical phenotype compared with when a broad phenotype was used is consistent with prior meta-analyses that have demonstrated higher frailty prevalence when using broad definitions vs the physical phenotype.3,99 Other studies3 have shown considerable variability in the literature regarding the use of the deficit accumulation approach (as also observed in the present study), thus contributing to wide estimates of frailty burden. Therefore, a harmonized definition of frailty may be useful.

    Limitations and Future Directions

    Our study had some limitations. There was substantial heterogeneity of the included studies. Nonetheless, heterogeneity is often inevitable in meta-analyses of observational studies, and it does not necessarily invalidate the findings.109 We decided a priori to pool incidence data across studies that met our inclusion criteria. Furthermore, potential sources of heterogeneity were investigated via subgroup and random-effects meta-regression, which showed considerable heterogeneity in incidence rates by frailty measurement method, country income level, and publication years of studies. Meta-analysis of incidence data is also complicated by variable duration of follow-up. We sought to overcome this by estimating person-years on the basis of the median follow-up duration. While this method is considered robust and is widely applied in the literature,27,31-33 a more precise approach would have required the use of the actual data on person-years, which were unavailable in more than 90% of studies. While frailty incidence varies by age, we could not perform age-stratified analysis due to limited data, and we were unable to account for the influence of the mean age of participants in the individual studies in the regression models due to poor reporting. People who develop frailty or prefrailty may regress27,36; however, the present analysis does not incorporate regression rates. Finally, our abstract screening may have missed relevant studies in which frailty was not the main focus, but which contained information on the incidence of frailty (eg, frailty as a covariate).

    Overall, the study results reiterate the need for regular screening programs to assess older people’s vulnerability to frailty development so that appropriate interventions can be implemented in a timely manner.16 For example, frailty assessment could be considered as part of routine health screening or could be instituted as a part of the core services delivered to older people within primary health care and general practice settings.41 Because not all older people develop frailty, future studies should examine protective factors against frailty so as to inform preventive strategies. Our data could also inform health care planning and design of preventive strategies. However, the inequality in the availability of frailty data according to geographical locations requires attention because it hampers the opportunity to reliably forecast the future trajectory of the global burden of frailty, which is needed to inform efficient planning and resource allocation, mindful of the growing aging population.21

    Conclusions

    There is a high risk of frailty among community-dwelling older adults, and we observed that the incidence of frailty varies by sex, region, country income level, and diagnostic criteria used. It is imperative to improve understanding of the factors that confer increased risk of frailty. This will help inform the design of interventions to prevent frailty or minimize its negative consequences on health.

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    Article Information

    Accepted for Publication: June 13, 2019.

    Published: August 2, 2019. doi:10.1001/jamanetworkopen.2019.8398

    Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2019 Ofori-Asenso R et al. JAMA Network Open.

    Corresponding Author: Danny Liew, MBBS(Hons), FRACP, PhD, School of Public Health and Preventive Medicine, Monash University, 553 St Kilda Rd, Melbourne, Victoria, Australia 3004 (danny.liew@monash.edu).

    Author Contributions: Drs Ofori-Asenso and Chin had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

    Concept and design: Ofori-Asenso, Chin, Liew.

    Acquisition, analysis, or interpretation of data: All authors.

    Drafting of the manuscript: Ofori-Asenso, Liew.

    Critical revision of the manuscript for important intellectual content: All authors.

    Statistical analysis: Ofori-Asenso, Chin.

    Supervision: Liew.

    Conflict of Interest Disclosures: Dr Zomer reported receiving grants and/or personal fees from Amgen, AstraZeneca, Pfizer, and Shire. Dr Zullo reported being supported in part by a Brown University Office of the Vice President for Research Seed Funding Award, receiving an Agency for Healthcare Research and Quality award, and receiving grants from Sanofi Pasteur. Dr Bell reported receiving grants from the National Health and Medical Research Council, Dementia Australia Research Foundation, Victorian Government Department of Health and Human Services, and aged care provider organizations. Dr Liew reported receiving grants from Pfizer, AbbVie, AstraZeneca, and CSL-Behring and personal fees and/or other financial support from Bayer and Novartis. No other disclosures were reported.

    Additional Contributions: We thank the study authors who provided us with additional data.

    References
    1.
    Sander  M, Oxlund  B, Jespersen  A,  et al.  The challenges of human population ageing.  Age Ageing. 2015;44(2):185-187. doi:10.1093/ageing/afu189PubMedGoogle ScholarCrossref
    2.
    United Nations Department of Economic and Social Affairs (DESA)/Population Division. World Population Prospects 2019. https://population.un.org/wpp/Download/Standard/Population/. Accessed January 26, 2019.
    3.
    Collard  RM, Boter  H, Schoevers  RA, Oude Voshaar  RC.  Prevalence of frailty in community-dwelling older persons: a systematic review.  J Am Geriatr Soc. 2012;60(8):1487-1492. doi:10.1111/j.1532-5415.2012.04054.xPubMedGoogle ScholarCrossref
    4.
    Clegg  A, Young  J, Iliffe  S, Rikkert  MO, Rockwood  K.  Frailty in elderly people.  Lancet. 2013;381(9868):752-762. doi:10.1016/S0140-6736(12)62167-9PubMedGoogle ScholarCrossref
    5.
    Cheng  MH, Chang  SF.  Frailty as a risk factor for falls among community dwelling people: evidence from a meta-analysis.  J Nurs Scholarsh. 2017;49(5):529-536. doi:10.1111/jnu.12322PubMedGoogle ScholarCrossref
    6.
    Persico  I, Cesari  M, Morandi  A,  et al.  Frailty and delirium in older adults: a systematic review and meta-analysis of the literature.  J Am Geriatr Soc. 2018;66(10):2022-2030. doi:10.1111/jgs.15503PubMedGoogle ScholarCrossref
    7.
    Kojima  G.  Frailty as a predictor of nursing home placement among community-dwelling older adults: a systematic review and meta-analysis.  J Geriatr Phys Ther. 2018;41(1):42-48. doi:10.1519/JPT.0000000000000097PubMedGoogle ScholarCrossref
    8.
    Kojima  G.  Frailty as a predictor of disabilities among community-dwelling older people: a systematic review and meta-analysis.  Disabil Rehabil. 2017;39(19):1897-1908. doi:10.1080/09638288.2016.1212282PubMedGoogle ScholarCrossref
    9.
    Kojima  G, Iliffe  S, Walters  K.  Frailty Index as a predictor of mortality: a systematic review and meta-analysis.  Age Ageing. 2018;47(2):193-200. doi:10.1093/ageing/afx162PubMedGoogle ScholarCrossref
    10.
    Lin  HS, Watts  JN, Peel  NM, Hubbard  RE.  Frailty and post-operative outcomes in older surgical patients: a systematic review.  BMC Geriatr. 2016;16(1):157. doi:10.1186/s12877-016-0329-8PubMedGoogle ScholarCrossref
    11.
    Kojima  G.  Frailty as a predictor of emergency department utilization among community-dwelling older people: a systematic review and meta-analysis.  J Am Med Dir Assoc. 2019;20(1):103-105. doi:10.1016/j.jamda.2018.10.004PubMedGoogle ScholarCrossref
    12.
    Bock  JO, König  HH, Brenner  H,  et al.  Associations of frailty with health care costs: results of the ESTHER cohort study.  BMC Health Serv Res. 2016;16:128. doi:10.1186/s12913-016-1360-3PubMedGoogle ScholarCrossref
    13.
    Gwyther  H, Shaw  R, Jaime Dauden  EA,  et al.  Understanding frailty: a qualitative study of European healthcare policy-makers’ approaches to frailty screening and management.  BMJ Open. 2018;8(1):e018653. doi:10.1136/bmjopen-2017-018653PubMedGoogle ScholarCrossref
    14.
    Morley  JE.  Frailty: diagnosis and management.  J Nutr Health Aging. 2011;15(8):667-670. doi:10.1007/s12603-011-0338-4PubMedGoogle ScholarCrossref
    15.
    Buckinx  F, Rolland  Y, Reginster  JY, Ricour  C, Petermans  J, Bruyère  O.  Burden of frailty in the elderly population: perspectives for a public health challenge.  Arch Public Health. 2015;73(1):19. doi:10.1186/s13690-015-0068-xPubMedGoogle ScholarCrossref
    16.
    Ambagtsheer  RC, Beilby  JJ, Visvanathan  R, Dent  E, Yu  S, Braunack-Mayer  AJ.  Should we screen for frailty in primary care settings? a fresh perspective on the frailty evidence base: a narrative review.  Prev Med. 2019;119:63-69. doi:10.1016/j.ypmed.2018.12.020PubMedGoogle ScholarCrossref
    17.
    Fried  LP, Tangen  CM, Walston  J,  et al; Cardiovascular Health Study Collaborative Research Group.  Frailty in older adults: evidence for a phenotype.  J Gerontol A Biol Sci Med Sci. 2001;56(3):M146-M156. doi:10.1093/gerona/56.3.M146PubMedGoogle ScholarCrossref
    18.
    Rockwood  K, Stadnyk  K, MacKnight  C, McDowell  I, Hébert  R, Hogan  DB.  A brief clinical instrument to classify frailty in elderly people.  Lancet. 1999;353(9148):205-206. doi:10.1016/S0140-6736(98)04402-XPubMedGoogle ScholarCrossref
    19.
    Dent  E, Kowal  P, Hoogendijk  EO.  Frailty measurement in research and clinical practice: a review.  Eur J Intern Med. 2016;31:3-10. doi:10.1016/j.ejim.2016.03.007PubMedGoogle ScholarCrossref
    20.
    Lang  PO, Michel  JP, Zekry  D.  Frailty syndrome: a transitional state in a dynamic process.  Gerontology. 2009;55(5):539-549. doi:10.1159/000211949PubMedGoogle ScholarCrossref
    21.
    Galluzzo  L, O’Caoimh  R, Rodríguez-Laso  Á,  et al; Work Package 5 of the Joint Action ADVANTAGE.  Incidence of frailty: a systematic review of scientific literature from a public health perspective.  Ann Ist Super Sanita. 2018;54(3):239-245.PubMedGoogle Scholar
    22.
    Kaeberlein  M, Rabinovitch  PS, Martin  GM.  Healthy aging: the ultimate preventative medicine.  Science. 2015;350(6265):1191-1193. doi:10.1126/science.aad3267PubMedGoogle ScholarCrossref
    23.
    Moher  D, Liberati  A, Tetzlaff  J, Altman  DG; PRISMA Group.  Preferred Reporting Items for Systematic Reviews and Meta-analyses: the PRISMA statement.  BMJ. 2009;339:b2535. doi:10.1136/bmj.b2535PubMedGoogle ScholarCrossref
    24.
    Stroup  DF, Berlin  JA, Morton  SC,  et al; Meta-analysis of Observational Studies in Epidemiology (MOOSE) Group.  Meta-analysis of Observational Studies in Epidemiology: a proposal for reporting.  JAMA. 2000;283(15):2008-2012. doi:10.1001/jama.283.15.2008PubMedGoogle ScholarCrossref
    25.
    PROSPERO. Incidence of Frailty Among Community-Dwelling Older Adults. CRD42019121302. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=121302. Accessed January 26, 2019.
    26.
    Xue  QL.  The frailty syndrome: definition and natural history.  Clin Geriatr Med. 2011;27(1):1-15. doi:10.1016/j.cger.2010.08.009PubMedGoogle ScholarCrossref
    27.
    Ofori-Asenso  R, Lee Chin  K, Mazidi  M,  et al.  Natural regression of frailty among community-dwelling older adults: a systematic review and meta-analysis.  Gerontologist. 2019;gnz064. doi:10.1093/geront/gnz064PubMedGoogle Scholar
    28.
    Aguayo  GA, Donneau  AF, Vaillant  MT,  et al.  Agreement between 35 published frailty scores in the general population.  Am J Epidemiol. 2017;186(4):420-434. doi:10.1093/aje/kwx061PubMedGoogle ScholarCrossref
    29.
    Kojima  G.  Prevalence of frailty in nursing homes: a systematic review and meta-analysis.  J Am Med Dir Assoc. 2015;16(11):940-945. doi:10.1016/j.jamda.2015.06.025PubMedGoogle ScholarCrossref
    30.
    Munn  Z, Moola  S, Lisy  K, Riitano  D, Tufanaru  C.  Methodological guidance for systematic reviews of observational epidemiological studies reporting prevalence and cumulative incidence data.  Int J Evid Based Healthc. 2015;13(3):147-153. doi:10.1097/XEB.0000000000000054PubMedGoogle ScholarCrossref
    31.
    Sikkema  M, de Jonge  PJ, Steyerberg  EW, Kuipers  EJ.  Risk of esophageal adenocarcinoma and mortality in patients with Barrett’s esophagus: a systematic review and meta-analysis.  Clin Gastroenterol Hepatol. 2010;8(3):235-244. doi:10.1016/j.cgh.2009.10.010PubMedGoogle ScholarCrossref
    32.
    Tansel  A, Katz  LH, El-Serag  HB,  et al.  Incidence and determinants of hepatocellular carcinoma in autoimmune hepatitis: a systematic review and meta-analysis.  Clin Gastroenterol Hepatol. 2017;15(8):1207-1217.e4. doi:10.1016/j.cgh.2017.02.006PubMedGoogle ScholarCrossref
    33.
    Yousef  F, Cardwell  C, Cantwell  MM, Galway  K, Johnston  BT, Murray  L.  The incidence of esophageal cancer and high-grade dysplasia in Barrett’s esophagus: a systematic review and meta-analysis.  Am J Epidemiol. 2008;168(3):237-249. doi:10.1093/aje/kwn121PubMedGoogle ScholarCrossref
    34.
    Sutton  A, Abrams  K, Jones  D, Sheldon  T, Song  F.  Methods for Meta-analysis in Medical Research. London, United Kingdom: Wiley; 2000.
    35.
    Delgado-Rodríguez  M, Llorca  J.  Bias.  J Epidemiol Community Health. 2004;58(8):635-641. doi:10.1136/jech.2003.008466PubMedGoogle ScholarCrossref
    36.
    Kojima  G, Taniguchi  Y, Iliffe  S, Jivraj  S, Walters  K.  Transitions between frailty states among community-dwelling older people: a systematic review and meta-analysis.  Ageing Res Rev. 2019;50:81-88. doi:10.1016/j.arr.2019.01.010PubMedGoogle ScholarCrossref
    37.
    Higgins  JP, Thompson  SG, Deeks  JJ, Altman  DG.  Measuring inconsistency in meta-analyses.  BMJ. 2003;327(7414):557-560. doi:10.1136/bmj.327.7414.557PubMedGoogle ScholarCrossref
    38.
    World Bank. World Bank country and lending groups. https://datahelpdesk.worldbank.org/knowledgebase/articles/906519-world-bank-country-and-lending-groups. Published 2019. Accessed January 29, 2019.
    39.
    Egger  M, Davey Smith  G, Schneider  M, Minder  C.  Bias in meta-analysis detected by a simple, graphical test.  BMJ. 1997;315(7109):629-634. doi:10.1136/bmj.315.7109.629PubMedGoogle ScholarCrossref
    40.
    Barendregt  JJ, Doi  SA, Lee  YY, Norman  RE, Vos  T.  Meta-analysis of prevalence.  J Epidemiol Community Health. 2013;67(11):974-978. doi:10.1136/jech-2013-203104PubMedGoogle ScholarCrossref
    41.
    Ahmad  NS, Hairi  NN, Said  MA,  et al.  Prevalence, transitions and factors predicting transition between frailty states among rural community-dwelling older adults in Malaysia.  PLoS One. 2018;13(11):e0206445. doi:10.1371/journal.pone.0206445PubMedGoogle ScholarCrossref
    42.
    Alencar  MA, Dias  JMD, Figueiredo  LC, Dias  RC.  Transitions in frailty status in community-dwelling older adults.  Top Geriatr Rehabil. 2015;31(2):105-112. doi:10.1097/TGR.0000000000000055Google ScholarCrossref
    43.
    Ayers  E, Shapiro  M, Holtzer  R, Barzilai  N, Milman  S, Verghese  J.  Symptoms of apathy independently predict incident frailty and disability in community-dwelling older adults.  J Clin Psychiatry. 2017;78(5):e529-e536. doi:10.4088/JCP.15m10113PubMedGoogle ScholarCrossref
    44.
    Baulderstone  L, Yaxley  A, Luszcz  M, Miller  M.  Diet liberalisation in older Australians decreases frailty without increasing the risk of developing chronic disease.  J Frailty Aging. 2012;1(4):174-182.PubMedGoogle Scholar
    45.
    Bentur  N, Sternberg  SA, Shuldiner  J.  Frailty transitions in community dwelling older people.  Isr Med Assoc J. 2016;18(8):449-453.PubMedGoogle Scholar
    46.
    Borrat-Besson  C, Ryser  V, Wernli  B. Transitions between frailty states: a European comparison. In: Börsch-Supan  A, Brandt  M, Litwin  H, Weber  G, eds.  Active Ageing and Solidarity Between Generations in Europe: First Results From SHARE After the Economic Crisis. Gottingen, Germany: Hubert & Co; 2013:175-185. doi:10.1515/9783110295467.175
    47.
    Castrejón-Pérez  RC, Jiménez-Corona  A, Bernabé  E,  et al.  Oral disease and 3-year incidence of frailty in Mexican older adults.  J Gerontol A Biol Sci Med Sci. 2017;72(7):951-957.PubMedGoogle Scholar
    48.
    Chhetri  JK, Zheng  Z, Xu  X, Ma  C, Chan  P.  The prevalence and incidence of frailty in pre-diabetic and diabetic community-dwelling older population: results from Beijing Longitudinal Study of Aging II (BLSA-II).  BMC Geriatr. 2017;17(1):47. doi:10.1186/s12877-017-0439-yPubMedGoogle ScholarCrossref
    49.
    Dalrymple  LS, Katz  R, Rifkin  DE,  et al.  Kidney function and prevalent and incident frailty.  Clin J Am Soc Nephrol. 2013;8(12):2091-2099. doi:10.2215/CJN.02870313PubMedGoogle ScholarCrossref
    50.
    Doba  N, Tokuda  Y, Goldstein  NE, Kushiro  T, Hinohara  S.  A pilot trial to predict frailty syndrome: the Japanese Health Research Volunteer Study.  Exp Gerontol. 2012;47(8):638-643. doi:10.1016/j.exger.2012.05.016PubMedGoogle ScholarCrossref
    51.
    Doi  T, Makizako  H, Tsutsumimoto  K,  et al.  Transitional status and modifiable risk of frailty in Japanese older adults: a prospective cohort study.  Geriatr Gerontol Int. 2018;18(11):1562-1566. doi:10.1111/ggi.13525PubMedGoogle ScholarCrossref
    52.
    Ensrud  KE, Ewing  SK, Fredman  L,  et al; Study of Osteoporotic Fractures Research Group.  Circulating 25-hydroxyvitamin D levels and frailty status in older women.  J Clin Endocrinol Metab. 2010;95(12):5266-5273. doi:10.1210/jc.2010-2317PubMedGoogle ScholarCrossref
    53.
    Espinoza  SE, Jung  I, Hazuda  H.  Frailty transitions in the San Antonio Longitudinal Study of Aging.  J Am Geriatr Soc. 2012;60(4):652-660. doi:10.1111/j.1532-5415.2011.03882.xPubMedGoogle ScholarCrossref
    54.
    Gale  CR, Baylis  D, Cooper  C, Sayer  AA.  Inflammatory markers and incident frailty in men and women: the English Longitudinal Study of Ageing.  Age (Dordr). 2013;35(6):2493-2501. doi:10.1007/s11357-013-9528-9PubMedGoogle ScholarCrossref
    55.
    García-Esquinas  E, José García-García  F, León-Muñoz  LM,  et al.  Obesity, fat distribution, and risk of frailty in two population-based cohorts of older adults in Spain.  Obesity (Silver Spring). 2015;23(4):847-855. doi:10.1002/oby.21013PubMedGoogle ScholarCrossref
    56.
    García-Esquinas  E, Rahi  B, Peres  K,  et al.  Consumption of fruit and vegetables and risk of frailty: a dose-response analysis of 3 prospective cohorts of community-dwelling older adults.  Am J Clin Nutr. 2016;104(1):132-142. doi:10.3945/ajcn.115.125781PubMedGoogle ScholarCrossref
    57.
    Gill  TM, Gahbauer  EA, Allore  HG, Han  L.  Transitions between frailty states among community-living older persons.  Arch Intern Med. 2006;166(4):418-423. doi:10.1001/archinte.166.4.418PubMedGoogle ScholarCrossref
    58.
    Gnjidic  D, Hilmer  SN, Blyth  FM,  et al.  High-risk prescribing and incidence of frailty among older community-dwelling men.  Clin Pharmacol Ther. 2012;91(3):521-528. doi:10.1038/clpt.2011.258PubMedGoogle ScholarCrossref
    59.
    Gomes  CDS, Guerra  RO, Wu  YY,  et al.  Social and economic predictors of worse frailty status occurrence across selected countries in North and South America and Europe.  Innov Aging. 2018;2(3):igy037. doi:10.1093/geroni/igy037PubMedGoogle ScholarCrossref
    60.
    Gruenewald  TL, Seeman  TE, Karlamangla  AS, Sarkisian  CA.  Allostatic load and frailty in older adults.  J Am Geriatr Soc. 2009;57(9):1525-1531. doi:10.1111/j.1532-5415.2009.02389.xPubMedGoogle ScholarCrossref
    61.
    Hyde  Z, Flicker  L, Smith  K,  et al.  Prevalence and incidence of frailty in Aboriginal Australians, and associations with mortality and disability.  Maturitas. 2016;87:89-94. doi:10.1016/j.maturitas.2016.02.013PubMedGoogle ScholarCrossref
    62.
    Iwasaki  M, Yoshihara  A, Sato  M,  et al.  Dentition status and frailty in community-dwelling older adults: a 5-year prospective cohort study.  Geriatr Gerontol Int. 2018;18(2):256-262. doi:10.1111/ggi.13170PubMedGoogle ScholarCrossref
    63.
    Kalyani  RR, Tian  J, Xue  QL,  et al.  Hyperglycemia and incidence of frailty and lower extremity mobility limitations in older women.  J Am Geriatr Soc. 2012;60(9):1701-1707. doi:10.1111/j.1532-5415.2012.04099.xPubMedGoogle ScholarCrossref
    64.
    Kim  M, Suzuki  T, Kojima  N,  et al.  Association between serum β2-microglobulin levels and prevalent and incident physical frailty in community-dwelling older women.  J Am Geriatr Soc. 2017;65(4):e83-e88. doi:10.1111/jgs.14733PubMedGoogle ScholarCrossref
    65.
    Lanziotti Azevedo da Silva  S, Campos Cavalcanti Maciel  Á, de Sousa Máximo Pereira  L, Domingues Dias  JM, Guimarães de Assis  M, Corrêa Dias  R.  Transition patterns of frailty syndrome in community-dwelling elderly individuals: a longitudinal study.  J Frailty Aging. 2015;4(2):50-55.PubMedGoogle Scholar
    66.
    Lee  JSW, Auyeung  TW, Leung  J, Kwok  T, Woo  J.  Transitions in frailty states among community-living older adults and their associated factors.  J Am Med Dir Assoc. 2014;15(4):281-286. doi:10.1016/j.jamda.2013.12.002PubMedGoogle ScholarCrossref
    67.
    Liu  ZY, Wei  YZ, Wei  LQ,  et al.  Frailty transitions and types of death in Chinese older adults: a population-based cohort study.  Clin Interv Aging. 2018;13:947-956. doi:10.2147/CIA.S157089PubMedGoogle ScholarCrossref
    68.
    Lorenzo-López  L, López-López  R, Maseda  A, Buján  A, Rodríguez-Villamil  JL, Millán-Calenti  JC.  Changes in frailty status in a community-dwelling cohort of older adults: the VERISAÚDE study.  Maturitas. 2019;119:54-60. doi:10.1016/j.maturitas.2018.11.006PubMedGoogle ScholarCrossref
    69.
    Ottenbacher  KJ, Graham  JE, Al Snih  S,  et al.  Mexican Americans and frailty: findings from the Hispanic established populations epidemiologic studies of the elderly.  Am J Public Health. 2009;99(4):673-679. doi:10.2105/AJPH.2008.143958PubMedGoogle ScholarCrossref
    70.
    Pilleron  S, Ajana  S, Jutand  MA,  et al.  Dietary patterns and 12-year risk of frailty: results from the Three-City Bordeaux Study.  J Am Med Dir Assoc. 2017;18(2):169-175. doi:10.1016/j.jamda.2016.09.014PubMedGoogle ScholarCrossref
    71.
    Pollack  LR, Litwack-Harrison  S, Cawthon  PM,  et al.  Patterns and predictors of frailty transitions in older men: the Osteoporotic Fractures in Men Study.  J Am Geriatr Soc. 2017;65(11):2473-2479. doi:10.1111/jgs.15003PubMedGoogle ScholarCrossref
    72.
    Potier  F, Degryse  JM, Bihin  B,  et al.  Health and frailty among older spousal caregivers: an observational cohort study in Belgium.  BMC Geriatr. 2018;18(1):291. doi:10.1186/s12877-018-0980-3PubMedGoogle ScholarCrossref
    73.
    Ramsay  SE, Papachristou  E, Watt  RG,  et al.  Influence of poor oral health on physical frailty: a population‐based cohort study of older British men.  J Am Geriatr Soc. 2018;66(3):473-479. doi:10.1111/jgs.15175PubMedGoogle ScholarCrossref
    74.
    Sandoval-Insausti  H, Pérez-Tasigchana  RF, López-García  E, García-Esquinas  E, Rodríguez-Artalejo  F, Guallar-Castillón  P.  Macronutrients intake and incident frailty in older adults: a prospective cohort study.  J Gerontol A Biol Sci Med Sci. 2016;71(10):1329-1334. doi:10.1093/gerona/glw033PubMedGoogle ScholarCrossref
    75.
    Saum  KU, Schöttker  B, Meid  AD,  et al.  Is polypharmacy associated with frailty in older people? results from the ESTHER cohort study.  J Am Geriatr Soc. 2017;65(2):e27-e32. doi:10.1111/jgs.14718PubMedGoogle ScholarCrossref
    76.
    Semba  RD, Bartali  B, Zhou  J, Blaum  C, Ko  CW, Fried  LP.  Low serum micronutrient concentrations predict frailty among older women living in the community.  J Gerontol A Biol Sci Med Sci. 2006;61(6):594-599. doi:10.1093/gerona/61.6.594PubMedGoogle ScholarCrossref
    77.
    Serra-Prat  M, Papiol  M, Vico  J, Palomera  E, Arús  M, Cabré  M.  Incidence and risk factors for frailty in the community-dwelling elderly population: a two-year follow-up cohort study.  J Gerontol Geriatr Res. 2017;6(6):452. doi:10.4172/2167-7182.1000452Google Scholar
    78.
    Shah  M, Paulson  D, Nguyen  V.  Alcohol use and frailty risk among older adults over 12 years: the Health and Retirement Study.  Clin Gerontol. 2018;41(4):315-325. doi:10.1080/07317115.2017.1364681PubMedGoogle ScholarCrossref
    79.
    Stephan  AJ, Strobl  R, Holle  R,  et al.  Male sex and poverty predict abrupt health decline: deficit accumulation patterns and trajectories in the KORA-Age cohort study.  Prev Med. 2017;102:31-38. doi:10.1016/j.ypmed.2017.06.032PubMedGoogle ScholarCrossref
    80.
    Swiecicka  A, Eendebak  RJAH, Lunt  M,  et al; European Male Ageing Study Group.  Reproductive hormone levels predict changes in frailty status in community-dwelling older men: European Male Ageing Study prospective data.  J Clin Endocrinol Metab. 2018;103(2):701-709. doi:10.1210/jc.2017-01172PubMedGoogle ScholarCrossref
    81.
    Thompson  MQ, Theou  O, Adams  RJ, Tucker  GR, Visvanathan  R.  Frailty state transitions and associated factors in South Australian older adults.  Geriatr Gerontol Int. 2018;18(11):1549-1555. doi:10.1111/ggi.13522PubMedGoogle ScholarCrossref
    82.
    Tom  S, Wyman  A, Woods  N,  et al.  Regional differences in incident prefrailty and frailty.  J Womens Health (Larchmt). 2017;26(9):992-998. doi:10.1089/jwh.2016.6041Google ScholarCrossref
    83.
    Trevisan  C, Veronese  N, Maggi  S,  et al.  Marital status and frailty in older people: gender differences in the Progetto Veneto Anziani longitudinal study.  J Womens Health (Larchmt). 2016;25(6):630-637. doi:10.1089/jwh.2015.5592PubMedGoogle ScholarCrossref
    84.
    Wang  MC, Li  TC, Li  CI,  et al.  Frailty, transition in frailty status and all-cause mortality in older adults of a Taichung community-based population.  BMC Geriatr. 2019;19(1):26. doi:10.1186/s12877-019-1039-9PubMedGoogle ScholarCrossref
    85.
    Woods  NF, LaCroix  AZ, Gray  SL,  et al; Women’s Health Initiative.  Frailty: emergence and consequences in women aged 65 and older in the Women’s Health Initiative Observational Study [published correction appears in J Am Geriatr Soc. 2017;65(7):1631-1632].  J Am Geriatr Soc. 2005;53(8):1321-1330. PubMedGoogle ScholarCrossref
    86.
    Zaslavsky  O, Walker  RL, Crane  PK, Gray  SL, Larson  EB.  Glucose levels and risk of frailty.  J Gerontol A Biol Sci Med Sci. 2016;71(9):1223-1229. doi:10.1093/gerona/glw024PubMedGoogle ScholarCrossref
    87.
    Doi  T, Makizako  H, Tsutsumimoto  K,  et al.  Transitional status and modifiable risk of frailty in Japanese older adults: a prospective cohort study.  Geriatr Gerontol Int. 2018;18(11):1562-1566. doi:10.1111/ggi.13525PubMedGoogle ScholarCrossref
    88.
    Hanlon  P, Nicholl  BI, Jani  BD, Lee  D, McQueenie  R, Mair  FS.  Frailty and pre-frailty in middle-aged and older adults and its association with multimorbidity and mortality: a prospective analysis of 493 737 UK Biobank participants.  Lancet Public Health. 2018;3(7):e323-e332. doi:10.1016/S2468-2667(18)30091-4PubMedGoogle ScholarCrossref
    89.
    Vetrano  DL, Palmer  K, Marengoni  A,  et al; Joint Action ADVANTAGE WP4 Group.  Frailty and multimorbidity: a systematic review and meta-analysis.  J Gerontol A Biol Sci Med Sci. 2018.PubMedGoogle Scholar
    90.
    Ofori-Asenso  R, Chin  KL, Curtis  AJ, Zomer  E, Zoungas  S, Liew  D.  Recent patterns of multimorbidity among older adults in high-income countries.  Popul Health Manag. 2019;22(2):127-137. doi:10.1089/pop.2018.0069PubMedGoogle ScholarCrossref
    91.
    Peralta  M, Ramos  M, Lipert  A, Martins  J, Marques  A.  Prevalence and trends of overweight and obesity in older adults from 10 European countries from 2005 to 2013.  Scand J Public Health. 2018;46(5):522-529. doi:10.1177/1403494818764810PubMedGoogle ScholarCrossref
    92.
    Samper-Ternent  R, Al Snih  S.  Obesity in older adults: epidemiology and implications for disability and disease.  Rev Clin Gerontol. 2012;22(1):10-34. doi:10.1017/S0959259811000190PubMedGoogle ScholarCrossref
    93.
    García-Esquinas  E, José García-García  F, León-Muñoz  LM,  et al.  Obesity, fat distribution, and risk of frailty in two population-based cohorts of older adults in Spain.  Obesity (Silver Spring). 2015;23(4):847-855. doi:10.1002/oby.21013PubMedGoogle ScholarCrossref
    94.
    Stenholm  S, Strandberg  TE, Pitkälä  K, Sainio  P, Heliövaara  M, Koskinen  S.  Midlife obesity and risk of frailty in old age during a 22-year follow-up in men and women: the Mini-Finland follow-up survey.  J Gerontol A Biol Sci Med Sci. 2014;69(1):73-78. doi:10.1093/gerona/glt052PubMedGoogle ScholarCrossref
    95.
    Feng  Z, Lugtenberg  M, Franse  C,  et al.  Risk factors and protective factors associated with incident or increase of frailty among community-dwelling older adults: a systematic review of longitudinal studies.  PLoS One. 2017;12(6):e0178383. doi:10.1371/journal.pone.0178383PubMedGoogle ScholarCrossref
    96.
    Ng  TP, Feng  L, Nyunt  MS, Larbi  A, Yap  KB.  Frailty in older persons: multisystem risk factors and the Frailty Risk Index (FRI).  J Am Med Dir Assoc. 2014;15(9):635-642. doi:10.1016/j.jamda.2014.03.008PubMedGoogle ScholarCrossref
    97.
    Espinoza  SE, Fried  LP.  Risk factors for frailty in the older adult.  Clin Geriatr. 2007;15(6):37-44.Google Scholar
    98.
    Kojima  G, Iliffe  S, Walters  K.  Smoking as a predictor of frailty: a systematic review.  BMC Geriatr. 2015;15:131. doi:10.1186/s12877-015-0134-9PubMedGoogle ScholarCrossref
    99.
    Siriwardhana  DD, Hardoon  S, Rait  G, Weerasinghe  MC, Walters  KR.  Prevalence of frailty and prefrailty among community-dwelling older adults in low-income and middle-income countries: a systematic review and meta-analysis.  BMJ Open. 2018;8(3):e018195. doi:10.1136/bmjopen-2017-018195PubMedGoogle ScholarCrossref
    100.
    Franse  CB, van Grieken  A, Qin  L, Melis  RJF, Rietjens  JAC, Raat  H.  Socioeconomic inequalities in frailty and frailty components among community-dwelling older citizens.  PLoS One. 2017;12(11):e0187946. doi:10.1371/journal.pone.0187946PubMedGoogle ScholarCrossref
    101.
    Epping-Jordan  JE, Pruitt  SD, Bengoa  R, Wagner  EH.  Improving the quality of health care for chronic conditions.  Qual Saf Health Care. 2004;13(4):299-305. doi:10.1136/qshc.2004.010744PubMedGoogle ScholarCrossref
    102.
    Gordon  EH, Peel  NM, Samanta  M, Theou  O, Howlett  SE, Hubbard  RE.  Sex differences in frailty: a systematic review and meta-analysis.  Exp Gerontol. 2017;89:30-40. doi:10.1016/j.exger.2016.12.021PubMedGoogle ScholarCrossref
    103.
    Puts  MTE, Toubasi  S, Andrew  MK,  et al.  Interventions to prevent or reduce the level of frailty in community-dwelling older adults: a scoping review of the literature and international policies.  Age Ageing. 2017;46(3):383-392.PubMedGoogle Scholar
    104.
    Apóstolo  J, Cooke  R, Bobrowicz-Campos  E,  et al.  Effectiveness of interventions to prevent pre-frailty and frailty progression in older adults: a systematic review.  JBI Database System Rev Implement Rep. 2018;16(1):140-232. doi:10.11124/JBISRIR-2017-003382PubMedGoogle ScholarCrossref
    105.
    Chin A Paw  MJ, van Uffelen  JG, Riphagen  I, van Mechelen  W.  The functional effects of physical exercise training in frail older people: a systematic review.  Sports Med. 2008;38(9):781-793. doi:10.2165/00007256-200838090-00006PubMedGoogle ScholarCrossref
    106.
    de Labra  C, Guimaraes-Pinheiro  C, Maseda  A, Lorenzo  T, Millán-Calenti  JC.  Effects of physical exercise interventions in frail older adults: a systematic review of randomized controlled trials.  BMC Geriatr. 2015;15:154. doi:10.1186/s12877-015-0155-4PubMedGoogle ScholarCrossref
    107.
    Giné-Garriga  M, Roqué-Fíguls  M, Coll-Planas  L, Sitjà-Rabert  M, Salvà  A.  Physical exercise interventions for improving performance-based measures of physical function in community-dwelling, frail older adults: a systematic review and meta-analysis.  Arch Phys Med Rehabil. 2014;95(4):753-769.e3. doi:10.1016/j.apmr.2013.11.007PubMedGoogle ScholarCrossref
    108.
    Travers  J, Romero-Ortuno  R, Bailey  J, Cooney  MT.  Delaying and reversing frailty: a systematic review of primary care interventions.  Br J Gen Pract. 2019;69(678):e61-e69. doi:10.3399/bjgp18X700241PubMedGoogle ScholarCrossref
    109.
    Noubiap  JJ, Balti  EV, Bigna  JJ, Echouffo-Tcheugui  JB, Kengne  AP.  Dyslipidaemia in Africa: comment on a recent systematic review: authors’ reply.  Lancet Glob Health. 2019;7(3):e308-e309. doi:10.1016/S2214-109X(18)30517-5PubMedGoogle ScholarCrossref
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