Determinants of frailty development and progression using a multidimensional frailty index: Evidence from the English Longitudinal Study of Ageing
Autoři:
Nils Georg Niederstrasser aff001; Nina Trivedy Rogers aff002; Stephan Bandelow aff003
Působiště autorů:
School of Applied Social Sciences, De Montfort University, Leicester, England, United Kingdom
aff001; Department of Epidemiology and Public Health, University College London, London, England, United Kingdom
aff002; Department of Physiology, Neuroscience and Behavioural Sciences, St. George’s University, St. George’s, Grenada
aff003
Vyšlo v časopise:
PLoS ONE 14(10)
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pone.0223799
Souhrn
Objective
To identify modifiable risk factors for development and progression of frailty in older adults living in England, as conceptualised by a multidimensional frailty index (FI).
Methods
Data from participants aged 50 and over from the English Longitudinal Study of Ageing (ELSA) was used to examine potential determinants of frailty, using a 56-item FI comprised of self-reported health conditions, disabilities, cognitive function, hearing, eyesight, depressive symptoms and ability to carry out activities of daily living. Cox proportional hazards regression models were used to measure frailty development (n = 7420) and linear regression models to measure frailty progression over 12 years follow-up (n = 8780).
Results
Increasing age (HR: 1.08 (CI: 1.08–1.09)), being in the lowest wealth quintile (HR: 1.79 (CI: 1.54–2.08)), lack of educational qualifications (HR: 1.19 (CI: 1.09–1.30)), obesity (HR: 1.33 (CI: 1.18–1.50) and a high waist-hip ratio (HR: 1.25 (CI: 1.13–1.38)), being a current or previous smoker (HR: 1.29 (CI: 1.18–1.41)), pain (HR: 1.39 (CI: 1.34–1.45)), sedentary behaviour (HR: 2.17 (CI: 1.76–2.78) and lower body strength (HR: 1.07 (CI: 1.06–1.08)), were all significant risk factors for frailty progression and incidence after simultaneous adjustment for all examined factors.
Conclusion
The findings of this study suggest that there may be scope to reduce both frailty incidence and progression by trialling interventions aimed at reducing obesity and sedentary behaviour, increasing intensity of physical activity, and improving success of smoking cessation tools. Furthermore, improving educational outcomes and reducing poverty may also reduce inequalities in frailty.
Klíčová slova:
Body Mass Index – Nurses – Physical activity – Obesity – Frailty – Elderly – Smoking habits – Medical risk factors
Zdroje
1. Clegg A, Young J, Iliffe S, Rikkert MO, Rockwood K. Frailty in elderly people. Lancet. Elsevier; 2013;381: 752–762. doi: 10.1016/S0140-6736(12)62167-9 23395245
2. Cesari M, Prince M, Thiyagarajan JA, De Carvalho IA, Bernabei R, Chan P, et al. Frailty: An Emerging Public Health Priority. J Am Med Dir Assoc. 2016;17: 188–192. doi: 10.1016/j.jamda.2015.12.016 26805753
3. Rodríguez-Mañas L, Féart C, Mann G, Viña J, Chatterji S, Chodzko-Zajko W, et al. Searching for an operational definition of frailty: A delphi method based consensus statement. the frailty operative definition-consensus conference project. Journals Gerontol—Ser A Biol Sci Med Sci. Oxford University Press; 2013;68: 62–67. doi: 10.1093/gerona/gls119
4. Bouillon K, Kivimaki M, Hamer M, Sabia S, Fransson EI, Singh-Manoux A, et al. Measures of frailty in population-based studies: an overview. BMC Geriatr. 2013;13: 64. doi: 10.1186/1471-2318-13-64 23786540
5. Fried LP, Tangen CM, Walston J, Newman ABA, Hirsch C, Gottdiener J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001;56: 46–56. doi: 10.1093/gerona/56.3.M146
6. Aguayo GA, Donneau A-F, Vaillant MT, Schritz A, Franco OH, Stranges S, et al. Agreement Between 35 Published Frailty Scores in the General Population. Am J Epidemiol. Narnia; 2017;186: 420–434. doi: 10.1093/aje/kwx061 28633404
7. Searle SD, Mitnitski A, Gahbauer EA, Gill TM, Rockwood K. A standard procedure for creating a frailty index. BMC Geriatr. BioMed Central; 2008;8: 24. doi: 10.1186/1471-2318-8-24 18826625
8. Mitnitski AB, Mogilner AJ, Rockwood K. Accumulation of deficits as a proxy measure of aging. ScientificWorldJournal. 2001;
9. Rockwood K, Howlett SE. Fifteen years of progress in understanding frailty and health in aging. BMC Medicine. 2018. doi: 10.1186/s12916-018-1223-3
10. Walston JD, Bandeen-Roche K. Frailty: A tale of two concepts. BMC Medicine. 2015. doi: 10.1186/s12916-015-0420-6
11. Rockwood K, Andrew M, Mitnitski A. A Comparison of Two Approaches to Measuring Frailty in Elderly People. Journals Gerontol Ser A Biol Sci Med Sci. 2007;62: 738–743. doi: 10.1093/gerona/62.7.738
12. Ding YY, Kuha J, Murphy M. Multidimensional predictors of physical frailty in older people: identifying how and for whom they exert their effects. Biogerontology. 2017;18: 237–252. doi: 10.1007/s10522-017-9677-9 28160113
13. Robertson DA, Savva GM, Kenny RA. Frailty and cognitive impairment-A review of the evidence and causal mechanisms. Ageing Res Rev. 2013;12: 840–851. doi: 10.1016/j.arr.2013.06.004 23831959
14. Buchman AS, Yu L, Wilson RS, Boyle PA, Schneider JA, Bennett DA. Brain pathology contributes to simultaneous change in physical frailty and cognition in old age. Journals Gerontol—Ser A Biol Sci Med Sci. Oxford University Press; 2014;69: 1536–1544. doi: 10.1093/gerona/glu117
15. Shimada H, Makizako H, Lee S, Doi T, Lee S, Tsutsumimoto K, et al. Impact of cognitive frailty on daily activities in older persons. J Nutr Heal Aging. Springer Paris; 2016;20: 729–735. doi: 10.1007/s12603-016-0685-2
16. Feng L, Zin Nyunt MS, Gao Q, Feng L, Yap KB, Ng TP. Cognitive Frailty and Adverse Health Outcomes: Findings From the Singapore Longitudinal Ageing Studies (SLAS). J Am Med Dir Assoc. Elsevier; 2017;18: 252–258. doi: 10.1016/j.jamda.2016.09.015 27838339
17. Roppolo M, Mulasso A, Rabaglietti E. Cognitive frailty in Italian community-dwelling older adults: Prevalence rate and its association with disability. J Nutr Heal Aging. Springer Paris; 2017;21: 631–636. doi: 10.1007/s12603-016-0828-5
18. Ruan Q, D’Onofrio G, Sancarlo D, Greco A, Lozupone M, Seripa D, et al. Emerging biomarkers and screening for cognitive frailty. Aging Clinical and Experimental Research. 2017. pp. 1075–1086. doi: 10.1007/s40520-017-0741-8 28260159
19. Luppa M, Luck T, Weyerer S, König HH, Brähler E, Riedel-Heller SG. Prediction of institutionalization in the elderly. A systematic review. Age Ageing. Narnia; 2009;39: 31–38. doi: 10.1093/ageing/afp202 19934075
20. Hao Q, Dong B, Yang M, Dong B, Wei Y. Frailty and Cognitive Impairment in Predicting Mortality Among Oldest-Old People. Front Aging Neurosci. Frontiers; 2018;10: 295. doi: 10.3389/fnagi.2018.00295 30405390
21. Steptoe A, Breeze E, Banks J, Nazroo J. Cohort profile: The English Longitudinal Study of Ageing. Int J Epidemiol. 2013;42: 1640–1648. doi: 10.1093/ije/dys168 23143611
22. Rockwood K, Mitnitski A. Frailty in relation to the accumulation of deficits. Journals Gerontol—Ser A Biol Sci Med Sci. 2007;62: 722–727. doi: 10.1093/gerona/62.7.722
23. Mitnitski AB, Mogilner AJ, Rockwood K. Accumulation of Deficits as a Proxy Measure of Aging. Sci World J. 2001;1: 323–336. doi: 10.1100/tsw.2001.58
24. Mitnitski A, Song X, Skoog I, Broe GA, Cox JL, Grunfeld E, et al. Relative fitness and frailty of elderly men and women in developed countries and their relationship with mortality. J Am Geriatr Soc. 2005;53: 2184–2189. doi: 10.1111/j.1532-5415.2005.00506.x 16398907
25. Kulminski A, Yashin A, Arbeev K, Akushevich I, Ukraintseva S, Land K, et al. Cumulative index of health disorders as an indicator of aging-associated processes in the elderly: Results from analyses of the National Long Term Care Survey. Mech Ageing Dev. 2007;128: 250–258. doi: 10.1016/j.mad.2006.12.004 17223183
26. Goggins WB, Woo J, Sham A, Ho SC. Frailty Index as a Measure of Biological Age in a Chinese Population. Journals Gerontol Ser A Biol Sci Med Sci. 2005;60: 1046–1051. doi: 10.1093/gerona/60.8.1046
27. Woo J, Goggins W, Sham A, Ho SC. Social determinants of frailty. Gerontology. 2005;51: 402–408. doi: 10.1159/000088705 16299422
28. Stekhoven DJ, Bühlmann P. Missforest-Non-parametric missing value imputation for mixed-type data. Bioinformatics. 2012; doi: 10.1093/bioinformatics/btr597
29. Terry M, Therneau M. Package “survival” Title Survival Analysis [Internet]. 2018. Available: https://github.com/therneau/survival
30. Shankar A, McMunn A, Banks J, Steptoe A. Loneliness, Social Isolation, and Behavioral and Biological Health Indicators in Older Adults. Heal Psychol. 2011;30: 377–385. doi: 10.1037/a0022826
31. Hughes ME, Waite LJ, Hawkley LC, Cacioppo JT. A short scale for measuring loneliness in large surveys: Results from two population-based studies. Research on Aging. 2004. doi: 10.1177/0164027504268574
32. Nishida C, Ko GT, Kumanyika S. Body fat distribution and noncommunicable diseases in populations: overview of the 2008 WHO Expert Consultation on Waist Circumference and Waist-Hip Ratio. Eur J Clin Nutr. 2010;64: 2–5. doi: 10.1038/ejcn.2009.139 19935820
33. Bunt S, Steverink N, Olthof J, van der Schans CP, Hobbelen JSM. Social frailty in older adults: a scoping review. European Journal of Ageing. 2017. doi: 10.1007/s10433-017-0414-7
34. Solfrizzi V, Scafato E, Lozupone M, Seripa D, Schilardi A, Custodero C, et al. Biopsychosocial frailty and the risk of incident dementia: The Italian longitudinal study on aging. Alzheimer’s Dement. 2019;15: 1019–1028. doi: 10.1016/j.jalz.2019.04.013
35. Fallah N, Mitnitski A, Searle SD, Gahbauer EA, Gill TM, Rockwood K. Transitions in frailty status in older adults in relation to mobility: A multistate modeling approach employing a deficit count. J Am Geriatr Soc. 2011;59: 524–529. doi: 10.1111/j.1532-5415.2011.03300.x 21391943
36. Samper-Ternent R, Karmarkar A, Graham J, Reistetter T, Ottenbacher K. Frailty as a predictor of falls in older Mexican Americans. J Aging Health. 2012;24: 641–653. doi: 10.1177/0898264311428490 22187090
37. Hajek A, Brettschneider C, Posselt T, Lange C, Mamone S, Wiese B, et al. Predictors of frailty in old age–results of a longitudinal study. J Nutr Heal Aging. 2016;20: 952–957. doi: 10.1007/s12603-015-0634-5
38. García-Esquinas E, José García-García F, Leõn-Muñoz LM, Carnicero JA, Guallar-Castillõn P, Gonzalez-Colaço Harmand M, et al. Obesity, fat distribution, and risk of frailty in two population-based cohorts of older adults in Spain. Obesity. John Wiley & Sons, Ltd; 2015;23: 847–855. doi: 10.1002/oby.21013 25683024
39. Liao Q, Zheng Z, Xiu S, Chan P. Waist circumference is a better predictor of risk for frailty than BMI in the community-dwelling elderly in Beijing. Aging Clin Exp Res. 2018;30: 1319–1325. doi: 10.1007/s40520-018-0933-x 29589287
40. Rogers NT, Power C, Pinto Pereira SM. Birthweight, lifetime obesity and physical functioning in mid-adulthood: a nationwide birth cohort study. Int J Epidemiol. 2019; doi: 10.1093/ije/dyz120
41. Porter Starr KN, McDonald SR, Bales CW. Obesity and physical frailty in older adults: A scoping review of lifestyle intervention trials. J Am Med Dir Assoc. NIH Public Access; 2014;15: 240–250. doi: 10.1016/j.jamda.2013.11.008 24445063
42. Shoelson SE, Herrero L, Naaz A. Obesity, Inflammation, and Insulin Resistance. Gastroenterology. Elsevier; 2007;132: 2169–2180. doi: 10.1053/j.gastro.2007.03.059 17498510
43. Bray GA. Medical consequences of obesity. J Clin Endocrinol Metab. Oxford University Press; 2004;89: 2583–2589. doi: 10.1210/jc.2004-0535 15181027
44. Luchsinger JA, Gustafson DR. Adiposity and Alzheimer’s disease. Curr Opin Clin Nutr Metab Care. NIH Public Access; 2009;12: 15–21. doi: 10.1097/MCO.0b013e32831c8c71 19057182
45. Kim S, Kim Y, Park SM. Body mass index and decline of cognitive function. PLoS One. Public Library of Science; 2016;11: e0148908. doi: 10.1371/journal.pone.0148908 26867138
46. Bauman AE, Reis RS, Sallis JF, Wells JC, Loos RJF, Martin BW, et al. Correlates of physical activity: Why are some people physically active and others not? The Lancet. 2012. doi: 10.1016/S0140-6736(12)60735-1
47. Rogers NT, Marshall A, Roberts CH, Demakakos P, Steptoe A, Scholes S. Physical activity and trajectories of frailty among older adults: Evidence from the English Longitudinal Study of Ageing. Ginsberg SD, editor. PLoS One. 2017;12: e0170878. doi: 10.1371/journal.pone.0170878 28152084
48. Leblanc A, Taylor BA, Thompson PD, Capizzi JA, Clarkson PM, Michael White C, et al. Relationships between physical activity and muscular strength among healthy adults across the lifespan. Springerplus. Springer; 2015;4: 557. doi: 10.1186/s40064-015-1357-0 26435903
49. 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 Physical functioning, physical health and activity. BMC Geriatrics. 2015. doi: 10.1186/s12877-015-0155-4
50. Yoshida H, Nishi M, Watanabe N, Fujiwara Y, Fukaya T, Ogawa K, et al. [Predictors of frailty development in a general population of older adults in Japan using the Frailty Index for Japanese elderly patients]. Nihon Ronen Igakkai Zasshi. 2012;49: 442. Available: http://www.ncbi.nlm.nih.gov/pubmed/23269023 doi: 10.3143/geriatrics.49.442 23269023
51. Lally F, Crome P. Understanding frailty. Postgrad Med J. BMJ Publishing Group; 2007;83: 16–20. doi: 10.1136/pgmj.2006.048587 17267673
52. Batista FS, Gomes GA de O, D’Elboux MJ, Cintra FA, Neri AL, Guariento ME, et al. Relationship between lower-limb muscle strength and functional independence among elderly people according to frailty criteria: a cross-sectional study. Sao Paulo Med J. Associação Paulista de Medicina; 2014;132: 282–289. doi: 10.1590/1516-3180.2014.1325669 25054965
53. Rosenberg IH. Sarcopenia: Origins and clinical relevance. Clin Geriatr Med. 2011;27: 337–339. doi: 10.1016/j.cger.2011.03.003 21824550
54. Daniels R, Metzelthin S, van Rossum E, de Witte L, van den Heuvel W. Interventions to prevent disability in frail community-dwelling older persons: An overview. Eur J Ageing. BioMed Central; 2010;7: 37–55. doi: 10.1007/s10433-010-0141-9 28798616
55. Wang C, Song X, Mitnitski A, Yu P, Fang X, Tang Z, et al. Gender differences in the relationship between smoking and frailty: Results from the Beijing longitudinal study of aging. Journals Gerontol—Ser A Biol Sci Med Sci. Oxford University Press; 2013;68: 338–346. doi: 10.1093/gerona/gls166
56. Kojima G, Iliffe S, Walters K. Smoking as a predictor of frailty: A systematic review. BMC Geriatr. BioMed Central; 2015;15: 131. doi: 10.1186/s12877-015-0134-9 26489757
57. Kojima G, Iliffe S, Jivraj S, Liljas A, Walters K. Does current smoking predict future frailty? The English longitudinal study of ageing. Age Ageing. 2018; doi: 10.1093/ageing/afx136
58. Lu L, F Mackay D, Pell JP. Meta-analysis of the association between cigarette smoking and peripheral arterial disease. Heart. 2014; doi: 10.1136/heartjnl-2013-304082
59. Vestbo J, Hurd SS, Agustí AG, Jones PW, Vogelmeier C, Anzueto A, et al. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med. American Thoracic Society; 2013;187: 347–365. doi: 10.1164/rccm.201204-0596PP 22878278
60. Pan B, Jin X, Jun L, Qiu S, Zheng Q, Pan M. The relationship between smoking and stroke. Medicine (Baltimore). 2019;98: e14872. doi: 10.1097/MD.0000000000014872
61. Hackshaw A, Morris JK, Boniface S, Tang JL, Milenkovi D. Low cigarette consumption and risk of coronary heart disease and stroke: Meta-analysis of 141 cohort studies in 55 study reports. BMJ (Online). 2018. doi: 10.1136/bmj.j5855
62. Wade KF, Marshall A, Vanhoutte B, Wu FCW, O’Neill TW, Lee DM. Does pain predict frailty in older men and women? findings from the english longitudinal study of ageing (ELSA). Journals Gerontol—Ser A Biol Sci Med Sci. 2017; doi: 10.1093/gerona/glw226
63. Crombez G, Vlaeyen JWS, Heuts PHTG, Lysens R. Pain-related fear is more disabling than pain itself: Evidence on the role of pain-related fear in chronic back pain disability. Pain. 1999;80: 329–339. doi: 10.1016/s0304-3959(98)00229-2 10204746
64. Eggermont LHP, Swaab DF, Hol EM, Scherder EJA. Walking the line: A randomised trial on the effects of a short term walking programme on cognition in dementia. J Neurol Neurosurg Psychiatry. England; 2009;80: 802–804. doi: 10.1136/jnnp.2008.158444 19531688
65. Agüera-Ortiz L, Failde I, Mico JA, Cervilla J, López-Ibor JJ. Pain as a symptom of depression: Prevalence and clinical correlates in patients attending psychiatric clinics. J Affect Disord. 2011; doi: 10.1016/j.jad.2010.10.022
66. Gerrits MMJG, Van Oppen P, Van Marwijk HWJ, Penninx BWJH, Van Der Horst HE. Pain and the onset of depressive and anxiety disorders. Pain. 2014; doi: 10.1016/j.pain.2013.09.005
67. Gale CR, Westbury L, Cooper C. Social isolation and loneliness as risk factors for the progression of frailty: the English Longitudinal Study of Ageing. Age Ageing. 2018;47: 392–397. doi: 10.1093/ageing/afx188 29309502
68. Cacioppo JT, Cacioppo S. Older adults reporting social isolation or loneliness show poorer cognitive function 4 years later. Evidence-Based Nursing. 2014. pp. 59–60. doi: 10.1136/eb-2013-101379
69. Weiss R. The Study of Loneliness. Loneliness: The Experience of Emotional and Social Isolation. 1974.
70. Szanton SL, Seplaki CL, Thorpe RJ, Allen JK, Fried LP. Socioeconomic status is associated with frailty: The Women’s Health and Aging Studies. J Epidemiol Community Health. NIH Public Access; 2010;64: 63–67. doi: 10.1136/jech.2008.078428 19692719
71. Myers V, Drory Y, Goldbourt U, Gerber Y. Multilevel socioeconomic status and incidence of frailty post myocardial infarction. Int J Cardiol. 2014;170: 338–343. doi: 10.1016/j.ijcard.2013.11.009 24275158
72. Cookson R, Propper C, Asaria M, Raine R. Socio-Economic Inequalities in Health Care in England. Fisc Stud. John Wiley & Sons, Ltd (10.1111); 2016;37: 371–403. doi: 10.1111/j.1475-5890.2016.12109
73. Mackenbach JP, Cavelaars AEJM, Kunst AE, Groenhof F, Andersen O, Borgan JK, et al. Socioeconomic inequalities in cardiovascular disease mortality. An international study. Eur Heart J. 2000;21: 1141–1151. doi: 10.1053/euhj.1999.1990 10924297
74. Singh V, Sahu PK, Sahu BC, Mobin SM. Diels-Alder cycloaddition and ring-closing metathesis: A versatile, stereoselective, and general route to embellished bridged bicyclic systems, carbocyclic framework of secoatisanes, and homologues. J Org Chem. 2009;74: 6092–6104. doi: 10.1021/jo901279g 19610638
75. Bennett DA, Wilson RS, Schneider JA, Evans DA, Mendes de Leon CF, Arnold SE, et al. Education modifies the relation of AD pathology to level of cognitive function in older persons. Neurology. 2003; doi: 10.1212/01.WNL.0000069923.64550.9F
76. Hoogendijk EO, van Hout HPJ, Heymans MW, van der Horst HE, Frijters DHM, Broese van Groenou MI, et al. Explaining the association between educational level and frailty in older adults: Results from a 13-year longitudinal study in the Netherlands. Ann Epidemiol. 2014;24: 538–44.e2. doi: 10.1016/j.annepidem.2014.05.002
77. Stern Y, Albert S, Tang M-X, Tsai W-Y. Rate of memory decline in AD is related to education and occupation: Cognitive reserve? Neurology. 1999; doi: 10.1212/wnl.53.9.1942
78. Everson SA, Maty SC, Lynch JW, Kaplan GA. Epidemiologic evidence for the relation between socioeconomic status and depression, obesity, and diabetes. Journal of Psychosomatic Research. 2002. doi: 10.1016/S0022-3999(02)00303-3
79. Waters DL, van Kan GA, Cesari M, Vidal K, Rolland Y, Vellas B. Gender Specific Associations between Frailty and Body Composition. J frailty aging. 2012;1: 18–23. doi: 10.14283/jfa.2012.4 27092933
80. Shibasaki K, Kin SK, Yamada S, Akishita M, Ogawa S. Sex-related differences in the association between frailty and dietary consumption in Japanese older people: a cross-sectional study. BMC Geriatr. BioMed Central; 2019;19: 211. doi: 10.1186/s12877-019-1229-5 31382881
81. Zhang Q, Guo H, Gu H, Zhao X. Gender-associated factors for frailty and their impact on hospitalization and mortality among community- dwelling older adults: A cross-sectional population-based study. PeerJ. 2018; doi: 10.7717/peerj.4326
82. Rogers NT, Fancourt D. Cultural Engagement Is a Risk-Reducing Factor for Frailty Incidence and Progression. Journals Gerontol Ser B. 2019; doi: 10.1093/geronb/gbz004
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