To compare the capacity of blood myostatin concentration and physical, cognitive, and affective function tests to predict frailty among long-term care (LTC) residents.
Methods
This cross-sectional analysis used baseline data from three randomized controlled trials involving 260 older adults in 14 LTC centers. Serum myostatin levels were analyzed by enzyme-linked immunosorbent assay. Frailty, physical fitness, cognitive and affective functions were assessed using validated tests and scales.
Results
The Timed Up and Go, gait speed, 6-minute walk, and Berg Balance Scale had excellent capabilities in identifying frail individuals in accordance with Fried’s Frailty Phenotype (FFP). The best tests for identifying frailty in accordance with the Clinical Frailty Scale (CFS) were Timed Up and Go and Berg Balance Scale. For the Tilburg Frailty Indicator (TFI), the best tests were Quality of Life in Alzheimer’s Disease (QoL-AD) and Goldberg Anxiety. Myostatin, along with physical, cognitive, and affective function tests, improved the capability of the hand grip, arm-curl, Montreal Cognitive Assessment, Goldberg Anxiety, Goldberg Depression, and QoL-AD to identify frailty according to FFP, while myostatin improved CFS-defined frailty identification by the hand grip, arm-curl, 6-minute walk test, Berg Balance Scale, 30-second chair-stand, gait speed, Montreal Cognitive Assessment, Goldberg Anxiety, and De Jong-Gierveld Loneliness Scale.
Conclusion
Among LTC residents, serum myostatin was associated with being frail according to FFP and CFS. However, this measure was less discriminating of frailty than physical fitness tests (for FFP and CFS) and affective function parameters (for TFI). However, evaluated concurrently with physical, cognitive, and affective parameters, myostatin improved the capabilities of these measures to predict CFS-defined frailty.
Al SaediA.FeehanJ.PhuS.DuqueG. (2019). Current and emerging biomarkers of frailty in the elderly. Clinical Interventions in Aging, 14, 389−398. https://doi.org/10.2147/CIA.S168687.
2.
ArrietaH.HervásG.Rezola-PardoC.Ruiz-LitagoF.IturburuM.YanguasJ. J.GilS. M.Rodriguez-LarradA.IrazustaJ. (2019a). Serum myostatin levels are higher in fitter, more active, and non-frail long-term nursing home residents and increase after a physical exercise intervention. Gerontology, 65(3), 229−239. https://doi.org/10.1159/000494137.
3.
ArrietaH.Rezola‐PardoC.GilS. M.VirgalaJ.IturburuM.AntónI.González-TempladoV.IrazustaJ.Rodriguez‐LarradA. (2019b). Effects of multicomponent exercise on frailty in long‐term nursing homes: A randomized controlled trial. Journal of the American Geriatrics Society, 67(6), 1145−1151. https://doi.org/10.1111/jgs.15824.
4.
BergenH. R.FarrJ. N.VanderboomP. M.AtkinsonE. J.WhiteT. A.SinghR. J.KhoslaS.LeBrasseurN. K. (2015). Myostatin as a mediator of sarcopenia versus homeostatic regulator of muscle mass: Insights using a new mass spectrometry-based assay. Skeletal Muscle, 5(1), 21. https://doi.org/10.1186/s13395-015-0047-5.
5.
BergK. O.Wood-DauphineeS. L.WilliamsJ. I.MakiB. (1992). Measuring balance in the elderly: Validation of an instrument. Canadian Journal of Public Health, 83(Suppl 2), S7−S11.
6.
Bernal‐LópezC.PotvinO.Avila‐FunesJ. A. (2012). Frailty is associated with anxiety in community‐dwelling elderly adults. Journal of the American Geriatrics Society, 60(12), 2373−2374. https://doi.org/10.1111/jgs.12014.
7.
BuckinxF.ReginsterJ. Y.PetermansJ.CroisierJ. L.BeaudartC.BrunoisT.BruyèreO. (2016). Relationship between frailty, physical performance and quality of life among nursing home residents: The SENIOR cohort. Aging Clinical and Experimental Research, 28(6), 1149−1157. https://doi.org/10.1007/s40520-016-0616-4.
8.
CalvaniR.PiccaA.MariniF.BiancolilloA.GervasoniJ.PersichilliS.PrimianoA.Coelho-JuniorH. J.CesariM.BossolaM.UrbaniA.OnderG.LandiF.BernabeiR.MarzettiE. (2021). Identification of biomarkers for physical frailty and sarcopenia through a new multi-marker approach: Results from the BIOSPHERE study. GeroScience, 43(2), 727−740. https://doi.org/10.1007/s11357-020-00197-x.
9.
CardosoA. L.FernandesA.Aguilar-PimentelJ. A.de AngelisM. H.GuedesJ. R.BritoM. A.OrtolanoS.PaniG.AthanasopoulouS.GonosE. S.SchossererM.GrillariJ.PetersonP.TunaB. G.DoganS.MeyerA.van OsR.TrendelenburgA. U. (2018). Towards frailty biomarkers: Candidates from genes and pathways regulated in aging and age-related diseases. Ageing Research Reviews, 47, 214−277. https://doi.org/10.1016/j.arr.2018.07.004.
10.
CesariM.PrinceM.ThiyagarajanJ. A.De CarvalhoI. A.BernabeiR.ChanP.Gutierrez-RobledoL. M.MichelJ. P.MorleyJ. E.OngP.Rodriguez-MañasL.SinclairA.WonC. W.BeardJ.VellasB. (2016). Frailty: An emerging public health priority. Journal of the American Medical Directors Association, 17(3), 188−192. https://doi.org/10.1016/j.jamda.2015.12.016.
11.
ChenS.HondaT.NarazakiK.ChenT.NofujiY.KumagaiS. (2016). Global cognitive performance and frailty in non‐demented community‐dwelling older adults: Findings from the S asaguri G enkimon Study. Geriatrics and Gerontology International, 16(6), 729−736. https://doi.org/10.1111/ggi.12546.
12.
ChuW.ChangS. F.HoH. Y.LinH. C. (2019). The relationship between depression and frailty in community‐dwelling older people: A systematic review and meta‐analysis of 84,351 older adults. Journal of Nursing Scholarship, 51(5), 547−559. httsp://doi.org/10.1111/jnu.12501.
13.
CoenR. F.RobertsonD. A.KennyR. A.King-KallimanisB. L. (2016). Strengths and limitations of the MoCA for assessing cognitive functioning: Findings from a large representative sample of Irish older adults. Journal of Geriatric Psychiatry and Neurology, 29(1), 18−24. httsp://doi.org/10.1177/0891988715598236.
14.
CohenA. A.LegaultV.FuellenG.FülöpT.FriedL. P.FerrucciL. (2018). The risks of biomarker-based epidemiology: associations of circulating calcium levels with age, mortality, and frailty vary substantially across populations. Experimental Gerontology, 107, 11−17. httsp://doi.org/10.1016/j.exger.2017.07.011.
15.
De Jong-GierveldJ.KamphulsF. (1985). The development of a Rasch-type loneliness scale. Applied Psychological Measurement, 9(3), 289−299. httsp://doi.org/10.1177/014662168500900307.
16.
De la Rica-EscuínM.González-VacaJ.Varela-PérezR.Arjonilla-GarcíaM. D.Silva-IglesiasM.Oliver-CarbonellJ. L.AbizandaP. (2014). Frailty and mortality or incident disability in institutionalized older adults: The FINAL study. Maturitas, 78(4), 329−334. httsp://doi.org/10.1016/j.maturitas.2014.05.022.
17.
De Souto BarretoP.MorleyJ. E.Chodzko-ZajkoW.PitkalaK. H.Weening-DjiksterhuisE.Rodriguez-ManasL.BarbagalloM.RosendahlE.SinclairA.LandiF.IzquierdoM.VellasB.RollandY. (2016). Recommendations on physical activity and exercise for older adults living in long-term care facilities: A taskforce report. Journal of the American Medical Directors Association, 17(5), 381−392. httsp://doi.org/10.1016/j.jamda.2016.01.021.
18.
DeLongE. R.DeLongD. M.Clarke-PearsonD. L. (1988). Comparing the areas under two or more correlated receiver operating characteristic curves: A nonparametric approach. Biometrics, 44(3), 837−845. httsp://doi.org/10.2307/2531595.
19.
DuboisV.LaurentM. R.SinnesaelM.CielenN.HelsenC.ClinckemalieL.SpansL.Gayan-RamirezG.DeldicqueL.HespelP.CarmelietG.VanderschuerenD.ClaessensF. (2014). A satellite cell‐specific knockout of the androgen receptor reveals myostatin as a direct androgen target in skeletal muscle. The FASEB Journal, 28(7), 2979−2994. httsp://doi.org/10.1096/fj.14-249748.
20.
EcheverriaI.BesgaA.SanzB.AmaseneM.HervásG.BarrosoJ.Rodriguez-LarradA.IrazustaJ. (2020). Identification of frailty and sarcopenia in hospitalised older people. European Journal of Clinical Investigation, 51(4), e13420. https://doi.org/10.1111/eci.13420.
21.
FessE. (1992). Grip strength. In: CasanovaJ. S. (ed.), Clinical assessment recommendations (pp. 41−45). American society of hand therapists.
22.
FifeE.KostkaJ.KrocŁ.GuligowskaA.PigłowskaM.SołtysikB.Kaufman-SzymczykA.Fabianowska-MajewskaK.KostkaT. (2018). Relationship of muscle function to circulating myostatin, follistatin and GDF11 in older women and men. BMC Geriatrics, 18(1), 1−10. https://doi.org/10.1186/s12877-018-0888-y.
23.
FriedL. P.TangenC. M.WalstonJ.NewmanA. B.HirschC.GottdienerJ.SeemanT.TracyR.KopW. J.BurkeG.McBurnieM. A. (2001). Frailty in older adults: Evidence for a phenotype. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 56(3), M146−M157. https://doi.org/10.1093/gerona/56.3.M146.
24.
GaleC. R.WestburyL.CooperC. (2018). Social isolation and loneliness as risk factors for the progression of frailty: The English longitudinal study of ageing. Age and Ageing, 47(3), 392−397. https://doi.org/10.1093/ageing/afx188.
25.
GielenE.VerschuerenS.O’neillT. W.PyeS. R.O’connellM. D. L.LeeD. M.RavindrarajahR.ClaessensF.LaurentM.MilisenK.TournoyJ.DejaegerM.WuF. C.VanderschuerenD.BoonenS. (2012). Musculoskeletal frailty: A geriatric syndrome at the core of fracture occurrence in older age. Calcified Tissue International, 91(3), 161−177. https://doi.org/10.1007/s00223-012-9622-5.
26.
GobbensR. J.van AssenM. A.LuijkxK. G.Wijnen-SponseleeM. T.ScholsJ. M. (2010). The Tilburg frailty indicator: Psychometric properties. Journal of the American Medical Directors Association, 11(5), 344−355. https://doi.org/10.1016/j.jamda.2009.11.003.
27.
GoldbergD.BridgesK.Duncan-JonesP.GraysonD. (1988). Detecting anxiety and depression in general medical settings. Bmj: British Medical Journal, 297(6653), 897−899. https://doi.org/10.1136/bmj.297.6653.897.
28.
Gómez-GallegoM.Gómez-AmorJ.Gómez-GarcíaJ. (2012). Validación de la versión española de la escala QoL-AD en pacientes con enfermedad de Alzheimer, cuidadores y profesionales sanitarios. Neurología, 27(1), 4−10. https://doi.org/10.1016/j.nrl.2011.03.006.
29.
GuralnikJ. M.FerrucciL.PieperC. F.LeveilleS. G.MarkidesK. S.OstirG. V.StudenskiS.BerkmanL. F.WallaceR. B. (2000). Lower extremity function and subsequent disability: Consistency across studies, predictive models, and value of gait speed alone compared with the short physical performance battery. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 55(4), M221−M231. https://doi.org/10.1093/gerona/55.4.M221.
30.
JonesA. L.DwyerL. L.BercovitzA. R.StrahanG. W ( (2009). The national nursing home survey: 2004 overview. National center for health statistics. Vital Health Stat, 13(167).
31.
KhezrianM.MyintP. K.McNeilC.MurrayA. D. (2017). A review of frailty syndrome and its physical, cognitive and emotional domains in the elderly. Geriatrics, 2(4), 36. https://doi.org/10.3390/geriatrics2040036.
32.
KojimaG. (2015). Prevalence of frailty in nursing homes: A systematic review and meta-analysis. Journal of the American Medical Directors Association, 16(11), 940−945. https://doi.org/10.1016/j.jamda.2015.06.025.
33.
KojimaG.LiljasA. E.IliffeS. (2019). Frailty syndrome: Implications and challenges for health care policy. Risk Management and Healthcare Policy, 12, 23−30. https://doi.org/10.2147/RMHP.S168750.
34.
LakshmanK. M.BhasinS.CorcoranC.Collins-RacieL. A.TchistiakovaL.ForlowS. B.LedgerSt.K.BurczynskiM. E.DornerA. J.LaVallieE. R. (2009). Measurement of myostatin concentrations in human serum: Circulating concentrations in young and older men and effects of testosterone administration. Molecular and Cellular Endocrinology, 302(1), 26−32. https://doi.org/10.1016/j.mce.2008.12.019.
35.
LangmannG. A.PereraS.FerchakM. A.NaceD. A.ResnickN. M.GreenspanS. L. (2017). Inflammatory markers and frailty in long‐term care residents. Journal of the American Geriatrics Society, 65(8), 1777−1783. https://doi.org/10.1111/jgs.14876.
LoboA.SazP.MarcosG.DíaJ. L.de la CámaraC.VenturaT.AsínF. M.PascualL. F.MontañésJ. A.AznarS.LacámaraC. (1999). Revalidación y normalización del Mini-Examen Cognoscitivo (primera versión en castellano del Mini-Mental Status Examination) en la población general geriátrica. Medicina Clínica, 112(20), 767−774.
38.
MandrekarJ. N. (2010). Receiver operating characteristic curve in diagnostic test assessment. Journal of Thoracic Oncology, 5(9), 1315−1316. https://doi.org/10.1097/JTO.0b013e3181ec173d.
39.
Martínez-VelillaN.HerceP. A.HerreroÁ. C.Gutiérrez-ValenciaM.de AsteasuM. L. S.MateosA. S.ZubillagaA. C.BeroizB. I.JiménezA. G.IzquierdoM. (2017). Heterogeneity of different tools for detecting the prevalence of frailty in nursing homes: Feasibility and meaning of different approaches. Journal of the American Medical Directors Association, 18(10), 898. https://doi.org/10.1016/j.jamda.2017.06.016.
40.
MhaoláinA. M. N.GallagherD.CrosbyL.RyanD.LaceyL.CoenR. F.CoakleyD.WalshJ. B.CunninghamC.LawlorB. (2012). Frailty and quality of life for people with Alzheimer’s dementia and mild cognitive impairment. American Journal of Alzheimer's Disease and Other Dementias, 27(1), 48−54. https://doi.org/10.1177/1533317511435661.
41.
Navarrete-VillanuevaD.Gómez-CabelloA.Marín-PuyaltoJ.MorenoL. A.Vicente-RodríguezG.CasajúsJ. A. (2021). Frailty and physical fitness in elderly people: A systematic review and meta-analysis. Sports Medicine, 51(1), 143−160. https://doi.org/10.1007/s40279-020-01361-1.
42.
PiccaA.Coelho-JuniorH. J.CalvaniR.MarzettiE.VetranoD. L. (2022). Biomarkers shared by frailty and sarcopenia in older adults: A systematic review and meta-analysis. Ageing Research Reviews, 73, 101530. https://doi.org/10.1016/j.arr.2021.101530.
43.
PodsiadloD.RichardsonS. (1991). The timed “up & go”: A test of basic functional mobility for frail elderly persons. Journal of the American Geriatrics Society, 39(2), 142−148. https://doi.org/10.1111/j.1532-5415.1991.tb01616.x.
Rezola-PardoC.ArrietaH.GilS. M.ZarrazquinI.YanguasJ. J.LópezM. A.IrazustaJ.Rodriguez-LarradA. (2019). Comparison between multicomponent and simultaneous dual-task exercise interventions in long-term nursing home residents: The Ageing-ON DUAL-TASK randomized controlled study. Age and Ageing, 48(6), 817−823. https://doi.org/10.1093/ageing/afz105.
46.
Rezola-PardoC.Rodriguez-LarradA.Gomez-DiazJ.Lozano-RealG.Mugica-ErrazquinI.PatiñoM. J.Bidaurrazaga-LetonaI.IrazustaJ.GilS. M. (2020). Comparison between multicomponent exercise and walking interventions in long-term nursing homes: A randomized controlled trial. The Gerontologist, 60(7), 1364−1373. https://doi.org/10.1093/geront/gnz177.
RikliR. E.JonesC. J. (2001). Senior fitness test manual. : Human Kinetics.
49.
RobertsonD. A.SavvaG. M.KennyR. A. (2013). Frailty and cognitive impairment—A review of the evidence and causal mechanisms. Ageing Research Reviews, 12(4), 840−851. https://doi.org/10.1016/j.arr.2013.06.004.
50.
RockwoodK.SongX.MacKnightC.BergmanH.HoganD. B.McDowellI.MitnitskiA. (2005). A global clinical measure of fitness and frailty in elderly people. Canadian Medical Association Journal, 173(5), 489−495. https://doi.org/10.1503/cmaj.050051.
51.
RodgersB. D.GarikipatiD. K. (2008). Clinical, agricultural, and evolutionary biology of myostatin: A comparative review. Endocrine Reviews, 29(5), 513−534. https://doi.org/10.1210/er.2008-0003.
52.
Rodriguez-MañasL.Araujo de CarvalhoI.BhasinS.Bischoff-FerrariH. A.CesariM.EvansW.HareJ. M.PahorM.PariniA.RollandY.FieldingR. A.WalstonJ.VellasB. (2020). ICFSR task force perspective on biomarkers for sarcopenia and frailty. The Journal of Frailty & Aging, 9(1), 4−8. https://doi.org/10.14283/jfa.2019.32.
53.
RoquebertQ.SicsicJ.Santos-EggimannB.SirvenN.RappT. (2021). Frailty, sarcopenia and long term care utilization in older populations: A systematic review. The Journal of Frailty & Aging, 10(3), 272−280. https://doi.org/10.14283/jfa.2021.7.
54.
SantosK. T.FernandesM. H.CarneiroJ. A.da Silva CoqueiroR. (2016). Motor performance tests as screening instruments for frailty in the older adults. Applied Nursing Research, 32, 80−84. https://doi.org/10.1016/j.apnr.2016.06.003.
55.
SanzB.ArrietaH.HervásG.Rezola-PardoC.Ruiz-LitagoF.IturburuM.GilS. M.Rodriguez-LarradA.IrazustaJ. (2019). Serum adiponectin is associated with body composition and cognitive and psychological status in older adults living in long-term nursing homes. Experimental Gerontology, 121, 1−9. https://doi.org/10.1016/j.exger.2019.03.005.
56.
SanzB.ArrietaH.Rezola-PardoC.Fernández-AtutxaA.Garin-BalerdiJ.ArizagaN.Rodriguez-LarradA.IrazustaJ. (2021). Low serum klotho concentration is associated with worse cognition, psychological components of frailty, dependence, and falls in nursing home residents. Scientific Reports, 11(1), 1−10. https://doi.org/10.1038/s41598-021-88455-6.
57.
SanzB.Rezola-PardoC.ArrietaH.Fernández-AtutxaA.Lora-DiazI.Gil-GoikouriaJ.Rodriguez-LarradA.IrazustaJ. (2022). High serum angiotensin-converting enzyme 2 activity as a biomarker of frailty in nursing home residents. Experimental Gerontology, 158, 111655. https://doi.org/10.1016/j.exger.2021.111655.
58.
SanzB.Rezola-PardoC.ArrietaH.Fraile-BermúdezA. B.Alonso-PuyoJ.MolanoI.Rodriguez-LarradA.IrazustaJ. (2022). Serum sestrin-1 concentration is higher in frail than non-frail older people living in nursing homes. International Journal of Environmental Research and Public Health, 19(3), 1079. https://doi.org/10.3390/ijerph19031079.
59.
SavvaG. M.DonoghueO. A.HorganF.O’ReganC.CroninH.KennyR. A. (2013). Using timed up-and-go to identify frail members of the older population. Journals of Gerontology Series A: Biomedical Sciences and Medical Sciences, 68(4), 441−446. https://doi.org/10.1093/gerona/gls190.
60.
SicsicJ.RavesteijnB.RappT. (2020). Are frail elderly people in Europe high-need subjects? First evidence from the SPRINTT data. Health Policy, 124(8), 865−872. https://doi.org/10.1016/j.healthpol.2020.05.009.
61.
SmithG. D.KyddA. (2017). Getting care of older people right: The need for appropriate frailty assessment?Journal of Advanced Nursing, 73(1), 3−4. https://doi.org/10.1111/jan.13190.
62.
SutoriusF. L.HoogendijkE. O.PrinsB. A.van HoutH. P. (2016). Comparison of 10 single and stepped methods to identify frail older persons in primary care: Diagnostic and prognostic accuracy. BMC Family Practice, 17(1), 102. https://doi.org/10.1186/s12875-016-0487-y.
63.
Tabue-TeguoM.DartiguesJ. F.SimoN.Kuate-TegueuC.VellasB.CesariM. (2018). Physical status and frailty index in nursing home residents: Results from the INCUR study. Archives of Gerontology and Geriatrics, 74, 72−76. https://doi.org/10.1016/j.archger.2017.10.005.
64.
TseM. M. Y.LaiC.LuiJ. Y. W.KwongE.YeungS. Y. (2016). Frailty, pain and psychological variables among older adults living in Hong Kong nursing homes: Can we do better to address multimorbidities?Journal of Psychiatric and Mental Health Nursing, 23(5), 303−311. https://doi.org/10.1111/jpm.12303.
WadeD. T.CollinC. (1988). The Barthel ADL Index: A standard measure of physical disability?International Disability Studies, 10(2), 64−67. https://doi.org/10.3109/09638288809164105.
67.
YarasheskiK. E.BhasinS.Sinha-HikimI.Pak-LoducaJ.Gonzalez-CadavidN. F. (2002). Serum myostatin-immunoreactive protein is increased in 60-92 year old women and men with muscle wasting. The Journal of Nutrition, Health and Aging, 6(5), 343−348.
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
