Abstract

The purpose of present study was to analyze the magnitude of the effect-size in the assessment of the cognitive status of populations over 60 years of age. The search strategy included PubMed, B-on, Ebsco, Ebsco Health, Scielo, Eric, Lilacs and Sportdiscus data bases. Only observational, cohort and cross-sectional studies were included in the meta-analysis. The central descriptors were elderly-frail, older adults, cognition and geriatric assessment and other additional terms. After applying the additional search criteria, 12 manuscripts were selected from an initial universe of 1,078 identified. When comparing the mean cognitive profile scores of the participants of the pre-frail (n =11,265) and frail (n = 2,460) groups, significant statistical differences were found (p<0,001), with lower mean scores emerging in frail-group. The results showed that cognitive decline is strongly associated with frailty, being a probable main clinical outcome. In this sense, any strategy aimed at mitigating or reversing the incidence of frailty with ageing should take into account that physical and cognitive frailty seem to have similar temporal trajectories.

Key words
Frail-older adults; Mild cognitive impairment; Geriatric assessment; Cognition

Introduction

The frailty syndrome (FS) is a complex condition characterized by the decline of multiple physiological systems, leading to progressive loss of the energy reserves, compromising the ability to resist the adverse effects of chronic stress¹1. García-García FJ, Larrión Zugasti JL, Rodríguez Mañas L. [Frailty: a phenotype under review]. Gac Sanit [Internet]. 2011 Dec [cited 2014 Sep 27];25(Supl. 2):51-58. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22033007
http://www.ncbi.nlm.nih.gov/pubmed/22033... . There are several approaches related to FS, but recently the study developed by Fried et al.²2. Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, Seeman T, Racy R, Kop WJ, Burke G, Mc Burnie M. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci [Internet]. 2001 Mar;56(3):M146-M156. Available from: http://www.ncbi.nlm.nih.gov/pubmed/11253156
http://www.ncbi.nlm.nih.gov/pubmed/11253... , is one of the most important. From this construct, emerged the main pillars considered as the pathological core of FS, such as negative energy balance, sarcopenia and low levels of physical activity.

From a frailty state, the individual tends to go through institutionalization and/or hospitalization often followed by precociously death³3. Clegg A, Young J, Iliffe S, Rikkert MO, Rockwood K. Frailty in elderly people. Lancet [Internet]. 2013 Mar 2 [cited 2014 Jul 14];381(9868):752-762. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23395245
http://www.ncbi.nlm.nih.gov/pubmed/23395... ^,44. Gruver AL, Hudson LL, Sempowski GD. Immunosenescence of ageing. J Pathol [Internet]. 2007 Jan [cited 2014 Dec 26];211(2):144-56. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1931833&tool=pmcentrez&rendertype=abstract
http://www.pubmedcentral.nih.gov/article... . The vulnerability acquired by these losses can lead to a frail state, due to exposure to aggression in multiple physiological systems³3. Clegg A, Young J, Iliffe S, Rikkert MO, Rockwood K. Frailty in elderly people. Lancet [Internet]. 2013 Mar 2 [cited 2014 Jul 14];381(9868):752-762. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23395245
http://www.ncbi.nlm.nih.gov/pubmed/23395... ^,55. Yao X, Li H, Leng SX. Inflammation and immune system alterations in frailty. Clin Geriatr Med [Internet]. 2011 Feb [cited 2015 Apr 23];27(1):79-87. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3011971&tool=pmcentrez&rendertype=abstract
http://www.pubmedcentral.nih.gov/article... . For this reason, much of the money spent on health care for the population is concentrated on the frail individuals who progress to developing more severe clinical conditions⁶6. Nelson ME, Rejeski WJ, Blair SN, Duncan PW, Judge JO, King AC, Macera C, Castaneda-Sceppa, C. Physical activity and public health in older adults: recommendation from the American College of Sports Medicine and the American Heart Association. Med Sci Sports Exerc [Internet]. 2007 Aug [cited 2014 Aug 1];39(8):1435-1445. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17762378
http://www.ncbi.nlm.nih.gov/pubmed/17762... . This represents an average of 20-35% of the elderly population in contemporary societies, according to recent research¹1. García-García FJ, Larrión Zugasti JL, Rodríguez Mañas L. [Frailty: a phenotype under review]. Gac Sanit [Internet]. 2011 Dec [cited 2014 Sep 27];25(Supl. 2):51-58. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22033007
http://www.ncbi.nlm.nih.gov/pubmed/22033... ^,22. Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, Seeman T, Racy R, Kop WJ, Burke G, Mc Burnie M. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci [Internet]. 2001 Mar;56(3):M146-M156. Available from: http://www.ncbi.nlm.nih.gov/pubmed/11253156
http://www.ncbi.nlm.nih.gov/pubmed/11253... ^,77. Morley JE, Vellas B, van Kan GA, Anker SD, Bauer JM, Bernabei R. Frailty consensus: a call to action. J Am Med Dir Assoc [Internet]. 2013 Jun [cited 2015 Jan 8];14(6):392-397. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=4084863&tool=pmcentrez&rendertype=abstract
http://www.pubmedcentral.nih.gov/article... .

The FS is aging-related, although it does not exclusively result from the aging process⁸8. Romero-Ortuno R. The Frailty Instrument for primary care of the Survey of Health, Ageing and Retirement in Europe predicts mortality similarly to a frailty index based on comprehensive geriatric assessment. Geriatr Gerontol Int [Internet]. 2013 Apr [cited 2015 Feb 17];13(2):497-504. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3530023&tool=pmcentrez&rendertype=abstract
http://www.pubmedcentral.nih.gov/article... . The gender differences indicated that frail men are more susceptible to early which was proven in studies linking the FS and the incidence of morbidity⁹9. Chang S-F, Lin P-L. Frail phenotype and mortality prediction: A systematic review and meta-analysis of prospective cohort studies. Int J Nurs Stud [Internet]. 2015; 52(8):1362-1374. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0020748915001066
http://linkinghub.elsevier.com/retrieve/... , however, the incidence in women has exponentially increased. In general, older frail individuals are those at increased risk for adverse clinical outcomes¹⁰10. Robinson TN, Eiseman B, Wallace JI, Church SD, McFann KK, Pfister SM. Redefining geriatric preoperative assessment using frailty, disability and co-morbidity. Ann Surg [Internet]. 2009 Sep [cited 2015 Jan 5];250(3):449-455. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19730176
http://www.ncbi.nlm.nih.gov/pubmed/19730...

11. Schuurmans H, Steverink N, Lindenberg S, Frieswijk N, Slaets JPJ. Old or frail: what tells us more? J Gerontol A Biol Sci Med Sci [Internet]. 2004 Sep [cited 2015 Feb 25];59(9):M962-M965. Available from: http://www.ncbi.nlm.nih.gov/pubmed/15472162
http://www.ncbi.nlm.nih.gov/pubmed/15472... ^-1212. Gobbens RJJ, Luijkx KG, van Assen MALM. Explaining quality of life of older people in the Netherlands using a multidimensional assessment of frailty. Qual Life Res [Internet]. 2013 Oct [cited 2015 Feb 17];22(8):2051-2061. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23274572
http://www.ncbi.nlm.nih.gov/pubmed/23274... . The consistent relationship between FS and the physical-functional decline does not invalidate the importance of other dimensions associated with a frailty condition¹³13. Kim M-J, Yabushita N, Kim M-K, Nemoto M, Seino S, Tanaka K. Mobility performance tests for discriminating high risk of frailty in community-dwelling older women. Arch Gerontol Geriatr [Internet]. 2010 Jan [cited 2015 Feb 2];51(2):192-198. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19939477
http://www.ncbi.nlm.nih.gov/pubmed/19939... ^–1515. Greene BR, Doheny EP, O’Halloran A, Anne Kenny R. Frailty status can be accurately assessed using inertial sensors and the TUG test. Age Ageing [Internet]. 2014 May [cited 2015 Jan 10];43(3):406-411. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24212918
http://www.ncbi.nlm.nih.gov/pubmed/24212... . Recent research has tried to identify other clinical conditions associated with the FS³3. Clegg A, Young J, Iliffe S, Rikkert MO, Rockwood K. Frailty in elderly people. Lancet [Internet]. 2013 Mar 2 [cited 2014 Jul 14];381(9868):752-762. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23395245
http://www.ncbi.nlm.nih.gov/pubmed/23395... ^,55. Yao X, Li H, Leng SX. Inflammation and immune system alterations in frailty. Clin Geriatr Med [Internet]. 2011 Feb [cited 2015 Apr 23];27(1):79-87. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3011971&tool=pmcentrez&rendertype=abstract
http://www.pubmedcentral.nih.gov/article... ^,1616. Coelho FGDM, Gobbi S, Andreatto CAA, Corazza DI, Pedroso RV, Santos-Galduróz RF. Physical exercise modulates peripheral levels of brain-derived neurotrophic factor (BDNF): a systematic review of experimental studies in the elderly. Arch Gerontol Geriatr [Internet]. 2013 [cited 2014 Sep 4];56(1):10-15. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22749404
http://www.ncbi.nlm.nih.gov/pubmed/22749... ^,1717. Darvin K, Randolph A, Ovalles S, Halade D, Breeding L, Richardson A, Espinoza, S. Plasma protein biomarkers of the geriatric syndrome of frailty. J Gerontol A Biol Sci Med Sci [Internet]. 2014 Feb [cited 2015 Feb 17];69(2):182-186. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=4038243&tool=pmcentrez&rendertype=abstract
http://www.pubmedcentral.nih.gov/article... , such as the ‘frailty’ of neurocognitive functions¹⁸18. Alencar MA, Dias JMD, Figueiredo LC, Dias RC. Frailty and cognitive impairment among community-dwelling elderly. Arq Neuropsiquiatr [Internet]. 2013 Jun [cited 2015 Feb 9];71(6):362-367. Available from: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0004-282X2013000600362&lng=en&nrm=iso&tlng=en
http://www.scielo.br/scielo.php?script=s... ^,1919. Avila-Funes JA, Amieva H, Barberger-Gateau P, Le Goff M, Raoux N, Ritchie K, Carrière I, Tavernier B, Tzourio C, Gutiérrez-Robledo L, Dartigues J. Cognitive impairment improves the predictive validity of the phenotype of frailty for adverse health outcomes: the three-city study. J Am Geriatr Soc [Internet]. 2009 Mar [cited 2015 Feb 1];57(3):453-461. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19245415
http://www.ncbi.nlm.nih.gov/pubmed/19245... .

An imminent consequence is the clinical outcomes related to mental health²⁰20. Nóbrega PVN, Maciel ACC, Almeida Holanda CM, Oliveira Guerra R, Araújo JF. Sleep and frailty syndrome in elderly residents of long-stay institutions: a cross-sectional study. Geriatr Gerontol Int [Internet]. 2014 Jul [cited 2015 Jul 26];14(3):605-612. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24020502
http://www.ncbi.nlm.nih.gov/pubmed/24020... , which can also be characterized by traumas caused by falls or a high fear (risk) of falling²¹21. de la Rica-Escuín M, González-Vaca J, Varela-Pérez R, Arjonilla-García MD, Silva-Iglesias M, Oliver-Carbonell JL. Frailty and mortality or incident disability in institutionalized older adults: the FINAL study. Maturitas [Internet]. 2014 Aug [cited 2015 Jul 7];78(4):329-334. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24929996
http://www.ncbi.nlm.nih.gov/pubmed/24929... , acute neurological outcomes triggered suddenly (dementia caused by a stroke)²²22. Faria CA, Lourenço RA, Ribeiro PC, Lopes CS. Desempenho cognitivo e fragilidade em idosos clientes de operadora de saúde. Rev Saude Publica [Internet]. 2013 Oct [cited 2015 Jun 2];47(5):923-930. Available from: http://www.scielosp.org/scielo.php?script=sci_arttext&pid=S0034-89102013000700923&lng=en&nrm=iso&tlng=pt
http://www.scielosp.org/scielo.php?scrip... , Alzheimer and/or Parkinson¹⁹19. Avila-Funes JA, Amieva H, Barberger-Gateau P, Le Goff M, Raoux N, Ritchie K, Carrière I, Tavernier B, Tzourio C, Gutiérrez-Robledo L, Dartigues J. Cognitive impairment improves the predictive validity of the phenotype of frailty for adverse health outcomes: the three-city study. J Am Geriatr Soc [Internet]. 2009 Mar [cited 2015 Feb 1];57(3):453-461. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19245415
http://www.ncbi.nlm.nih.gov/pubmed/19245... . However, recent studies try to make it increasingly clear that there is an association between the FS and low cognitive profile or so-called mild cognitive impairment (MCI)¹⁸18. Alencar MA, Dias JMD, Figueiredo LC, Dias RC. Frailty and cognitive impairment among community-dwelling elderly. Arq Neuropsiquiatr [Internet]. 2013 Jun [cited 2015 Feb 9];71(6):362-367. Available from: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0004-282X2013000600362&lng=en&nrm=iso&tlng=en
http://www.scielo.br/scielo.php?script=s... ^,2222. Faria CA, Lourenço RA, Ribeiro PC, Lopes CS. Desempenho cognitivo e fragilidade em idosos clientes de operadora de saúde. Rev Saude Publica [Internet]. 2013 Oct [cited 2015 Jun 2];47(5):923-930. Available from: http://www.scielosp.org/scielo.php?script=sci_arttext&pid=S0034-89102013000700923&lng=en&nrm=iso&tlng=pt
http://www.scielosp.org/scielo.php?scrip... . This condition is characterized by the transient state between normal cognitive aging and mild dementia²³23. Robertson DA, Savva GM, Kenny RA. Frailty and cognitive impairment—A review of the evidence and causal mechanisms. Ageing Res Rev [Internet]. 2013 Sep [cited 2016 Aug 18];12(4):840-851. Available from: http://linkinghub.elsevier.com/retrieve/pii/S1568163713000482
http://linkinghub.elsevier.com/retrieve/... . This condition results in progressive memory loss greater than expected for its age and educational level²⁴24. Gray SL, Anderson ML, Hubbard RA, Lacroix A, Crane PK, McCormick W, Bowen JD, McCurry S, M, Larson EB. Frailty and incident dementia. Journals Gerontol - Ser A Biol Sci Med Sci 2013;68(9):1083-1090., although other cognitive functions are generally preserved and do not interfere with the daily living tasks. Several studies have shown statistically significant differences in cognitive status when analyzed according to subgroups of Frailty, that is those who are pre-frail or frail tend to be more affected by MCI when compared with non-frail groups²⁵25. Woo J, Yu R, Wong M, Yeung F, Wong M, Lum C. Frailty Screening in the Community Using the FRAIL Scale. J Am Med Dir Assoc [Internet]. 2015 May 1 [cited 2015 May 15];16(5):412-419. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25732832
http://www.ncbi.nlm.nih.gov/pubmed/25732... ^–2727. Ávila-Funes JA, Pina-Escudero SD, Aguilar-Navarro S, Gutierrez-Robledo LM, Ruiz-Arregui L, Amieva H. Cognitive impairment and low physical activity are the components of frailty more strongly associated with disability. J Nutr Health Aging [Internet]. 2011 Aug [cited 2015 Jul 27];15(8):683-689. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21968865
http://www.ncbi.nlm.nih.gov/pubmed/21968... .

Currently, there is a large number of studies carried out in large population databases aimed at screening and detecting the FS⁶6. Nelson ME, Rejeski WJ, Blair SN, Duncan PW, Judge JO, King AC, Macera C, Castaneda-Sceppa, C. Physical activity and public health in older adults: recommendation from the American College of Sports Medicine and the American Heart Association. Med Sci Sports Exerc [Internet]. 2007 Aug [cited 2014 Aug 1];39(8):1435-1445. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17762378
http://www.ncbi.nlm.nih.gov/pubmed/17762... ^,1919. Avila-Funes JA, Amieva H, Barberger-Gateau P, Le Goff M, Raoux N, Ritchie K, Carrière I, Tavernier B, Tzourio C, Gutiérrez-Robledo L, Dartigues J. Cognitive impairment improves the predictive validity of the phenotype of frailty for adverse health outcomes: the three-city study. J Am Geriatr Soc [Internet]. 2009 Mar [cited 2015 Feb 1];57(3):453-461. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19245415
http://www.ncbi.nlm.nih.gov/pubmed/19245... ^,3434. Bouillon K, Sabia S, Jokela M, Gale CR, Singh-Manoux A, Shipley MJ, Kivimäki M, Batty D. Validating a widely used measure of frailty: are all sub-components necessary? Evidence from the Whitehall II cohort study. Age (Dordr) [Internet]. 2013 Aug [cited 2015 Feb 17];35(4):1457-1465. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3705104&tool=pmcentrez&rendertype=abstract
http://www.pubmedcentral.nih.gov/article... : Their results confirm the hypothetical premise of the existence of a ‘new frailty subgroup’ as a more recurring pattern, that results from a physical-functional decline and an associated neurocognitive decline¹⁹19. Avila-Funes JA, Amieva H, Barberger-Gateau P, Le Goff M, Raoux N, Ritchie K, Carrière I, Tavernier B, Tzourio C, Gutiérrez-Robledo L, Dartigues J. Cognitive impairment improves the predictive validity of the phenotype of frailty for adverse health outcomes: the three-city study. J Am Geriatr Soc [Internet]. 2009 Mar [cited 2015 Feb 1];57(3):453-461. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19245415
http://www.ncbi.nlm.nih.gov/pubmed/19245... ^,3030. Mitnitski A, Fallah N, Rockwood MRH, Rockwood K. Transitions in cognitive status in relation to frailty in older adults: a comparison of three frailty measures. J Nutr Health Aging [Internet]. 2011 Dec [cited 2015 Feb 16];15(10):863-867. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22159774
http://www.ncbi.nlm.nih.gov/pubmed/22159... . Unlike some systematic reviews on the topic³¹31. Brigola AG, Rossetti ES, Santos BR dos, Neri AL, Zazzetta MS, Inouye K, Pavarini SC. Relationship between cognition and frailty in elderly: A systematic review. Dement Neuropsychol [Internet]. 2015 Jun [cited 2016 Apr 26]; 9(2):110-119. Available from: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1980-57642015000200110&lng=en&nrm=iso&tlng=en
http://www.scielo.br/scielo.php?script=s... , the objective of this study was to investigate, through a systematic review followed by meta-analysis (SRM), the magnitude of the effects of different frailty levels (pre-frail vs. frail) in evaluating cognitive status of people over 60 years of age.

Methods

Search strategies

Scientific research studies were conducted in the following databases: PubMed, ‘B-on, Scielo, Sportdiscus and PsycINFO, with access made between the months of July 2015 and January 2016, using the advanced meta-search option, in which original articles of epidemiological studies of cross-sectional, observational, cohort and population-based published between 2000-2016 were selected. To refine the search, the combination of the indexed descriptors in Medical Subjects Headings³²32. Huang M, Névéol A, Lu Z. Recommending MeSH terms for annotating biomedical articles. J Am Med Inform Assoc [Internet]. 2011 Jan [cited 2015 May 22];18(5):660-667. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3168302&tool=pmcentrez&rendertype=abstract
http://www.pubmedcentral.nih.gov/article... , was used: (((“frail elderly”[MeSH Terms] OR “frail” [MeSH Terms]) AND “cognition”[MeSH Terms]) OR ([mild cognitive impariment]] AND “frail older adults”[MeSH Terms]) OR “frail older adults”[MeSH Terms] AND”[mini-mental State exam]”AND”Fried criteria”AND”Frailty Phenotype AND”Phenotype of Fried.”

For the search in Lilacs and Scielo database, we selected Health Sciences Descriptors (DeCS), available at the online Health Library portal [http://decs.bvs.br], with the following combination: elderly-frail [Subject descriptor] and cognition [subject descriptor] and elderly [Subject descriptor] OR (weakened elderly) AND (slight state of mind) OR mild cognitive impairment AND (tw: (Fried criteria)) OR (tw: of Fragility)) OR (tw: (Fried Phenotype)). The terms ‘Fried criteria’, ‘Fried fragility phenotype’ and ‘Fried phenotype’ in English and Portuguese were used as additional search terms, following a strategy used in a previous study⁹9. Chang S-F, Lin P-L. Frail phenotype and mortality prediction: A systematic review and meta-analysis of prospective cohort studies. Int J Nurs Stud [Internet]. 2015; 52(8):1362-1374. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0020748915001066
http://linkinghub.elsevier.com/retrieve/... .

Central criterion studies selection

The main criterion for the selection of articles in the SRM, is reflected in the inclusion of articles that used the evaluation criteria of the FS, according to the Phenotype of Frailty (PF) Theory²2. Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, Seeman T, Racy R, Kop WJ, Burke G, Mc Burnie M. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci [Internet]. 2001 Mar;56(3):M146-M156. Available from: http://www.ncbi.nlm.nih.gov/pubmed/11253156
http://www.ncbi.nlm.nih.gov/pubmed/11253... , as well as the use of the test Mini-Mental State Examination (MMSE)³³33. Mungas D. In-office mental status testing: a practical guide. Geriatrics [Internet]. 1991 Jul [cited 2014 Dec 21];46(7):54-58,63,66. Available from: http://www.ncbi.nlm.nih.gov/pubmed/2060803
http://www.ncbi.nlm.nih.gov/pubmed/20608... in the assessment of cognitive status in the populations.

The criterion of ‘weight loss’ is checked by self-report, which questions the individual on the loss of ‘ four or more kilograms of weight’ in the last year or, when there is a loss of 5% of total body weight in the three months prior to the evaluation date. The dimension “exhaustion” is verified through the negative concordance between two questions (number seven and twenty) of the assessment questionnaire called the CES-D³⁴34. Bouillon K, Sabia S, Jokela M, Gale CR, Singh-Manoux A, Shipley MJ, Kivimäki M, Batty D. Validating a widely used measure of frailty: are all sub-components necessary? Evidence from the Whitehall II cohort study. Age (Dordr) [Internet]. 2013 Aug [cited 2015 Feb 17];35(4):1457-1465. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3705104&tool=pmcentrez&rendertype=abstract
http://www.pubmedcentral.nih.gov/article... . For measurement of the ‘physical activity levels’ through weekly energy expenditure in the elderly, we used the short version of the Minnesota Questionnaire³⁵35. van Kan GA, Rolland Y, Houles M, Gillette-Guyonnet S, Soto M, Vellas B. The assessment of frailty in older adults. Clin Geriatr Med 2010; 26(2):275-286.. ‘Walking speed’ is measured through a walking test of 4.6 meters, measuring the time taken by the elderly to go this distance at a comfortable speed, and whose values are adjusted for age and gender³⁶36. Wilson CM, Kostsuca SR, Boura JA. Utilization of a 5-Meter Walk Test in Evaluating Self-selected Gait Speed during Preoperative Screening of Patients Scheduled for Cardiac Surgery. Cardiopulm Phys Ther J [Internet]. 2013 Sep [cited 2015 Jul 24];24(3):36-43. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3751713&tool=pmcentrez&rendertype=abstract
http://www.pubmedcentral.nih.gov/article... . ‘Strength’ is assessed using the handgrip test for grip strength, adjusting the values according to age and body mass index³⁷37. Sasaki H, Kasagi F, Yamada M, Fujita S. Grip strength predicts cause-specific mortality in middle-aged and elderly persons. Am J Med [Internet]. 2007 Apr [cited 2015 Jan 6];120(4):337-342. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17398228
http://www.ncbi.nlm.nih.gov/pubmed/17398... . The evaluation of these criteria allows to classify the individual in frail (three or more obvious criteria), pre-frail (two of the obvious conditions) and non-frail or ‘robust’ (with nullity in five criteria)²2. Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, Seeman T, Racy R, Kop WJ, Burke G, Mc Burnie M. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci [Internet]. 2001 Mar;56(3):M146-M156. Available from: http://www.ncbi.nlm.nih.gov/pubmed/11253156
http://www.ncbi.nlm.nih.gov/pubmed/11253... ^,1515. Greene BR, Doheny EP, O’Halloran A, Anne Kenny R. Frailty status can be accurately assessed using inertial sensors and the TUG test. Age Ageing [Internet]. 2014 May [cited 2015 Jan 10];43(3):406-411. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24212918
http://www.ncbi.nlm.nih.gov/pubmed/24212... .

The Mini-Mental State Examination (MMSE)³³33. Mungas D. In-office mental status testing: a practical guide. Geriatrics [Internet]. 1991 Jul [cited 2014 Dec 21];46(7):54-58,63,66. Available from: http://www.ncbi.nlm.nih.gov/pubmed/2060803
http://www.ncbi.nlm.nih.gov/pubmed/20608... is an instrument composed of 30 questions, which is able to assess the five dimensions of cognitive profile³⁸38. Han ES, Lee Y, Kim J. Association of cognitive impairment with frailty in community-dwelling older adults. Int Psychogeriatr [Internet]. 2014 Jan [cited 2015 Jul 27];26(1):155-163. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24153029
http://www.ncbi.nlm.nih.gov/pubmed/24153... . Its score can range from zero to 30 points, and according to the criteria established in several studies, cut-off values that classify individuals on the following cognitive profiles are accepted: a) Severe Cognitive Disorder (from 1 to 9 points), b) Moderate Cognitive Disorder (10 to 18 points) c) Mild Cognitive Impairment (19 to 24 points), d) Normal Cognitive Profile (equal to or over 25 points)³⁹39. Folstein MF, Folstein SE, McHugh PR. ‘Mini-mental state’. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12(3):189-198.. The MMSE is the most used assessment tool of cognitive status in studies of frailty since it is able to assess what it is intended to evaluate⁴⁰40. Melo DM, Barbosa AJG. [Use of the Mini-Mental State Examination in research on the elderly in Brazil: a systematic review]. Cien Saude Colet [Internet]. 2015 Dec [cited 2016 Jan 4];20(12):3865-3876. Available from: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1413-81232015001203865&lng=en&nrm=iso&tlng=pt
http://www.scielo.br/scielo.php?script=s... .

The exclusion criteria of this study presented the elimination of all the manuscripts that did not meet the initial selection criteria, as well as all those that presented as opinion articles, letters to editor, systematic reviews and protocol format studies.

Data extraction

The initial search for the present SRM study was carried out by two researchers independently, following the ultimate criterion for selection of the articles. For the final selection we included all manuscripts that evaluated older populations by FS subgroups of ‘pre-frail’ and ‘frail’, as well as comparing the mean scores (as a continuous variable) of the results of the MMSE according to the aforementioned subgroups, regardless of the gender of the participants in study samples included in the review³⁹39. Folstein MF, Folstein SE, McHugh PR. ‘Mini-mental state’. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12(3):189-198..

Methodological design of the research

This study followed the PRISMA Positioning guidelines to aid in the methodological design of this study⁴¹41. Panic N, Leoncini E, De Belvis G, Ricciardi W, Boccia S. Evaluation of the endorsement of the preferred reporting items for systematic reviews and meta-analysis (PRISMA) statement on the quality of published systematic review and meta-analyses. PLoS ONE 2013; 8(12)e83138.. These guidelines describe the four stages (identification, screening, eligibility, final selection) needed to perform the search and selection of manuscripts under an RS, and feature the graphics option to draw a flowchart⁴²42. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JPA. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS Med [Internet]. 2009 Jul 21 [cited 2014 Jul 15];6(7):e1000100. Available from: http://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1000100
http://journals.plos.org/plosmedicine/ar... . At the same time, the SRM presents the PICOS acronym (‘patient, problem or population’, ‘intervention’, ‘comparison, control or comparison’, ‘outcomes’), which directs the refinement of the systematic search, making the process more effective (Table 1)⁴¹41. Panic N, Leoncini E, De Belvis G, Ricciardi W, Boccia S. Evaluation of the endorsement of the preferred reporting items for systematic reviews and meta-analysis (PRISMA) statement on the quality of published systematic review and meta-analyses. PLoS ONE 2013; 8(12)e83138..

Quality of information assessment

In addition to this method, we chose to use the Strobe Positioning⁴³43. Malta M, Cardoso LO, Bastos FI, Magnanini MMF, Silva CMFP. Iniciativa STROBE: subsídios para a comunicação de estudos observacionais. Rev Saude Publica 2010; 44(3):559-565.. This method consists of a checklist comprising 22 items, which characterizes a manuscript based on the Quality Assessment (QA) that it presents. In this study, we used a combined model of study designs, specific to assess observational, epidemiological, population-based, cross-sectional or cohort studies⁴⁴44. Abeysena C. Strengthening the reporting of observational studies in epidemiology (STROBE) statement: New guidelines for reporting observational studies. J Coll Community Physicians Sri Lanka 2011; 13(2):20-22.. After applying all the above criteria, to the total score of the 22 items has a value equal to 100%. However, the percentage was used to identify studies in which low QA could have interfered with the results of the SRM.

Statistical analysis

The results are expressed by calculating the values of the differences of mean MMSE values when comparing the groups of pre-frail and frail groups, as well as their respective standard deviation, variance, confidence intervals (95%), the magnitude of the effects and levels of statistical significance (p £ 0.05)⁴⁵45. Batterham AM, Hopkins WG. Making meaningful inferences about magnitudes. Int J Sports Physiol Perform [Internet]. 2006 Mar [cited 2014 Dec 25];1(1):50-57. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19114737
http://www.ncbi.nlm.nih.gov/pubmed/19114... . The global average of the studies included in the SRM was calculated based on the random effects model in relation to the methodological heterogeneity of the studies and their participants. The risk of publication bias was assessed by the method of the visual inspection method of scatter plot generated by the Egger's intercept test⁴⁶46. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ [Internet]. 1997 Sep 13 [cited 2015 Jan 2];315(7109):629-634. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2127453&tool=pmcentrez&rendertype=abstract
http://www.pubmedcentral.nih.gov/article... . The statistical heterogeneity of the studies included in the review was checked with the calculation of the Cochran Q test and the Higgin I², which represent the percentage of the variance attributed to the heterogeneity of the study, ranging from low (25% <I² <50%) to high (I²> 75%)⁴⁶46. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ [Internet]. 1997 Sep 13 [cited 2015 Jan 2];315(7109):629-634. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2127453&tool=pmcentrez&rendertype=abstract
http://www.pubmedcentral.nih.gov/article... . The statistical treatment was performed using the statistical program Comprehensive Meta-Analysis - Version 3.0⁴⁷47. Bax L, Yu L-M, Ikeda N, Moons KGM. A systematic comparison of software dedicated to meta-analysis of causal studies. BMC Med Res Methodol [Internet]. 2007 Jan [cited 2016 Apr 27];7:40. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2048970&tool=pmcentrez&rendertype=abstract
http://www.pubmedcentral.nih.gov/article... .

Results

Study manuscripts sample

Figure 1 depicts in detail the steps undertaken in conducting the SRM. After completion of the initial search, a total of 1078 manuscripts were initially identified. After applying the first study selection criteria, 954 were excluded and 124 studies passed the screening stage. At this stage, in which the selection criterion was to read the abstracts, 79 studies were excluded. From the 45 studies that passed the eligibility stage, 28 were excluded after a full reading of the manuscripts and 17 studies remained.

From the 17 manuscripts eligible for evaluation of the QA according to the criteria established by the Strobbe positioning⁴⁴44. Abeysena C. Strengthening the reporting of observational studies in epidemiology (STROBE) statement: New guidelines for reporting observational studies. J Coll Community Physicians Sri Lanka 2011; 13(2):20-22., two were excluded as they presented the values of the MMSE categorically. Three other studies were excluded at the end of the eligibility stage as they used different definitions of the FS or submitted incomplete or agglutinated subgroups of the FS. A total of 12 manuscripts were selected to be integrated into the quantitative analysis (Table 1).

Study sample

The 12 selected manuscripts defined the FS according to the operational criteria proposed by Fried et al.²2. Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, Seeman T, Racy R, Kop WJ, Burke G, Mc Burnie M. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci [Internet]. 2001 Mar;56(3):M146-M156. Available from: http://www.ncbi.nlm.nih.gov/pubmed/11253156
http://www.ncbi.nlm.nih.gov/pubmed/11253... . The use of this protocol for the evaluation of the participants requires a multidimensional, categorical approach, based on the evaluation of the five dimensions described above⁴⁸48. Malmstrom TK, Miller DK, Morley JE. A comparison of four frailty models. J Am Geriatr Soc [Internet]. 2014 May [cited 2015 Jan 30];62(4):721-726. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24635726
http://www.ncbi.nlm.nih.gov/pubmed/24635... . In the assessment of the cognitive status, all selected studies used the MMSE⁴⁹49. Macuco CRM, Batistoni SST, Lopes A, Cachioni M, da Silva Falcão DV, Neri AL, Yassuda, MS. Mini-Mental State Examination performance in frail, pre-frail, and non-frail community dwelling older adults in Ermelino Matarazzo, São Paulo, Brazil. Int Psychogeriatr [Internet]. 2012 Nov [cited 2016 Apr 26];24(11):1725-1731. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22652040
http://www.ncbi.nlm.nih.gov/pubmed/22652... in the form of a continuous variable, describing the mean values and standard deviation, and comparing these values to the subgroup of the FS.

Only one study has clearly presented the data in relation to gender³⁸38. Han ES, Lee Y, Kim J. Association of cognitive impairment with frailty in community-dwelling older adults. Int Psychogeriatr [Internet]. 2014 Jan [cited 2015 Jul 27];26(1):155-163. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24153029
http://www.ncbi.nlm.nih.gov/pubmed/24153... , being introduced and subsequently analyzed in the meta-analysis as two independent studies, thus justifying a total of 13 entries in the statistical meta-analysis. A total of eight studies analyzed the data without separation by gender, presenting values only for the total sample¹⁹19. Avila-Funes JA, Amieva H, Barberger-Gateau P, Le Goff M, Raoux N, Ritchie K, Carrière I, Tavernier B, Tzourio C, Gutiérrez-Robledo L, Dartigues J. Cognitive impairment improves the predictive validity of the phenotype of frailty for adverse health outcomes: the three-city study. J Am Geriatr Soc [Internet]. 2009 Mar [cited 2015 Feb 1];57(3):453-461. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19245415
http://www.ncbi.nlm.nih.gov/pubmed/19245... ^,2525. Woo J, Yu R, Wong M, Yeung F, Wong M, Lum C. Frailty Screening in the Community Using the FRAIL Scale. J Am Med Dir Assoc [Internet]. 2015 May 1 [cited 2015 May 15];16(5):412-419. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25732832
http://www.ncbi.nlm.nih.gov/pubmed/25732... ^,2626. Samper-Ternent R, Al Snih S, Raji MA, Markides KS, Ottenbacher KJ. Relationship between frailty and cognitive decline in older Mexican Americans. J Am Geriatr Soc [Internet]. 2008 Oct [cited 2015 Jul 27];56(10):1845-1852. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2628807&tool=pmcentrez&rendertype=abstract
http://www.pubmedcentral.nih.gov/article... ^,4949. Macuco CRM, Batistoni SST, Lopes A, Cachioni M, da Silva Falcão DV, Neri AL, Yassuda, MS. Mini-Mental State Examination performance in frail, pre-frail, and non-frail community dwelling older adults in Ermelino Matarazzo, São Paulo, Brazil. Int Psychogeriatr [Internet]. 2012 Nov [cited 2016 Apr 26];24(11):1725-1731. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22652040
http://www.ncbi.nlm.nih.gov/pubmed/22652... ^–5353. Al-Kuwaiti SJ, Aziz F, Blair I. Frailty in Community-Dwelling Older People in Abu Dhabi, United Arab Emirates: A Cross-Sectional Study. Front public Heal [Internet]. 2015 Jan [cited 2016 Apr 26];3:248. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=4630498&tool=pmcentrez&rendertype=abstract
http://www.pubmedcentral.nih.gov/article... , which determines the shape of the meta-analysis to be carried out. A total of two studies were developed only with samples of elderly men³⁸38. Han ES, Lee Y, Kim J. Association of cognitive impairment with frailty in community-dwelling older adults. Int Psychogeriatr [Internet]. 2014 Jan [cited 2015 Jul 27];26(1):155-163. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24153029
http://www.ncbi.nlm.nih.gov/pubmed/24153... ^,5454. Jacobs JM, Cohen A, Ein-Mor E, Maaravi Y, Stessman J. Frailty, cognitive impairment and mortality among the oldest old. J Nutr Health Aging [Internet]. 2011 Aug [cited 2015 Jul 27];15(8):678-682. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21968864
http://www.ncbi.nlm.nih.gov/pubmed/21968... , and three were prepared with samples of elderly female participants only¹⁸18. Alencar MA, Dias JMD, Figueiredo LC, Dias RC. Frailty and cognitive impairment among community-dwelling elderly. Arq Neuropsiquiatr [Internet]. 2013 Jun [cited 2015 Feb 9];71(6):362-367. Available from: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0004-282X2013000600362&lng=en&nrm=iso&tlng=en
http://www.scielo.br/scielo.php?script=s... ^,5555. Robertson DA, Savva GM, Coen RF, Kenny R-A. Cognitive function in the prefrailty and frailty syndrome. J Am Geriatr Soc [Internet]. 2014 Nov [cited 2015 Jul 27];62(11):2118-24. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25370593
http://www.ncbi.nlm.nih.gov/pubmed/25370... . Regarding the QA of the studies, an average value of 94% was recorded.

Characteristics of participants

Regard to the total number of participants analyzed in the selected studies under this SRM, we identified a total of n = 26,935 elderly participants. From these, a total of 13,725 participants (51.0%) represent the sum of the pre-frail and frail individuals in the total of people evaluated, being 11,265 considered pre-frail and 2,460 frail. Considering the absolute and relative values of the sample (n = 13725), the pre-frail presented percentage values ranging from 32 to 94%, being 75% the mean value of the individuals in this category. In the subgroup of the frail, the amplitude values range from 6 to 68% of the sample, being 25% the mean value of individuals in this category. The studies carried out in South Korea³⁸38. Han ES, Lee Y, Kim J. Association of cognitive impairment with frailty in community-dwelling older adults. Int Psychogeriatr [Internet]. 2014 Jan [cited 2015 Jul 27];26(1):155-163. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24153029
http://www.ncbi.nlm.nih.gov/pubmed/24153... , Spain¹⁹19. Avila-Funes JA, Amieva H, Barberger-Gateau P, Le Goff M, Raoux N, Ritchie K, Carrière I, Tavernier B, Tzourio C, Gutiérrez-Robledo L, Dartigues J. Cognitive impairment improves the predictive validity of the phenotype of frailty for adverse health outcomes: the three-city study. J Am Geriatr Soc [Internet]. 2009 Mar [cited 2015 Feb 1];57(3):453-461. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19245415
http://www.ncbi.nlm.nih.gov/pubmed/19245... and Ireland⁵⁵55. Robertson DA, Savva GM, Coen RF, Kenny R-A. Cognitive function in the prefrailty and frailty syndrome. J Am Geriatr Soc [Internet]. 2014 Nov [cited 2015 Jul 27];62(11):2118-24. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25370593
http://www.ncbi.nlm.nih.gov/pubmed/25370... are the ones with broader samples (Table 2).

From the 12 studies included (13 entries) in this meta-analysis, they all started from the same research assumption, in which the elderly with classifications according to the FS (pre-frail versus frail) differ in the assessment of their cognitive performance, having frail individuals’ lower cognitive performance in comparison to the pre-frail. The effect size is represented here by the difference in means (Table 3).

Effect Size of the differences between groups

Regarding the central hypothesis of the present study, it was verified that the difference of averages found between the two subgroups of the FS for the evaluation of the DC was equal to 2,676, which means that the pre-frail had higher mean values (2.7 points) compared to frail subgroups. The confidence interval for the mean difference is 1.794 to 3.558, which means that the gross difference of means is within this range. On the other hand, this range does not include the difference of zero, which means that the true difference of averages is probably non-zero. The Z values obtained to test the null hypothesis, according to which the means difference is zero, showed a Z = 5.948, with the corresponding value of p <0.001. In this way, we can reject the null hypothesis and affirm that the sample presented different DC levels in by FS subgroups, these differences being statistically significant.

Homogeneity of the effects

It is known that the magnitude of the observed effects may vary between studies, due to sample error⁵⁶56. Kulinskaya E, Dollinger MB, Bjørkestøl K. Testing for Homogeneity in Meta-Analysis I. The One-Parameter Case: Standardized Mean Difference. Biometrics [Internet]. 2011 Mar [cited 2017 Feb 9];67(1):203-212. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20528863
http://www.ncbi.nlm.nih.gov/pubmed/20528... . Thus, it was necessary to determine if the observed variation was located within the range attributed to the sampling error, which translates into an absence of evidence as to the variation of the true effects. To this, we determined the value expected from the Q Cochran statistics, normally used as a significance test and we also tested the null hypothesis according to which all the studies involved in this meta-analysis share a magnitude of common effects, being that any variation would result from the sampling error within the studies. If all studies share the same magnitude of effects, the expected value of Q will be equal to the degrees of freedom, i.e., the number of studies minus 1⁵⁶56. Kulinskaya E, Dollinger MB, Bjørkestøl K. Testing for Homogeneity in Meta-Analysis I. The One-Parameter Case: Standardized Mean Difference. Biometrics [Internet]. 2011 Mar [cited 2017 Feb 9];67(1):203-212. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20528863
http://www.ncbi.nlm.nih.gov/pubmed/20528... . The value obtained from Q is 361.762 with 12 degrees of freedom and with a value of p < 0.001. Thus, we can accept the alternative hypothesis, according to which the true magnitude of the effect varies from study to study.

The statistics of I² corresponds to the ratio of the real heterogeneity of the total variation of the observed effects, that is, it tells us what proportion (percentage) of the observed variance reflects the differences in the true magnitude of the effect rather than in the error of the sample⁵⁷57. Dinnes J, Deeks J, Kirby J, Roderick P. A methodological review of how heterogeneity has been examined in systematic reviews of diagnostic test accuracy. Health Technol Assess [Internet]. 2005 Mar [cited 2016 May 22];9(12):1-113, iii. Available from: http://www.ncbi.nlm.nih.gov/pubmed/15774235
http://www.ncbi.nlm.nih.gov/pubmed/15774... . In the current meta-analysis, the obtained value of I² is 96,683, which means that about 96.7% of the variance on the observed effects reflects the variance of the true effects. T² corresponds to the variance of the true effect sizes among studies which, in the current study, depicts a value of 2.358. On the other hand, the value of T², refers to the standard deviation of the true magnitude of the effects, being in this meta-analysis equal to 1.536. Regarding the publication bias of integrated studies in this SRM, we used the visual inspection of the funnel plot, which is the effect size of each study in relation to its standard error.

For the visual analysis of the graph, it is assumed that when there is no publication bias, the distribution of the studies should be symmetric around the magnitude of the effect of the true population and the graph becomes narrower as the size of the sample increases⁵⁸58. Sterne JA, Egger M, Smith GD. Systematic reviews in health care: Investigating and dealing with publication and other biases in meta-analysis. BMJ [Internet]. 2001 Jul 14 [cited 2015 Jul 28];323(7304):101-105. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1120714&tool=pmcentrez&rendertype=abstract
http://www.pubmedcentral.nih.gov/article... . Additionally, the Egger intercept test was performed which is intended to test the null hypothesis according to which the intercept is equal to zero, in the population. In Figure 2, the intercept is 1.34143. 95% of the confidence interval (-3.18799, 5.87086), with t = 0,65184, gl = 11. The recommended value of p (2-tailed) is 0.52789. Thus, there is no statistical evidence of the existence of publication bias.

Discussion

A great number of studies use the FS construct designed by Fried et al.²2. Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, Seeman T, Racy R, Kop WJ, Burke G, Mc Burnie M. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci [Internet]. 2001 Mar;56(3):M146-M156. Available from: http://www.ncbi.nlm.nih.gov/pubmed/11253156
http://www.ncbi.nlm.nih.gov/pubmed/11253... to evaluate the FS⁵⁹59. Drubbel I, Numans ME, Kranenburg G, Bleijenberg N, de Wit NJ, Schuurmans MJ. Screening for frailty in primary care: a systematic review of the psychometric properties of the frailty index in community-dwelling older people. BMC Geriatr [Internet]. 2014;14(1):27. Available from: http://www.biomedcentral.com/1471-2318/14/27.
http://www.biomedcentral.com/1471-2318/1... ^–6161. Wells JL, Seabrook JA, Stolee P, Borrie MJ, Knoefel F. State of the art in geriatric rehabilitation. Part I: review of frailty and comprehensive geriatric assessment. Arch Phys Med Rehabil [Internet]. 2003 Jun [cited 2015 Jan 29];84(6):890-897. Available from: http://www.ncbi.nlm.nih.gov/pubmed/12808544
http://www.ncbi.nlm.nih.gov/pubmed/12808... . Nevertheless, the literature contains over twenty different methods of assessing FS. However, there is some evidence that the multidimensional assessment provided by this construct seems to be more sensitive to detect the FS in the populations aged 60 years and over, as well as to establish associations with mortality, morbidity and other adverse clinical outcomes⁵⁹59. Drubbel I, Numans ME, Kranenburg G, Bleijenberg N, de Wit NJ, Schuurmans MJ. Screening for frailty in primary care: a systematic review of the psychometric properties of the frailty index in community-dwelling older people. BMC Geriatr [Internet]. 2014;14(1):27. Available from: http://www.biomedcentral.com/1471-2318/14/27.
http://www.biomedcentral.com/1471-2318/1... , and its replication in large³⁸38. Han ES, Lee Y, Kim J. Association of cognitive impairment with frailty in community-dwelling older adults. Int Psychogeriatr [Internet]. 2014 Jan [cited 2015 Jul 27];26(1):155-163. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24153029
http://www.ncbi.nlm.nih.gov/pubmed/24153... or small samples⁶²62. Abizanda P, Romero L, Sánchez-Jurado PM, Martínez-Reig M, Alfonso-Silguero SA, Rodríguez-Mañas L. Age, frailty, disability, institutionalization, multimorbidity or comorbidity. Which are the main targets in older adults? J Nutr Health Aging [Internet]. 2014 Jan [cited 2015 Jul 26];18(6):622-627. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24950154
http://www.ncbi.nlm.nih.gov/pubmed/24950... . In the final selection stage of the study, studies were removed from the systematic review in which the change of evaluation criteria for each dimension was introduced. The QA studies that integrated the SRM show the scientific rigor of the researchers in this area. However, it is important to note that in the original study²2. Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, Seeman T, Racy R, Kop WJ, Burke G, Mc Burnie M. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci [Internet]. 2001 Mar;56(3):M146-M156. Available from: http://www.ncbi.nlm.nih.gov/pubmed/11253156
http://www.ncbi.nlm.nih.gov/pubmed/11253... , the QA was reported systematically and accurately, which may have influenced the replication, with high quality, of the studies in other countries³¹31. Brigola AG, Rossetti ES, Santos BR dos, Neri AL, Zazzetta MS, Inouye K, Pavarini SC. Relationship between cognition and frailty in elderly: A systematic review. Dement Neuropsychol [Internet]. 2015 Jun [cited 2016 Apr 26]; 9(2):110-119. Available from: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1980-57642015000200110&lng=en&nrm=iso&tlng=en
http://www.scielo.br/scielo.php?script=s... .

The fact that the subgroup of frail older people has lower values in cognitive status when evaluated using the MMSE test, was clearly shown in this SRM. The values found for all analyzed studies showed significant values statistically. Some of these studies explicitly related the FS to the cognitive performance¹⁸18. Alencar MA, Dias JMD, Figueiredo LC, Dias RC. Frailty and cognitive impairment among community-dwelling elderly. Arq Neuropsiquiatr [Internet]. 2013 Jun [cited 2015 Feb 9];71(6):362-367. Available from: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0004-282X2013000600362&lng=en&nrm=iso&tlng=en
http://www.scielo.br/scielo.php?script=s... ^,5555. Robertson DA, Savva GM, Coen RF, Kenny R-A. Cognitive function in the prefrailty and frailty syndrome. J Am Geriatr Soc [Internet]. 2014 Nov [cited 2015 Jul 27];62(11):2118-24. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25370593
http://www.ncbi.nlm.nih.gov/pubmed/25370... . However, this seems to be the first SRM that sought to test the magnitude of the effect of the differences between the groups of pre-frail and frail. On the other hand, a very recent SRM carried out by Chang and Lin⁹9. Chang S-F, Lin P-L. Frail phenotype and mortality prediction: A systematic review and meta-analysis of prospective cohort studies. Int J Nurs Stud [Internet]. 2015; 52(8):1362-1374. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0020748915001066
http://linkinghub.elsevier.com/retrieve/... , also pointed to the existence of a strong association between mortality and the FS in the population evaluated using the Fried protocol. Individuals with higher levels of FS (pre-frail and frail) also have a higher risk of mortality when compared to non-frail elderly individuals.

The results found in this study corroborate with the literature, it being increasingly evident that the FS is strongly related to cognitive status²²22. Faria CA, Lourenço RA, Ribeiro PC, Lopes CS. Desempenho cognitivo e fragilidade em idosos clientes de operadora de saúde. Rev Saude Publica [Internet]. 2013 Oct [cited 2015 Jun 2];47(5):923-930. Available from: http://www.scielosp.org/scielo.php?script=sci_arttext&pid=S0034-89102013000700923&lng=en&nrm=iso&tlng=pt
http://www.scielosp.org/scielo.php?scrip... ^,2626. Samper-Ternent R, Al Snih S, Raji MA, Markides KS, Ottenbacher KJ. Relationship between frailty and cognitive decline in older Mexican Americans. J Am Geriatr Soc [Internet]. 2008 Oct [cited 2015 Jul 27];56(10):1845-1852. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2628807&tool=pmcentrez&rendertype=abstract
http://www.pubmedcentral.nih.gov/article... . The present study makes it more evident that the pre-frail and frail groups, respectively, have a tendency to an imminent risk of suffering from more severe cognitive impairments, when the FS is detected. The geographic distribution and diversity in the countries involved in the study of this issue show that there is a global concern about the phenomenon of the FS in adverse populations²⁵25. Woo J, Yu R, Wong M, Yeung F, Wong M, Lum C. Frailty Screening in the Community Using the FRAIL Scale. J Am Med Dir Assoc [Internet]. 2015 May 1 [cited 2015 May 15];16(5):412-419. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25732832
http://www.ncbi.nlm.nih.gov/pubmed/25732... ^,5050. Abizanda P, Romero L, Sánchez-Jurado PM, Martínez-Reig M, Gómez-Arnedo L, Alfonso SA. Frailty and mortality, disability and mobility loss in a Spanish cohort of older adults: the FRADEA study. Maturitas [Internet]. 2013 Jan [cited 2015 Jul 27];74(1):54-60. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23107816
http://www.ncbi.nlm.nih.gov/pubmed/23107... ^,5252. Kiely DK, Cupples LA, Lipsitz LA. Validation and comparison of two frailty indexes: The MOBILIZE Boston Study. J Am Geriatr Soc [Internet]. 2009 Sep [cited 2015 Jan 28];57(9):1532-1539. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2792729&tool=pmcentrez&rendertype=abstract
http://www.pubmedcentral.nih.gov/article... , accompanied by an increasing interest in terms of research, as well as evidence that this pattern occurs in countries on several continents. Currently, the term ‘cognitive frailty’ associated with the concept of disorder or MCI appears, which shows a growing interest in the search for other explanations for this phenomenon⁶³63. Panza F, Seripa D, Solfrizzi V, Tortelli R, Greco A, Pilotto A. Targeting Cognitive Frailty: Clinical and Neurobiological Roadmap for a Single Complex Phenotype. J Alzheimers Dis [Internet]. 2015 Jan [cited 2016 Apr 29];47(4):793-813. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26401761
http://www.ncbi.nlm.nih.gov/pubmed/26401... .

The non-consideration of data from non-frail individuals under this SRM as the first limitation of this study. The participants from the group of non-frail showed average values below 24.0 points, i.e., a score that, according to the cut-off values of the MMSE, indicates the existence of an MCI¹⁸18. Alencar MA, Dias JMD, Figueiredo LC, Dias RC. Frailty and cognitive impairment among community-dwelling elderly. Arq Neuropsiquiatr [Internet]. 2013 Jun [cited 2015 Feb 9];71(6):362-367. Available from: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0004-282X2013000600362&lng=en&nrm=iso&tlng=en
http://www.scielo.br/scielo.php?script=s... ^,2121. de la Rica-Escuín M, González-Vaca J, Varela-Pérez R, Arjonilla-García MD, Silva-Iglesias M, Oliver-Carbonell JL. Frailty and mortality or incident disability in institutionalized older adults: the FINAL study. Maturitas [Internet]. 2014 Aug [cited 2015 Jul 7];78(4):329-334. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24929996
http://www.ncbi.nlm.nih.gov/pubmed/24929... . In this sense, it is reinforced that overall, non-frail individuals have a ‘preserved’ cognitive status. Regarding gender differences, it is valid to indicate that the literature points to a trend similar to the FS for both genders³⁸38. Han ES, Lee Y, Kim J. Association of cognitive impairment with frailty in community-dwelling older adults. Int Psychogeriatr [Internet]. 2014 Jan [cited 2015 Jul 27];26(1):155-163. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24153029
http://www.ncbi.nlm.nih.gov/pubmed/24153... , with earlier death for men, due to a higher incidence of metabolic diseases when compared to older women. However, in this study, it was not possible to further explore these differences, since only one of the studies presented analyses by gender and most samples investigated only females.

Thus, we can infer that cognition, as well as frailty, can appear as potential predictors of early mortality in the populations aged 60 and over, besides pointing out that the evaluation of the FS cannot be dissociated from the assessment of the cognitive function⁵⁴54. Jacobs JM, Cohen A, Ein-Mor E, Maaravi Y, Stessman J. Frailty, cognitive impairment and mortality among the oldest old. J Nutr Health Aging [Internet]. 2011 Aug [cited 2015 Jul 27];15(8):678-682. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21968864
http://www.ncbi.nlm.nih.gov/pubmed/21968... ^,6464. Cano C, Samper-Ternent R, Al Snih S, Markides K, Ottenbacher KJ. Frailty and cognitive impairment as predictors of mortality in older Mexican Americans. J Nutr Health Aging [Internet]. 2012 Feb [cited 2015 Jul 27];16(2):142-147. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3281306&tool=pmcentrez&rendertype=abstract
http://www.pubmedcentral.nih.gov/article... ^,6565. Mohler MJ, Fain MJ, Wertheimer AM, Najafi B, Nikolich-Žugich J. The Frailty syndrome: clinical measurements and basic underpinnings in humans and animals. Exp Gerontol [Internet]. 2014 Jun [cited 2015 Feb 17];54:6-13. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24503059
http://www.ncbi.nlm.nih.gov/pubmed/24503... . Comparing a pre-frail population pool with a frail population sample, the poor cognitive function associated with the FS is a likely clinical outcome in these populations which should be assessed²⁷27. Ávila-Funes JA, Pina-Escudero SD, Aguilar-Navarro S, Gutierrez-Robledo LM, Ruiz-Arregui L, Amieva H. Cognitive impairment and low physical activity are the components of frailty more strongly associated with disability. J Nutr Health Aging [Internet]. 2011 Aug [cited 2015 Jul 27];15(8):683-689. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21968865
http://www.ncbi.nlm.nih.gov/pubmed/21968... .

Conclusion

By analyzing the magnitude of the effect in the mean difference of the studies included in this SRM, we found a low cognitive function associated with the FS, i.e., we identified this as a probable clinical outcome, with the occurrence of a decrease in cognitive performance as the elderly progress from a pre-condition of frailty to a frail condition. Therefore, any strategy or public health policy that aims to mitigate or reverse the incidence of this condition should take into account that these two outcomes seem to have similar temporal trajectories, caused in a population phenotype to be investigated with due attention.

Acknowledgement

This work was carried out within the framework of the project entitled: Hormonal mediation of exercise in stress cognition and immunity. JP Ferreira and AB Teixeira are registered in CIDAF.

References

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