今日の臨床サポート

フレイル・サルコペニア

著者: 関口健二 信州大学医学部附属病院 総合診療科

監修: 大蔵暢 やまと在宅診療所 大崎

著者校正/監修レビュー済:2020/07/03
参考ガイドライン:
  1. The Asia-Pacific Clinical Practice Guidelines for the Management of Frailty. J Am Med Dir Assoc. 2017 Jul 1;18(7):564-575. Erratum in: J Am Med Dir Assoc. 2018 Jan;19(1):94.
  1. Best practice guidelines for the management of frailty: a British Geriatrics Society, Age UK and Royal College of General Practitioners report. Age Ageing. 2014 Nov;43(6):744-7.
  1. サルコペニア診療ガイドライン2017年版 一部改訂(2019年)

概要・推奨   

フレイルとは
  1. フレイルとは、高齢期に生理的予備能が低下して、ストレスに対する脆弱性が亢進した状態である。
  1. フレイルはサルコペニアを含有する概念である。
  1. フレイルは、急性疾患、入院、手術、環境要因などのストレスに耐えられず、望ましくない転帰(転倒、急性疾患、生活機能障害、死亡など)に陥りやすい。
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薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
関口健二 : 特に申告事項無し[2021年]
監修:大蔵暢 : 特に申告事項無し[2021年]

改訂のポイント:
  1. サルコペニア診療ガイドライン2017年版 一部改訂(2019年)に基づき、近年ますます重要性を増すサルコペニア(主に病歴と身体所見)について追記した。

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文献 

著者: Rose M Collard, Han Boter, Robert A Schoevers, Richard C Oude Voshaar
雑誌名: J Am Geriatr Soc. 2012 Aug;60(8):1487-92. doi: 10.1111/j.1532-5415.2012.04054.x. Epub 2012 Aug 6.
Abstract/Text OBJECTIVES: To systematically compare and pool the prevalence of frailty, including prefrailty, reported in community-dwelling older people overall and according to sex, age, and definition of frailty used.
DESIGN: Systematic review of the literature using the key words elderly, aged, frailty, prevalence, and epidemiology.
SETTING: Cross-sectional data from community-based cohorts.
PARTICIPANTS: Community-dwelling adults aged 65 and older.
MEASUREMENTS: In the studies that were found, frailty and prefrailty were measured according to physical phenotype and broad phenotype, the first defining frailty as a purely physical condition and the second also including psychosocial aspects.
RESULTS: Reported prevalence in the community varies enormously (range 4.0-59.1%). The overall weighted prevalence of frailty was 10.7% (95% confidence interval (CI) = 10.5-10.9; 21 studies; 61,500 participants). The weighted prevalence was 9.9% for physical frailty (95% CI = 9.6-10.2; 15 studies; 44,894 participants) and 13.6% for the broad phenotype of frailty (95% CI = 13.2-14.0; 8 studies; 24,072 participants) (chi-square (χ(2) ) = 217.7, degrees of freedom (df)=1, P < .001). Prevalence increased with age (χ(2) = 6067, df = 1, P < .001) and was higher in women (9.6%, 95% CI = 9.2-10.0%) than in men (5.2%, 95% CI = 4.9-5.5%; χ(2) = 298.9 df = 1, P < .001).
CONCLUSION: Frailty is common in later life, but different operationalization of frailty status results in widely differing prevalence between studies. Improving the comparability of epidemiological and clinical studies constitutes an important step forward.

© 2012, Copyright the Authors Journal compilation © 2012, The American Geriatrics Society.
PMID 22881367  J Am Geriatr Soc. 2012 Aug;60(8):1487-92. doi: 10.1111/・・・
著者: Andrew Clegg, John Young, Steve Iliffe, Marcel Olde Rikkert, Kenneth Rockwood
雑誌名: Lancet. 2013 Mar 2;381(9868):752-62. doi: 10.1016/S0140-6736(12)62167-9. Epub 2013 Feb 8.
Abstract/Text Frailty is the most problematic expression of population ageing. It is a state of vulnerability to poor resolution of homoeostasis after a stressor event and is a consequence of cumulative decline in many physiological systems during a lifetime. This cumulative decline depletes homoeostatic reserves until minor stressor events trigger disproportionate changes in health status. In landmark studies, investigators have developed valid models of frailty and these models have allowed epidemiological investigations that show the association between frailty and adverse health outcomes. We need to develop more efficient methods to detect frailty and measure its severity in routine clinical practice, especially methods that are useful for primary care. Such progress would greatly inform the appropriate selection of elderly people for invasive procedures or drug treatments and would be the basis for a shift in the care of frail elderly people towards more appropriate goal-directed care.

Copyright © 2013 Elsevier Ltd. All rights reserved.
PMID 23395245  Lancet. 2013 Mar 2;381(9868):752-62. doi: 10.1016/S0140・・・
著者: John E Morley, Bruno Vellas, G Abellan van Kan, Stefan D Anker, Juergen M Bauer, Roberto Bernabei, Matteo Cesari, W C Chumlea, Wolfram Doehner, Jonathan Evans, Linda P Fried, Jack M Guralnik, Paul R Katz, Theodore K Malmstrom, Roger J McCarter, Luis M Gutierrez Robledo, Ken Rockwood, Stephan von Haehling, Maurits F Vandewoude, Jeremy Walston
雑誌名: J Am Med Dir Assoc. 2013 Jun;14(6):392-7. doi: 10.1016/j.jamda.2013.03.022.
Abstract/Text Frailty is a clinical state in which there is an increase in an individual's vulnerability for developing increased dependency and/or mortality when exposed to a stressor. Frailty can occur as the result of a range of diseases and medical conditions. A consensus group consisting of delegates from 6 major international, European, and US societies created 4 major consensus points on a specific form of frailty: physical frailty. 1. Physical frailty is an important medical syndrome. The group defined physical frailty as "a medical syndrome with multiple causes and contributors that is characterized by diminished strength, endurance, and reduced physiologic function that increases an individual's vulnerability for developing increased dependency and/or death." 2. Physical frailty can potentially be prevented or treated with specific modalities, such as exercise, protein-calorie supplementation, vitamin D, and reduction of polypharmacy. 3. Simple, rapid screening tests have been developed and validated, such as the simple FRAIL scale, to allow physicians to objectively recognize frail persons. 4. For the purposes of optimally managing individuals with physical frailty, all persons older than 70 years and all individuals with significant weight loss (>5%) due to chronic disease should be screened for frailty.

Copyright © 2013 American Medical Directors Association, Inc. Published by Elsevier Inc. All rights reserved.
PMID 23764209  J Am Med Dir Assoc. 2013 Jun;14(6):392-7. doi: 10.1016/・・・
著者: Moyra Elizabeth Mortby, Andreas Maercker, Simon Forstmeier
雑誌名: Aging Clin Exp Res. 2012 Aug;24(4):305-16. doi: 10.3275/8105. Epub 2011 Nov 16.
Abstract/Text Apathy and depression are the most prevalent neuropsychiatric symptoms in Alzheimer's disease and mild cognitive impairment. Despite much research on apathy and depression in dementia, the nosological position of apathy as a separate syndrome from depression remains debated. This literature review provides a critical analysis of the areas of clinical manifestation, symptomatology, assessment, prevalence and neuropathology. Evidence does not provide a clear view of the nosological position of apathy in dementia for symptoms and neuropathology. However, the ambiguity of the evidence may be attributed in large part to a lack of clarity in definition and etiology, clinical criteria and assessment overlap. Given the evidence, it is concluded that the argument in favor of apathy as a separate syndrome from depression in dementia is persuasive. Reaching a consensus on the definition and nosological position of apathy within dementia is vital to provide patients and caregivers with the support they require, increase understanding of risk factors, and enable comparisons across research and practice.

PMID 22102508  Aging Clin Exp Res. 2012 Aug;24(4):305-16. doi: 10.3275・・・
著者: Gotaro Kojima, Steve Iliffe, Yu Taniguchi, Hiroyuki Shimada, Hiromi Rakugi, Kate Walters
雑誌名: J Epidemiol. 2017 Aug;27(8):347-353. doi: 10.1016/j.je.2016.09.008. Epub 2016 Nov 15.
Abstract/Text Japan's population is aging more rapidly than that of any other country. Frailty has recently been recognized as an important priority. Understanding the basic epidemiology of frailty in Japan, which is an example of a rapidly aging society, will be beneficial for Japan as well as other countries expecting an aging population. A systematic literature search of 11 electronic databases was conducted in March 2016 using a comprehensive set of Medical Subject Heading and text terms for any studies published in 2000 or later that report the prevalence of frailty among Japanese community-dwelling older people aged 65 years or older. A total of 1529 studies were identified in the systematic search, of which five studies were included in this review. The pooled prevalence of frailty, prefrailty, and robustness was 7.4% (95% confidence interval [CI], 6.1%-9.0%), 48.1% (95% CI, 41.6%-54.8%), and 44.4% (95% CI, 37.2%-51.7%), respectively. A significant degree of heterogeneity was observed. There was no evidence of publication bias. Age-stratified meta-analyses of four studies showed the pooled prevalence of frailty was 1.9%, 3.8%, 10.0%, 20.4%, and 35.1% for those aged 65-69, 70-74, 75-79, 80-84, and ≥85 years, respectively. Pooled prevalence of frailty was 8.1% for women and 7.6% for men. This review showed an overall pooled prevalence of frailty among Japanese community-dwelling older people of 7.4%. The age-stratified analysis suggested that Japanese older people are less frail before their late 70's but frailer in later life than older people in other countries. These findings provide important basic information for all parties involved in Japanese frailty research.

Copyright © 2016 The Authors. Production and hosting by Elsevier B.V. All rights reserved.
PMID 28142044  J Epidemiol. 2017 Aug;27(8):347-353. doi: 10.1016/j.je.・・・
著者: Hiroyuki Shimada, Hyuma Makizako, Takehiko Doi, Daisuke Yoshida, Kota Tsutsumimoto, Yuya Anan, Kazuki Uemura, Tadashi Ito, Sangyoon Lee, Hyuntae Park, Takao Suzuki
雑誌名: J Am Med Dir Assoc. 2013 Jul;14(7):518-24. doi: 10.1016/j.jamda.2013.03.010. Epub 2013 May 10.
Abstract/Text OBJECTIVE: Preventive strategies for frailty and mild cognitive impairment (MCI) are important for avoiding future functional decline and dementia in older adults. The purpose of this study was to use a population-based survey to ascertain the single and combined prevalence of frailty and MCI and to identify the relationships between frailty and MCI in older Japanese adults.
DESIGN: Cross-sectional study.
SETTING: General community.
PARTICIPANTS: A total of 5104 older adults (aged 65 years or older, mean age 71 years) who were enrolled in the Obu Study of Health Promotion for the Elderly (OSHPE).
MEASUREMENTS: Each participant underwent detailed physical and cognitive testing to assess frailty and MCI. We considered the frailty phenotype to be characterized by limitations in 3 or more of the following 5 domains: mobility, strength, endurance, physical activity, and nutrition. Screening for MCI included a standardized personal interview, the Mini-Mental State Examination, and the National Center for Geriatrics and Gerontology-Functional Assessment Tool (NCGG-FAT), which included 8 tasks used to assess logical memory (immediate and delayed recognition), word list memory (immediate and delayed recall), attention and executive function (tablet version of Trail Making Test-part A and B), processing speed (tablet version of digit symbol substitution test), and visuospatial skill (figure selection).
RESULTS: The overall prevalence of frailty, MCI, and frailty and MCI combined was 11.3%, 18.8%, and 2.7%, respectively. We found significant relationships between frailty and MCI (the odds ratio adjusted for age, sex, and education was 2.0 (95% confidence interval 1.5-2.5).
CONCLUSIONS: Using the OSHPE criteria, we found more participants with MCI than with frailty. The prevalence of frailty and MCI combined was 2.7% in our population. Future investigation is necessary to determine whether this population is at increased risk for disability or mortality.

Copyright © 2013 American Medical Directors Association, Inc. Published by Elsevier Inc. All rights reserved.
PMID 23669054  J Am Med Dir Assoc. 2013 Jul;14(7):518-24. doi: 10.1016・・・
著者: Alfonso J Cruz-Jentoft, Francesco Landi, Stéphane M Schneider, Clemente Zúñiga, Hidenori Arai, Yves Boirie, Liang-Kung Chen, Roger A Fielding, Finbarr C Martin, Jean-Pierre Michel, Cornel Sieber, Jeffrey R Stout, Stephanie A Studenski, Bruno Vellas, Jean Woo, Mauro Zamboni, Tommy Cederholm
雑誌名: Age Ageing. 2014 Nov;43(6):748-59. doi: 10.1093/ageing/afu115. Epub 2014 Sep 21.
Abstract/Text OBJECTIVE: to examine the clinical evidence reporting the prevalence of sarcopenia and the effect of nutrition and exercise interventions from studies using the consensus definition of sarcopenia proposed by the European Working Group on Sarcopenia in Older People (EWGSOP).
METHODS: PubMed and Dialog databases were searched (January 2000-October 2013) using pre-defined search terms. Prevalence studies and intervention studies investigating muscle mass plus strength or function outcome measures using the EWGSOP definition of sarcopenia, in well-defined populations of adults aged ≥50 years were selected.
RESULTS: prevalence of sarcopenia was, with regional and age-related variations, 1-29% in community-dwelling populations, 14-33% in long-term care populations and 10% in the only acute hospital-care population examined. Moderate quality evidence suggests that exercise interventions improve muscle strength and physical performance. The results of nutrition interventions are equivocal due to the low number of studies and heterogeneous study design. Essential amino acid (EAA) supplements, including ∼2.5 g of leucine, and β-hydroxy β-methylbutyric acid (HMB) supplements, show some effects in improving muscle mass and function parameters. Protein supplements have not shown consistent benefits on muscle mass and function.
CONCLUSION: prevalence of sarcopenia is substantial in most geriatric settings. Well-designed, standardised studies evaluating exercise or nutrition interventions are needed before treatment guidelines can be developed. Physicians should screen for sarcopenia in both community and geriatric settings, with diagnosis based on muscle mass and function. Supervised resistance exercise is recommended for individuals with sarcopenia. EAA (with leucine) and HMB may improve muscle outcomes.

© The Author 2014. Published by Oxford University Press on behalf of the British Geriatrics Society.
PMID 25241753  Age Ageing. 2014 Nov;43(6):748-59. doi: 10.1093/ageing/・・・
著者: Qian-Li Xue, Karen Bandeen-Roche, Ravi Varadhan, Jing Zhou, Linda P Fried
雑誌名: J Gerontol A Biol Sci Med Sci. 2008 Sep;63(9):984-90. doi: 10.1093/gerona/63.9.984.
Abstract/Text BACKGROUND: Understanding points of onset of the frailty syndrome is vital to early identification of at-risk individuals and to targeting intervention efforts to those components that are first affected, when reversal may be most possible. This study aims to characterize natural history by which commonly used frailty criteria manifest and to assess whether the rate of progression to frailty depends on initial manifestations.
METHODS: The investigation was based on a 7.5-year observational study of 420 community-dwelling women aged 70-79 years who were not frail at baseline, with frailty defined as meeting>or=3 of 5 criteria: weight loss, slow walking speed, weakness, exhaustion, and low physical activity level.
RESULTS: The 7.5-year incidence of frailty was 9% among women who were nonfrail at baseline. Despite significant heterogeneity, weakness was the most common first manifestation, and occurrence of weakness, slowness, and low physical activity preceded exhaustion and weight loss in 76% of the women who were nonfrail at baseline. Women with exhaustion or weight loss as initial presenting symptoms were 3-5 times more likely to become frail than were women without any criterion (p<.05).
CONCLUSIONS: Our findings suggest that weakness may serve as a warning sign of increasing vulnerability in early frailty development, and weight loss and exhaustion may help to identify women most at risk for rapid adverse progression.

PMID 18840805  J Gerontol A Biol Sci Med Sci. 2008 Sep;63(9):984-90. d・・・
著者: Theodore K Malmstrom, John E Morley
雑誌名: J Am Med Dir Assoc. 2013 Aug;14(8):531-2. doi: 10.1016/j.jamda.2013.05.018. Epub 2013 Jun 25.
Abstract/Text
PMID 23810110  J Am Med Dir Assoc. 2013 Aug;14(8):531-2. doi: 10.1016/・・・
著者: J E Morley, T K Malmstrom, D K Miller
雑誌名: J Nutr Health Aging. 2012 Jul;16(7):601-8.
Abstract/Text OBJECTIVE: To validate the FRAIL scale.
DESIGN: Longitudinal study.
SETTING: Community.
PARTICIPANTS: Representative sample of African Americans age 49 to 65 years at onset of study.
MEASUREMENTS: The 5-item FRAIL scale (fatigue, resistance, ambulation, illnesses, and loss of weight), at baseline and activities of daily living (ADLs), instrumental activities of daily living (IADLs), mortality, short physical performance battery (SPPB), gait speed, one-leg stand, grip strength and injurious falls at baseline and 9 years. Blood tests for CRP, SIL6R, STNFR1, STNFR2 and 25 (OH) vitamin D at baseline.
RESULTS: Cross-sectionally the FRAIL scale correlated significantly with IADL difficulties, SPPB, grip strength and one-leg stand among participants with no baseline ADL difficulties (N=703) and those outcomes plus gait speed in those with no baseline ADL dependencies (N=883). TNFR1 was increased in pre-frail and frail subjects and CRP in some subgroups. Longitudinally (N=423 with no baseline ADL difficulties or N=528 with no baseline ADL dependencies), and adjusted for the baseline value for each outcome, being pre-frail at baseline significantly predicted future ADL difficulties, worse one-leg stand scores, and mortality in both groups, plus IADL difficulties in the dependence-excluded group. Being frail at baseline significantly predicted future ADL difficulties, IADL difficulties, and mortality in both groups, plus worse SPPB in the dependence-excluded group.
CONCLUSION: This study has validated the FRAIL scale in a late middle-aged African American population. This simple 5-question scale is an excellent screening test for clinicians to identify frail persons at risk of developing disability as well as decline in health functioning and mortality.

PMID 22836700  J Nutr Health Aging. 2012 Jul;16(7):601-8.
著者: Liang-Kung Chen, Jean Woo, Prasert Assantachai, Tung-Wai Auyeung, Ming-Yueh Chou, Katsuya Iijima, Hak Chul Jang, Lin Kang, Miji Kim, Sunyoung Kim, Taro Kojima, Masafumi Kuzuya, Jenny S W Lee, Sang Yoon Lee, Wei-Ju Lee, Yunhwan Lee, Chih-Kuang Liang, Jae-Young Lim, Wee Shiong Lim, Li-Ning Peng, Ken Sugimoto, Tomoki Tanaka, Chang Won Won, Minoru Yamada, Teimei Zhang, Masahiro Akishita, Hidenori Arai
雑誌名: J Am Med Dir Assoc. 2020 Mar;21(3):300-307.e2. doi: 10.1016/j.jamda.2019.12.012. Epub 2020 Feb 4.
Abstract/Text Clinical and research interest in sarcopenia has burgeoned internationally, Asia included. The Asian Working Group for Sarcopenia (AWGS) 2014 consensus defined sarcopenia as "age-related loss of muscle mass, plus low muscle strength, and/or low physical performance" and specified cutoffs for each diagnostic component; research in Asia consequently flourished, prompting this update. AWGS 2019 retains the previous definition of sarcopenia but revises the diagnostic algorithm, protocols, and some criteria: low muscle strength is defined as handgrip strength <28 kg for men and <18 kg for women; criteria for low physical performance are 6-m walk <1.0 m/s, Short Physical Performance Battery score ≤9, or 5-time chair stand test ≥12 seconds. AWGS 2019 retains the original cutoffs for height-adjusted muscle mass: dual-energy X-ray absorptiometry, <7.0 kg/m2 in men and <5.4 kg/m2 in women; and bioimpedance, <7.0 kg/m2 in men and <5.7 kg/m2 in women. In addition, the AWGS 2019 update proposes separate algorithms for community vs hospital settings, which both begin by screening either calf circumference (<34 cm in men, <33 cm in women), SARC-F (≥4), or SARC-CalF (≥11), to facilitate earlier identification of people at risk for sarcopenia. Although skeletal muscle strength and mass are both still considered fundamental to a definitive clinical diagnosis, AWGS 2019 also introduces "possible sarcopenia," defined by either low muscle strength or low physical performance only, specifically for use in primary health care or community-based health promotion, to enable earlier lifestyle interventions. Although defining sarcopenia by body mass index-adjusted muscle mass instead of height-adjusted muscle mass may predict adverse outcomes better, more evidence is needed before changing current recommendations. Lifestyle interventions, especially exercise and nutritional supplementation, prevail as mainstays of treatment. Further research is needed to investigate potential long-term benefits of lifestyle interventions, nutritional supplements, or pharmacotherapy for sarcopenia in Asians.

Copyright © 2019 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.
PMID 32033882  J Am Med Dir Assoc. 2020 Mar;21(3):300-307.e2. doi: 10.・・・
著者: Richard W Bohannon
雑誌名: Percept Mot Skills. 2006 Aug;103(1):215-22. doi: 10.2466/pms.103.1.215-222.
Abstract/Text This meta-analysis was conducted to generate normative values for the 5-repetition sit-to-stand (STS) test suitable for application to individuals at least 60 years of age. A thorough review of the literature yielded 13 papers (14 studies) relevant to this purpose. After the exclusion of potentially unrepresentative data, meta-analysis of these 13 papers indicated that judgments about normal performance should be based on age. Analysis demonstrated that individuals with times for 5 repetitions of this test exceeding the following can be considered to have worse than average performance: 11.4 sec (60 to 69 years), 12.6 sec. (70 to 79 years), and 14.8 sec. (80 to 89 years).

PMID 17037663  Percept Mot Skills. 2006 Aug;103(1):215-22. doi: 10.246・・・
著者: D Podsiadlo, S Richardson
雑誌名: J Am Geriatr Soc. 1991 Feb;39(2):142-8. doi: 10.1111/j.1532-5415.1991.tb01616.x.
Abstract/Text This study evaluated a modified, timed version of the "Get-Up and Go" Test (Mathias et al, 1986) in 60 patients referred to a Geriatric Day Hospital (mean age 79.5 years). The patient is observed and timed while he rises from an arm chair, walks 3 meters, turns, walks back, and sits down again. The results indicate that the time score is (1) reliable (inter-rater and intra-rater); (2) correlates well with log-transformed scores on the Berg Balance Scale (r = -0.81), gait speed (r = -0.61) and Barthel Index of ADL (r = -0.78); and (3) appears to predict the patient's ability to go outside alone safely. These data suggest that the timed "Up & Go" test is a reliable and valid test for quantifying functional mobility that may also be useful in following clinical change over time. The test is quick, requires no special equipment or training, and is easily included as part of the routine medical examination.

PMID 1991946  J Am Geriatr Soc. 1991 Feb;39(2):142-8. doi: 10.1111/j.・・・
著者: L P Fried, C M Tangen, J Walston, A B Newman, C Hirsch, J Gottdiener, T Seeman, R Tracy, W J Kop, G Burke, M A McBurnie, Cardiovascular Health Study Collaborative Research Group
雑誌名: J Gerontol A Biol Sci Med Sci. 2001 Mar;56(3):M146-56. doi: 10.1093/gerona/56.3.m146.
Abstract/Text BACKGROUND: Frailty is considered highly prevalent in old age and to confer high risk for falls, disability, hospitalization, and mortality. Frailty has been considered synonymous with disability, comorbidity, and other characteristics, but it is recognized that it may have a biologic basis and be a distinct clinical syndrome. A standardized definition has not yet been established.
METHODS: To develop and operationalize a phenotype of frailty in older adults and assess concurrent and predictive validity, the study used data from the Cardiovascular Health Study. Participants were 5,317 men and women 65 years and older (4,735 from an original cohort recruited in 1989-90 and 582 from an African American cohort recruited in 1992-93). Both cohorts received almost identical baseline evaluations and 7 and 4 years of follow-up, respectively, with annual examinations and surveillance for outcomes including incident disease, hospitalization, falls, disability, and mortality.
RESULTS: Frailty was defined as a clinical syndrome in which three or more of the following criteria were present: unintentional weight loss (10 lbs in past year), self-reported exhaustion, weakness (grip strength), slow walking speed, and low physical activity. The overall prevalence of frailty in this community-dwelling population was 6.9%; it increased with age and was greater in women than men. Four-year incidence was 7.2%. Frailty was associated with being African American, having lower education and income, poorer health, and having higher rates of comorbid chronic diseases and disability. There was overlap, but not concordance, in the cooccurrence of frailty, comorbidity, and disability. This frailty phenotype was independently predictive (over 3 years) of incident falls, worsening mobility or ADL disability, hospitalization, and death, with hazard ratios ranging from 1.82 to 4.46, unadjusted, and 1.29-2.24, adjusted for a number of health, disease, and social characteristics predictive of 5-year mortality. Intermediate frailty status, as indicated by the presence of one or two criteria, showed intermediate risk of these outcomes as well as increased risk of becoming frail over 3-4 years of follow-up (odds ratios for incident frailty = 4.51 unadjusted and 2.63 adjusted for covariates, compared to those with no frailty criteria at baseline).
CONCLUSIONS: This study provides a potential standardized definition for frailty in community-dwelling older adults and offers concurrent and predictive validity for the definition. It also finds that there is an intermediate stage identifying those at high risk of frailty. Finally, it provides evidence that frailty is not synonymous with either comorbidity or disability, but comorbidity is an etiologic risk factor for, and disability is an outcome of, frailty. This provides a potential basis for clinical assessment for those who are frail or at risk, and for future research to develop interventions for frailty based on a standardized ascertainment of frailty.

PMID 11253156  J Gerontol A Biol Sci Med Sci. 2001 Mar;56(3):M146-56. ・・・
著者: Susan L Lakey, Andrea Z LaCroix, Shelly L Gray, Soo Borson, Carla D Williams, Darren Calhoun, Joseph S Goveas, Jordan W Smoller, Judith K Ockene, Kamal H Masaki, Mace Coday, Milagros C Rosal, Nancy F Woods
雑誌名: J Am Geriatr Soc. 2012 May;60(5):854-61. doi: 10.1111/j.1532-5415.2012.03940.x. Epub 2012 May 9.
Abstract/Text OBJECTIVES: To examine the associations between depressive symptoms, antidepressant use, and duration of use with incident frailty 3 years later in nonfrail women aged 65 and older.
DESIGN: Secondary analysis of the Women's Health Initiative Observational Study (WHI-OS), a prospective cohort study.
SETTING: WHI-OS was conducted in 40 U.S. clinical centers.
PARTICIPANTS: Women aged 65 to 79, not frail at baseline.
MEASUREMENTS: Antidepressant use was assessed through medication container inspection at baseline. Four groups were created according to baseline use and Burnam depression screen (range 0-1, 0.06 cutoff): antidepressant nonusers without depressive symptoms (reference group), antidepressant nonusers with depressive symptoms, antidepressant users without depressive symptoms, and antidepressant users with depressive symptoms. Frailty components included slowness or weakness, exhaustion, low physical activity, and unintended weight loss, ascertained through self-report and physical measurements at baseline and Year 3.
RESULTS: Of 27,652 women at baseline, 1,350 (4.9%) were antidepressant users and 1,794 (6.5%) were categorized as depressed. At Year 3, 4,125 (14.9%) were frail. All groups had a greater risk of incident frailty than the reference group. Odds ratios (ORs) ranged from 1.73 (95% confidence interval (CI) = 1.41-2.12) in antidepressant users who were not depressed to 3.63 in antidepressant users who were depressed (95% CI = 2.37-5.55). All durations of use were associated with incident frailty (<1 year OR = 1.95, 95% CI = 1.41-2.68; 1-3 years OR = 1.99, 95% CI = 1.45-2.74; >3 years OR = 1.60, 95% CI = 1.20-2.14).
CONCLUSION: In older adult women, depressive symptoms and antidepressant use were associated with frailty after 3 years of follow-up.

© 2012, Copyright the Authors Journal compilation © 2012, The American Geriatrics Society.
PMID 22568404  J Am Geriatr Soc. 2012 May;60(5):854-61. doi: 10.1111/j・・・
著者: João Apóstolo, Richard Cooke, Elzbieta Bobrowicz-Campos, Silvina Santana, Maura Marcucci, Antonio Cano, Miriam Vollenbroek-Hutten, Federico Germini, Barbara D'Avanzo, Holly Gwyther, Carol Holland
雑誌名: JBI Database System Rev Implement Rep. 2018 Jan;16(1):140-232. doi: 10.11124/JBISRIR-2017-003382.
Abstract/Text OBJECTIVE: To summarize the best available evidence regarding the effectiveness of interventions for preventing frailty progression in older adults.
INTRODUCTION: Frailty is an age-related state of decreased physiological reserves characterized by an increased risk of poor clinical outcomes. Evidence supporting the malleability of frailty, its prevention and treatment, has been presented.
INCLUSION CRITERIA: The review considered studies on older adults aged 65 and over, explicitly identified as pre-frail or frail, who had been undergoing interventions focusing on the prevention of frailty progression. Participants selected on the basis of specific illness or with a terminal diagnosis were excluded. The comparator was usual care, alternative therapeutic interventions or no intervention. The primary outcome was frailty. Secondary outcomes included: (i) cognition, quality of life, activities of daily living, caregiver burden, functional capacity, depression and other mental health-related outcomes, self-perceived health and social engagement; (ii) drugs and prescriptions, analytical parameters, adverse outcomes and comorbidities; (iii) costs, and/or costs relative to benefits and/or savings associated with implementing the interventions for frailty. Experimental study designs, cost effectiveness, cost benefit, cost minimization and cost utility studies were considered for inclusion.
METHODS: Databases for published and unpublished studies, available in English, Portuguese, Spanish, Italian and Dutch, from January 2001 to November 2015, were searched. Critical appraisal was conducted using standardized instruments from the Joanna Briggs Institute. Data was extracted using the standardized tools designed for quantitative and economic studies. Data was presented in a narrative form due to the heterogeneity of included studies.
RESULTS: Twenty-one studies, all randomized controlled trials, with a total of 5275 older adults and describing 33 interventions, met the criteria for inclusion. Economic analyses were conducted in two studies. Physical exercise programs were shown to be generally effective for reducing or postponing frailty but only when conducted in groups. Favorable effects on frailty indicators were also observed after the interventions, based on physical exercise with supplementation, supplementation alone, cognitive training and combined treatment. Group meetings and home visits were not found to be universally effective. Lack of efficacy was evidenced for physical exercise performed individually or delivered one-to-one, hormone supplementation and problem solving therapy. Individually tailored management programs for clinical conditions had inconsistent effects on frailty prevalence. Economic studies demonstrated that this type of intervention, as compared to usual care, provided better value for money, particularly for very frail community-dwelling participants, and had favorable effects in some of the frailty-related outcomes in inpatient and outpatient management, without increasing costs.
CONCLUSIONS: This review found mixed results regarding the effectiveness of frailty interventions. However, there is clear evidence on the usefulness of such interventions in carefully chosen evidence-based circumstances, both for frailty itself and for secondary outcomes, supporting clinical investment of resources in frailty intervention. Further research is required to reinforce current evidence and examine the impact of the initial level of frailty on the benefits of different interventions. There is also a need for economic evaluation of frailty interventions.

PMID 29324562  JBI Database System Rev Implement Rep. 2018 Jan;16(1):1・・・
著者: H A Bischoff-Ferrari, B Dawson-Hughes, H B Staehelin, J E Orav, A E Stuck, R Theiler, J B Wong, A Egli, D P Kiel, J Henschkowski
雑誌名: BMJ. 2009 Oct 1;339:b3692. Epub 2009 Oct 1.
Abstract/Text OBJECTIVE: To test the efficacy of supplemental vitamin D and active forms of vitamin D with or without calcium in preventing falls among older individuals.
DATA SOURCES: We searched Medline, the Cochrane central register of controlled trials, BIOSIS, and Embase up to August 2008 for relevant articles. Further studies were identified by consulting clinical experts, bibliographies, and abstracts. We contacted authors for additional data when necessary. Review methods Only double blind randomised controlled trials of older individuals (mean age 65 years or older) receiving a defined oral dose of supplemental vitamin D (vitamin D(3) (cholecalciferol) or vitamin D(2) (ergocalciferol)) or an active form of vitamin D (1alpha-hydroxyvitamin D(3) (1alpha-hydroxycalciferol) or 1,25-dihydroxyvitamin D(3) (1,25-dihydroxycholecalciferol)) and with sufficiently specified fall assessment were considered for inclusion.
RESULTS: Eight randomised controlled trials (n=2426) of supplemental vitamin D met our inclusion criteria. Heterogeneity among trials was observed for dose of vitamin D (700-1000 IU/day v 200-600 IU/day; P=0.02) and achieved 25-hydroxyvitamin D(3) concentration (25(OH)D concentration: <60 nmol/l v >or=60 nmol/l; P=0.005). High dose supplemental vitamin D reduced fall risk by 19% (pooled relative risk (RR) 0.81, 95% CI 0.71 to 0.92; n=1921 from seven trials), whereas achieved serum 25(OH)D concentrations of 60 nmol/l or more resulted in a 23% fall reduction (pooled RR 0.77, 95% CI 0.65 to 0.90). Falls were not notably reduced by low dose supplemental vitamin D (pooled RR 1.10, 95% CI 0.89 to 1.35; n=505 from two trials) or by achieved serum 25-hydroxyvitamin D concentrations of less than 60 nmol/l (pooled RR 1.35, 95% CI 0.98 to 1.84). Two randomised controlled trials (n=624) of active forms of vitamin D met our inclusion criteria. Active forms of vitamin D reduced fall risk by 22% (pooled RR 0.78, 95% CI 0.64 to 0.94).
CONCLUSIONS: Supplemental vitamin D in a dose of 700-1000 IU a day reduced the risk of falling among older individuals by 19% and to a similar degree as active forms of vitamin D. Doses of supplemental vitamin D of less than 700 IU or serum 25-hydroxyvitamin D concentrations of less than 60 nmol/l may not reduce the risk of falling among older individuals.

PMID 19797342  BMJ. 2009 Oct 1;339:b3692. Epub 2009 Oct 1.
著者: Adrian Bauman, Dafna Merom, Fiona C Bull, David M Buchner, Maria A Fiatarone Singh
雑誌名: Gerontologist. 2016 Apr;56 Suppl 2:S268-80. doi: 10.1093/geront/gnw031.
Abstract/Text PURPOSE OF THE STUDY: There is a global imperative to increase awareness of the emerging evidence on physical activity (PA) among older adults. "Healthy aging" has traditionally focused on preventing chronic disease, but greater efforts are required to reduce frailty and dependency and to maintain independent physical and cognitive function and mental health and well-being.
DESIGN AND METHODS: This integrated review updates the epidemiological data on PA, summarizes the existing evidence-based PA guidelines, describes the global magnitude of inactivity, and finally describes the rationale for action. The first section updates the epidemiological evidence for reduced cardiometabolic risk, reduced risks of falls, the burgeoning new evidence on improved cognitive function and functional capacity, and reduced risk of depression, anxiety, and dementia. This is followed by a summary of population prevalence studies among older adults. Finally, we present a "review of reviews" of PA interventions delivered from community or population settings, followed by a consideration of interventions among the "oldest-old," where efforts are needed to increase resistance (strength) training and balance.
RESULTS: This review identifies the global importance of considering "active aging" beyond the established benefits attributed to noncommunicable disease prevention alone.
IMPLICATIONS: Innovative population-level efforts are required to address physical inactivity, prevent loss of muscle strength, and maintain balance in older adults. Specific investment in healthy aging requires global policy support from the World Health Organization and is implemented at the national and regional levels, in order to reduce the burden of disease and disability among older adults.

© The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
PMID 26994266  Gerontologist. 2016 Apr;56 Suppl 2:S268-80. doi: 10.109・・・
著者: Anne C Milne, Jan Potter, Angela Vivanti, Alison Avenell
雑誌名: Cochrane Database Syst Rev. 2009 Apr 15;(2):CD003288. doi: 10.1002/14651858.CD003288.pub3. Epub 2009 Apr 15.
Abstract/Text BACKGROUND: Evidence for the effectiveness of nutritional supplements containing protein and energy, often prescribed for older people, is limited. Malnutrition is more common in this age group and deterioration of nutritional status can occur during illness. It is important to establish whether supplementing the diet is an effective way of improving outcomes for older people at risk from malnutrition.
OBJECTIVES: This review examined trials for improvement in nutritional status and clinical outcomes when extra protein and energy were provided, usually as commercial 'sip-feeds'.
SEARCH STRATEGY: We searched The Cochrane Library, MEDLINE, EMBASE, Healthstar, CINAHL, BIOSIS, CAB abstracts. We also hand searched nutrition journals and reference lists and contacted 'sip-feed' manufacturers.
SELECTION CRITERIA: Randomised and quasi-randomised controlled trials of oral protein and energy supplementation in older people, with the exception of groups recovering from cancer treatment or in critical care.
DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trials prior to inclusion and independently extracted data and assessed trial quality. Authors of trials were contacted for further information as necessary.
MAIN RESULTS: Sixty-two trials with 10,187 randomised participants have been included in the review. Maximum duration of intervention was 18 months. Most included trials had poor study quality. The pooled weighted mean difference (WMD) for percentage weight change showed a benefit of supplementation of 2.2% (95% confidence interval (CI) 1.8 to 2.5) from 42 trials. There was no significant reduction in mortality in the supplemented compared with control groups (relative risk (RR) 0.92, CI 0.81 to 1.04) from 42 trials. Mortality results were statistically significant when limited to trials in which participants (N = 2461) were defined as undernourished (RR 0.79, 95% CI 0.64 to 0.97).The risk of complications was reduced in 24 trials (RR 0.86, 95% CI 0.75 to 0.99). Few trials were able to suggest any functional benefit from supplementation. The WMD for length of stay from 12 trials also showed no statistically significant effect (-0.8 days, 95% CI -2.8 to 1.3). Adverse effects included nausea or diarrhoea.
AUTHORS' CONCLUSIONS: Supplementation produces a small but consistent weight gain in older people. Mortality may be reduced in older people who are undernourished. There may also be a beneficial effect on complications which needs to be confirmed. However, this updated review found no evidence of improvement in functional benefit or reduction in length of hospital stay with supplements. Additional data from large-scale multi-centre trials are still required.

PMID 19370584  Cochrane Database Syst Rev. 2009 Apr 15;(2):CD003288. d・・・
著者: A M Beck, E Dent, C Baldwin
雑誌名: J Hum Nutr Diet. 2016 Dec;29(6):733-745. doi: 10.1111/jhn.12382. Epub 2016 May 27.
Abstract/Text BACKGROUND: Nutritional intervention is increasingly recognised as having an important role in functional rehabilitation for older people. Nonetheless, a greater understanding of the functional benefit of nutritional interventions is needed.
METHODS: A systematic review and meta-analysis examined randomised controlled trials (RCTs) published between 2007 and 2014 with the aim of determining whether nutritional intervention combined with rehabilitation benefited older people with reduced functional ability. Six electronic databases were searched. RCTs including people aged 65 years and older with reduced physical, social and/or cognitive function were included. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were followed, and gradepro computer software (http://gradepro.org) was used for the quality assessment of critical and important outcomes. Included studies considered to be clinical homogenous were combined in a meta-analysis.
RESULTS: Of the 788 studies screened, five were identified for inclusion. Nutritional intervention given with functional rehabilitation improved energy and protein intake, although it failed to provide any improvement in final body weight, hand-grip strength or muscle strength. There was no difference between groups in the critical outcomes; balance, cognition, activities of daily living and mortality at long-term follow-up. Nutritional intervention given with functional rehabilitation was associated with an increased likelihood of both mortality (odds ratio = 1.77; 95% confidence interval = 1.13-2.76) and hospitalisation (odds ratio = 2.29; 95% confidence interval = 1.10-4.79) during the intervention. Meta-analysis of the baseline data showed that, overall, the intervention cohort had a lower body weight and cognition.
CONCLUSIONS: This meta-analysis highlights concerns regarding the quality of the randomisation of participants at baseline. Future high-quality research is essential to establish whether older people with loss of functional abilities can benefit from nutritional intervention.

© 2016 The British Dietetic Association Ltd.
PMID 27231148  J Hum Nutr Diet. 2016 Dec;29(6):733-745. doi: 10.1111/j・・・
著者: Deepa Sumukadas, Miles D Witham, Allan D Struthers, Marion E T McMurdo
雑誌名: CMAJ. 2007 Oct 9;177(8):867-74. doi: 10.1503/cmaj.061339.
Abstract/Text BACKGROUND: Physical function and exercise capacity decline with age and are a major source of disability in older people. Recent evidence suggests a potential role for the renin-angiotensin system in modulating muscle function. We sought to examine the effect of the angiotensin-converting-enzyme (ACE) inhibitor perindopril on physical function in elderly people with functional impairment who had no heart failure or left ventricular systolic dysfunction.
METHODS: In this double-blind randomized controlled trial, participants aged 65 years and older who had problems with mobility or functional impairment were randomly assigned to receive either perindopril or placebo for 20 weeks. The primary outcome was the change in the 6-minute walking distance over the 20 weeks. Secondary outcomes were changes in muscle function, daily activity levels, self-reported function and health-related quality of life.
RESULTS: A total of 130 participants were enrolled in the study (mean age 78.7, standard deviation 7.7 years); 95 completed the trial. At 20 weeks, the mean 6-minute walking distance was significantly improved in the perindopril group relative to the placebo group (mean between-group difference 31.4 m, 95% confidence interval [CI] 10.8 to 51.9 m; p = 0.003). There was a significant impact on health-related quality of life: although the mean score for part 1 of the EQ-5D questionnaire deteriorated over time in the placebo group, quality of life was maintained in the perindopril group, for a between-group difference of 0.09 (p = 0.046). There were no significant differences between the 2 groups in the other outcomes.
INTERPRETATION: Use of the ACE inhibitor perindopril improved exercise capacity in functionally impaired elderly people who had no heart failure and maintained health-related quality of life. The degree of improvement was equivalent to that reported after 6 months of exercise training. (International Standard Randomised Controlled Trial Register no. ISRCTN67679521).

PMID 17923654  CMAJ. 2007 Oct 9;177(8):867-74. doi: 10.1503/cmaj.06133・・・
著者: Gill Turner, Andrew Clegg, British Geriatrics Society, Age UK, Royal College of General Practioners
雑誌名: Age Ageing. 2014 Nov;43(6):744-7. doi: 10.1093/ageing/afu138.
Abstract/Text UNLABELLED: Older people are majority users of health and social care services in the UK and internationally. Many older people who access these services have frailty, which is a state of vulnerability to adverse outcomes. The existing health care response to frailty is mainly secondary care-based and reactive to the acute health crises of falls, delirium and immobility. A more proactive, integrated, person-centred and community-based response to frailty is required. The British Geriatrics Society Fit for Frailty guideline is consensus best practice guidance for the management of frailty in community and outpatient settings.
RECOGNITION OF FRAILTY: The BGS recommends that all encounters between health and social care staff and older people in community and outpatient settings should include an assessment for frailty. A gait speed <0.8m/s; a timed-up-and-go test >10s; and a score of ≥3 on the PRISMA 7 questionnaire can indicate frailty. The common clinical presentations of frailty (falls, delirium, sudden immobility) can also be used to indicate the possible presence of frailty.
MANAGEMENT OF FRAILTY: The BGS recommends an holistic medical review based on the principles of comprehensive geriatric assessment (CGA) for all older people identified with frailty. This will: diagnose medical illnesses to optimise treatment; apply evidence-based medication review checklists (e.g. STOPP/START criteria); include discussion with older people and carers to define the impact of illness; work with the older person to create an individualised care and support plan.
SCREENING FOR FRAILTY: The BGS does not recommend population screening for frailty using currently available instruments.

© The Author 2014. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
PMID 25336440  Age Ageing. 2014 Nov;43(6):744-7. doi: 10.1093/ageing/a・・・

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