老年人衰弱( 课件)

TheNewEngland

journalof

medicine2024Aug8;391(6):538-548DOI:10.

1056/NEJMra2301292Q1

IF:96.2Frailty

inOlder

Adults老年人衰弱老年衰弱衰

弱是临床上一种生理储备下降，易引发不良健康结局的状态。随着年龄的增长，衰弱的发生率不断增加。一份涵盖了62个国家的报告中得出：50~59岁老人中衰弱人数占11%,

≥90岁的老年人中衰弱占比高达51%。此外，住在急救中心和养老院的老年人、低收入或中等收入国家以及处于社会弱势地位的老年人发生衰弱的风险增加。衰弱的定义衰弱的生物学机制

衰弱评估衰弱筛查与管理证据缺口与未来方向结论0102040506|||

|衰弱的定义衰弱的定义衰弱的定义尚不统一，但衰弱的概念主要有两种：衰弱综合征Fried衰弱表型是由代谢改变和应激反应异常导致的临床综合征。典型表现：疲惫(最初)

、虚弱

、行动迟缓

、身体活动量减少和体重减轻(最终)。是否衰弱和衰弱程度是由出现上述表现的数量决定。0项→

强壮1~2项→衰弱前期3~5项→衰弱5项→预示着死亡风险急剧上升，而逆转的机会越来越小衰弱的定义健康缺陷累积状态是指与年龄相关的综合健康缺陷所导致的健康不良状态。衰弱程度通过衰弱指数FI

进行量化，衰弱指数指的是存在的健康缺陷数量占所评估的健康缺陷总数(至少评估30项)的比例。选择哪些健康缺陷进行评估取决于具体情况和可用信息。如诊断、认知和身体损伤、失能、营养状况不良和实验室检查结果异常。FI<0.08为无衰弱，0.08≤FI<0.25为衰弱前期，FI≥0.25

为衰弱FI>0.70,

提示健康缺陷程度已威胁到生存。衰弱的生物学机制激素变化线粒体功能障碍营养素感应失调衰弱慢性炎症细胞衰老衰弱的生物学机制衰弱的生物学机制慢性炎症可能是由细胞衰老和线粒体功能障碍等非感染性因素引起。会抑制生长因子表达并且增加分解代谢，进而导致肌肉减少和衰弱。还可能削弱免疫应答，增加感染易感性，并损害接种疫苗后的抗体应答。细胞衰老DNA损伤、癌症突变和氧化应激的触发下，一些细胞会进入永久性细胞周期停滞状态(细胞衰老),并分泌促炎分子

(衰老相关分泌表型)。衰弱的生物学机制>线粒体功能障碍线粒体DNA基因突变、呼吸链复合物不稳定以及线粒体稳态失调导致的线粒体功能障碍是造成衰弱的另一个关键机制。其后果是细胞能量生成减少、活性氧生成增加以及

炎症。骨骼肌线粒体功能障碍与肌肉无力、运动不耐受和疲劳相关。线粒体DNA

拷贝数减少(线粒体耗竭的标志)与Fried衰弱表型和健康缺陷累积性衰弱相关。>营养素感应失调营养素感应通路包括哺乳动物雷帕霉素靶蛋白(

mTOR)复合物1(营养素感应器)、AMPK激活蛋白激酶

(

AMPK)以及sirtuins1和3(营养素不足感应器)。

限制热量摄入

通过激活AMPK和sirtuin通路以及抑制mTOR通路的方式，有益于健康和长寿。衰弱的生物学机制激素变化合成代谢激素(如硫酸脱氢表雄酮

、睾酮、生长激素或胰岛素样生长因子1)减少和分解代谢激素(如皮质醇)增加，会抑制骨骼肌生长并促进其分解，可能会导致恢复力丧失和衰弱。衰弱评估简易筛查工具很多，可用于门诊、住院部、急诊科和术前门诊这些工具依赖于患者报告(如FRAIL问卷[疲劳、耐力减退、

自由活动减少、疾病和体重下降]

、临床判断(如临床衰弱量表)或电子病历。步速(<0.8米/秒)对Fried衰弱表型的检测灵敏度为99%。简易工具往往无法提供充分信息，因此无法通过个体化医疗计划或干预措施降低风险。衰弱评估衰弱评估基于老年综合评估的多维度工具，如健康缺陷累积性衰弱指数和埃德蒙顿衰弱量表，可揭示可逆状况或干预的目标维度。老年综合评估是由多学科团队或专家医师进行的多维度评估，明确老年人的疾病、认知、身体、心理和社会环境状况，以便制定协调、综合的治疗和随访计划。在应激较大的治疗(化疗、手术)制定决策时，在特定治疗人群中测试过的工具可能比通用工具能更好的预测治疗结局。体能指标

(如步速和握力)会受到急性病的影响，不适合住院患者使用，不涉及体能测试的评估工具对这类患者很有用。为避免将急性病症状归因于衰弱，评估内容应包括近期健康状况

(如评估前2周内)。了解既往衰弱状况可以揭示老年人健康轨迹，为年度复查奠定基础。Fried衰弱表型和健康缺陷累积性衰弱的恶化轨迹与较高死亡风险和生活质量下降相关。对不同衰弱程度评估工具的结果进行比较时应谨慎。修改对Fried衰弱表型的评估或改变衰弱指数中使用的健康缺陷列表可能会导致评估结果不一致。为避免错误解读，应说明所使用的衰弱程度评估工具。可根据指南对常用的衰弱程度评估工具进行比较。衰弱评估衰弱筛查与管理衰弱筛查与管理目前有关衰弱筛查和干预的证据有限。大部分临床试验规模较小，试验人群不尽相同，筛查工具、干预措施和结局指标不统一，导致证据质量较低。但有些干预措施已被证明可改善衰弱和相关结局

(如活动能力、肌肉力量和功能状态下降，以及跌倒风险增加)。衰弱程度筛查的价值在肿瘤科和外科得到最明确证明。在临床试验的受控环境中被证明有效的干预措施，在实际的医疗环境中并未呈现出类似效果。与其得出这些干预措施无效的结论，我们不如花更多精力了解如何更好地实施干预措施。衰弱筛查与管理衰弱指导的临床管理方法：衰弱的概念使临床医师可以预测与年龄相关的健康状况的结局和风险，有针对性地提供循证干预措施，并定制临床管理方案，包括对应激大的治疗(如化疗和大手术)作出决策。评估老年人衰弱程度可以为应用老年医疗的证据和原则提供框架。Preventive

VaccinationCareCancer

screeningInterventionsfor

FrailtyPatientPatient-centeredgoal

EngagementVaccinationStopcancer

screeningComprehensivemedication

reviewPatient-centered

goalSocialsupport

(family

and

caregiver)Treat

reversible

causes

of

frailtyRehabilitation

(PT

and

OT)Nutritional

counseling

and

supplementationCGAand

multidisciplinary

interventionComprehensive

medication

reviewPatient-centered

goalSocial

support(family

andcaregiver)TreatreversiblecausesoffrailtyExerciseandphysical

activityNutritionalcounseling

and

supplementationCGA

and

multidisciplinary

interventionComprehensive

medication

reviewPatient-centered

goalSocial

support(family

andcaregiverFitFried

frailty

phenotype,0

pointsDeficit-accumulation

frailtyindex

of

<0.10Scoreon

Clinical

Fraity

Scale,

1-3Preservephysiologicalreserve

andpreventavoidable

stressorsLess

intenseexercisemay

be

bettertoleratedHigh-quality

diet

(protein

intake)

Social

engagementScoreonClinicalFrailtyScale,ScoreonClinical

Frailty

Scale,Score

on

Clinical

Fraity

Scale,

45-78or9IncreasephysiologicalreserveExerciseandphysical

activityHigh-quality

diet(protein

intake)

Social

engagementIncreasephysiologicalreserveExerciseandphysical

activity

High-qualitydietSocialengagementEnd-Stage

FrailtyFried

frailty

phenotype,

5

pointsDeficit-accumulationfrailtyindex

of≥0.55FrailtyFried

frailty

phenotype,

3

or

4

pointsDeficit-accumulationfrailty

index

of

0.20

to

<0.55PrefrailtyFried

frailty

phenotype,

1or

2

pointsDeficit-accumulationfrailty

index

of

0.10

to

<0.20VaccinationIndividualizecancer

screening

(time

to

benefit

vs.remaininglife

expectancy)ProvidecomfortPhysicalactivityDietas

toleratedSocial

engagementtoleratedDeescalatetreatments

easeand

treatmentburdenSocial

support(family

andcaregiver)GoalLifestyleas

toleratedasVaccinationCancer

screeninges

Apply

disease-based

guidelinesDisease

ManagementApply

disease-based

guidelinSocial

SupportFrailty

Score根据虚弱程度对老年患者进行临床护理的建议方法

CGA表示老年综合评估衰弱筛查与管理Considertrade-offbetween

dis-临床管理的目标：>身体健康或衰弱前期，侧重于增加生理储备和控制慢性疾病，

以避免对健康造成长期负面影响。衰弱，侧重于保护生理储备，预防或减轻应激。

由于这些人患多种疾病，而且使用多种药物，因此往往需要根据患者个人目标和偏好重新调整治疗方法。衰弱末期，侧重于使患者舒适和保护其尊严。临床衰弱量表用于衡量死亡或住院风险，其评分临界点是合理估计值，并不能作为严格规则使用。在临床工作或研究中首次使用这些临界点时，可能需要根据临床情况进行调整。应根据患者目标和偏好指导临床管理，不应以衰弱为由阻止患者接受潜在有效治疗。衰弱筛查与管理衰弱筛查与管理衰弱使老年人更易遭受治疗相关的风险。临床管理的一个重要组成部分是降低常规医疗对衰弱患者的危害。将衰弱纳入预后模型可改善对预期寿命的估计，有助于指导癌症筛查决策。个体化、适应性应对策略

(如在熟悉环境中保持日常生活规律、保持社交等)可以帮助患者在受

到衰弱限制的情况下仍然实现自理并保持其社会角色。随着衰弱程度加重，

社会支持在确保医疗计划实施以及协助健康管理和日常活动方面非常重要。疫苗接种和改变家居环境对于预防可避免的应激因素非常重要。衰弱末期，临床管理侧重于通过姑息治疗和临终关怀，使患者舒适和保护其尊严。Table

1.Evidence

for

Interventions

to

Prevent

or

Ameliorate

Frailty

and

Associated

Clinical

Outcomes,°Intervention

and

PatientPopulationExerciseCommunity-dwelling

olderpersonsatrisk

for

fraltyCommunity-dwellingolderpersonswithfrailtyHospitalizedolderpatientsNursinghomeresidentsNutritionCommunity-dwellingolderpersonsatrisk

for

frailtyEvidence

(Quality

of

Evidence)?Exercisewithnutritional

interventionmayameliorateFriedfrailtyphenotype

(low

certainty)"Exercise

is

likelyto

improvemobility

(moderatecertainty)andmayameliorateFriedfrailty

phenotype(low

certainty),improve

ADL

(low

certainty),and

improve

score

on

SOF

scalet

(very

low

certainty);effectonfalls

isuncertain

(very

low

certainty)"Yoga

is

likely

to

improve

mobility

and

muscle

strength

(moderate

certainty)and

may

improve

balance(low

certainty)ExercisewithnutritionainterventionmayameliorateFriedfrailtyphenotype

(lowcertainty)and

improvemobility

(very

low

certainty)

;effect

onADL

is

uncertain

(very

low

certainty)³Exercise

is

likely

to

improve

mobility

and

ADI,

(moderate

certainty)and

may

ameliorate

Fried

frailty

phe-notype

(low

certainty)and

improve

score

on

Edmonton

Frail

Scale(very

low

certainty)²Tai

chi

may

improve

muscle

strength

(low

certainty)and

balance

(very

low

certainty)and

may

reducefalls

(low

certainty)

;effect

on

mobility

is

uncertain(very

low

certainty)“Exercisewithnutritional

interventionmayameliorateFriedfrailtyphenotype

(lowcertainty),decreasei(

a

mucl

n

)a;i

e(

r

nl

l

r

i

c)e,

:ve(v

i

y

ce(

:n

w)¹certainty),and

improvenot

increase

fallsExercisemaynot

improveADL

(lowcertainty)

;effectonmoblty

isuncertain(very

low

certainty)Exercisemayimprovemobility

(very

lowcertainty);effectonADL

and

falls

is

uncertain

(very

lowcertainty)Yogamayimprovebalance

(very

lowcertainty)

;effectonmobility

andmuscle

strength

is

uncertain(very

lowcertainty)Nutritionalsupplernentation

(ONSorfortifiedfoods)may

ameliorate

Fried

frailty

phenotype(low

cer-tainty)and

improveADL

(verylowcertainty)

;effectonmobility

andrisk

of

death

is

uncertain

(verylow

certainty)²7,355Vitamin

Dsupplementationdoes

notimprovemobility

(highcertainty)and

may

notimprove

musclestrength(lowcertainty)ordeficit-accumulationfralty

(verylowcertainty)

;effecton

Fried

frailtyphenotype

is

uncertain

(very

low

certainty)20-8n-3

fatty

acid

supplementationmay

not

improvemobility(low

certainty),muscle

strength(very

lowcertainty),ordeficit-accumulationfrailty

(verylowcertainty)

;effect

on

Fried

frailtyphenotypeis

uncertain

(very

low

certainty)3.59Nutritionalsupplementation

(ONSorfortifiedfoods)alone

may

ameliorate

Fried

frailty

phenotype(lowcertainty)and

improve

mobility

(very

low

certainty);effect

on

ADL

is

uncertain(very

low

certainty)³EffectofvitaminD

supplementation

onmuscle

strength

isuncertain(very

low

certainty)²Nutritionalsupplementation

(ONSorfortifiedfoods)alonemay

improve

mobility

(very

low

certainty)

;effectonmuscle

strength,ADL,riskofdeath,and

hospitalization

isuncertain

(very

low

certainty)Effectofnutritionasupplementation(ONSorfortifiedfoods)alone

onmuscle

strength,ADL,risk

ofdeath,andhospitalizationisuncertain(very

lowcertainty)"EffectofvitaminD

supplementation

onmuscle

strength

isuncertain(very

low

certainty)

°Community-dwellingolder

personswithfrailtyHospitalizedolderpatientsNursinghomeresidentsyotliytelowlitybemt

ampnysaitlsc

efaowoyc

tvee

f

fltyt

yfraotiealowc

c

uy-veciADLdefRDA

for

protein

intake,0.8g/kg/day,maybe

inadequate

in

older

persons

because

ofanabolic

resistance(the

reducedabilityto

synthesize

muscle

protein

in

response

to

dietary

protein

and

resis-tance

exercise)Experts

recommend

1.0-1.2

g/kg/day

forhealthy

older

persons

and

1.2-1.5

g/kg/

day

for

patients

with

acute

or

chronic

illnesswhoareatrisk

formalnutrition,

exceptforthosewith

chronic

kidneydiseaseoProteiningestion

intemporalproximitytoresistanceexercisemay

inducegreater

muscleprotein

synthesis“Mostofthe

evidence

is

for

resistance

trainingThemost

effective

exerciseprogram

isunknown

;atypicalprogram

involvedaerobicexercise

andmuscle

strengthen-ing,with30-60min/session

and

1-4sessions/wk²Exerciseinhospitalizedolderpatients

is

typicallysupervisedbya

physicalthera-

pist,focusingonresistance

training,

with20-90min/session

and2-5

ses-

sions/wk³³Exerciseinhospitalizedolderpatientsdid衰弱筛查与管理预防或改善虚弱和相关临床结果的干预措施的证据CommentsCGA

and

multidisciplinaryintervention

lower

the

risk

of

Fried

frailty

phenotype

(high

certainty)39CGA

and

multidisciplinary

intervention

ameliorate

Fried

frailty

phenotype(high

certainty)and

may

reduceunplanned

hospitalization(lowcertainty)butdo

notreducenursinghomeadmission(highcertainty)andare

unlikely

to

reduce

risk

of

death

(moderate

certainty);their

effect

on

emergency

department

visits

isuncertain(very

low

certainty)¹0ACGAreduces

nursing

homeadmission(highcertainty)andis

likely

to

increase

homedischarge(moderatecertainty)

”in

patients

with

acute

medical

condition

or

injury,CGA

reduces

hospital

falls

(high

certainty);?in

patients

with

trauma

from

hip

fracture,CGA

reduces

delirium(high

certainty),is

likely

to

improve

mobility(moderatecertainty),mayreduceriskof

death

(lowcertainty),and

may

improve

ADL(verylowcertainty)¹Innonorthopedicsurgicalpatients,CGA

is

likelyto

reducedelirium(moderatecertainty)”in

patients

undergoing

emergency

surgery,CGA

is

likely

to

reduce

risk

of

death(moderate

certainty)"Medicationoptimizationmayreducerisk

of

death(low

certainty);itisunlikelytoreduce

hospitalization(moderatecertainty)andmaynot

reducefalls(lowcertainty)⁰Medication

optimization

may

reduce

functional

decline

(very

low

certainty);its

effect

on

falls

is

uncertain(very

low

certainty)6⁴Medication

optimization

may

reduce

emergency

department

visits(very

low

certainty)but

may

not

reducehospitalization(low

certainty);its

effect

on

ADL,falls,delirium,and

risk

of

death

is

uncertain

(very

lowcertainty)Medicationoptimizationreduces

falls(highcertainty),riskof

death

(highcertainty),and

hospitalization(hgh

certainty);it

may

improve

score

on

Edmonton

Frail

Scale(very

low

certainty)⁴STestosterone

supplementation

may

reduce

risk

of

death(low

certainty)but

may

not

improve

mobility(low

certainty);its

effect

on

Fried

frailty

phenotype

or

deficit-accumulation

frailty

is

uncertain(very

lowcertainty)Effect

of

estrogen

and

progesterone

replacement

on

mobility

and

muscle

strength

is

uncertain

in

post-menopausawomen(verylow

certainy)Effectofgrowth

hormonesupplementationonmusclestrength

is

uncertain(very

lowcertainty)"Effect

of

testosterone

supplementation

on

mobility

is

uncertain

(very

low

certainty)⁶CGAandmultidisciplinary

interventionCommunity-dwellingolderpersonsat

riskforfrailtyCommunity-dwellingolderpersonswithfrailtyHospitalizedolderpatientsMedicationoptimizationfCommunity-dwellingolderpersons

at

risk

for

frailtyCommunity-dwellingolderpersonswithfrailtyHospitalizedolderpatientsNursing

homeresidentsHormone

supplementationCommunity-dwellingolder

persons

at

riskforfrailtyCommunity-dwellingolder

personswithfrailtyCGAisasystematic,multidimensionalevaluation

focused

on

determining

afrailolderperson'smedical,functional,

physical,psychological,andsocioenvi-ronmental

status

in

order

to

develop

acoordinated,integratedplanfortreat-mentandfollow-upForinpatients,CGA

is

performed

by

a

spe-cialistteam

or

ina

dedicatedcareunitThe

AmericanGeriatricsSociety

Beescriteria⁶²

and

theSTOPP

andSTARTcriteriacan

behelpfulfor

medication

optimizationComprehensivemedicationreview

isoften

part

ofCGA衰弱筛查与管理预防或改善虚弱和相关临床结果的干预措施的证据衰弱筛查与管理>有衰弱风险的社区老年人单独或联合运动和补充营养，

以及老年综合评估，可改善Fried衰弱表型。运动干预(如每周一至四次、每次30~60分钟有氧运动和肌力强化训练，以及瑜伽和太极拳)可能增强活动能力和肌肉力量，改善日常生活活动，并减少跌倒。>

衰

弱

老

年

人老年综合评估可能预防计划外住院，而不会影响入住养老院或死亡风险。优化用药

(用药情况全面回顾，以及减量或停用有害或无明确益处的药物)可能降低死亡和功能衰退。补充维生素D

、n-3脂肪酸、性激素或生长激素对衰弱状态、身体机能或日常生活活动几乎没有影响。衰弱筛查与管理>住院老年患者运动结合补充营养可能改善Fried衰弱表型，减少健康缺陷累积性衰弱，并改善活动能力和日常生活活动。单纯运动或单纯口服营养补充对身体机能和日常生活活动的益处并不明显。老年综合评估可减少入住养老院和医院内跌倒，预防术后谵妄和死亡，并改善髋部骨折后的活动能力。优化用药可能减少急诊就诊。养老院居民优化用药可降低跌倒、死亡和住院风险。

运动和瑜伽可能改善活动能力和平衡能力。口服营养补充和补充维生素D的益处尚不明确。衰弱筛查与管理初级诊疗机构和急救中心的衰弱筛查：以初级诊疗机构为基础的综合医疗模式(包括常规衰弱筛查、对筛查结果阳性患者的老年综合评估以及定制的干预措施)在预防和管理衰弱方面具有潜力。·

然而，对荷兰六项随机对照试验和两项对照