Frailty: what, who and why do we care?

Frailty: what, who and why do we care?
Jane F Potter, MD

I have no conflicts of interest with respect to any product or commercial interest .

Objectives Understand what frailty is and why it is important to patient outcomes Learn how to identify frail patients in practice Be able to apply evidence based interventions to improve outcomes in frail patients.

Objective 1 Understand what frailty is and why it is important to patient outcomes What is it? What causes it? Why is it important?

Overview: What Is It? Walston, ““The biological basis of frailty has been difficult to establish owing to the lack of a standard definition, its complexity, and its frequent coexistence with illness.”

van den Beld and Lamberts,
Overview: What Is It? van den Beld and Lamberts, “frailty is characterized by generalized weakness, impaired mobility and balance and poor endurance. Loss of muscle strength is an important factor in the process of frailty, and is the limiting factor for an individual’s chances of living an independent life until death.”

Frailty: What is it? Definition:
vulnerability which precedes disability physiologic decline in multiple body systems marked by loss of function loss of physiologic reserve increased vulnerability to disease and death.

Frailty: What causes it?
Dimensions- physical, social, cognitive, psychological, co-morbidities Physiologic correlates: weakness, fatigue Sarcopenia is likely a key component

Sarcopenia Loss of skeletal mm mass & strength with aging
Visceral- may also be important in frailty NHANES prevalence of sarcopenia >60 yrs 10% women, 7% men Sarcopenia (from the Greek meaning "poverty of flesh") is the degenerative loss of skeletal muscle mass and strength associated with aging. Images From Microsoft Clip Art

What might cause weakness and fatigue?
Endocrine changes Effects of inflammation Interaction of systemic changes Image From Microsoft Clip Art

Endocrine changes DECREASES in: Estrogen and testosterone
Dehydroepiandosterone, DHEA Growth hormone Insulin-like growth factor 1, IGF-1 Cortisol (loss of diurnal variation) Vitamin-D Discuss why these are potentially important DHEA a precursor for both estrogen and testosterone

Women’s Health & Aging Study
Vitamin D Odds of frailty if: deficient (< 15) = 2.5 insufficient (15-30) =3.6 All other studies examining Vit D find it is a risk factor Troen Review In a large epidemiological study of 1,271 independent, community-dwelling individuals in Ihe Netherlands ages65 or older, low vitamin D levels were associated withrhe presence of fVailry (OR 2.04; 95% CI ).”Frail elderly women in WHAS had a significantly lowermean serum 25-hydroxyviramin D concentration (43.85nmol/L) compared ro nonfrail women (50.9 nmoI/L).^Hypoviraminosis D was also ideiirified as a strong predictorof frailty in the InCHIANTI study (OR 2.27;95% CI ).^Vitamin D plus calcium improves balance, reducesfalls, and lowers rhe risk of fractures,"'' **' whichmay lower the risk for reduced walking speed and inactivity.A single intramuscular dose of 600,000 IU ergocalciferol (vitamin D2) reduced postural sway inambulatory subjects ages 65 and older with inadequate vitamin D levels (< 12 mcg/L).''^ Daily administration of800 IU cholecalciferol (vitamin D3) and 1,000 mg calcium improved postural sway and quadriceps strengthin 242 healrhy elderly Germans/'* An epidemiologicalstudy of 4,100 ambulatory persons ages 60 and olderrevealed those subjects who had viramin D levels below60 nniol/L needed more time to stand from a seatedposition and walked ar a slower speed.'" Higher levelsof viramin D predicted better performance on severalneuromuscular performance tasks in a study of 1,300older subjects.“Vitamin D decreases he risk of falls even in individualswith sufficient dietary caicium.^^'^ The resultsof a meta-analysis revealed vitamin D supplementationresulted in a 22'percenr lower risk of falls wirh a numberneeded to treat of 15.^' Although supplementation with a vitamin D dose as low as 400 IU did not reducefalls, older individuals supplemented wirh eirher IV or 1,000 IU" exhibired a significantly lowerrisk of falling.Many studies have also shown viramin D prorecrs against fractures. Supplementation with vitaminD in older, independently-living individuals resultedin a lowering of non-verrebral fracture risk by 10-30percent.^^•^*' Daily administration of 800 IU cholecalciferolto 583 institutionalized but ambulatory olderwomen lowered the rare of hip fracrures by 40 percentover two years.'' Three thousand elderly individuals(mean age 84) treated with 800 IU vitamin D daily for1.5 years demonstrated a 32-percent decrease in nonvertebralfractures and a 43-percent decrease in hipfracture rate.'" Supplemenrarion wirh 700 IU viramin D daily over rhree years decreased verrebral fractures by68 percent.'^ A meta-analysis ot the effect of vitamin D indicated thar 800 IU, bur nor 400 IU, lowered fracrurerisk.^'^ Not all studies have confirmed a reduced fracture risk with vitamin D supplementation. A total of 8,000 elderly individuals in two studies were supplemented with 800 IU vitamin D and 1,000 mg calcium daily or an informational leaflet on dietary calcium (conrrol group),'" or in a double-blind, placebo-conrrolled fashion were assigned ro one of four treatment groups: (1) 1,000 mg calcium, (2) 800 IU vitamin D, (3) both, or (4) double placebo." In the first study, after 18-42 months the fracture rate was not significantly lower in the treatment group, although both groups demonstrated a lower than expected fracture rate.'" In the second study, after monrhs there were no significant differences in fracture rates among the four groups.*" It should be noted, however, that compliance rates were rather low - approximately 55 percent in both studies - and vitamin D levels were not tested in rhe majority of subjects. Therefore, supplemenrarion roo low ro normalize serum vitamin D levels might account for the different findings. Page Image From Microsoft Clip Art

Women’s Health & Aging Study
IGF-1, DHEAS , and free testosterone If one deficiency not more likely to be frail If 2 or 3 deficiencies likelihood of being frail increased almost fold (OR=2.79)

Inflammation: Duke EPESE
Both high IL-6 and D-dimer increase mortality; Those with both have highest mortality and greatest functional decline Established Populations for Epidemiologic Studies of the Elderly Image From Microsoft Clip Art

What Might Cause Weakness and Fatigue?
Inflammation in frail people: IL-6 ↑ CRP ↑ May cause Catabolism Anorexia, ↓ GH & IGF-1 Image From Microsoft Clip Art

Effects of Inflammation
↑ IL-6 strongly associated with: Weight loss, Sarcopenia Susceptibility to infection Lower physical activity correlates with higher IL-6 Image From Microsoft Clip Art

Contributes to anemia by : directly inhibiting production of erythropoietin or by interfering with normal iron metabolism Higher Il-6, lower Hb

Chronic inflammation may: Trigger coagulation cascade Frail elderly have higher levels of: Factor VIII, Fibrinogen D-dimer

What might cause weakness and fatigue?
Interaction of: Endocrine changes Inflammation Systemic changes

INTERACTING FACTORS IN FRAILTY
ENDOCRINE CHANGES FRAILTY SARCOPENIA ANEMIA CLOTTING INFLAMMATORY MARKERS Espinoza & Walston, 2005

Frailty: Why is it important?
High Prevalence 20–30% over 75 years 30% after 80 years Twice as common in women 28% of moderately-severely disabled women ≥65 Image From Microsoft Clip Art

Predicts outcomes Falls, fractures Hospitalization Mortality Institutionalization

One characteristic of frailty that distinguishes it from aging is the potential reversibility of many of its features.

Learn how to identify frail patients in practice
Objective 2 Learn how to identify frail patients in practice Many Definitions & Tools Have Been Proposed

Identifying Frailty Chin 1999
Frailty= inactivity combined with: low energy intake or weight loss or low body mass index

Identifying Frailty Gait speed alone & with chair stands, & tandem balance test Predicts 12-mo rates of hospitalization, ↓ health, and ↓ function Proposed: “vital signs” to screen older adults Studenski (2003): To assess the ability of gait speed alone and a three-item lower extremity performance battery to predict 12-month rates of hospitalization, decline in health, and decline in function in primary care settings serving. Both performance measures predicted decline in function and health status in both health systems. MEASUREMENTS: Lower extremity performance Established Population for Epidemiologic Studies of the Elderly (EPESE) battery including gait speed, chair stands, and tandem balance tests; demographics; health care use; health status; functional status; probability of repeated admission scale (Pra); and primary physician’s hospitalization. Gait speed and a physical performance battery are brief, quantitative estimates of future risk for hospitalization and decline in health and function in clinical populations of older adults. Physical performance measures might serve as easily accessible “vital signs” to screen older adults in clinical settings (2003) OBJECTIVES: To assess the ability of gait speed alone and a three-item lower extremity performance battery to and decline in function in primary care settings serving predict 12-month rates of hospitalization, decline in health, older adults. DESIGN: Prospective cohort study. Primary care programs of a Medicare health SETTING: maintenance organization (HMO) and Veterans Affairs (VA) system. PARTICIPANTS: 65 and older. Four hundred eighty-seven persons aged MEASUREMENTS: Lower extremity performance Established Population for Epidemiologic Studies of the Elderly tandem balance tests; demographics; health care use; (EPESE) battery including gait speed, chair stands, and health status; functional status; probability of repeated admission scale (Pra); and primary physician’s hospitalization risk estimate. Veterans had poorer health and higher use than HMO members. Gait speed alone and the EPESE battery predicted hospitalization; 41% (21/51) of slow walkers (gait speed 0.6 m/s) were hospitalized at least once, compared with 26% (70/266) of intermediate walkers (0.6–1.0 m/s) and 11% (15/136) of fast walkers ( 1.0 m/s) ( p .0001). The relationship was stronger in the HMO than in the VA. Both performance measures remained independent predictors after accounting for Pra. The EPESE battery was superior to gait speed when both Pra and primary physician’s risk estimate were included. Both performance measures predicted decline in function and health status in both health systems. Performance measures, alone or in combination with self-report measures, were more able to predict outcomes than self-report alone. RESULTS: CONCLUSION: Gait speed and a physical performance battery are brief, quantitative estimates of future risk for hospitalization and decline in health and function in clinical populations of older adults. Physical performance measures might serve as easily accessible “vital signs” to screen J Am Geriatr Soc 51:314– older adults in clinical settings. 322, 2003. Key words: geriatric assessment; risk assessment; locomotion; health maintenance organizations; hospitalization; lder activities of daily living Medicare HMO & VA, 2003

Canadian Study of Health & Aging
Frailty is identified by counting accumulation of deficits in: cognition, mood, motivation, communication, mobility, balance, bowel & bladder function, ADL, IADL, nutrition, social resources, and comorbidities Highly predictive of death or institutionalization Image From Microsoft Clip Art

The French Three-City Study
The frail scored lower on MMSE and IST than the prefrail and nonfrail. Frail with cognitive impairment were more likely to develop disability in ADLs and IADLs over 4 yrs. Cognitive impairment improves prediction of frailty, because it ↑risk of adverse outcomes. Image From Microsoft Clip Art

Cardiovascular Health Study, 2001
Frailty= a syndrome with a critical mass of signs and symptoms. Three out of five: Slow walking speed Poor hand grip Exhaustion Weight loss Low energy expenditure Defined and prospectively tested

CHS FRAILTY Criteria CHS= cardiovascular health study
Slow walking speed Poor hand grip Weight loss Exhaustion Low energy expenditure Images From Microsoft Clip Art

Study of Osteoporotic Fracture (SOF)
CHS criteria are unrealistic for clinical use SOF tested simpler criteria in both men & women. Exclusion inability to walk without the assistance of another person CHS and SOF were concordant in 71% SOF is easily evaluated in a few minutes

Comparison Of Frailty Indexes
SOF CHS Shrinking Wt loss ≥ 5% over 3 yrs Unintentional wt loss 5% over 3 yrs Weakness Unable to do 5 chair stands Grip strength in lowest quartile Poor energy “Do you feel full of energy”= no Slowness Walking speed in lowest quartile Low physical activity Physical Activity Scale for the Elderly

Study of Osteoporotic Fracture (SOF) Criteria for Frailty
Frailty Criteria Data Collection Score Weight loss ≥ 5% over 3 yrs Weight 3 years ago Weight today Change in weight/ Weight 3 years ago= % loss Score=1 if weight loss ≥ 5% Otherwise, Score=0 Inability to do 5 chair stands Sit in chair, do not use arms, rise 5 times Score=1, if unable “Do you feel full of energy?” Ask the question, must answer yes or no Score=1, if yes Sum above scores If summed score is 2 or 3, patient is frail; If score is 1 patient is prefrail; If score=0 the patient is robust

Objective 3 Be able to apply evidence based interventions to improve outcomes in frail patients. non-pharmacologic and Pharmacologic interventions

Set patient centered goals Family & caregiver support
Symptom relief Set patient centered goals Family & caregiver support From Espinoza & Walston Exercise Interventions CGA, GEM, PACE, ACE Comprehensive geriatric assessment and treatment Once an elderly patient is determined to be vulnerable or frail, the risk of adverse outcomes may be reduced via a comprehensive geriatric assessment with the development and implementation of an interdisciplinary treatment plan. The overall goals are to improve physical and psychological function, decrease the need for nursing home placement and hospitalization, reduce the risk of death, and improve patient satisfaction. The interdisciplinary care team usually includes a geriatrician or other medical practitioner knowledgeable in the care of older adults, a nurse, a social worker, and an occupational or physical therapist, if available. In some cases, the geriatric assessment interdisciplinary team follows the patient and manages his or her specific issues, a model or approach referred to as geriatric evaluation and management. In other cases the team makes recommendations to the patient’s primary care physician, a model referred to as comprehensive geriatric assessment.35 Although com-prehensive geriatric assessment is not always targeted at frailty per se, vulnerable older adults are thought to be most likely to benefit. The Acute Care for Elders model is designed to prevent functional decline and improve functional independence if decline has already occurred. The model typically includes a specially designed, more home-like environment; patient-centered medical care to prevent disability; and comprehensive discharge planning and management.43 In a randomized controlled trial of 1,531 community dwelling adults age 70 and older, this model was shown to decrease the likelihood of decline in the ability to perform activities of daily living or a decline in nursing home placement both at hospital discharge and at 12 months, without an increase in hospital length of stay or hospital costs.43 Hospice, comfort & dignity INCREASINGLY FRAIL

Interventions: Assessment
Inpatient CGA improves functional outcomes Outpatient CGA improves mental health Neither affect survival No increase in cost VA Population

Interventions: Assessment
≥ 70 yrs at risk for hospital admission CGA group less likely to: Lose functional ability Have restrictions in ADLs Have depressive symptoms Use HHC services Mortality & Medicare payments not differ. Intervention cost $1,350/person. CONCLUSION: Targeted outpatient CGA slows functional decline. Boult Boult et al conducted a randomized controlled trial of intervention with geriatric evaluation and management, specifically targeting outpatients at increased risk for repeated hospitalization. Intervention resulted in decreased health care utilization, improved depressive symptoms, and, most importantly, slowed functional decline. The study also showed the importance of ensuring that specific recommendations are implemented. In this study, the intervention group received continued primary care from the interdisciplinary team until the patient’s significant issues had resolved or until a stable management plan had been established. In general, poor implementation of recommendations from the comprehensive geriatric assessment team is the main reason that a single visit without continued management by an interdisciplinary team is less effective.37 Patient adherence to treatment plans also determines the effectiveness of comprehensive geriatric assessment.38 Physicians are more likely to implement the plan and patients are more likely to adhere to it if the patient and primary care physician share a collaborative relationship.39 Medicare Population

Complex Interventions: meta-analysis
Randomized trials of 97,984 pts. Interventions reduced risk of :not living at home, NH & hospital admits & falls (not death); & physical function was better In populations with increased death rates, interventions were associated with reduced nursing-home admission. Interpretation: Complex interventions help elderly live safely & independently. Lancet 2008 Summary Background In old age, reduction in physical function leads to loss of independence, the need for hospital and long-term nursing-home care, and premature death. We did a systematic review to assess the eff ectiveness of community-based complex interventions in preservation of physical function and independence in elderly people. Methods We searched systematically for randomised controlled trials assessing community-based multifactorial interventions in elderly people (mean age at least 65 years) living at home with at least 6 months of follow-up. Outcomes studied were living at home, death, nursing-home and hospital admissions, falls, and physical function. We did a meta-analysis of the extracted data. Findings We identifi ed 89 trials including people. Interventions reduced the risk of not living at home (relative risk [RR] 0·95, 95% CI 0·93–0·97). Interventions reduced nursing-home admissions (0·87, 0·83–0·90), but not death (1·00, 0·97–1·02). Risk of hospital admissions (0·94, 0·91–0·97) and falls (0·90, 0·86–0·95) were reduced, and physical function (standardised mean diff erence −0·08, −0·11 to −0·06) was better in the intervention groups than in other groups. Benefi t for any specifi c type or intensity of intervention was not noted. In populations with increased death rates, interventions were associated with reduced nursing-home admission. Benefi t in trials was particularly evident in studies started before 1993. Interpretation Complex interventions can help elderly people to live safely and independently, and could be tailored to meet individuals’ needs and preferences.

What Were the Interventions?
Geriatric assessment of general elderly people Geriatric assessment of elderly people selected as frail Community-based care after hospital discharge Falls prevention programs Group education and counseling

INTERACTING FACTORS IN FRAILTY
ENDOCRINE CHANGES FRAILTY SARCOPENIA ANEMIA CLOTTING From before, but let’s talk a little more about sarcopenia or low muscle mass and think about the interventions that might be helpful for that problem. Sarcopenia is the loss of muscle mass and strength that occurs with aging [38], and is defined as a decrease in appendicular muscle mass two standard deviations below the mean for young healthy adults INFLAMMATORY MARKERS

Sarcopenia Total body protein= muscle + visceral
Declines with age, faster after 65 yrs Major contributor is disuse atrophy Image From Microsoft Clip Art

Sarcopenia Protein Inadequate protein & calories
↑ body fat masks sarcopenia Sarcopenia in NHANES > 60 yrs 10 % women 7 % men Image From Microsoft Clip Art

Aging of skeletal muscle
True longitudinal data looking at what happens to muscles over 12 years

Nutritional components of frailty in selected studies
Study/cohort Nutrition criteria WHI BMI <18.5; 10% wt loss since 60 yrs overweight associated with prefrailty Cardiovascular Health Study wt loss >10 pounds in past yr wt loss >5% or reported loss of >5 lb inChIANTI Study wt loss: 4.5 kg in past yr Canadian Health & Aging cooking, GI problems Zutphen & SENECA Studies wt loss 6% or more, 4–5 yrs, low BMI EPIDOS shopping, cooking Toulouse & Albuquerque Mini-Nutrition Assessment poor scores

Interventions for Sarcopenia
Randomized, placebo-controlled trial progressive resistance exercise training, multinutrient supplement, both, and neither in 100 frail NH residents over 10-wks a randomized, placebo-controlled trial comparing progressive resistance exercise training, multinutrient supplementation, both interventions, and neither in 100 frail nursing home residents over a 10-week period63 women and 37 men 87.1 ±0.6 years (range, 72 to 98); Muscle strength increased by 113 ±8 percent in the subjects who underwent exercise trainingGait velocity increased by 11.8 ±3.8 percent Stair-climbing power also improved as did the level of spontaneous physical activitythigh-muscle area increased by 2.7 ±1.8 percent in the exercisers The nutritional supplement had no effect Total energy intake was significantly increased only in the exercising subjects High-intensity resistance exercise training is a feasible and effective means of counteracting muscle weakness and physical frailty Nursing Home (NH) Residents Image From Microsoft Clip Art

Outcomes for Resistance Training
NH Residents, Age ≈ 87 yrs Resistance training: ↑muscle strength >100% ↑ LE muscle size 3% ↑ gait velocity 12% ↑ mobility ↑spontaneous activity Image From Microsoft Clip Art

Sarcopenia and Hip Fracture Study:
5-yr prospective cohort study admitted to hospitals for hip fracture. 193 participants enrolled 71% were sarcopenic, 58% undernourished, and 55% vitamin D deficient. Poorer nutrition & walking endurance, greater pre-fracture disability and inactivity predicted ↑ length of hospital stay As a final note on how important this is likely to be, is from a recent Australian study looking at the prevalence of Sarcopenia in hip fracture patients

Therapy for Functional Decline
Frail: Fails chair rise without using arms, or Slow 6 meter walk (>10 seconds) Intervention: 6 mo home-based PT to improve function, balance, muscle strength, transfers and mobility vs control education program. Outcome: change in function score at 3, 7 & 12 months. Intervention significantly slowed functional decline Gill:2002 Home Based Frail Gill

Exercise Reducing Disability
Systematic Review: What works? Multicomponent: endurance, flexibility, balance, strength Duration: 3, 9, 12 mos. Intensity: 2-3 supervised/week, with/without daily home program

Group-Based Exercises Reduce Fall Risk: and is maintained
98 women, with low bone mass. Interventions: 6 mo resistance or agility training, or general stretching Primary outcome= fall risk Fall risk at end of 12 mo 43.3% lower with resistance training 40.1% lower in the agility-training 37.4% lower in the general stretching group The Beneficial Effects of Group-Based Exercises on Fall Risk Profile and Physical Activity Persist 1 Year Posti ntervention in Older Women with Low Bone Mass: Follow-Up After Withdrawal of Exercise OBJECTIVES: To determine whether exercise-induced reductions in fall risk are maintained in older women 1 year after the cessation of three types of interventions resistance training, agility training, and general stretching. DESIGN: One-year observational study. SETTING: Community. PARTICIPANTS: Ninety-eight women aged 75 to 85 with low bone mass. MEASUREMENTS: Primary outcome measure was fall risk, measured using the Physiological Profile Assessment tool. Secondary outcome measures were current physical activity level, assessed using the Physical Activity Scale for the Elderly, and formal exercise participation, assessed using an interview. RESULTS: At the end of the follow-up, the fall risk of former participants of all three exercise programs was maintained (i.e., still reduced) from trial completion. Mean fall risk value at the end of follow-up was 43.3% lower than mean baseline value in former participants of the resistancetraining group, 40.1% lower in the agility-training group, and 37.4% lower in the general stretching group. Physical activity levels were also maintained from trial completion.Specifically, there was a 3.8% increase in physical activity from baseline for the resistance-training group, a 29.2% increase for the agility-training group, and a 37.7% increase for the general stretching group. CONCLUSION: After three types of group-based exercise programs, benefits are sustained for at least 12 months without further formal exercise intervention. Thus, these 6- month exercise interventions appeared to act as a catalyst for increasing physical activity with resultant reductions in fall risk profile that were maintained for at least 18 months in older women with low bone mass. J Am Geriatr Soc 53:1767–1773, 2005. Key words: fall risk; physical activity; detraining; aged; low bone mass

Low-Moderate Vs High-Intensity Progressive Resistance Training in Frail Elders
Measured dose–response to free weight resistance program in 22 NH elders Low-moderate (LI) & high (HI) of the knee extensor (KE) muscles Results: KE strength & endurance, stair-climbing power, and chair-rising time improved in the HI and LI groups

Low-Moderate Vs High-Intensity Progressive Resistance Training in Frail Elders
Results (cont’d) 6-min walk distance improved in HI but not in the LI group Changes in strength were related to changes in functional outcomes Strong dose–response relationships between training intensity & strength gains, & between strength gains and functional improvements

Exercise Interventions
Summary: Muscle mass and strength ↓ with age, more so in frail Benefits frail people Improves mobility, ADL, gait, fewer falls, ↑BMD, improves well being Image From Microsoft Clip Art

Pharmacotherapy: DHEA
280 healthy people yrs. Double blind placebo controlled trial DHEA was restored to the range for adults yrs. Measurement: handgrip strength, knee muscle strength, and thigh cross-sectional area after 12 mo. Results: no positive effect on muscle strength cross-sectional areas. Measurement: handgrip strength, knee muscle strength, and thighcross-sectional area after 12 months

Pharmacotherapy: Ace-Inhibitors (AIs)
AIs ↓ morbidity, mortality, #admissions & decline in function & exercise capacity in HF Population: WHI Study Findings: ↓ in knee extensor strength & walking speed in continuous AI users was less than in intermittent (p=0·015), & never users (p=0·001). Interpretation: ACE inhibitor Rx may halt or slow decline in muscle strength in elderly women with hypertension and without HF. A second associational study suggested same effect, while a third study using WHI data saw no reduction in incident frailty. 2009 STUDY 1: J Am Geriatr Soc Feb;57(2): Angiotensin-converting enzyme inhibitor use and incident frailty in women aged 65 and older: prospective findings from the Women's Health Initiative Observational Study. Gray SL, LaCroix AZ, Aragaki AK, McDermott M, Cochrane BB, Kooperberg CL, Murray AM, Rodriguez B, Black H, Woods NF; Women's Health Initiative Observational Study. University of Washington, Seattle, 98195, USA. OBJECTIVES: To examine the associations between current use, duration, and potency of angiotensin-converting enzyme (ACE) inhibitors and incident frailty in women aged 65 and older who were not frail at baseline. DESIGN: Data were from the Women's Health Initiative Observational Study (WHI-OS), a prospective study conducted at 40 U.S. clinical centers. PARTICIPANTS: Women aged 65 to 79 at baseline who were not frail (N=27,378). MEASUREMENTS: Current ACE inhibitor use was ascertained through direct inspection of medicine containers at baseline. Components of frailty were self-reported low physical function or impaired walking, exhaustion, low physical activity, and unintended weight loss. Frailty was ascertained through self-reported and physical measurements data at baseline and 3-year clinic contacts. RESULTS: By the 3-year follow-up, 3,950 (14.4%) women had developed frailty. Current ACE inhibitor use had no association with incident frailty (multivariate adjusted odds ratio=0.96, 95% confidence interval= ). Duration and potency of ACE inhibitor use were also not significantly associated with incident frailty. A similar pattern of results was observed when incident cardiovascular disease events were studied as a separate outcome or when the sample was restricted to subjects with hypertension. CONCLUSION: Overall, incidence of frailty was similar in current ACE inhibitor users and nonusers. PMID:

Prospective ACE Trial Drug=perindopril
Double-blind randomized controlled trial Change in the 6-min walk distance over 20 wks 130 participants; 95 completed Health-related quality of life was maintained in the perindopril group. Improvement = to 6 mos of exercise training Subject selection: A total of 2551 patients were assessed for eligibility in the study. Of these, 1929 were excluded because they did not meet the inclusion critiera (892 were taking an ACE inhibitor or angiotensin II receptor blocker, 347 had left ventricular systolic dysfunction, 283 had symptomatic orthostatic hypotension, 58 had a serum creatinine level above 200 μmol/L, 49 had significant aortic stenosis, 130 had another contraindication to ACE inhibitor therapy, 136 were wheelchair bound, and 180 had a Mini-Mental State Examination score below 15), 489 refused to participate, and 3 died before recruitment. Of the remaining 130 participants who were enrolled, 95 (73%) completed the trial (Figure 1 ). The baseline characteristics of the 130 participants are shown in Table 1 alongside the characteristics of the 95 who completed the study. 2551 screened

Hormones not recommended
Testosterone ↑ muscle mass & strength in hypo and eugonadal men, especially with exercise But affects lipids, and ± prostate size. Hormones not recommended for frail unless clearly deficient

Vitamin D Deficiency Linked to weak muscles, ↓function, falls & fracture Check levels and replace older adults & those with dark skin Use IU orally daily to achieve 25 OHD ≥30 ng/ml (75 nmol/L) to improve muscle performance & reduce risk of fall and to reduce fx The objective of this article was to consider key evidence that treatment of vitamin D insufficiency has measurable clinical benefits for the musculoskeletal system in the elderly. The functional outcomes considered were increased bone mass, decreased rates of bone loss, improved muscle performance, reduced risk of falls, and reduced fracture incidence. Available evidence suggests that the elderly need a mean serum concentration of >/=65 nmol/L of vitamin D to improve muscle performance and reduce the risk of falling and >/=75 nmol/L to reduce the risk of fracture. Many elderly persons in the United States and elsewhere have serum 25-hydroxyvitamin D concentrations below these levels. For this reason, supplementation is likely to provide significant benefit to this segment of the population. Lack of sun exposure, impaired skin synthesis of previtamin D, and decreased hydroxylation in the kidney with advancing age contribute to marginal vitamin D status in many older adults [87]. Inadequate vitamin D status has been linked with muscle weakness, functional impairment, and increased risk of falls and fractures [88,89]. Lower serum 25-hydroxyvitamin D concentrations in older persons have also been associated with a greater risk of future nursing home admission [90]. Increased consumption of dietary sources of vitamin D should be encouraged in all older adults. The 2005 Dietary Guidelines for Americans recommend that older adults, people with dark skin, and those exposed to insufficient sunlight increase vitamin D intake from vitamin D-fortified foods and/or supplements [91]. Individuals in these high-risk groups should consume 25 mcg or 1000 IU (1 mcg = 40 IU) of vitamin D daily to maintain adequate blood concentrations of 25-hydroxyvitamin D, the best laboratory indicator of vitamin D status. (See "Treatment of vitamin D deficient states"). Routine monitoring of 25-hydroxyvitamin D levels in high risk individuals is recommended with the goal of achieving levels ≥30 ng/mL. Heaney in nutritional reviews: The functional status indicator for vitamin D, for both safety and efficacy, is serum 25-hydroxyvitamin D concentration. Efficacy for several health endpoints requires levels of 80 nmol/L or higher. Toxicity occurs at levels of 500 nmol/L or higher. The input needed for efficacy, in addition to typical food and cutaneous inputs, will usually be 1000–2000 IU/day of supplemental cholecalciferol. Toxicity is associated only with excessive supplemental intake (usually well above 20,000 IU/day). Image From Microsoft Clip Art

Summary Frailty= vulnerability which precedes disability
Predicts: falls, fractures, hospitalization, mortality, institutionalization However, many features may be reversible SOF probably identifies many (most) Wt loss ≥ 5% over 3 yrs Unable to do 5 chair stands “Do you feel full of energy”= no

Summary 2 Therapy may include: Complex Interventions
Correcting inadequate protein & calories* Aggressive Exercise which improves mobility, ADL, gait, ↓ falls, ↑BMD, improves well being Correcting Vitamin D Deficiency * Least data on this

Set patient centered goals Family & caregiver support
Symptom relief Set patient centered goals Family & caregiver support From Espinoza & Walston Exercise Interventions CGA, GEM, PACE, ACE Comprehensive geriatric assessment and treatment Once an elderly patient is determined to be vulnerable or frail, the risk of adverse outcomes may be reduced via a comprehensive geriatric assessment with the development and implementation of an interdisciplinary treatment plan. The overall goals are to improve physical and psychological function, decrease the need for nursing home placement and hospitalization, reduce the risk of death, and improve patient satisfaction. The interdisciplinary care team usually includes a geriatrician or other medical practitioner knowledgeable in the care of older adults, a nurse, a social worker, and an occupational or physical therapist, if available. In some cases, the geriatric assessment interdisciplinary team follows the patient and manages his or her specific issues, a model or approach referred to as geriatric evaluation and management. In other cases the team makes recommendations to the patient’s primary care physician, a model referred to as comprehensive geriatric assessment.35 Although com-prehensive geriatric assessment is not always targeted at frailty per se, vulnerable older adults are thought to be most likely to benefit. The Acute Care for Elders model is designed to prevent functional decline and improve functional independence if decline has already occurred. The model typically includes a specially designed, more home-like environment; patient-centered medical care to prevent disability; and comprehensive discharge planning and management.43 In a randomized controlled trial of 1,531 community dwelling adults age 70 and older, this model was shown to decrease the likelihood of decline in the ability to perform activities of daily living or a decline in nursing home placement both at hospital discharge and at 12 months, without an increase in hospital length of stay or hospital costs.43 Hospice, comfort & dignity INCREASINGLY FRAIL

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