Blood Disorders in the Elderly - part 2 docx

38 Oscar A. Cepeda, Julie K. Gammack, John E. Morley 53. Tinetti ME, Baker DI, McAvay G, et al. A multifactorial intervention to reduce the risk of falling among elderly people living in the community. N Engl J Med 1994; 331: 821–7. 54. Mathias S, Nayak US, Isaacs B. Balance in elderly patients: the “get-up and go” test. Arch Phys Med Rehabil 1986; 67: 387–9. 55. Foley K, Palmer RM. Offi ce evaluation of the frail older: practical tips. Home Med 1996; 32: 21. 56. Marwick C. NHANES III health data relevant for aging nation. JAMA 1997; 227: 100–2. 57. Potter J, Langhorne P, Roberts M. Routine protein energy supplementation in adults: systematic review. BMJ 1998; 317: 495–501. 58. Guigoz Y, Vellas B, Garry PJ. Mini nutritional assessment: a practical assessment tool for grading the nutritional state of elderly patients In Facts, Research, Interventions in Geriatrics (New York: Serdi, 1997), 15–60. 59. Balducci L, Wallace C, Khansur T, Vance RB, Thigpen JT, Hardy C. Nutrition, cancer and aging: an annotated review. J Am Geriatr Soc 1986; 34: 127–36. 60. Aslani A, Smith RC, Allen BJ, Pavlakis N, Levi JA. The predictive value of body protein for chemotherapy- induced toxicity. Cancer 2000; 88: 796–803. 61. Fantl JA, Newman DK, Colling J. Urinary Incontinence in Adults: Acute and Chronic Management. AHCPR publication No 96-0682 (Rockville, MD: US Department of Health and Human Services, 1996). 62. Salive ME, Guralnik J, Christen W, Glynn RJ, Colsher P, Ostfeld AM. Functional blindness and visual impair- ment in older adults from three communities. Ophthalmology 1992; 99: 1840–7. 63. Sommer A, Tieslch JM, Katz J, et al. Racial differences in the cause-specifi c prevalence of blindness in east Baltimore. N Engl J Med 1991; 325: 1412–17. 64 Tieslch JM, Sommer A, Witt K, Katz J, Royall RM. Blindness and visual impairment in an American urban population: the Baltimore Eye Survey. Arch Ophthalmol 1990; 108: 286–90. 65. Macphee GJA, Crowther JA, McAlpine CH. A sim- ple screening test for hearing impairment in elderly patients. Age Ageing 1988; 17: 347–51. 66. Popelka MM, Cruickshanks KJ, Wiley TL, Tweed TS, Klein BE, Klein R. Low prevalence of hearing aid use among older adults with hearing loss. J Am Geriatr Soc 1998; 46: 1075–8. 67. Cella DF, Tulsky DS, Gray G, et al. The Functional Assessment of Cancer Therapy scale: development and validation of the general measure. J Clin Oncol 1993; 11: 570–9. 68. Karnofsky DA. Meaningful clinical classifi cation of therapeutic responses to anticancer drugs. Clin Pharm Ther 1961; 2: 709–12. 39 3 Introduxtion Oswald Steward Reeve-Irvine research center, departments of anatomy & nurobiology, nurobiology & behavior, and neurosurgery, university of california at irvine, Irvine, CA 92697 Introduction In exploring the assessment of the older aged per- son, this chapter has two goals. The fi rst is to esti- mate a person’s life expectancy, tolerance of stress, medical, rehabilitative, and supportive needs in planning the management of hematologic condi- tions. The second is to relate hematologic fi ndings to a physiologic rather than chronologic classifi cation of age, refl ecting the function and the health status of each individual. A special assessment is needed because aging occurs at different rates for different individuals, and, in the same individual, for differ- ent functions. Various forms of geriatric assessment were devel- oped by geriatricians with the goal to preserve or restore health and functional independence, that is the ability to survive alone. In the scope of these assessments, the older population was composed of two groups of individuals. The fi rst group, which becomes larger with increasing age, includes people who are functionally dependent, for whom the goal of management is to restore function and to prevent fur- ther functional deterioration. These individuals may be affected by multiple medical conditions that con- tribute to their dependence. The second group, which becomes smaller with advancing age, includes people who are still independent. In this case, the assessment is aimed to identify those at risk of functional decline, disease, and death, and the goal of management is to try to prevent or delay these occurrences. After an outline of the biology and physiology of aging we will review different forms of geriatric 4 From fi tness to frailty: toward a nosologic classifi cation of the older aged person Lodovico Balducci, Claudia Beghe assessment and their clinical utilization, we will discuss the meaning of the common geriatric terms frailty and disability, and we will conclude by trying to integrate the different information in a nosologic classifi cation of aging. Biology and physiology of aging Aging has been defi ned as a loss of entropy [1,2] and of fractality [3]. Loss of entropy implies that the energy available for daily activities diminishes pro- gressively with aging, and the survival and the func- tion of the elder hinge upon energy saving. Loss of fractality implies a progressive decline in the ability to deal with the surrounding world due to sensorial impairment, limited mobility, and waning social net- work. This construct of aging may be translated into measurable clinical data, including life expectancy, tolerance of stress, and ability of independent living. Figure 4.1 illustrates the biology of aging and its ultimate clinical consequences, and suggests ways of assessing an individual’s physiologic age. A pro- gressive exhaustion of functional reserve of multiple organ systems occurs as a result of genetically deter- mined programs (a very reasonable, albeit never conclusively proven, hypothesis), environmental impact, and disease. Both disease and reduced func- tional reserve conspire in reducing a person’s life expectancy and tolerance of stress, and in increas- ing the risk of disease and functional dependence. A number of systemic changes, such as increased concentration of cytotoxic cytokines in the circulation, Blood Disorders in the Elderly, ed. Lodovico Balducci, William Ershler, Giovanni de Gaetano. Published by Cambridge University Press. © Cambridge University Press 2008. parameters. In the following discussion we will describe three forms of geriatric assessment – clinical, functional, and biochemical – and we will explore ways to integrate the geriatric assessment into a reproducible clinical classifi cation of older individuals. Clinical assessment of aging Aging is multidimensional and involves decline in functional reserve as well as increased prevalence of chronic diseases, including a number of conditions, called “geriatric syndromes,” that become more common with age. In addition, age involves emo- tional and social changes, such as increased preva- lence of depression, waning economic resources, and social isolation, that may be associated with reduced access to care and poor nutritional and health habits. Not surprisingly, the most common and time-honored evaluation of the older aged per- son is a multidimensional assessment. Comprehensive geriatric assessment (CGA) Though the CGA has not been standardized, there is general agreement on its main components (Table 4.1) [23–31]. Function Function is assessed as performance status (PS), activities of daily living (ADL), and instrumental activities of daily living (IADL). ADLs include trans- ferring, bathing, dressing, eating, toileting, and continence; dependence in one or more of these activities, with the exception of incontinence, indi- cates that the person needs a home caregiver, and is associated with a two-year mortality rate of 27%. ADL dependence may prompt admission to an assisted living facility [32–35]. IADLs are necessary to maintain an independent life and include use of transportation, shopping, ability to take medica- tions, provide for one’s meals, use the telephone, and manage fi nances. Dependence in one or more endocrine, immune, and proliferative senescence, effect and catalyze the decline in functional reserve and the susceptibility to stress and disease [4,5]. Infl ammatory cytokines are responsible in part for sar- copenia [6–8], osteoporosis [9,10], and dysfunction of multiple organ systems [4,11–13], including the central nervous system [14–17] and the hematopoietic system [18,19]. Endocrine senescence involves decreased pro- duction of sexual hormones and chronic hypersecre- tion of adrenal corticosteroids [20] that together may lead to sarcopenia, osteoporosis, fatigue, and func- tional dependence. Immunosenescence involves pro- gressive loss of cell-mediated immunity, which may predispose to infection by intracellular organisms, especially viruses [21], and to highly immunogenic tumors [21]. Proliferative senescence, best described in stromal cells, involves the loss of a cell’s self- replicative capacity, associated with production of growth factors and lytic enzymes that may in the meantime destroy normal tissues and promote the growth of neoplastic ones [22]. Figure 4.1 suggests a number of ways of assessing a person’s physiologic aging, including evaluation of function, of medical conditions, and of laboratory 40 Lodovico Balducci, Claudia Beghe Figure 4.1 The biology of aging and its clinical consequences. Genome Environment Reduced life expectancy Disease Loss of independent living Declining functional reserve Reduced stress tolerance Catabolic cytokines Endocrine, Immune and Proliferative Senescence From fi tness to frailty 41 IADLs is associated with a 16% two-year mortality rate and indicates that the person cannot survive alone for a long period of time and needs the sup- port of a caregiver, albeit not necessarily a home caregiver. In addition, dependence in one of more IADLs is harbinger of dementia in approximately 50% of cases [34, 35] and of complications from cyto- toxic chemotherapy, especially neutropenic infec- tions [36, 37]. Two studies found a poor correlation between functional dependence and PS, and rec- ommended that both be evaluated [26, 27]. Though they are not part of the CGA, the advanced activi- ties of daily living (AADL) are generating increasing interest. The AADLs are those that make life pleasur- able and include leisure as well as professional and other working activities. Seemingly AADLs may rep- resent an indirect measurement of the quality of life of the older person [38, 39]. Comorbidity In the CGA, comorbidity refers mainly to chronic diseases. It is important to remember, however, that the mortality from acute conditions, especially infections and emergency surgery, increases with age [40,41]. Comorbidity is associated with decreased survival and function, and may affect hematopoiesis and hemostasis. For example, anemia of chronic infl ammation and anemia of chronic renal insuf- fi ciency are among the most common forms of anemia in older individuals [42]. The assessment of comorbidity has not been standardized and is a subject of ongoing geriatric research. From a prac- tical standpoint it is helpful to recognize that some comorbidities are independent risk factors of death. These include congestive heart failure and chronic renal insuffi ciency [43,44]. Of special interest to the readers of this book, anemia was also found to be an independent risk factor of mortality for individuals aged 65 and older [45–49], but it is not clear whether anemia itself is a cause of mortality or simply a marker of underlying diseases. After compiling a list of con- ditions associated with decreased survival in the general population, two approaches have been taken for the assessment of comorbidity. One approach is to sum the number of comorbid conditions [44]. The other utilizes comorbidity scales, accounting for the severity as well as the number of these condi- tions. The Charlson scale and the Cumulative Illness Rating Scale for Geriatrics (CIRS-G) have been used Table 4.1. Comprehensive geriatric assessment and clinical implications. Functional status Dependence in one or more of these activities is associated with Activities of daily living (ADL) and instrumental decreased life expectancy and with functional dependence activities of daily living (IADL) Comorbidity Comorbidity is associated with reduced life expectancy and with Number of comorbid conditions and comorbidity functional dependence. In addition, comorbidity may be indices associated with polypharmacy and may affect hematopoiesis and hemostasis Emotional conditions Depression has been associated with decreased life expectancy Geriatric Depression Scale (GDS) and function. It may reduce motivation for health care Nutritional status Reversible condition. Possible relationship to survival. May Mini Nutritional Assessment (MNA) affect hematopoiesis Polypharmacy Risk of drug interactions and hematopoietic suppression. Risk of drug-induced hemolytic anemia and bleeding Geriatric syndromes Virtually all geriatric syndromes are associated with reduced Delirium, dementia, depression, falls, incontinence, life expectancy and with functional dependence spontaneous bone fractures, neglect and abuse, failure to thrive, vertigo 42 Lodovico Balducci, Claudia Beghe in the majority of studies [44]. The Charlson scale is suitable for epidemiologic studies, as it is simpler to use and may be scored based on data derived from medical and insurance records, whereas the CIRS- G appears more appropriate for individual assess- ment of comorbidity in clinical studies [41]. The CIRS-G is more cumbersome and time-consuming, but is more sensitive [44]. Another advantage of the CIRS-G is that its score may be translated into a Charlson score. In addition to providing an estimate of physiologic aging, the assessment of comorbidity reveals con- ditions that may be reversed or arrested, at least in part, and whose management may delay aging. For the non-geriatrician this emphasis on comorbidity assessment may appear redundant, as it should be part of all good practice. The fact is, however, that disease manifestations in the elderly may often be neglected or misinterpreted by the patients them- selves or by the healthcare provider, because they are attributed to a pre-existing condition or are wrongly considered normal manifestations of aging. For example, the diagnosis of bone cancer may be delayed as bone pain may be ascribed to pre-existing arthritis or to pain and ache typical of age. For this reason a careful medical history with special empha- sis on new symptoms is recommended at each encounter with older patients. Atypical presentation of diseases is another reason why comorbidity may be under-diagnosed. Coronary ischemia in individu- als over 70 may present as fatigue as commonly as it does with chest pain [50], and delirium is a harbinger of underlying organic disorders, such as infections, electrolyte imbalance, pain, and medication-related problems [51]. Geriatric syndromes These conditions are typical of aging, if not specifi c, and include dementia, depression, delirium, incon- tinence, falls, spontaneous bone fractures, failure to thrive, neglect and abuse, and vertigo. They are associated with reduced life expectancy and almost always with some degree of functional dependence [34,35,51–57]. Effective management may reverse depression, falls, and osteoporosis, and may arrest the progression of other geriatric syndromes, including dementia. Screening older individuals for dementia, depression, osteoporosis, and risks of falling may be benefi cial by allowing early diagnosis and timely management [51,58,59]. Failure to thrive, the inability to gain weight despite adequate food intake, is a sign of advanced aging and is seldom reversible. The cause is unknown in most cases and the mechanism may include overwhelm- ing concentration of catabolic cytokines in the cir- culation leading to progressive sarcopenia [60]. Neglect and abuse is the least defi nable of the geriat- ric syndromes and is recognizable because patients are poorly kept and withdrawn. This is also a sign of advanced aging and of inadequate caregiving. Geriatric syndromes are recognized as such when they interfere with a person’s daily life. Dementia must be severe enough to disconnect an individual from daily activities; delirium must occur as a result of medications or organic diseases that do not com- monly affect the central nervous system (e.g., uri- nary or upper respiratory infections); incontinence must cause a restriction of one’s social life; depres- sion must prevent pleasurable interactions and be associated with eating or sleeping disorders; falls must occur at least three times a month or the fear of falling must prevent regular activities, such as walking; vertigo must be continuous and so annoy- ing as to cause a restriction in mobility. Social resources The adequacy of social resources is determined by individual needs. Those who are dependent in one or more ADLs do need a home caregiver, at least part of the time; those dependent in one or more IADLs do need a caregiver that is reachable and available on a short-time notice. Even for individuals who are fully independent and with negligible comor- bidity it may be useful to identify a potential care- giver, as any acute disease or strenuous treatment, such as cancer chemotherapy, may precipitate func- tional dependence. Generally the caregiver or pro- spective caregiver is an older spouse with health From fi tness to frailty 43 problem of his/her own or an adult child, more often a daughter, who has to manage competing requests, from parents, from her/his family and from her/his profession. In addition to improving the quality of caregiving, appropriate planning may minimize the emotional stress [61,62]. Living conditions, access to transportation and to food, and income are interrelated and determine the quality of health even for individuals who are functionally independent. It is clear that a person in a wealthy retirement community, with close neigh- bors and shopping centers, and a choice of public transportations, has a better chance to survive an acute problem, causing momentary loss of func- tion, than a person living in a run-down and unsafe neighborhood or one living alone in the countryside far from shops or public transportation. Simple adjustments in home environment may go a long way in preventing common complications of aging. Good illumination, removal of carpets or obstacles, creation of a walking pathway where an individual can always fi nd a support, prevent falls and allow the older person rapid access to the phone in case of emergency. In addition, changes in home environment, such as bathroom bars, may avoid the transformation of disability into handicap [63]. Nutrition The prevalence of protein/calorie malnutrition increases with age [64]. Isolation, depression, eco- nomic restriction, reduced appreciation of hunger, may all contribute to insuffi cient food intake, while chronic diseases, infl ammatory cytokines, and lack of exercise may impede the synthesis of new proteins [65]. The Mini Nutritional Assessment (MNA) is a sim- ple nutritional screening test of worldwide use that identifi es patients who are malnourished and those at risk of becoming malnourished, and allows the prevention and early reversal of malnutrition [66]. Polypharmacy The prevalence of polypharmacy increases with age, and among cancer patients aged 70 and older was found as high as 41% [44,67]. Polypharmacy may include redundant prescriptions as well as danger- ous drug interactions, and highlights a common problem of older individuals in developed countries: the absence of a primary care provider responsible for supervising the various medications. According to a recent study, more than 50% of individuals aged 70 and older in the USA, Canada, and Israel, while attending multiple specialty clinics, lacked a pri- mary care physician [68]. Clinical application of the CGA In general geriatric practice, the CGA has generated interventions able to preserve the health and inde- pendence of older individuals, resulting in a decline in admissions to hospital and to assisted living facilities. According to early studies, the CGA also improved the survival of older individuals [27–30]. In addition, the CGA may be used to estimate a person’s life expectancy [69]. Walter and Covinsky integrated the results of the CGA with the US life tables. The life expectancy of each age cohort was subdivided into quartiles and the CGA determined to which quartile each individual belonged (Fig. 4.2). The same group of investigators established criteria to estimate the one-year mortality rate for older individuals discharged from the hospital (Table 4.2) [43] and the two-year mortality rate for home-dwelling older individuals based on function and comorbidity (Table 4.3) [70]. The benefi ts of the CGA extend beyond the realm of general geriatrics. In the management of cancer in older patients, the geriatric assessment has allowed the identifi cation of a number of conditions including comorbidity, cognitive disorders, depression, and malnutrition that would have remained otherwise unrecognized [71–73], and it has identifi ed risk factors for chemo- therapy-related toxicity [37]. Of special interest to the readers of this book, the geriatric assessment may allow a nosologic classifi cation of age based on physiologic rather than chronologic parameters. Hamerman has pro- posed a frame of reference for this classifi cation (Table 4.4) [74]. 44 Lodovico Balducci, Claudia Beghe Limitation of the geriatric assessment The CGA has allowed a formal, systematic, and largely reproducible exploration of aging and has demonstrated that aging is multidimensional, highly individualized, and poorly refl ected in chron- ologic age. The clinical repercussions of the CGA include improved management of older individuals with preservation of function and quality of life and possibly improvement of comorbidity and of sur- vival. The CGA may thus be considered the gold- standard geriatric evaluation and the reference for the development of new instruments. Several areas of geriatric assessment need improvement and fi ne- tuning, as suggested by its current limitations: • Originally the CGA was designed to improve the management of patients with advanced Figure 4.2 Estimate of life expectancy using the life tables: upper, middle, and lower quartiles for women (A) and men (B) at selected ages. From Walter & Covinsky, 2001 [69], with permission. 25 20 15 10 5 0 Years 70 75 80 85 90 95 Life expectancy for women 21.3 15.7 9.5 17 11.9 6.8 13 8.6 4.6 9.6 5.9 2.9 6.8 3.9 1.8 4.8 2.7 1.1 Top 25th Percentile Lowest 25th Percentile 50th Percentile (A) 25 20 15 10 5 0 Years Life expectancy for men 70 75 80 85 90 95 18 12.4 6.7 14.2 9.3 4.9 10.8 6.7 3.3 7.9 4.7 2.2 5.8 3.2 1.5 4.3 2.3 1 (B) Age, y From fi tness to frailty 45 functional impairment and multiple comorbidi- ties, such as those living in assisted living facilities and nursing homes, or attending outpatient geri- atric clinics. As the majority of individuals over 65 enjoy good health and independence it is legiti- mate to ask two questions: Is a full CGA necessary and benefi cial for these individuals? Is the CGA able to identify those healthy older individuals who are at risk of more rapid functional decline and for whom immediate management would be benefi cial? • The CGA has not been standardized, which makes it diffi cult to compare research and clinical data from different institutions and different prac- tices. Its multidimensional nature makes stand- ardization problematic. The two major variables include the number of different tools available for the assessment of each domain, and the person(s) performing the assessment. In many cases the CGA is based on patients’ self-reports; in others it is performed by a nurse or a research assistant; and in others it involves different professionals (nurse, dietitian, social worker, pharmacist). • The CGA may be redundant in the sense that it provides an excess of information. It is well Table 4.2. Estimate of one-year mortality risk for individuals aged 70 and older discharged from hospital [43]. Scoring system Risk factor Odds ratio p-value Score Male 1.4 (1.1–1.8) Ͻ0.01 1 ADL 1–4 2.1 (1.6–2.8) Ͻ0.0001 2 all 5.7 (4.2–7.7) Ͻ0.0001 5 Comorbidity CHF 2.0 (1.5–2.5) Ͻ0.001 2 Early cancer 2.2 (1.2–3.2) Ͻ0.001 3 Metastatic cancer 13.4 (6.2–39.0) Ͻ0.001 8 Creatinine Ͼ3.0 1.7 (1.2–2.5) Ͻ0.01 1 Serum albumin 3.0–3.4 1.7 (1.2–2.3) Ͻ0.001 1 Ͻ3.0 2.1 (1.4–3.0) Ͻ0.001 2 One-year mortality risk Score Mortality risk 0–1 Ͻ10% 2–3 18% 4–6 31% Ͼ6 62% Table 4.3. Estimate of two-year mortality rate for home- dwelling individuals aged 70 and older [70]. Scoring system Risk factor p-value Score Male Ͻ0.01 2 Age 76–80 Ͻ0.05 1 Ͼ80 Ͻ0.01 2 Function Bathing Ͻ0.01 1 Shopping Ͻ0.0001 2 Walking more than 3 blocks Ͻ0.001 2 Pulling or pushing Ͻ0.05 1 Two-year mortality risk Score Mortality risk 0–2 3% 3–6 13% Ͼ6 34% Table 4.4. A nosologic classifi cation of aging based on the geriatric functional continuum proposed by Hamerman [74]. Group Characteristics Primary No functional dependence Negligible comorbidity Intermediate Dependence in one or more IADLs Stable comorbidity (for example stable angina, chronic renal insuffi ciency, etc.) Secondary or frailty One of the following criteria: • Dependence in one or more ADLs • Three or more comorbid conditions or one poorly controlled comorbid conditions • One or more geriatric syndrome Tertiary Near death 46 Lodovico Balducci, Claudia Beghe known that a correlation exists among the differ- ent parameters of the CGA (function and comor- bidity, function and cognitive decline, function and depression, etc.) [35,75,76]. Ideally one would like to be able to compress the wealth of informa- tion into a small number of indexes predicting life expectancy and risk of functional decline, and identifying patients in need of special medical, nutritional, and social interventions. • The CGA is complex, time-consuming, resource- intense and costly. In the last ten years a number of short instruments have been developed to screen older individuals and identify those who may benefi t from a CGA. Some of these instruments have also identifi ed individuals at risk for functional decline, hospitalization, and death. Shortened forms of assessment There are several shortened forms of assessment that may be used to identify individuals in need of a full CGA. A review of all tests proposed to screen older individuals is beyond the scope of this chapter. We will provide three examples of tests that are widely used in clinical practice and in clinical studies. In the “get up and go” test an individual is asked to get up from an armchair, walk 3 m (10 feet) forward and back, and sit down again. The performance requires less than a minute, and is scored from 0 (the best), to 3 (the worst). One point is assigned for using the arms in getting up, for taking more than 10 seconds to complete the exercise, and for unstable gait [77]. The higher the score, the higher is the risk of mortality and functional dependence. It appears reasonable to limit the full CGA to those individu- als who score 1 or higher. This test, which has been validated in a prospective study, has the advantage of being very simple, but it may not be sensitive enough to identify healthy older individuals at risk for functional deterioration. The Vulnerable Elders Survey (VES-13) is a 13-item questionnaire concerning age, self-reported health, selected ADL/IADL, and the performance of common activities (Table 4.5) [78]. In a group of 290 individuals aged 70 and over a score of 4 or higher indicated a fourfold increased risk of mor- tality or functional decline during the following fi ve years. The main advantage of the VES-13 is that it is self-administered; the main disadvantage is the fact that it is age-weighted, that is chronologic age heav- ily infl uences the fi nal score. Like the “get up and go” the VES-13 may not be sensitive enough to identify healthy individuals at risk for functional deterioration. In the Cardiovascular Health Study (CHS), approx- imately 8500 home-dwelling individuals aged 65 and older have been followed yearly for 11 years. The primary goal of the CHS was to identify factors of risk for coronary artery disease and congestive heart failure in the elderly. At the same time data on mortality, hospitalization, and functional decline were collected. Of approximately 200 variables examined, fi ve were independent factors of risk for mortality and functional decline (Table 4.6). Based Table 4.5. The Vulnerable Elders Survey (VES-13) questionnaire for the defi nition of vulnerability [78]. Element of assessment Score Age 75–84 1 у85 3 Self-reported health Good or excellent 0 Fair or poor 1 ADL/IADL. Needs helps in Shopping 1 Money management 1 Light housework 1 Transferring 1 Bathing 1 Activities. Needs help in Stooping, crouching, or kneeling 1 Lifting or carrying 10 lb (4.5 kg) 1 Writing or handling small objects 1 Reaching or extending arm above shoulder 1 Walking 1/4 mile (0.4 km) 1 Heavy housework 1 From fi tness to frailty 47 Table 4.6. Independent risk factors for mortality and functional decline in the Cardiovascular Health Study (CHS) [79]. Evaluation of frailty according to the CHS 1. Weight loss. Unintentional weight loss of у10 lb (4.5 kg) in prior year, by direct measurement of weight 2. Grip strength Ͻ20% below standard for BMI, measured with Jamar Hydraulic Dynamometer (see below) 3. Walk time below a cutoff point for sex and height (see below) 4. Exhaustion, measured by two statements from the CES-D depression scale (see below) 5. Physical activity, measured on the short version of the Minnesota Leisure Time activity (see below). Men Kcal/week Ͻ383; women Ͻ270 Grip strength by body mass index (BMI) derived from height and body surface BMI Cutoff grip strength (kg) Man р24 р29 24.1–26 р30 26.1–28 р30 Ͼ28 р32 Woman р23 р17 23.1–26 р17.3 26.1–29 р18 Ͼ29 р21 Walk time Height (cm) Cutoff point (seconds) Man р173 у7 Ͼ173 у6 Woman р159 у7 Ͼ159 у6 Exhaustion: score 2 or 3 on two questions of the Center of Epidemiologic Studies Depression Scale (CES-D) a. I felt everything I did was an effort b. I could not get going Score: 0 ϭ never; 1 ϭ 1–2 days a week; 2 ϭ 3–4 days a week; 3 ϭ most of the time Physical activity. Patients are asked whether they engaged in any of the following activities in the past two weeks High-intensity activities Moderate or light-intensity activities Swimming Gardening Hiking Mowing Anaerobics Raking Tennis Golfi ng Jogging Bowling Racquetball Biking Walked for exercise for Dancing at least 1 hour Ͼ4 miles/hour Calisthenics Exercise cycle Walked for exercise for at least one hour at a strolling pace Patients who did not engage in any of these activities over the past two weeks will be considered at low physical activity [...]... determination in these two strains Congenic mice were then generated where we crossed the QTLcontaining interval from the D2 strain onto a B6 background (B6.D2 Chr 2) to test the mapping data Phenotyping of the congenic mice revealed a twofold decrease in the HSC compartment of old mice compared to old B6 animals, thus confirming the role of the chromosome 2 locus in the aging-associated change in HSC numbers... complexity in its secretion: clinical implications J Clin Endocrinol Metab 20 05; 90: 25 22 30 15 Yaffe K, Lindquist K, Penninx BW, et al In ammatory markers and cognition in well-functioning African American and white elders Neurology 20 03; 61: 76–8 16 Wilson CJ, Cohen HJ, Pieper CF Cross-linked fibrin degradation products (D-Dimer), plasma cytokines, and cognitive decline in community-dwelling elderly. .. aging may affect the staining profiles of HSCs and their What is aging? When does it begin? What are its targets? These are questions for which there are no easy answers For instance, does aging begin at birth, at which point development has culminated in an independently functioning individual, or does it begin at puberty, when the individual has attained reproductive maturity, the putative endpoint... fell in D2 mice while they continued to rise in the B6 mice Thus, we surmised that the aging of the stem cells in these two strains differed according to their unique genetic background QTL mapping revealed a locus on mouse chromosome 2 from 135 to150 Mbp that was linked to this particular trait Intriguingly, we found that this locus overlapped a separately mapped locus involved in lifespan determination... in very old community dwelling men and women: the Framingham Heart Study Am J Med 20 03; 115: 429 –35 9 Abrahamsen B, Bonnevie-Nielsen V, Ebbesen EN, Gram J, Beck-Nielsen H Cytokines and bone loss in a 5-year longitudinal study-hormone replacement therapy suppresses serum soluble interleukin 6 receptor and increases interleukin-1-receptor antagonist: the Danish Osteoporosis Prevention Study J Bone Miner... of the mouse klotho gene leads to a syndrome resembling ageing Nature 1997; 390: 45–51 22 Kurosu H, Yamamoto M, Clark JD, et al Suppression of aging in mice by the hormone Klotho Science 20 05; 309: 1 829 –33 23 Edwards BK, Brown ML, Wingo PA, et al Annual report to the nation on the status of cancer, 1975 20 02, featuring population-based trends in cancer treatment J Natl Cancer Inst 20 05; 97: 1407 27 24 ... during steady-state hematopoiesis as well For instance, peripheral blood of mice contains low levels of BM progenitor cells Furthermore, using parabiotic mice, these progenitor cells in the peripheral blood engraft non-conditioned BM of the partner mouse [63] However, no studies have conclusively determined whether aging has an effect on either homeostatic or cytokine-induced HSC mobilization Dose-response... regulating cellular proliferation or intrinsic factors that were present within the cells To address this question, we constructed chimeric (allophenic) mice by combining pre-implantation embryos from B6 and D2 mice and injecting them into pseudo-pregnant female mice In this way the extrinsic signals from the microenvironment would be common to the HSCs of both mouse strains, while the cell-autonomous... ten fold from the highest to lowest cycling strains, as was seen previously using the CFU-S assay Because we had previously observed that this trait seemed to correlate to lifespan in at least the D2 and B6 strains, we plotted the CAFC day-7 cycling data against the mean lifespan of the eight respective strains and found a striking inverse linear correlation of the two traits among all strains [10] We... cycling and lifespan The identification of QTL regulating stem cell function is just the first step in a long and potentially laborious path to identify the gene underlying the locus A candidate-gene approach, whereby genes mapping to QTL-containing intervals are tested for their functional impact, is certainly a valid option in this context However, the regions spanning the 95% confidence interval of the . living (IADL). ADLs include trans- ferring, bathing, dressing, eating, toileting, and continence; dependence in one or more of these activities, with the exception of incontinence, indi- cates. by body mass index (BMI) derived from height and body surface BMI Cutoff grip strength (kg) Man 24 29 24 .1 26 р30 26 .1 28 р30 28 р 32 Woman 23 р17 23 .1 26 р17.3 26 .1 29 р18 29 21 Walk time Height. higher indicated a fourfold increased risk of mor- tality or functional decline during the following fi ve years. The main advantage of the VES-13 is that it is self-administered; the main disadvantage