39Neurologie - Psychiatrie - Gériatrie / Année 5/Juin 2005. © Masson, 2005.Tous droits réservés.

Frailty in the older adult is an increasingly common syndrome.Frailty plays a dominant role in geriatric medicine.The notion offrailty may be clear, its definition, however, has proven to be elu-sive; Hamerman (1) has noted that geriatric care providers “inhe-rently associate the word frailty with patients whom they per-ceive as frail”.Frailty in the very old can be considered as a condition of impai-red strength and balance and vulnerability to trauma and otherstressors. Frailty is associated with higher risks of morbidity, disa-bility, and death. Bergman (2) has identified three domains defi-ning frailty in a detailed literature review. Dependency (requi-ring assistance in ADLs), vulnerability (loss of physiologicalreserves) and disease states (chronic co-morbidities) were thecited domains.Frailty has been considered to be at the midpoint of a geriatricfunctional continuum. Older independent adults who have agedsuccessfully are at its origin while wasted, bed bound eldersoccupy its end. Frailty has an operational definition described byFried (3). Frailty is present when three of the five following ele-ments are present:unintentional weight loss,weakness,slow gait,exhaustion, and diminished physical activity. Reid (4) has lucidlydemonstrated the limitations to current definitions of frailty.The incidence of frailty is underestimated. Four point eight per-cent of community-dwelling 65-year-old are defined as frail.TheAMA has projected that 46% of community-dwelling personsover 85 years of age are frail. Older men are more often frail thanfemales in a circumscribed population (6).Frailty has many putative causes: genetic disorders, diseases andinjuries, lifestyle, and aging. Aging may be linked to frailty but itappears that it is not a necessary aspect of aging. The cycle offrailty and its intricacy is demonstrated in figure 1.

Sarcopenia, loss of muscle mass and strength, is a keystone thatstabilizes the cycle of frailty construct (figure 1). Sarcopenia iscaused by a decline in testosterone, lack of physical activity,inadequate calorie intake and a decline in insulin growthfactor-I (7). Trials in the laboratory and clinic have shown these4 factors to be (temporarily) reversible. Resistance exercise trai-ning has restrained sarcopenia in a randomized controlled clini-cal trial by Yurasheski (8).Markers of inflammation are commonly elevated in frail olderadults. The markers are proinflammatory cytokines with inter-leukin-I and VI (IL-1, IL-6) and tumor necrosis factor alpha (TNF-a) being more commonly identified. A subset of elderly patientsfrom the Framingham Study with acute myocardial infarctionand elevation of IL-6, TNF-a and C-reactive protein (CRP) had afour-fold risk of developing congestive heart failure (CHF) (8).Physical training reduces cytokine levels and improves cardio-pulmonary physiology (9).Markers of coagulation and fibrinolysis predict the developmentof atherosclerosis. Artherosclerosis reflects a state of chronicinflammation. D-dimer, fibrinogen and plasminogen activatingfactor-I elevation predict the development of atherosclerosis andcoronary artery disease. Cohen (10) has looked at mortality inolder community-dwelling adults. Subjects with the highest IL-6 and D-dimer elevations had a two-fold risk of mortality at fiveyears and a marked decline in functional status at four years.The four measures of the latter end point were the Katz, Nagi,Rasow-Breslau and I-ADL scales.Hypoalbuminenia and hypocholesterolemia are risk factors inolder adults for increased mortality. Volpato (11) has assayedhigh-density lipoprotein cholesterol (HDL-C) and albumin in anelderly population. Those with higher levels of HDL-C and albu-min and hypocholesterolemia did not have an increased morta-lity. Angiotensin converting enzyme (ACE) inhibitors (and sta-tins) reduce proinflammatory cytokines and therefore modulatethe cycle of frailty model.

Psychiatrie

Neurologie

Gériatrie

Réflexions et perspectives

Frailty in the older adultD. I.WollnerMD, FACP, AGSF, FAAHPM, Director of Palliative Care Services, VA New York Harbor Healthcare System, VISN 03 of the Veterans HealthAdministration (VHA). Address : Palliative Care Services, 800 Poly PL9-228 Brooklyn, New Tork City (NY) 11209, USA.

Correspondance : D. I. Wollner, address above.E-mail : Wollner@aol.com

David I.Wollner,MD,FACP,AGSF,FAAHPM is a Founding Member and a Directoron the Board of the AAHPM. He serves on the faculties of the Albert EinsteinCollege of Medicine and the SUNY Health Sciences Center both in New York.David Hamerman, MD is Director of the Resnick Gerontology Center andProfessor of Medicine at the Albert Einstein College of Medicine. I thank him forhis comments in the preparation of this manuscript.

40 Neurologie - Psychiatrie - Gériatrie / Année 5/Juin 2005. © Masson, 2005.Tous droits réservés.

Réflexions et perspectives

Figure 1 : cycle of frailty, integrating known pairwise causal relationships between symptoms and signs. Factors central to the cycle are indicated in bold. Potential etio-logic causes and outcomes are also indicated. (From Ref. 3, with permission of Springer-Verlag New York, Inc.). Copyright © 2003 Spring-Verlag New York, Inc. All rightsreserved.

Anorexia is common in neoplasic disease and seen in 40-80% ofadults with advanced illness. Weight loss occurs with sarcope-nia and malnutrition. Debility, in sensitivity to antineoplastictherapies and mortality follow. Hypercatabolism occurs with theanorexia-cachexia syndrome and thusly meshes with the cycleof frailty.There are several factors linked to the evolution of the anorexia-cachexia syndrome (12). Peripheral signaling factors (insulin, lep-tin, cholecystokinin (CCK) and malonyl coenzyme-A (malonyl Co-A), an energy signal, inhibits the prophagic factor neuropeptideY. The hypothalamic response to proinflammatory cytokines,including interferon gamma (IFA-γ) trigger anorexia. Elevatedlevels of serotonin in the hypothalamus are found in laboratorymodels of the anorexia-cachexia syndrome.Effective therapies for anorexia-cachexia include dietary anddrug strategies (13). Modification of dietary habits (energy densefood, frequent small meals) may be useful. Drug therapies avai-lable are conventional or experimental. Progestagens, corticos-teroids, cannabinoids, androgens, prokinetic agents and antide-pressants each, and in combination at times, improve nutritionalparameters and quality of life (QOL). Fish oils contain eicoso-pentaoic acid (EPA) and docosahexanoic acid (DHA). These N-3polyunsaturated fatty agents may cause weight stabilization inexperimental studies. When death is imminent, however, nur-

turing supercedes nutritional parameters, as comfort becomesthe primary goal of care.Depressive symptoms are very common in older adults and latelife depression is a chronic disorder. Anorexia and weight lossare two somatic symptoms commonly seen in depression. Aprospective study has shown that older adults with majordepression have a 1.8-fold higher risk of death (14). Adjustmentsfor health status and socioeconomic factors did not nullify thisobservation. Covinsky (15) has shown in an older, acutely ill popu-lation that the presence of six or more depressive symptomsleads to a 1.34-fold increase in mortality at 3 years when otherfactors are adjusted.De Jonge (16) has reported on a prospective study from theNetherlands. Five hundred fifty eight older adults having one offour sentinel events within a five-year period of baseline testingwere studied. Pre-event depressive symptoms were associatedwith an increased risk of poor social and role functioning, well-being and general health. All subjects had no prior evidence offrailty; therefore, depressive symptoms prior to a somatic eventmay imply psychological frailty and its poor outcomes.Research shows some important data. Falls can initiate a cas-cade of events leading to frailty. Depressed older adults mayhave an increased risk of falls. Guttman (17) has shown thatwhite matter hyperdensities on brain MRI studies in older adults

41Neurologie - Psychiatrie - Gériatrie / Année 5/Juin 2005. © Masson, 2005.Tous droits réservés.

Frailty in the older adultD. I. Wollner

who have fallen. Frontal lobe abnormalities may be linked toneurovegatative depressive symptoms. Cytokine induced inflam-mation of cerebral vessels links depression and falls to the syn-drome of frailty.The field of psycho-oncology has added vivid insights into thepsychological matrix of individuals with cancer and their clinicaloutcomes (18). Proinflammatory cytokines play a role in “sick-ness behaviors” frequently seen in cancer (fatigue, weakness,depression, anxiety). Cleeland (19) has looked at symptom clus-ters in cancer. His concept invokes the cytokine, prostaglandin,nitric oxide and substance-P effects on the mid-brain. Theseeffects induce symptom clusters including the picture of frailty.Aging and frailty are linked. Older adults are becoming an increa-singly larger proportion of many populations and the oldest-old(≥ 85 years) represent the most rapidly growing segment. Frailtyis an international public health issue (20). The challenges ofequity, quality of care, health services continuity and caregiversupports are daunting. Covinsky (21) has done a retrospectivestudy looking at the last two years of life of 917 frail older peopleenrolled in the Program of All-inclusive Care for the Elderly(PACE). All showed a progressive decline in function. The cogni-tively impaired, as measured by the Short Portable Mental StatusQuestionnaire (SPMSQ) had particularly high rates of functionalimpairment.Palliative care is a model of care and is defined by the AAHPM(22) :“Palliative care is comprehensive, specialized care providedby an interdisciplinary team to patients and families living witha life-threatening or severe advanced illness expected to pro-gress toward dying and where care is particularly focused onalleviating suffering and promoting quality of life. Majorconcerns are pain and symptom management, information sha-ring and advance care planning, psychosocial and spiritual sup-port, and coordination of care”.Frailty fits precisely within this definition as seen by its effects onphysical, psychosocio-spiritual, family, societal and globaldomains. Frailty as a syndrome has variable trajectories andwhen survival is limited, hospice, as a palliative care delivery sys-tem, will play an integral part in honoring preferences, assuringa safe and accompanied death and providing bereavement sup-port for caregivers. Frailty may be the final common pathway forchronic illness as death approaches. A uniform approach to this“phase terminale” can synchronize care and (23) lead to a “gooddeath”.Research in the defining, screening, diagnosis and treatment offrailty is urgently needed today. The nascent body of palliativecare researchers in the USA must forge partnerships with geron-tologists, oncology professionals and others to propose labora-tory and clinical studies. We, as hospice and palliative care pro-fessionals, will then be able to face the challenges of the 21stcentury epidemic of frailty in the older adult. ■

References

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